#METABOLOMICS WORKBENCH dowdytm_20210611_111543 DATATRACK_ID:2684 STUDY_ID:ST001838 ANALYSIS_ID:AN002980 PROJECT_ID:PR001160 VERSION 1 CREATED_ON June 24, 2021, 2:45 pm #PROJECT PR:PROJECT_TITLE Reversing Epigenetic Gene Silencing to Overcome Immune Evasion in CNS PR:PROJECT_TITLE Malignancies PR:PROJECT_SUMMARY Glioblastoma is an aggressive brain malignancy with a dismal prognosis. With PR:PROJECT_SUMMARY emerging evidence that disproves the immune privileged environment in the brain, PR:PROJECT_SUMMARY there is much interest in examining various immunotherapy strategies to treat PR:PROJECT_SUMMARY these incurable cancers. Unfortunately, to date, clinical studies investigating PR:PROJECT_SUMMARY immunotherapy regimens have not provided much evidence of efficacy, leading to PR:PROJECT_SUMMARY questions about the suitability of immunotherapy strategies for these tumors. PR:PROJECT_SUMMARY Inadequate inherent populations of lymphocytes in tumor (TILs) and limited PR:PROJECT_SUMMARY trafficking of systemic circulating T cells into the central nervous system PR:PROJECT_SUMMARY (CNS) likely contribute to the poor response to immunotherapy treatment for PR:PROJECT_SUMMARY primary CNS cancers. This paucity of TILs is in concert with the finding of PR:PROJECT_SUMMARY epigenetic silencing of genes that promote immune cell movement (chemotaxis) to PR:PROJECT_SUMMARY the tumor. In this study we evaluated the ability of GSK126, a blood-brain PR:PROJECT_SUMMARY barrier permeable small molecule inhibitor of EZH2, to reverse the epigenetic PR:PROJECT_SUMMARY silencing of chemokines like CXCL9 and CXCL10. When combined with anti-PD-1 PR:PROJECT_SUMMARY treatment, these IFN driven chemokines promote T cell infiltration, resulting in PR:PROJECT_SUMMARY decreased tumor growth and enhanced survival in immunocompetent murine PR:PROJECT_SUMMARY sub-cutaneous and intracranial tumor syngeneic models of GBM. Examination of the PR:PROJECT_SUMMARY tumor micro-environment revealed that the decrease in tumor growth in the mice PR:PROJECT_SUMMARY treated with the drug combination was accompanied by increased tumor CD8 T cell PR:PROJECT_SUMMARY infiltration along with higher IFN expression. Additionally, a significant PR:PROJECT_SUMMARY increase in CXCR3+ T cells in the draining lymph nodes was also found. Taken PR:PROJECT_SUMMARY together, our data suggests that in glioblastoma, epigenetic modulation using PR:PROJECT_SUMMARY GSK126 could improve current immunotherapy strategies by reversing the PR:PROJECT_SUMMARY epigenetic changes that enable immune cell evasion leading to enhanced immune PR:PROJECT_SUMMARY c-ll trafficking to the tumor. PR:INSTITUTE National Cancer Institute PR:DEPARTMENT Neuro-Oncology Branch PR:LABORATORY Cancer Metabolism PR:LAST_NAME Dowdy PR:FIRST_NAME Tyrone PR:ADDRESS 37 convent dr, Bldg 37 rm 1142 PR:EMAIL tyrone.dowdy@nih.gov PR:PHONE 2407607066 PR:CONTRIBUTORS Nivedita M. Ratnam1, Heather M. Sonnemann1, Stephen C. Frederico1, Huanwen PR:CONTRIBUTORS Chen1, Marsha-Kay N.D. Hutchinson1, Tyrone Dowdy1, Caitlin M. Reid1, Jinkyu PR:CONTRIBUTORS Jung1, Wei Zhang1, Hua Song1, Meili Zhang1, Dionne Davis1, Mioara Larion1, Amber PR:CONTRIBUTORS J. Giles1 and Mark R. Gilbert1*. #STUDY ST:STUDY_TITLE Reversing Epigenetic Gene Silencing to Overcome Immune Evasion in CNS ST:STUDY_TITLE Malignancies ST:STUDY_SUMMARY Glioblastoma is an aggressive brain malignancy with a dismal prognosis. With ST:STUDY_SUMMARY emerging evidence that disproves the immune privileged environment in the brain, ST:STUDY_SUMMARY there is much interest in examining various immunotherapy strategies to treat ST:STUDY_SUMMARY these incurable cancers. Unfortunately, to date, clinical studies investigating ST:STUDY_SUMMARY immunotherapy regimens have not provided much evidence of efficacy, leading to ST:STUDY_SUMMARY questions about the suitability of immunotherapy strategies for these tumors. ST:STUDY_SUMMARY Inadequate inherent populations of lymphocytes in tumor (TILs) and limited ST:STUDY_SUMMARY trafficking of systemic circulating T cells into the central nervous system ST:STUDY_SUMMARY (CNS) likely contribute to the poor response to immunotherapy treatment for ST:STUDY_SUMMARY primary CNS cancers. This paucity of TILs is in concert with the finding of ST:STUDY_SUMMARY epigenetic silencing of genes that promote immune cell movement (chemotaxis) to ST:STUDY_SUMMARY the tumor. In this study we evaluated the ability of GSK126, a blood-brain ST:STUDY_SUMMARY barrier permeable small molecule inhibitor of EZH2, to reverse the epigenetic ST:STUDY_SUMMARY silencing of chemokines like CXCL9 and CXCL10. When combined with anti-PD-1 ST:STUDY_SUMMARY treatment, these IFN driven chemokines promote T cell infiltration, resulting in ST:STUDY_SUMMARY decreased tumor growth and enhanced survival in immunocompetent murine ST:STUDY_SUMMARY sub-cutaneous and intracranial tumor syngeneic models of GBM. Examination of the ST:STUDY_SUMMARY tumor micro-environment revealed that the decrease in tumor growth in the mice ST:STUDY_SUMMARY treated with the drug combination was accompanied by increased tumor CD8 T cell ST:STUDY_SUMMARY infiltration along with higher IFN expression. Additionally, a significant ST:STUDY_SUMMARY increase in CXCR3+ T cells in the draining lymph nodes was also found. Taken ST:STUDY_SUMMARY together, our data suggests that in glioblastoma, epigenetic modulation using ST:STUDY_SUMMARY GSK126 could improve current immunotherapy strategies by reversing the ST:STUDY_SUMMARY epigenetic changes that enable immune cell evasion leading to enhanced immune ST:STUDY_SUMMARY cell trafficking to the tumor. ST:INSTITUTE National Cancer Institute ST:DEPARTMENT Neuro-Oncology Branch ST:LABORATORY Cancer Metabolism ST:LAST_NAME Dowdy ST:FIRST_NAME Tyrone ST:ADDRESS 37 convent dr, Bldg 37 rm 1142 ST:EMAIL tyrone.dowdy@nih.gov ST:PHONE 2407607066 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENOTYPE_STRAIN albino C57BL/6 SU:AGE_OR_AGE_RANGE 6-8 weeks SU:GENDER Female SU:ANIMAL_HOUSING NCI-Bethesda Animal Facility SU:ANIMAL_ANIMAL_SUPPLIER Jackson Laboratories (Bar Harbor, ME) #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS blank Blank_S14.d Treatment:blank | Gsk Exposure Time (h):- Specimen Group=blank; Mice Tumor SI#=blank; sample quantity)=-; (units)=blank; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S14.d SUBJECT_SAMPLE_FACTORS blank blank_S22.d Treatment:blank | Gsk Exposure Time (h):- Specimen Group=blank; Mice Tumor SI#=blank; sample quantity)=-; (units)=blank; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S22.d SUBJECT_SAMPLE_FACTORS blank blank_Sr62.d Treatment:blank | Gsk Exposure Time (h):- Specimen Group=blank; Mice Tumor SI#=blank; sample quantity)=-; (units)=blank; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr62blk.d SUBJECT_SAMPLE_FACTORS Intra1_BRN_g1_2h_mg19.335 BRN_g1 _Intra1_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=BRN_g1; Mice Tumor SI#=Intracranial1; sample quantity)=19.335; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr73.d SUBJECT_SAMPLE_FACTORS Intra2_BRN_g1_2h_mg19.835 BRN_g1 _Intra2_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=BRN_g1; Mice Tumor SI#=Intracranial2; sample quantity)=19.835; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr74.d SUBJECT_SAMPLE_FACTORS Intra3_BRN_g1_2h_mg20.96 BRN_g1 _Intra3_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=BRN_g1; Mice Tumor SI#=Intracranial3; sample quantity)=20.96; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr75.d SUBJECT_SAMPLE_FACTORS Intra4_BRN_g1_6h_mg25.175 BRN_g1 _Intra4_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=BRN_g1; Mice Tumor SI#=Intracranial4; sample quantity)=25.175; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr76.d SUBJECT_SAMPLE_FACTORS Intra5_BRN_g1_6h_mg16.81 BRN_g1 _Intra5_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=BRN_g1; Mice Tumor SI#=Intracranial5; sample quantity)=16.81; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr77.d SUBJECT_SAMPLE_FACTORS Intra7_BRN_g1_10h_mg18.28 BRN_g1 _Intra7_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=BRN_g1; Mice Tumor SI#=Intracranial7; sample quantity)=18.28; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr78.d SUBJECT_SAMPLE_FACTORS Intra8_BRN_g1_10h_mg16 BRN_g1 _Intra8_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=BRN_g1; Mice Tumor SI#=Intracranial8; sample quantity)=16; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr79.d SUBJECT_SAMPLE_FACTORS Intra10_BRN_g2_2h_mg22.06 BRN_ctrl_g2_Intra10_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=BRN_g2; Mice Tumor SI#=Intracranial10; sample quantity)=22.06; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr93.d SUBJECT_SAMPLE_FACTORS Intra11_BRN_g2_2h_mg16.44 BRN_ctrl_g2_Intra11_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=BRN_g2; Mice Tumor SI#=Intracranial11; sample quantity)=16.44; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr94.d SUBJECT_SAMPLE_FACTORS Intra12_BRN_g2_6h_mg18.26 BRN_ctrl_g2_Intra12_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=BRN_g2; Mice Tumor SI#=Intracranial12; sample quantity)=18.26; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr95.d SUBJECT_SAMPLE_FACTORS Intra13_BRN_g2_6h_mg18.35 BRN_ctrl_g2_Intra13_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=BRN_g2; Mice Tumor SI#=Intracranial13; sample quantity)=18.35; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr96.d SUBJECT_SAMPLE_FACTORS Intra14_BRN_g2_6h_mg16 BRN_ctrl_g2_Intra14_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=BRN_g2; Mice Tumor SI#=Intracranial14; sample quantity)=16; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr97.d SUBJECT_SAMPLE_FACTORS Intra15_BRN_g2_10h_mg21.2 BRN_ctrl_g2_Intra15_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=BRN_g2; Mice Tumor SI#=Intracranial15; sample quantity)=21.2; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr98.d SUBJECT_SAMPLE_FACTORS Intra16_BRN_g2_10h_mg18.6 BRN_ctrl_g2_Intra16_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=BRN_g2; Mice Tumor SI#=Intracranial16; sample quantity)=18.6; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr99.d SUBJECT_SAMPLE_FACTORS SubCu1_DLN_g1_2h_mg1.92 SubCu1_DLN_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu1_DLN; sample quantity)=1.92; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_004.d SUBJECT_SAMPLE_FACTORS SubCu2_DLN_g1_2h_mg8.04 SubCu2_DLN_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu2_DLN; sample quantity)=8.04; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_008.d SUBJECT_SAMPLE_FACTORS SubCu3_DLN_g1_2h_mg2.945 SubCu3_DLN_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu3_DLN; sample quantity)=2.945; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_007.d SUBJECT_SAMPLE_FACTORS SubCu4_DLN_g1_6h_mg1.82 SubCu4_DLN_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu4_DLN; sample quantity)=1.82; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_017.d SUBJECT_SAMPLE_FACTORS SubCu5_DLN_g1_6h_mg3.145 SubCu5_DLN_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu5_DLN; sample quantity)=3.145; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_018.d SUBJECT_SAMPLE_FACTORS SubCu6_DLN_g1_6h_mg2.21 SubCu6_DLN_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu6_DLN; sample quantity)=2.21; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_021.d SUBJECT_SAMPLE_FACTORS SubCu7_DLN_g1_10h_mg1.5 SubCu7_DLN_g1_10 Treatment:GSK | Gsk Exposure Time (h):10 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu7_DLN; sample quantity)=1.5; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_023.d SUBJECT_SAMPLE_FACTORS SubCu8_DLN_g1_10h_mg3 SubCu8_DLN_g1_10 Treatment:GSK | Gsk Exposure Time (h):10 Specimen Group=DLN_g1; Mice Tumor SI#=SubCu8_DLN; sample quantity)=3; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_024.d SUBJECT_SAMPLE_FACTORS SubCu9_DLN_g2_2h_mg10.475 SubCu9_DLN_ctrl_g2_2h_ Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=DLN_g2; Mice Tumor SI#=SubCu9_DLN; sample quantity)=10.475; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_065.d SUBJECT_SAMPLE_FACTORS SubCu10_DLN_g2_2h_mg3.07 SubCu10_DLN_ctrl_g2_2h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=DLN_g2; Mice Tumor SI#=SubCu10_DLN; sample quantity)=3.07; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_066.d SUBJECT_SAMPLE_FACTORS SubCu11_DLN_g2_2h_mg2.49 SubCu11_DLN_ctrl_g2_2h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=DLN_g2; Mice Tumor SI#=SubCu11_DLN; sample quantity)=2.49; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_068.d SUBJECT_SAMPLE_FACTORS SubCu12_DLN_g2_6h_mg4.505 SubCu12_DLN_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=DLN_g2; Mice Tumor SI#=SubCu12_DLN; sample quantity)=4.505; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_069.d SUBJECT_SAMPLE_FACTORS SubCu13_DLN_g2_6h_mg12.535 SubCu13_DLN_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=DLN_g2; Mice Tumor SI#=SubCu13_DLN; sample quantity)=2.535; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_072.d SUBJECT_SAMPLE_FACTORS SubCu15_DLN_g2_10h_mg6.26 SubCu15_DLN_ctrl_g2_10h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=DLN_g2; Mice Tumor SI#=SubCu15_DLN; sample quantity)=6.26; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_075.d SUBJECT_SAMPLE_FACTORS SubCu16_DLN_g2_10h_mg5.39 SubCu16_DLN_ctrl_g2_10h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=DLN_g2; Mice Tumor SI#=SubCu16_DLN; sample quantity)=5.39; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_078.d SUBJECT_SAMPLE_FACTORS Intra1_LLN_g1_2h_mg3.05 LLN_g1 _Intra1_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=LLN_g1; Mice Tumor SI#=Intracranial1; sample quantity)=3.05; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1004.d SUBJECT_SAMPLE_FACTORS Intra2_LLN_g1_2h_mg5 LLN_g1 _Intra2_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=LLN_g1; Mice Tumor SI#=Intracranial2; sample quantity)=5; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1005.d SUBJECT_SAMPLE_FACTORS Intra3_LLN_g1_2h_mg1.975 LLN_g1 _Intra3_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=LLN_g1; Mice Tumor SI#=Intracranial3; sample quantity)=1.975; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1006.d SUBJECT_SAMPLE_FACTORS Intra4_LLN_g1_6h_mg1.03 LLN_g1 _Intra4_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=LLN_g1; Mice Tumor SI#=Intracranial4; sample quantity)=1.03; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1007.d SUBJECT_SAMPLE_FACTORS Intra6_LLN_g1_6h_mg0.975 LLN_g1 _Intra6_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=LLN_g1; Mice Tumor SI#=Intracranial6; sample quantity)=0.975; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1008.d SUBJECT_SAMPLE_FACTORS Intra7_LLN_g1_10h_mg0.975 LLN_g1 _Intra7_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=LLN_g1; Mice Tumor SI#=Intracranial7; sample quantity)=0.975; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1009.d SUBJECT_SAMPLE_FACTORS Intra8_LLN_g1_10h_mg1.935 LLN_g1 _Intra8_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=LLN_g1; Mice Tumor SI#=Intracranial8; sample quantity)=1.935; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1010.d SUBJECT_SAMPLE_FACTORS Intra10_LLN_g2_2h_mg0.87 LLN_ctrl_g2_Intra10_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=LLN_g2; Mice Tumor SI#=Intracranial10; sample quantity)=0.87; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1013.d SUBJECT_SAMPLE_FACTORS Intra11_LLN_g2_2h_mg1.65 LLN_ctrl_g2_Intra11_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=LLN_g2; Mice Tumor SI#=Intracranial11; sample quantity)=1.65; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1014.d SUBJECT_SAMPLE_FACTORS Intra12_LLN_g2_6h_mg0.965 LLN_ctrl_g2_Intra12_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=LLN_g2; Mice Tumor SI#=Intracranial12; sample quantity)=0.965; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1015.d SUBJECT_SAMPLE_FACTORS Intra13_LLN_g2_6h_mg2.885 LLN_ctrl_g2_Intra13_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=LLN_g2; Mice Tumor SI#=Intracranial13; sample quantity)=2.885; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1016.d SUBJECT_SAMPLE_FACTORS Intra15_LLN_g2_10h_mg1.345 LLN_ctrl_g2_Intra15_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=LLN_g2; Mice Tumor SI#=Intracranial15; sample quantity)=1.345; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1018.d SUBJECT_SAMPLE_FACTORS Intra16_LLN_g2_10h_mg1.25 LLN_ctrl_g2_Intra16_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=LLN_g2; Mice Tumor SI#=Intracranial16; sample quantity)=1.25; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1019.d SUBJECT_SAMPLE_FACTORS Intra9_LLN_g2_2h_mg0.8 LLN_ctrl_g2 _Intra9_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=LLN_g2; Mice Tumor SI#=Intracranial9; sample quantity)=0.8; (units)=mg; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1012.d SUBJECT_SAMPLE_FACTORS SubCu1_NLN_g1_2h_mg2.08 SubCu1_NLN_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu1_NLN; sample quantity)=2.08; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_005.d SUBJECT_SAMPLE_FACTORS SubCu2_NLN_g1_2h_mg5.82 SubCu2_NLN_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu2_NLN; sample quantity)=5.82; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_006.d SUBJECT_SAMPLE_FACTORS SubCu3_NLN_g1_2h_mg2.03 SubCu3_NLN_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu3_NLN; sample quantity)=2.03; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_009.d SUBJECT_SAMPLE_FACTORS SubCu4_NLN_g1_6h_mg3.64 SubCu4_NLN_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu4_NLN; sample quantity)=3.64; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_016.d SUBJECT_SAMPLE_FACTORS SubCu5_NLN_g1_6h_mg1.8 SubCu5_NLN_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu5_NLN; sample quantity)=1.8; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_020.d SUBJECT_SAMPLE_FACTORS SubCu6_NLN_g1_6h_mg1.62 SubCu6_NLN_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu6_NLN; sample quantity)=1.62; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_019.d SUBJECT_SAMPLE_FACTORS SubCu7_NLN_g1_10h_mg2.36 SubCu7_NLN_g1_10 Treatment:GSK | Gsk Exposure Time (h):10 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu7_NLN; sample quantity)=2.36; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_022.d SUBJECT_SAMPLE_FACTORS SubCu8_NLN_g1_10h_mg3.48 SubCu8_NLN_g1_10 Treatment:GSK | Gsk Exposure Time (h):10 Specimen Group=NLN_g1; Mice Tumor SI#=SubCu8_NLN; sample quantity)=3.48; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_025.d SUBJECT_SAMPLE_FACTORS SubCu9_NLN_g2_2h_mg4.45 SubCu9_NLN_ctrl_g2_2h_ Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu9_NLN; sample quantity)=4.45; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_067.d SUBJECT_SAMPLE_FACTORS SubCu10_NLN_g2_2h_mg2.58 SubCu10_NLN_ctrl_g2_2h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu10_NLN; sample quantity)=2.58; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_063.d SUBJECT_SAMPLE_FACTORS SubCu11_NLN_g2_2h_mg4.5 SubCu11_NLN_ctrl_g2_2h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu11_NLN; sample quantity)=4.5; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_064.d SUBJECT_SAMPLE_FACTORS SubCu12_NLN_g2_6h_mg7.29 SubCu12_NLN_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu12_NLN; sample quantity)=7.29; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_070.d SUBJECT_SAMPLE_FACTORS SubCu13_NLN_g2_6h_mg3.37 SubCu13_NLN_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu13_NLN; sample quantity)=3.37; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_071.d SUBJECT_SAMPLE_FACTORS SubCu14_NLN_g2_6h_mg8.03 SubCu14_NLN_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu14_NLN; sample quantity)=8.03; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_074.d SUBJECT_SAMPLE_FACTORS SubCu15_NLN_g2_10h_mg2.81 SubCu15_NLN_ctrl_g2_10h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu15_NLN; sample quantity)=2.81; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_076.d SUBJECT_SAMPLE_FACTORS SubCu16_NLN_g2_10h_mg3.16 SubCu16_NLN_ctrl_g2_10h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=NLN_g2; Mice Tumor SI#=SubCu16_NLN; sample quantity)=3.16; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_077.d SUBJECT_SAMPLE_FACTORS QcBRN QcBRN_S45.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QcBRN; Mice Tumor SI#=QcBRN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S45.d SUBJECT_SAMPLE_FACTORS QcBRN QcBRN_Sr91.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QcBRN; Mice Tumor SI#=QcBRN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr91.d SUBJECT_SAMPLE_FACTORS QcBRN QcBRN_Sr111.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QcBRN; Mice Tumor SI#=QcBRN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr111.d SUBJECT_SAMPLE_FACTORS QcBRN QcBRN_Sr65.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QcBRN; Mice Tumor SI#=QcBRN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr65.d SUBJECT_SAMPLE_FACTORS QcLLN QcLLN_L1002.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QcLLN_Intra; Mice Tumor SI#=QcLLN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_L1002.d SUBJECT_SAMPLE_FACTORS QCpool g1 D_NLN QCpool g1 D_NLN_subcu_055.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 D_NLN; Mice Tumor SI#=QCpool g1 D_NLN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_055.d SUBJECT_SAMPLE_FACTORS QCpool g1 D_NLN QCpool g1 D_NLN_subcu_081.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 D_NLN; Mice Tumor SI#=QCpool g1 D_NLN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_081.d SUBJECT_SAMPLE_FACTORS QCpool g1 D_NLN QCpool g1 D_NLN_subcu_135.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 D_NLN; Mice Tumor SI#=QCpool g1 D_NLN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_135.d SUBJECT_SAMPLE_FACTORS QCpool g1 D_NLN QCpool g1 D_NLN_subcu_012.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 D_NLN; Mice Tumor SI#=QCpool g1 D_NLN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_012.d SUBJECT_SAMPLE_FACTORS QCpool g1 D_NLN QCpool g1 D_NLN_subcu_028.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 D_NLN; Mice Tumor SI#=QCpool g1 D_NLN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_028.d SUBJECT_SAMPLE_FACTORS QCpool g1 D_NLN QCpool g1 D_NLN_subcu_037.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 D_NLN; Mice Tumor SI#=QCpool g1 D_NLN; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_037.d SUBJECT_SAMPLE_FACTORS QCpool g1 SubTum QCpool g1 SubTum_038.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 SubTum; Mice Tumor SI#=QCpool g1 SubTum; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_038.d SUBJECT_SAMPLE_FACTORS QCpool g1 SubTum QCpool g1 SubTum_056.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 SubTum; Mice Tumor SI#=QCpool g1 SubTum; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_056.d SUBJECT_SAMPLE_FACTORS QCpool g1 SubTum QCpool g1 SubTum_082.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 SubTum; Mice Tumor SI#=QCpool g1 SubTum; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_082.d SUBJECT_SAMPLE_FACTORS QCpool g1 SubTum QCpool g1 SubTum_136.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QCpool g1 SubTum; Mice Tumor SI#=QCpool g1 SubTum; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_136.d SUBJECT_SAMPLE_FACTORS QcSer QcSer_S24.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QcSer; Mice Tumor SI#=QcSer_; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S24.d SUBJECT_SAMPLE_FACTORS QcSer QcSer_S44.d Treatment:QC | Gsk Exposure Time (h):- Specimen Group=QcSer; Mice Tumor SI#=QcSer; sample quantity)=-; (units)=Qc; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S44.d SUBJECT_SAMPLE_FACTORS Subcutaneous1_SER_g1_2h_mL0.05 SER_g1 _Subcutaneous1_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous1; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S6.d SUBJECT_SAMPLE_FACTORS Subcutaneous2_SER_g1_2h_mL0.05 SER_g1 _Subcutaneous2_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous2; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S7.d SUBJECT_SAMPLE_FACTORS Subcutaneous3_SER_g1_2h_mL0.05 SER_g1 _Subcutaneous3_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous3; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S8.d SUBJECT_SAMPLE_FACTORS Subcutaneous4_SER_g1_6h_mL0.05 SER_g1 _Subcutaneous4_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous4; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S9.d SUBJECT_SAMPLE_FACTORS Subcutaneous5_SER_g1_6h_mL0.05 SER_g1 _Subcutaneous5_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous5; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S10.d SUBJECT_SAMPLE_FACTORS Subcutaneous6_SER_g1_6h_mL0.05 SER_g1 _Subcutaneous6_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous6; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S11.d SUBJECT_SAMPLE_FACTORS Subcutaneous7_SER_g1_10h_mL0.05 SER_g1 _Subcutaneous7_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous7; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S12.d SUBJECT_SAMPLE_FACTORS Subcutaneous8_SER_g1_10h_mL0.05 SER_g1 _Subcutaneous8_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=SER_g1; Mice Tumor SI#=Subcutaneous8; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S13.d SUBJECT_SAMPLE_FACTORS Intra1_SER_g1_2h_mL0.05 SER_g1 _Intra1_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial1; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S35.d SUBJECT_SAMPLE_FACTORS Intra2_SER_g1_2h_mL0.05 SER_g1 _Intra2_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial2; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S36.d SUBJECT_SAMPLE_FACTORS Intra3_SER_g1_2h_mL0.05 SER_g1 _Intra3_2h Treatment:GSK | Gsk Exposure Time (h):2.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial3; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S37.d SUBJECT_SAMPLE_FACTORS Intra4_SER_g1_6h_mL0.05 SER_g1 _Intra4_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial4; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S38.d SUBJECT_SAMPLE_FACTORS Intra7_SER_g1_10h_mL0.05 SER_g1 _Intra7_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial7; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S41.d SUBJECT_SAMPLE_FACTORS Intra8_SER_g1_10h_mL0.05 SER_g1 _Intra8_10h Treatment:GSK | Gsk Exposure Time (h):10.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial8; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S42s.d SUBJECT_SAMPLE_FACTORS Intra5_SER_g1_6h_mL0.05 SER_g1 _Intra5_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial5; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr69.d SUBJECT_SAMPLE_FACTORS Intra6_SER_g1_6h_mL0.05 SER_g1 _Intra6_6h Treatment:GSK | Gsk Exposure Time (h):6.0 Specimen Group=SER_g1; Mice Tumor SI#=Intracranial6; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_Sr70.d SUBJECT_SAMPLE_FACTORS Subcutaneous10_SER_g2_2h_mL0.05 SER_ctrl_g2_Subcutaneous10_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Subcutaneous10; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S16.d SUBJECT_SAMPLE_FACTORS Subcutaneous12_SER_g2_6h_mL0.05 SER_ctrl_g2_Subcutaneous12_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Subcutaneous12; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S17.d SUBJECT_SAMPLE_FACTORS Subcutaneous13_SER_g2_6h_mL0.05 SER_ctrl_g2_Subcutaneous13_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Subcutaneous13; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S18.d SUBJECT_SAMPLE_FACTORS Subcutaneous14_SER_g2_6h_mL0.05 SER_ctrl_g2_Subcutaneous14_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Subcutaneous14; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S19.d SUBJECT_SAMPLE_FACTORS Subcutaneous15_SER_g2_10h_mL0.05 SER_ctrl_g2_Subcutaneous15_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Subcutaneous15; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S20.d SUBJECT_SAMPLE_FACTORS Subcutaneous16_SER_g2_10h_mL0.05 SER_ctrl_g2_Subcutaneous16_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Subcutaneous16; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S21.d SUBJECT_SAMPLE_FACTORS Intra10_SER_g2_2h_mL0.05 SER_ctrl_g2_Intra10_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial10; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S27.d SUBJECT_SAMPLE_FACTORS Intra11_SER_g2_2h_mL0.05 SER_ctrl_g2_Intra11_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial11; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S28.d SUBJECT_SAMPLE_FACTORS Intra12_SER_g2_6h_mL0.05 SER_ctrl_g2_Intra12_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial12; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S29.d SUBJECT_SAMPLE_FACTORS Intra13_SER_g2_6h_mL0.05 SER_ctrl_g2_Intra13_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial13; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S30.d SUBJECT_SAMPLE_FACTORS Intra14_SER_g2_6h_mL0.05 SER_ctrl_g2_Intra14_6h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial14; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S31.d SUBJECT_SAMPLE_FACTORS Intra15_SER_g2_10h_mL0.05 SER_ctrl_g2_Intra15_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial15; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S32.d SUBJECT_SAMPLE_FACTORS Intra16_SER_g2_10h_mL0.05 SER_ctrl_g2_Intra16_10h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial16; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S33.d SUBJECT_SAMPLE_FACTORS Intra9_SER_g2_2h_mL0.05 SER_ctrl_g2 _Intra9_2h Treatment:Vehicle | Gsk Exposure Time (h):0.0 Specimen Group=SER_g2; Mice Tumor SI#=Intracranial9; sample quantity)=0.05; (units)=mL; RAW_FILE_NAME=1108.19 GSK126_quant527_3129_Nivi_S26.d SUBJECT_SAMPLE_FACTORS SubCu1_Tum_g1_2h_mg18.135 SubCu1_Tum_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu1_Tum; sample quantity)=8.135; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_045.d SUBJECT_SAMPLE_FACTORS SubCu2_Tum_g1_2h_mg16.89 SubCu2_Tum_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu2_Tum; sample quantity)=16.89; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_046.d SUBJECT_SAMPLE_FACTORS SubCu3_Tum_g1_2h_mg19.13 SubCu3_Tum_g1_2h Treatment:GSK | Gsk Exposure Time (h):2.00 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu3_Tum; sample quantity)=19.13; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_047.d SUBJECT_SAMPLE_FACTORS SubCu4_Tum_g1_6h_mg20.02 SubCu4_Tum_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu4_Tum; sample quantity)=20.02; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_048.d SUBJECT_SAMPLE_FACTORS SubCu5_Tum_g1_6h_mg21.3 SubCu5_Tum_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu5_Tum; sample quantity)=21.3; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_049.d SUBJECT_SAMPLE_FACTORS SubCu6_Tum_g1_6h_mg18.17 SubCu6_Tum_g1_6h Treatment:GSK | Gsk Exposure Time (h):6.00 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu6_Tum; sample quantity)=18.17; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_050.d SUBJECT_SAMPLE_FACTORS SubCu7_Tum_g1_10h_mg20.63 SubCu7_Tum_g1_10 Treatment:GSK | Gsk Exposure Time (h):10 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu7_Tum; sample quantity)=20.63; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_051.d SUBJECT_SAMPLE_FACTORS SubCu8_Tum_g1_10h_mg22 SubCu8_Tum_g1_10 Treatment:GSK | Gsk Exposure Time (h):10 Specimen Group=Tum_g1; Mice Tumor SI#=SubCu8_Tum; sample quantity)=22; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_052.d SUBJECT_SAMPLE_FACTORS SubCu9_Tum_g2_2h_mg20.28 SubCu9_Tum_ctrl_g2_2h_ Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu9_Tum; sample quantity)=20.28; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_089.d SUBJECT_SAMPLE_FACTORS SubCu10_Tum_g2_2h_mg17.5 SubCu10_Tum_ctrl_g2_2h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu10_Tum; sample quantity)=17.5; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_090.d SUBJECT_SAMPLE_FACTORS SubCu11_Tum_g2_2h_mg26.15 SubCu11_Tum_ctrl_g2_2h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu11_Tum; sample quantity)=26.15; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_091.d SUBJECT_SAMPLE_FACTORS SubCu12_Tum_g2_6h_mg22.8 SubCu12_Tum_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu12_Tum; sample quantity)=22.8; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_092.d SUBJECT_SAMPLE_FACTORS SubCu13_Tum_g2_6h_mg23 SubCu13_Tum_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu13_Tum; sample quantity)=23; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_093.d SUBJECT_SAMPLE_FACTORS SubCu14_Tum_g2_6h_mg19.2 SubCu14_Tum_ctrl_g2_6h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu14_Tum; sample quantity)=19.2; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_094.d SUBJECT_SAMPLE_FACTORS SubCu15_Tum_g2_10h_mg25.13 SubCu15_Tum_ctrl_g2_10h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu15_Tum; sample quantity)=25.13; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_095.d SUBJECT_SAMPLE_FACTORS SubCu16_Tum_g2_10h_mg18.89 SubCu16_Tum_ctrl_g2_10h Treatment:Vehicle | Gsk Exposure Time (h):0.00 Specimen Group=Tum_g2; Mice Tumor SI#=SubCu16_Tum; sample quantity)=18.89; (units)=mg; RAW_FILE_NAME=1126.19 GSK126_quant527_176_Nivi_subcu_096.d #COLLECTION CO:COLLECTION_SUMMARY All animal experiments were performed following the guidelines stipulated by the CO:COLLECTION_SUMMARY NCI-Bethesda Animal Care and Use Committee. All murine studies were performed CO:COLLECTION_SUMMARY using female albino C57BL/6 mice, 6-8 weeks of age, procured from Jackson CO:COLLECTION_SUMMARY Laboratories (Bar Harbor, ME). For sub-cutaneous tumor studies, 6x10^6 cells of CO:COLLECTION_SUMMARY stably transduced CT2A glioma cells with mCherry-firefly luciferase were CO:COLLECTION_SUMMARY injected in 100 μL PBS. For intracranial tumor studies, 1x10^2 CT2A cells with CO:COLLECTION_SUMMARY mCherry- firefly luciferase were injected in 2uL PBS. GSK126 for in vivo studies CO:COLLECTION_SUMMARY was obtained from the NCI- Drug Synthesis and Chemistry Branch and dissolved in CO:COLLECTION_SUMMARY 20% SBE-Cyclodextrin (MedChemExpress, HY-17031) pH 4-4.5 with 1N acetic acid. CO:COLLECTION_SUMMARY Vehicle was 20% SBE-Cyclodextrin pH 4-4.5 with 1N acetic acid. Water-soluble CO:COLLECTION_SUMMARY dexamethasone (Sigma Aldrich; D2915) was administered at 1mg/kg/day also by CO:COLLECTION_SUMMARY intraperitoneal injection. Anti PD-1(InVivoMAb; BE0146) or isotype control, rat CO:COLLECTION_SUMMARY IgG2a (InVivoMAb; BE0089) were also injected intraperitoneally. Subcutaneous CO:COLLECTION_SUMMARY tumor growth was measured using calipers and thereafter tumor volume was CO:COLLECTION_SUMMARY calculated using the formula for the volume of an ellipsoid given below. In the CO:COLLECTION_SUMMARY case of intracranial tumors, tumor growth was measured using the luminescence CO:COLLECTION_SUMMARY reader IVIS Ilumina and analyzed using LivingImage Software. Samples were CO:COLLECTION_SUMMARY collected from mice with three biological replicates. Serum (50 µL) was CO:COLLECTION_SUMMARY transferred to 200 μL ice-chilled (4°C) MilliQ H2O. Tissue (~16 mg) was CO:COLLECTION_SUMMARY measured from subcutaneous and intracranial samples followed by addition of 250 CO:COLLECTION_SUMMARY μL MilliQ H2O. Then, samples were sonicated at 40 amps (~30 s) until CO:COLLECTION_SUMMARY homogeneous. 80 μL of at 0.150 µg/mL debrisoquine in 60% methanol (MeOH)/40% CO:COLLECTION_SUMMARY water(aq) reagent was added. 500 μL chilled (-20°C) MeOH was added, vortexed CO:COLLECTION_SUMMARY (med) and incubated 15 min on ice. 250 μL chilled (-20°C) Chloroform was CO:COLLECTION_SUMMARY added, vortexed (high) and incubated 20 min in ice on rotating mixer. Mixture CO:COLLECTION_SUMMARY was centrifuged (13,000x g) for 18 min at 4°C. 705 μL of hydrophilic upper CO:COLLECTION_SUMMARY layer was aspirated and transferred to separate 1.5 mL microtubes, dried to CO:COLLECTION_SUMMARY completion under N2 gas sample concentrator, and stored at -80°C until LC/MS CO:COLLECTION_SUMMARY quantification of GSK126. CO:SAMPLE_TYPE Tumor cells CO:COLLECTION_METHOD Tumor Tissue/Serum Extract CO:COLLECTION_LOCATION Intracranial/Subcutaneous/Serum from Mice CO:COLLECTION_FREQUENCY Timepoints CO:COLLECTION_DURATION 0, 2h, 6h and 10h CO:VOLUMEORAMOUNT_COLLECTED Serum (50 µL)/Tumor (~16 mg) CO:STORAGE_CONDITIONS -80℃ CO:COLLECTION_VIALS 15 mL CO:STORAGE_VIALS 1.7 mL CO:COLLECTION_TUBE_TEMP On Ice CO:ADDITIVES Extraction reagent #TREATMENT TR:TREATMENT_SUMMARY Treatment details • The mice were euthanized 2h, 6h and10h after drug TR:TREATMENT_SUMMARY treatment 27days after tumor injections and 12 days of continuous drug TR:TREATMENT_SUMMARY treatment. • The mice injected with intracranial tumors weighed approximately TR:TREATMENT_SUMMARY 16g and received 100mg/kg dose of GSK126/ vehicle injected intra-peritoneally in TR:TREATMENT_SUMMARY 100uL volume. • The mice injected with subcutaneous tumors weighed TR:TREATMENT_SUMMARY approximately 19g and received 100mg/kg dose of GSK 126/ vehicle injected TR:TREATMENT_SUMMARY intra-peritoneally in 120uL volume. • For euthanasia, the mice were injected TR:TREATMENT_SUMMARY with 200mg/kg ketamine (200uL/mouse). • Tissues harvested (frozen immediately) TR:TREATMENT_SUMMARY include: Intracranial mice a) Brain bearing tumor b) Lumbar lymph node c) Serum TR:TREATMENT_SUMMARY from cardiac bleed Subcutaneous mice a) Sub-cutaneous tumor b) Tumor draining TR:TREATMENT_SUMMARY inguinal lymph node (DLN) c) Non- tumor draining inguinal lymph node (NDLN) d) TR:TREATMENT_SUMMARY Serum from cardiac bleed Drug Preparation • Dissolved 1g of GSK 126 powder in TR:TREATMENT_SUMMARY 8.325mL DMSO to get a conc. of 120.12mg/mL, aliquot and store in -80C. • TR:TREATMENT_SUMMARY Dilute the GSK126 stock in 7 parts of Cyclodextrin (2-hydroxy-beta-cyclodextrin) TR:TREATMENT_SUMMARY to get a concentration of 15mg/mL of drug (done fresh everyday) and then inject TR:TREATMENT_SUMMARY 100uL/120uL per mouse as indicated above. • Cyclodextrin was prepared by TR:TREATMENT_SUMMARY dissolving 45g in 100mL ddH20 as indicated by manufacturer’s description. • TR:TREATMENT_SUMMARY For the vehicle control, dilute 1 part of DMSO in 7 parts of Cyclodextrin (done TR:TREATMENT_SUMMARY fresh everyday) and then inject 100uL/120uL per mouse as indicated above. TR:TREATMENT_PROTOCOL_ID Treatment TR:TREATMENT Dissolved 1g of GSK 126 powder in 8.325mL DMSO to get a conc. of 120.12mg/mL, TR:TREATMENT aliquot and store in -80C. • Dilute the GSK126 stock in 7 parts of TR:TREATMENT Cyclodextrin (2-hydroxy-beta-cyclodextrin) to get a concentration of 15mg/mL of TR:TREATMENT drug (done fresh everyday) and then inject 100uL/120uL per mouse TR:TREATMENT_ROUTE Intra-peritoneal injection of GSK126 and/or vehicle TR:TREATMENT_DOSE 100mg/kg dose of GSK 126 TR:TREATMENT_DOSEVOLUME 100mg/kg dose of GSK 126/120 uL TR:TREATMENT_DOSEDURATION 0, 2, 6, 10h TR:TREATMENT_VEHICLE 1 part of DMSO in 7 parts of Cyclodextrin (done fresh everyday) and then inject TR:TREATMENT_VEHICLE 100uL/120uL per mouse TR:ANIMAL_ENDP_EUTHANASIA Mice were injected with 200mg/kg ketamine (200uL/mouse). TR:ANIMAL_ENDP_TISSUE_COLL_LIST Intracranial mice a) Brain bearing tumor b) Lumbar lymph node c) Serum from TR:ANIMAL_ENDP_TISSUE_COLL_LIST cardiac bleed Subcutaneous mice a) Sub-cutaneous tumor b) Tumor draining TR:ANIMAL_ENDP_TISSUE_COLL_LIST inguinal lymph node (DLN) c) Non- tumor draining inguinal lymph node (NDLN) d) TR:ANIMAL_ENDP_TISSUE_COLL_LIST Serum from cardiac bleed TR:TREATMENT_COMPOUND GSK126 #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Serum (50 µL) was transferred to 200 μL ice-chilled (4°C) MilliQ H2O. Tissue SP:SAMPLEPREP_SUMMARY (~16 mg) was measured from subcutaneous and intracranial samples followed by SP:SAMPLEPREP_SUMMARY addition of 250 μL MilliQ H2O. Then, samples were sonicated at 40 amps (~30 s) SP:SAMPLEPREP_SUMMARY until homogeneous. 80 μL of at 0.150 µg/mL debrisoquine in 60% methanol SP:SAMPLEPREP_SUMMARY (MeOH)/40% water(aq) reagent was added. 500 μL chilled (-20°C) MeOH was added, SP:SAMPLEPREP_SUMMARY vortexed (med) and incubated 15 min on ice. 250 μL chilled (-20°C) Chloroform SP:SAMPLEPREP_SUMMARY was added, vortexed (high) and incubated 20 min in ice on rotating mixer. SP:SAMPLEPREP_SUMMARY Mixture was centrifuged (13,000x g) for 18 min at 4°C. 705 μL of hydrophilic SP:SAMPLEPREP_SUMMARY upper layer was aspirated and transferred to separate 1.5 mL microtubes, dried SP:SAMPLEPREP_SUMMARY to completion under N2 gas sample concentrator, and stored at -80°C SP:SAMPLEPREP_PROTOCOL_ID Extraction SP:PROCESSING_STORAGE_CONDITIONS -80℃ SP:EXTRACTION_METHOD LCMS Extraction SP:EXTRACT_CLEANUP Bligh-Dyer biphasic separation, discard protein disk and dried to completion SP:EXTRACT_CLEANUP under N2 gas SP:SAMPLE_RESUSPENSION 80 uL 60% MeOH (aq) SP:SAMPLE_SPIKING Internal standard 0.150 µg/mL debrisoquine(IS) was added to each #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Samples were injected at 8 µL over an 8.3 min gradient on the AdvanceBio Glycan CH:CHROMATOGRAPHY_SUMMARY Map 2.1 x 100 mm 2.7µm column at 35°C with a flow rate of 0.220 mL/min. The LC CH:CHROMATOGRAPHY_SUMMARY gradient only utilized LC/MS grade reagents when preparing mobile phases, A CH:CHROMATOGRAPHY_SUMMARY (88:12 H2O/acetonitrile (ACN) and B 90% ACN (aq). Both mobile phases were CH:CHROMATOGRAPHY_SUMMARY composed with 10 mM ammonium acetate and titrated to pH 6.85 using formic acid CH:CHROMATOGRAPHY_SUMMARY and ammonium hydroxide. The LC gradient was initially 100% B for 0.25 min and CH:CHROMATOGRAPHY_SUMMARY then ramped to 55% B at 2.5 min; 49% B at 4.5 min; 35% B at 5.5 min; 20% B at 6 CH:CHROMATOGRAPHY_SUMMARY min; held for 0.5 min; 15% B at 7 min; 100%B at 8.3 min followed by CH:CHROMATOGRAPHY_SUMMARY equilibration for 1.2 min. CH:CHROMATOGRAPHY_TYPE HILIC CH:INSTRUMENT_NAME Agilent 1290 Infinity II CH:COLUMN_NAME Agilent AdvanceBio Glycan Map 2.1 x 100 mm 2.7µm column CH:FLOW_GRADIENT The LC gradient was initially 100% B for 0.25 min and then ramped to 55% B at CH:FLOW_GRADIENT 2.5 min; 49% B at 4.5 min; 35% B at 5.5 min; 20% B at 6 min; held for 0.5 min; CH:FLOW_GRADIENT 15% B at 7 min; 100%B at 8.3 min followed by equilibration for 1.2 min. CH:FLOW_RATE 0.220 mL/min CH:COLUMN_TEMPERATURE 35°C CH:SOLVENT_A 88:12 H2O/acetonitrile (ACN) with 10 mM ammonium acetate and titrated to pH 6.85 CH:SOLVENT_B 90% ACN (aq) with 10 mM ammonium acetate and titrated to pH 6.85 CH:COLUMN_PRESSURE 600 bar CH:INJECTION_TEMPERATURE 4°C CH:INTERNAL_STANDARD Continuous accurate mass correction was achieved by infusing proprietary Agilent CH:INTERNAL_STANDARD Technologies API-TOF reference mass standard solution CH:RETENTION_TIME 2.5-2.7 min CH:SAMPLE_INJECTION 8 uL CH:SAMPLING_CONE 2kV CH:ANALYTICAL_TIME 8.3 min CH:CAPILLARY_VOLTAGE 3 kV CH:SHEATH_LIQUID N2 #ANALYSIS AN:ANALYSIS_TYPE MS AN:LABORATORY_NAME NOB Cancer Metabolism AN:OPERATOR_NAME Dowdy AN:SOFTWARE_VERSION 8.0 AN:DATA_FORMAT .d.zip #MS MS:INSTRUMENT_NAME Agilent 6545 MS:INSTRUMENT_TYPE QTOF MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS MS/MS Using Masshunter Qtof Quant-My-Way 10.0 software, GSK126 was detected at MS:MS_COMMENTS elution time 2.6 min using precursor ion m/z 527.3129 and transition m/z MS:MS_COMMENTS 375.2183 generated via N2 gas collision-induced fragmentation (CID) at a MS:MS_COMMENTS collision energy (CE) of 12 V. Internal standard (IS) debrisoquine detected at MS:MS_COMMENTS elution time of 2.5 mins with precursor m/z 176.1182 and transition m/z 134.0964 MS:MS_COMMENTS generated at CE 12V. MS:CAPILLARY_TEMPERATURE 325°C MS:CAPILLARY_VOLTAGE 3kV MS:COLLISION_ENERGY 12V MS:COLLISION_GAS N2 MS:DRY_GAS_FLOW 9 L/min MS:DRY_GAS_TEMP 250°C MS:FRAGMENT_VOLTAGE 100 V MS:FRAGMENTATION_METHOD MS/MS MS:ION_SOURCE_TEMPERATURE 325°C MS:MASS_ACCURACY 2 kDa MS:SOURCE_TEMPERATURE 325°C MS:CDL_TEMPERATURE RT MS:DESOLVATION_TEMPERATURE 325°C MS:NEBULIZER 45 psig MS:OCTPOLE_VOLTAGE 750V #MS_METABOLITE_DATA MS_METABOLITE_DATA:UNITS ng MS_METABOLITE_DATA_START Samples Blank_S14.d blank_S22.d blank_Sr62.d BRN_g1 _Intra1_2h BRN_g1 _Intra2_2h BRN_g1 _Intra3_2h BRN_g1 _Intra4_6h BRN_g1 _Intra5_6h BRN_g1 _Intra7_10h BRN_g1 _Intra8_10h BRN_ctrl_g2_Intra10_2h BRN_ctrl_g2_Intra11_2h BRN_ctrl_g2_Intra12_6h BRN_ctrl_g2_Intra13_6h BRN_ctrl_g2_Intra14_6h BRN_ctrl_g2_Intra15_10h BRN_ctrl_g2_Intra16_10h SubCu1_DLN_g1_2h SubCu2_DLN_g1_2h SubCu3_DLN_g1_2h SubCu4_DLN_g1_6h SubCu5_DLN_g1_6h SubCu6_DLN_g1_6h SubCu7_DLN_g1_10 SubCu8_DLN_g1_10 SubCu9_DLN_ctrl_g2_2h_ SubCu10_DLN_ctrl_g2_2h SubCu11_DLN_ctrl_g2_2h SubCu12_DLN_ctrl_g2_6h SubCu13_DLN_ctrl_g2_6h SubCu15_DLN_ctrl_g2_10h SubCu16_DLN_ctrl_g2_10h LLN_g1 _Intra1_2h LLN_g1 _Intra2_2h LLN_g1 _Intra3_2h LLN_g1 _Intra4_6h LLN_g1 _Intra6_6h LLN_g1 _Intra7_10h LLN_g1 _Intra8_10h LLN_ctrl_g2_Intra10_2h LLN_ctrl_g2_Intra11_2h LLN_ctrl_g2_Intra12_6h LLN_ctrl_g2_Intra13_6h LLN_ctrl_g2_Intra15_10h LLN_ctrl_g2_Intra16_10h LLN_ctrl_g2 _Intra9_2h SubCu1_NLN_g1_2h SubCu2_NLN_g1_2h SubCu3_NLN_g1_2h SubCu4_NLN_g1_6h SubCu5_NLN_g1_6h SubCu6_NLN_g1_6h SubCu7_NLN_g1_10 SubCu8_NLN_g1_10 SubCu9_NLN_ctrl_g2_2h_ SubCu10_NLN_ctrl_g2_2h SubCu11_NLN_ctrl_g2_2h SubCu12_NLN_ctrl_g2_6h SubCu13_NLN_ctrl_g2_6h SubCu14_NLN_ctrl_g2_6h SubCu15_NLN_ctrl_g2_10h SubCu16_NLN_ctrl_g2_10h QcBRN_S45.d QcBRN_Sr91.d QcBRN_Sr111.d QcBRN_Sr65.d QcLLN_L1002.d QCpool g1 D_NLN_subcu_055.d QCpool g1 D_NLN_subcu_081.d QCpool g1 D_NLN_subcu_135.d QCpool g1 D_NLN_subcu_012.d QCpool g1 D_NLN_subcu_028.d QCpool g1 D_NLN_subcu_037.d QCpool g1 SubTum_038.d QCpool g1 SubTum_056.d QCpool g1 SubTum_082.d QCpool g1 SubTum_136.d QcSer_S24.d QcSer_S44.d SER_g1 _Subcutaneous1_2h SER_g1 _Subcutaneous2_2h SER_g1 _Subcutaneous3_2h SER_g1 _Subcutaneous4_6h SER_g1 _Subcutaneous5_6h SER_g1 _Subcutaneous6_6h SER_g1 _Subcutaneous7_10h SER_g1 _Subcutaneous8_10h SER_g1 _Intra1_2h SER_g1 _Intra2_2h SER_g1 _Intra3_2h SER_g1 _Intra4_6h SER_g1 _Intra7_10h SER_g1 _Intra8_10h SER_g1 _Intra5_6h SER_g1 _Intra6_6h SER_ctrl_g2_Subcutaneous10_2h SER_ctrl_g2_Subcutaneous12_6h SER_ctrl_g2_Subcutaneous13_6h SER_ctrl_g2_Subcutaneous14_6h SER_ctrl_g2_Subcutaneous15_10h SER_ctrl_g2_Subcutaneous16_10h SER_ctrl_g2_Intra10_2h SER_ctrl_g2_Intra11_2h SER_ctrl_g2_Intra12_6h SER_ctrl_g2_Intra13_6h SER_ctrl_g2_Intra14_6h SER_ctrl_g2_Intra15_10h SER_ctrl_g2_Intra16_10h SER_ctrl_g2 _Intra9_2h SubCu1_Tum_g1_2h SubCu2_Tum_g1_2h SubCu3_Tum_g1_2h SubCu4_Tum_g1_6h SubCu5_Tum_g1_6h SubCu6_Tum_g1_6h SubCu7_Tum_g1_10 SubCu8_Tum_g1_10 SubCu9_Tum_ctrl_g2_2h_ SubCu10_Tum_ctrl_g2_2h SubCu11_Tum_ctrl_g2_2h SubCu12_Tum_ctrl_g2_6h SubCu13_Tum_ctrl_g2_6h SubCu14_Tum_ctrl_g2_6h SubCu15_Tum_ctrl_g2_10h SubCu16_Tum_ctrl_g2_10h Factors Treatment:blank | Gsk Exposure Time (h):- Treatment:blank | Gsk Exposure Time (h):- Treatment:blank | Gsk Exposure Time (h):- Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):10 Treatment:GSK | Gsk Exposure Time (h):10 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):10 Treatment:GSK | Gsk Exposure Time (h):10 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:QC | Gsk Exposure Time (h):- Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):2.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:GSK | Gsk Exposure Time (h):10.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:GSK | Gsk Exposure Time (h):6.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:Vehicle | Gsk Exposure Time (h):0.0 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):2.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):6.00 Treatment:GSK | Gsk Exposure Time (h):10 Treatment:GSK | Gsk Exposure Time (h):10 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 Treatment:Vehicle | Gsk Exposure Time (h):0.00 GSK126 0 0 0 0 41.768 25.344 0 13.712 13.744 0 0 0 0 0 0 0 0 126.35 449.75 677.39 2245.46 765.45 530.67 502.53 746.97 0 0 0 0 0 0 0 311.784 605.704 156.192 31.888 20.512 22.808 42.184 0 0 0 0 0 0 0 189.42 255.78 295.4 1089.55 415.1 553.98 1230.67 459.97 0 0 0 0 0 0 0 0 0 0 0 0 69.28 634.83 637.42 640.01 605.64 597.24 615.65 361.27 453.39 354.97 416.29 41.216 45.976 72.528 22.848 91.624 24.312 46.088 55.04 0 32 160.768 220.832 149.024 0 41.792 14.352 147.568 15.256 0 0 0 0 0 0 0 0 0 0 0 0 0 0 694.4 0 248.36 267.19 225.05 1329.09 107.24 223.72 0 0 0 0 0 0 0 0 MS_METABOLITE_DATA_END #METABOLITES METABOLITES_START metabolite_name retention index quantified m/z PubChem ID KEGG ID GSK126 527.3129 68210102 K11430 METABOLITES_END #END