Summary of project PR002306
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002306. The data can be accessed directly via it's Project DOI: 10.21228/M8JR73 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002306 |
| Project DOI: | doi: 10.21228/M8JR73 |
| Project Title: | Photoaffinity ligand of Cystic Fibrosis corrector VX-445 identifies SCCPDH as an off-target |
| Project Type: | Untargeted Metabolomics analysis |
| Project Summary: | Cystic fibrosis (CF) pharmacological correctors such as VX-445 are used in combinations as highly effective modulator therapy (HEMT) at CF clinics due to their efficacy in improving Cystic Fibrosis transmembrane conductance regulator (CFTR) protein trafficking and function. We utilized LC-MS/MS to identify crosslinked proteins in CF bronchial epithelial cells expressing F508del CFTR, identifying SCCPDH, an uncharacterized putative oxidoreductase, as a VX-445 specific off-target. We then characterized changes in the metabolomic profiles of cells overexpressing SCCPDH to decipher its role and implications of VX-445 binding to SCCPDH-dependent metabolic changes. We found dysregulation of amino acid metabolism and a potential inhibitory activity of VX-445 on SCCPDH. The identified off-target may explain exacerbation of psychological symptoms observed in patients on HEMT, thus emphasizing the need for further optimization of corrector combinations. |
| Institute: | Vanderbilt University |
| Department: | Chemistry |
| Laboratory: | Center for Innovative Technology |
| Last Name: | CODREANU |
| First Name: | GABRIELA SIMONA |
| Address: | 1234 STEVENSON CENTER LANE |
| Email: | SIMONA.CODREANU@VANDERBILT.EDU |
| Phone: | 6158758422 |
Summary of all studies in project PR002306
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003713 | Photoaffinity ligand of Cystic Fibrosis corrector VX-445 identifies SCCPDH as an off-target | Homo sapiens | Vanderbilt University | MS* | 2025-08-07 | 1 | 15 | Uploaded data (17.1G)* |
