PR002306 (Project)

Id Namespace:

UCSD Metabolomics Workbench

Identifier Namespace (Entity type)

Dcc Asset:

MW submission packet 20250922.zip

Processed File (Entity type)

Dcc:

Metabolomics

DCC (Entity type)

Persistent Id:http://dx.doi.org/10.21228/M8JR73

Description: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.

Results found

Linked to

	Label	Description
	PPR00001 Project (Entity type)	Metabolomics
	SU003845 Subject (Entity type)	A subject from Metabolomics produced as part of the PR002306 project
	SA406617 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project
	SA406624 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project
	SA406628 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project
	SA406622 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project
	SA406618 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project
	SA406614 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project
	SA406627 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project
	SA406615 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR002306 project

PPR00001

Project (Entity type)

Metabolomics

SU003845

Subject (Entity type)

A subject from Metabolomics produced as part of the PR002306 project

SA406617

Biosample (Entity type)