PR002306 (Project)

Dcc Asset:

MW submission packet 20260310.zip

Processed File (Entity type)

Dcc:

Metabolomics

DCC (Entity type)

Child Project:

PPR00001

Project (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
	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
	SU003845 Subject (Entity type)	A subject produced as part of the PR002306 project
	ST003713 Rawdata mzml.zip File (Entity type)	A 2.41 GB file from Metabolomics produced from OBI:0003097 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

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

SU003845

Subject (Entity type)

A subject produced as part of the PR002306 project

ST003713 Rawdata mzml.zip

File (Entity type)

A 2.41 GB file from Metabolomics produced from OBI:0003097 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

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@CFDE Workbench 2026

The CFDE Workbench is actively being developed and maintained by the CFDE Data Resource Center (DRC).The DRC is funded by OT2OD036435 from the Common Fund at the National Institutes of Health.

Consortium

Community

Resources

CFDE Workbench

The CFDE Workbench is actively being developed and maintained by the CFDE Data Resource Center (DRC).The DRC is funded by OT2OD036435 from the Common Fund at the National Institutes of Health.

@CFDE Workbench 2026

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