Evidence map›Paper›PMID 40539870›Full record

ArticleACS chemical biology2025

Photoaffinity Ligand of Cystic Fibrosis Corrector VX-445 Identifies SCCPDH as an Off-Target.

Minsoo Kim, Kwangho Kim, Jesun Lee, Lea A Barny, Toya D Scaggs, Ian M Romaine, KyuOk Jeon, Simona G Codreanu, Stacy D Sherrod, John A McLean and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. AnResearch square · 2026
    Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Minsoo KimDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.
Kwangho KimDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.
Jesun LeeDivision of Pulmonary Medicine and Critical Care, Cedars-Sinai Medical Center, Los Angeles, California 90048, United States.
Lea A BarnyDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.
Toya D ScaggsVanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
Ian M RomaineVanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
KyuOk JeonVanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37232, United States.
Simona G CodreanuDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.
Stacy D SherrodDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.ORCID 0000-0002-2346-230X
John A McLeanDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.ORCID 0000-0001-8918-6419
Anjaparavanda P NarenDivision of Pulmonary Medicine and Critical Care, Cedars-Sinai Medical Center, Los Angeles, California 90048, United States.
Gary A SulikowskiDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.ORCID 0000-0002-1067-0767
Lars PlateDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee 37240, United States.ORCID 0000-0003-4363-6116

Funding

Pilot and Feasibility ProgramP30DK117467 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Raouf S. Amin, MICHAEL A. HELMRATH · 2018 to 2026
$11.4M
Coordination of chaperone interactions that dictate protein folding and traffickingR35GM133552 · NIGMS · VANDERBILT UNIVERSITY · PI Lars Plate · 2019 to 2026
$3.2M
Acetate and Endothelial PathobiologyR01HL167014 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany, Michael Simons · 2023 to 2026
$2.8M
Rational optimization of combinatorial therapies for the treatment of rare cystic fibrosis variantsR01HL167046 · NHLBI · PURDUE UNIVERSITY · PI Lars Plate, Jonathan Patrick Schlebach · 2023 to 2026
$2.7M
Investigating of the Mechanisms of Action of CFTR Correctors in RescuingDelta F508-CFTRR01HL147351 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI NAREN, ANJAPARAVANDA P · 2020 to 2023
$1.7M
NHLBI NIH HHS R01 HL147351NHLBI NIH HHS R01 HL167014NHLBI NIH HHS R01 HL167046NIDDK NIH HHS P30 DK117467NIGMS NIH HHS R35 GM133552
6 · The paper itself

Abstract

Cystic fibrosis (CF) pharmacological correctors improve the cystic fibrosis transmembrane conductance regulator (CFTR) protein trafficking and function. Several side effects of these correctors and adverse drug interactions have been reported, emphasizing the need to understand off-targets. We synthesized VU439, a functionalized photoaffinity ligand (PAL) of VX-445. Chemoproteomics analysis by mass spectrometry (MS) was used to identify cross-linked proteins in CF bronchial epithelial cells expressing F508del CFTR. We identified saccharopine dehydrogenase-like oxidoreductase (SCCPDH), an uncharacterized putative oxidoreductase, as a VX-445-specific off-target. We also characterized changes in the metabolomic profiles of cells overexpressing SCCPDH to determine the consequence of binding of VX-445 to SCCPDH. These data show dysregulation of amino acid metabolism and a potential inhibitory activity of VX-445 on SCCPDH. The identified off-target may explain the exacerbation of psychological symptoms observed in the clinic, thus emphasizing the need for further optimization of correctors.

Indexed as

Cystic FibrosisOxidoreductasesPhotoaffinity LabelsCell LineCystic Fibrosis Transmembrane Conductance RegulatorHumansLigandsCystic Fibrosis Transmembrane Conductance RegulatorLigandsOxidoreductasesPhotoaffinity Labels

Identifiers

PMID40539870
PMCPMC12281486

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.