Evidence map›Paper›PMID 40348014›Full record

ArticleMolecular metabolism2025

Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK.

Caitlyn E Bowman, Michael D Neinast, Ryo Kawakami, Nicholas Forelli, Cholsoon Jang, Jiten Patel, Megan C Blair, Michael C Noji, Emily T Mirek, William O Jonsson and 6 more

Abstract read
In one paragraph

Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Caitlyn E BowmanCardiovascular Institute, Philadelphia, PA, USA.
Michael D NeinastDepartment of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Ryo KawakamiCardiovascular Institute, Philadelphia, PA, USA.
Nicholas ForelliCardiovascular Institute, Philadelphia, PA, USA.
Cholsoon JangDepartment of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Jiten PatelCardiovascular Institute, Philadelphia, PA, USA.
Megan C BlairCardiovascular Institute, Philadelphia, PA, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael C NojiCardiovascular Institute, Philadelphia, PA, USA.
Emily T MirekDepartment of Nutritional Sciences, Rutgers School of Environmental and Biological Sciences, New Brunswick, NJ, USA.
William O JonssonDepartment of Nutritional Sciences, Rutgers School of Environmental and Biological Sciences, New Brunswick, NJ, USA.
Qingwei ChuInstitute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lauren MerloLankenau Institute for Medical Research, Wynnewood, PA, USA.
Laura Mandik-NayakLankenau Institute for Medical Research, Wynnewood, PA, USA.
Tracy G AnthonyDepartment of Nutritional Sciences, Rutgers School of Environmental and Biological Sciences, New Brunswick, NJ, USA.
Joshua D RabinowitzDepartment of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Zolt AranyCardiovascular Institute, Philadelphia, PA, USA; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: zarany@pennmedicine.upenn.edu.

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3M
Training Program in Cardiovascular Biology and MedicineT32HL007843 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI THOMAS P. CAPPOLA, Sharlene M Day · 1996 to 2026
$11.0M
Homeostatic Responses to Amino Acid InsufficiencyR01DK109714 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI ANTHONY, TRACY G., WEK, RONALD C · 2016 to 2024
$5.4M
Keeping fat out of muscle - Role of Branched Amino AcidsAmino Acids in Insulin ResistanceR01DK114103 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany · 2018 to 2026
$4.5M
Branched chain amino acids in heart failureR01HL152446 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany · 2020 to 2026
$3.7M
Branched chain amino acids in pancreatic carcinogenesisR01CA248315 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany, Kathryn Elaine Wellen · 2020 to 2026
$2.8M
Post-doctoral Training Program in Cancer Metabolism and Tumor-host InteractionsT32CA257957 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI KANG, YIBIN, ZONG, WEI-XING · 2021 to 2025
$1.2M
The role of branched-chain amino acid metabolism and hyperinsulinemia in pancreatic cancerF31CA261041 · NCI · UNIVERSITY OF PENNSYLVANIA · PI NOJI, MICHAEL · 2022 to 2024
$131k
NCI NIH HHS F31 CA261041NCI NIH HHS R01 CA248315NCI NIH HHS T32 CA257957NHLBI NIH HHS R01 HL152446NHLBI NIH HHS T32 HL007843NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK109714NIDDK NIH HHS R01 DK114103
6 · The paper itself

Abstract

The activation of branched chain amino acid (BCAA) catabolism has garnered interest as a potential therapeutic approach to improve insulin sensitivity, enhance recovery from heart failure, and blunt tumor growth. Evidence for this interest relies in part on BT2, a small molecule that promotes BCAA oxidation and is protective in mouse models of these pathologies. BT2 and other analogs allosterically inhibit branched chain ketoacid dehydrogenase kinase (BCKDK) to promote BCAA oxidation, which is presumed to underlie the salutary effects of BT2. Potential "off-target" effects of BT2 have not been considered, however. We therefore tested for metabolic off-target effects of BT2 in Bckdk

Indexed as

TryptophanAllosteric RegulationAmino Acids, Branched-ChainAnimalsKynurenineMaleMiceMice, Inbred C57BLMice, KnockoutOxidation-ReductionProtein Kinases(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinaseAmino Acids, Branched-ChainKynurenineProtein KinasesTryptophanAlbuminBranched chain amino acidBranched chain ketoacid dehydrogenase kinaseBT2Child-centered careTryptophanTryptophan 2,3-dioxygenase

Identifiers

PMID40348014
PMCPMC12149413

What OpenQuestion holds

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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 OpenQuestion graph.