ArticleNature communications2023
Small molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Causal role of genetically predicted impairment of branched-chain amino acid catabolism on insulin secretion and insulin resistance in type 2 diabetes.Diabetes, obesity & metabolism · 2026Pooled it
- BCKDK protects against obesity-induced cardiac remodelling and dysfunction by alleviating mitochondrial oxidative stress and ROS-driven MAPK signalling.Redox biology · 2026Article
- Loss of TAFAZZIN leads to perturbation of amino acid metabolism and reduction of collagen synthesis.bioRxiv : the preprint server for biology · 2026Article
- Covalent Reprogramming of Kinase Binders to Modulate Protein Abundance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Defective branched-chain amino acid catabolism promotes pulmonary fibrosis by inducing apoptosis resistance of myofibroblasts in mice.Cell communication and signaling : CCS · 2026Article
- Rapamycin Reverses the Hepatic Response to Diet-Induced Metabolic Stress That Is Amplified by Aging.Aging cell · 2026Article
- Hyperimonates A and B, a pair of unprecedented polyprenylated acylphloroglucinols fromActa pharmaceutica Sinica. B · 2026Article
- Angel or demon? The dual role of branched-chain amino acids in chronic inflammatory and injury-related diseases.Frontiers in immunology · 2026Review
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Biomarkers of Insulin Resistance and Their Performance as Predictors of Treatment Response in Overweight Adults.The Journal of clinical endocrinology and metabolism · 2025Article
- Persistent and Dose-Dependent Neural and Metabolic Gene Expression Changes Induced by Transient Citalopram Exposure in Zebrafish Embryos.International journal of molecular sciences · 2025Article
- Protein lipoylation in cancer: metabolic reprogramming and therapeutic potential.Cell death discovery · 2025Review
- Short-term Physical Activity Reduces Metabolic-associated Steatohepatitis by Promoting the Degradation of Branched-chain Amino Acids in Skeletal Muscle.Journal of clinical and translational hepatology · 2025Article
- Off-target depletion of plasma tryptophan by allosteric inhibitors of BCKDK.Molecular metabolism · 2025Article
- Quantitation of BCAA and BCKA in plasma and patient-centric dried blood microsamples in a clinical setting.Bioanalysis · 2025Article
- Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- BCAA catabolism targeted therapy for heart failure with preserved ejection fraction.Theranostics · 2025Article
- BCAA metabolism in cancer progression and therapy resistance: The balance between fuel and cell signaling.Frontiers in pharmacology · 2025Review
- Branched-chain amino acids and insulin resistance in type 2 diabetes: from metabolic dysregulation to therapeutic targets.Frontiers in endocrinology · 2025Review
- Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.Molecules (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
33 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. Branched chain ketoacid dehydrogenase (BCKDH) controls the rate limiting step in BCAA degradation, the activity of which is inhibited by BCKDH kinase (BDK)-mediated phosphorylation. Screening efforts to discover BDK inhibitors led to identification of thiophene PF-07208254, which improved cardiometabolic endpoints in mice. Structure-activity relationship studies led to identification of a thiazole series of BDK inhibitors; however, these inhibitors did not improve metabolism in mice upon chronic administration. While the thiophenes demonstrated sustained branched chain ketoacid (BCKA) lowering and reduced BDK protein levels, the thiazoles increased BCKAs and BDK protein levels. Thiazoles increased BDK proximity to BCKDH-E2, whereas thiophenes reduced BDK proximity to BCKDH-E2, which may promote BDK degradation. Thus, we describe two BDK inhibitor series that possess differing attributes regarding BDK degradation or stabilization and provide a mechanistic understanding of the desirable features of an effective BDK inhibitor.
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Registered trials
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.