ArticleACS chemical biology2013
Regulating the ARNT/TACC3 axis: multiple approaches to manipulating protein/protein interactions with small molecules.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Vicinal disubstitution of alkyl C-X synthons via alkene radical cation generation.Science (New York, N.Y.) · 2026Article
- Context-dependent variability of HIF heterodimers influences interactions with macromolecular and small molecule partners.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- Use of High Pressure NMR Spectroscopy to Rapidly Identify Proteins with Internal Ligand-Binding Voids.bioRxiv : the preprint server for biology · 2025Article
- A pipeline for screening small molecule-enhanced protein stability in a bacterial orphan receptor.Protein science : a publication of the Protein Society · 2025Article
- A Pipeline for Screening Small Molecule-Enhanced Protein Stability in A Bacterial Orphan Receptor.bioRxiv : the preprint server for biology · 2025Article
- Per-ARNT-Sim (PAS) Domains in Basic Helix-Loop-Helix (bHLH)-PAS Transcription Factors and Coactivators: Structures and Mechanisms.Journal of molecular biology · 2024Review
- PAS Dimerization at the Nexus of the Mammalian Circadian Clock.Journal of molecular biology · 2024Review
- Knockdown of TACC3 inhibits tumor cell proliferation and increases chemosensitivity in pancreatic cancer.Cell death & disease · 2023Article
- Integrated high-throughput analysis identifies super enhancers in metastatic castration-resistant prostate cancer.Frontiers in pharmacology · 2023Article
- Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Characterization of functionally deficient SIM2 variants found in patients with neurological phenotypes.The Biochemical journal · 2022Article
- Volume and compressibility differences between protein conformations revealed by high-pressure NMR.Biophysical journal · 2021Article
- Fragile protein folds: Sequence and environmental factors affecting the equilibrium of two interconverting, stably folded protein conformations.Magnetic resonance (Gottingen, Germany) · 2021Article
- Druggability assessment of mammalian Per-Arnt-Sim [PAS] domains using computational approaches.MedChemComm · 2019Article
- Bidirectional modulation of HIF-2 activity through chemical ligands.Nature chemical biology · 2019Article
- Article
- Hypoxia inducible factor (HIF) as a model for studying inhibition of protein-protein interactions.Chemical science · 2017Article
- Assembly and function of bHLH-PAS complexes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Systematic Identification of Oncogenic EGFR Interaction Partners.Journal of molecular biology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
For several well-documented reasons, it has been challenging to develop artificial small molecule inhibitors of protein/protein complexes. Such reagents are of particular interest for transcription factor complexes given links between their misregulation and disease. Here we report parallel approaches to identify regulators of a hypoxia signaling transcription factor complex, involving the ARNT subunit of the HIF (Hypoxia Inducible Factor) activator and the TACC3 (Transforming Acidic Coiled Coil Containing Protein 3) coactivator. In one route, we used in vitro NMR and biochemical screening to identify small molecules that selectively bind within the ARNT PAS (Per-ARNT-Sim) domain that recruits TACC3, identifying KG-548 as an ARNT/TACC3 disruptor. A parallel, cell-based screening approach previously implicated the small molecule KHS101 as an inhibitor of TACC3 signaling. Here, we show that KHS101 works indirectly on HIF complex formation by destabilizing both TACC3 and the HIF component HIF-1α. Overall, our data identify small molecule regulators for this important complex and highlight the utility of pursuing parallel strategies to develop protein/protein inhibitors.
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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.