ArticleJournal of medicinal chemistry2016
Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 155 citations in OpenAlex.
- Unraveling the secrets of novel PROTACs to improve degradation efficacy.Molecular diversity · 2026Review
- TRIM24 in Human Cancers: A Dual-Function Oncoprotein, Regulatory Mechanisms, and Emerging Therapeutic Strategies.International journal of cancer · 2026Review
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Epigenetic programming by H3K23ac defines lineage fate of Meg3Nature cell biology · 2026Article
- TIF1 Family Proteins as Modulators of Cell Death: Mechanisms and Therapeutic Opportunities.Biomolecules · 2026Review
- RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma.Cellular & molecular biology letters · 2026Review
- An epigenetic bifunctional that toggles between transactivation and repression.bioRxiv : the preprint server for biology · 2026Article
- High-Affinity Peptide-Drug Conjugate Ligands for the TRIM24 PHD and Bromodomain.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- BRPF1 in cancer epigenetics: a key regulator of histone acetylation and a promising therapeutic target.Cell death discovery · 2025Review
- TRIM24 as a therapeutic target in endocrine treatment-resistant breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oroxin A suppresses colorectal tumor growth by regulating the TRIM24-mediated ferroptosis and TSPO pathway.iScience · 2025Article
- Epigenetic regulators in cancer therapy and progression.NPJ precision oncology · 2025Review
- A lung cancer mouse model system based on an inbred C3H strain: Ultrasound imaging, pathological analysis, and proteomic biomarker identification.Veterinary world · 2025Article
- Workflow for E3 Ligase Ligand Validation for PROTAC Development.ACS chemical biology · 2025Article
- Insights into the protein domains of C-VI TRIM subfamily in viral infection.Frontiers in cellular and infection microbiology · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- The tripartite motif-containing 24 is a multifunctional player in human cancer.Cell & bioscience · 2024Review
- Exploring the Mechanisms, Biomarkers, and Therapeutic Targets of TRIM Family in Gastrointestinal Cancer.Drug design, development and therapy · 2024Review
- Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase.ACS medicinal chemistry letters · 2023Article
- Targeting TRIM24 promotes neuroblastoma differentiation and decreases tumorigenicity via LSD1/CoREST complex.Cellular oncology (Dordrecht, Netherlands) · 2023Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
The bromodomain containing proteins TRIM24 (tripartite motif containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are involved in the epigenetic regulation of gene expression and have been implicated in human cancer. Overexpression of TRIM24 correlates with poor patient prognosis, and BRPF1 is a scaffolding protein required for the assembly of histone acetyltransferase complexes, where the gene of MOZ (monocytic leukemia zinc finger protein) was first identified as a recurrent fusion partner in leukemia patients (8p11 chromosomal rearrangements). Here, we present the structure guided development of a series of N,N-dimethylbenzimidazolone bromodomain inhibitors through the iterative use of X-ray cocrystal structures. A unique binding mode enabled the design of a potent and selective inhibitor 8i (IACS-9571) with low nanomolar affinities for TRIM24 and BRPF1 (ITC Kd = 31 nM and ITC Kd = 14 nM, respectively). With its excellent cellular potency (EC50 = 50 nM) and favorable pharmacokinetic properties (F = 29%), 8i is a high-quality chemical probe for the evaluation of TRIM24 and/or BRPF1 bromodomain function in vitro and in vivo.
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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.