ArticleEMBO molecular medicine2019
The novel BET-CBP/p300 dual inhibitor NEO2734 is active in SPOP mutant and wild-type prostate cancer.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Androgen Receptor Variants Confer Castration Resistance in Prostate Cancer by Counteracting Antiandrogen-Induced Ferroptosis.Cancer research · 2023Pooled it
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Therapeutic potentials of curcumin in prostate cancer: a comprehensive review of pathways and clinical prospects.Prostate international · 2026Review
- Review
- Flipping the Switch: MeCP2-Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Patient-derived prostate cancer organoids: model development, therapeutic applications, and challenges for precision oncology.Frontiers in oncology · 2026Review
- Prevalence of SPOP and IDH Gene Mutations in Prostate Cancer in a Jordanian Population.Biochemical genetics · 2025Article
- CBP/p300, a promising therapeutic target for prostate cancer.Journal of translational medicine · 2025Review
- Harnessing organoid technology in urological cancer: advances and applications in urinary system tumors.World journal of surgical oncology · 2025Review
- The ESCRT protein CHMP5 promotes T cell leukemia by enabling BRD4-p300-dependent transcription.Nature communications · 2025Article
- The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.Cell biology and toxicology · 2025Review
- PROTAC technology for prostate cancer treatment.Acta materia medica · 2025Article
- SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer.Biomolecules · 2025Article
- A combinatorial screening protocol for identifying novel and highly potent dual-target inhibitor of BRD4 and STAT3 for kidney cancer therapy.Frontiers in pharmacology · 2025Article
- Acetylation and Deacetylation of Cytoskeleton-Associated Proteins.Results and problems in cell differentiation · 2025Review
- Coactivator networks orchestrating noncanonical AR programs in enzalutamide-resistant CRPC.Frontiers in oncology · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Article
- Synergistic effects of combined BET and FAK inhibition against Vestibular Schwannomas in NF2-related Schwannomatosis.Oncogene · 2024Article
- Advancement and Potential Applications of Epididymal Organoids.Biomolecules · 2024Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
CULLIN3-based E3 ubiquitin ligase substrate-binding adaptor gene SPOP is frequently mutated in prostate cancer (PCa). PCa harboring SPOP hotspot mutants (e.g., F133V) are resistant to BET inhibitors because of aberrant elevation of BET proteins. Here, we identified a previously unrecognized mutation Q165P at the edge of SPOP MATH domain in primary and metastatic PCa of a patient. The Q165P mutation causes structural changes in the MATH domain and impairs SPOP dimerization and substrate degradation. Different from F133V hotspot mutant tumors, Q165P mutant patient-derived xenografts (PDXs) and organoids were modestly sensitive to the BET inhibitor JQ1. Accordingly, protein levels of AR, BRD4 and downstream effectors such as RAC1 and phosphorylated AKT were not robustly elevated in Q165P mutant cells as in F133V mutant cells. However, NEO2734, a novel dual inhibitor of BET and CBP/p300, is active in both hotspot mutant (F133V) and non-hotspot mutant (Q165P) PCa cells in vitro and in vivo. These data provide a strong rationale to clinically investigate the anti-cancer efficacy of NEO2734 in SPOP-mutated PCa patients.
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