ArticleCancer research2016
A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers.
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.
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Who cites it
202 citing papers in PubMed, 316 citations in OpenAlex.
- Oral Hypoxia-Inducible Factor 2α Inhibitor Belzutifan in Ocular von Hippel-Lindau Disease: Subgroup Analysis of the Single-Arm Phase 2 LITESPARK-004 Study.Ophthalmology · 2024Trial
- Activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrence of glioblastoma.Journal of neuro-oncology · 2023Trial
- Identification of novel HIF2α inhibitors: a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Regulatory networks of non-coding RNAs in renal cell carcinogenesis and therapeutic intervention strategies.World journal of urology · 2026Review
- SET1B Drives Sustained HIF Activity and Disease Progression in Clear-Cell Renal Cell Carcinoma.Cancer research · 2026Article
- Discovery of NKT2152, a Potent and Selective HIF-2α Inhibitor with Favorable Pharmacokinetic Properties.ACS medicinal chemistry letters · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- IL-1β/EPAS1-Associated Ferroptotic Stress Impairs Skeletal Stem/Progenitor Cell Function in Inflammation-Associated Fracture Nonunion.Current issues in molecular biology · 2026Article
- Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism.The EMBO journal · 2026Article
- Rescuing the Function of Missense-Mutated Tumor SuppressorbioRxiv : the preprint server for biology · 2026Article
- The CLOCK-BMAL1 complex in circadian regulation: structure, mechanisms, and therapeutic targeting.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
- Small Molecule Regulation of CLOCK:BMAL1 DNA Binding Activity.bioRxiv : the preprint server for biology · 2026Article
- Oncometabolites and Hypoxia-Regulated Exosomes Shape HIF-Driven Macrophage Programs Across Type 2 Diabetes, Atherosclerosis, and Cancer.International journal of molecular sciences · 2026Review
- Enhancing the efficacy of VEGF inhibitors by co-inhibition of HIF in the treatment of glioblastoma.Apoptosis : an international journal on programmed cell death · 2026Review
- First-in-class HIF-2α therapy in genitourinary oncology: Belzutifan from von Hippel-Lindau disease to advanced renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Targeting and dissociating HIF2α from the molecular chaperone Hsp70 triggers apoptosis in kidney cancer.Communications medicine · 2026Article
- Hypoxic microenvironment in cancer: role in metabolic reprogramming.Frontiers in oncology · 2026Review
142 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
More than 90% of clear cell renal cell carcinomas (ccRCC) exhibit inactivation of the von Hippel-Lindau (pVHL) tumor suppressor, establishing it as the major underlying cause of this malignancy. pVHL inactivation results in stabilization of the hypoxia-inducible transcription factors, HIF1α and HIF2α, leading to expression of a genetic program essential for the initiation and progression of ccRCC. Herein, we describe the potent, selective, and orally active small-molecule inhibitor PT2385 as a specific antagonist of HIF2α that allosterically blocks its dimerization with the HIF1α/2α transcriptional dimerization partner ARNT/HIF1β. PT2385 inhibited the expression of HIF2α-dependent genes, including VEGF-A, PAI-1, and cyclin D1 in ccRCC cell lines and tumor xenografts. Treatment of tumor-bearing mice with PT2385 caused dramatic tumor regressions, validating HIF2α as a pivotal oncogenic driver in ccRCC. Notably, unlike other anticancer agents that inhibit VEGF receptor signaling, PT2385 exhibited no adverse effect on cardiovascular performance. Thus, PT2385 represents a novel class of therapeutics for the treatment of RCC with potent preclincal efficacy as well as improved tolerability relative to current agents that target the VEGF pathway. Cancer Res; 76(18); 5491-500. ©2016 AACR.
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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.