Synonyms: MK-3795 | MK3795 | PT-2385
Compound class:
Synthetic organic
Comment: PT2385 is a small-molecule antagonist of HIF2α that was designed for antitumour activity [1,3-5]. The molecule binds to an allosteric site on HIF2α and blocks its interaction with its dimerisation partner ARNT (aryl hydrocarbon receptor nuclear translocator, a.k.a. HIF1β). This action inhibits expression of HIF2α-dependent genes (e.g., VEGFA, PAI-1, and cyclin D1) in renal cancer models (cell lines and xenografts).
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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References |
1. Chen W, Hill H, Christie A, Kim MS, Holloman E, Pavia-Jimenez A, Homayoun F, Ma Y, Patel N, Yell P et al.. (2016)
Targeting renal cell carcinoma with a HIF-2 antagonist. Nature, 539 (7627): 112-117. [PMID:27595394] |
2. Courtney KD, Infante JR, Lam ET, Figlin RA, Rini BI, Brugarolas J, Zojwalla NJ, Lowe AM, Wang K, Wallace EM et al.. (2018)
Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma. J Clin Oncol, 36 (9): 867-874. [PMID:29257710] |
3. Martínez-Sáez O, Gajate Borau P, Alonso-Gordoa T, Molina-Cerrillo J, Grande E. (2017)
Targeting HIF-2 α in clear cell renal cell carcinoma: A promising therapeutic strategy. Crit Rev Oncol Hematol, 111: 117-123. [PMID:28259286] |
4. Toledo RA. (2017)
New HIF2α inhibitors: potential implications as therapeutics for advanced pheochromocytomas and paragangliomas. Endocr Relat Cancer, 24 (9): C9-C19. [PMID:28667082] |
5. Wallace EM, Rizzi JP, Han G, Wehn PM, Cao Z, Du X, Cheng T, Czerwinski RM, Dixon DD, Goggin BS et al.. (2016)
A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma. Cancer Res, 76 (18): 5491-500. [PMID:27635045] |