Home Epigenetics HIF antagonist PT2385 For research use only.

PT2385

PT2385 is a HIF-2α antagonist with luciferase EC50 of 27 nM and no significant off-target activity.

PT2385 Chemical Structure

PT2385 Chemical Structure

CAS No. 1672665-49-4

Purity & Quality Control

PT2385 Related Products

Signaling Pathway

HIF Signaling Pathways

HIF Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
786-O Function assay 24 hrs Antagonist activity at HIF-2alpha in human 786-O cells co-expressing HIF responsive element after 24 hrs by ONE-Glo luciferase reporter gene assay, EC50 = 0.027 μM. 30289716
786-O Function assay 24 hrs Antagonist activity at HIF-2alpha in human 786-O cells assessed as reduction in VEGFA concentration after 24 hrs by ELISA, EC50 = 0.041 μM. 30289716
786-O Function assay 24 hrs Antagonist activity at HIF-2alpha in human 786-O cells assessed as free plasma adjusted EC50 for reduction in VEGFA concentration after 24 hrs by ELISA, EC50 = 0.158 μM. 30289716
786-O Function assay 10 mg/kg 3 days In vivo inhibition of HIF-2alpha in SCID/Biege mouse xenografted with human 786-O cells assessed as reduction in CCND1 mRNA levels at 10 mg/kg, po bid for 3 days and measured after 12 hrs post last dose by qRT-PCR analysis 30289716
786-O Function assay 10 mg/kg 3 days In vivo inhibition of HIF-2alpha in SCID/Biege mouse xenografted with human 786-O cells assessed as reduction in VEGFA mRNA levels at 10 mg/kg, po bid for 3 days and measured after 12 hrs post last dose by qRT-PCR analysis 30289716
786-O Antitumor assay 10 mg/kg 21 days Antitumor activity against human 786-O cells xenografted in SCID/Biege mouse assessed as tumor regression at 10 mg/kg, po bid for 21 days 30289716
786-O Function assay 10 mg/kg 3 days Minimum drug level in SCID/Biege mouse xenografted with human 786-O cells at 10 mg/kg, po bid for 3 days and measured after 12 hrs post last dose by LC-MS/MS analysis 30289716
786-O Function assay 10 mg/kg 3 days In vivo inhibition of HIF-2alpha in SCID/Biege mouse xenografted with human 786-O cells assessed as reduction in tumor derived VEGFA protein levels at 10 mg/kg, po bid for 3 days and measured after 12 hrs post last dose by ELISA 30289716
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Biological Activity

Description PT2385 is a HIF-2α antagonist with luciferase EC50 of 27 nM and no significant off-target activity.
Targets
HIF-2α [1]
(Cell-free assay)
27 nM(EC50)
In vitro
In vitro

PT2385 blocks HIF-2α dimerization with the HIF1α/2α transcriptional dimerization partner ARNT/HIF1β. PT2385 inhibits the expression of HIF2α-dependent genes, including VEGF-A, PAI-1, and cyclin D1 in ccRCC cell lines and tumor xenografts. PT2385 has no effect on the proliferation or viability of 786-O and A498 cells in culture at concentration as high as 10 μmol/L. Treatment of 786-O cells with PT2385 significantly reduces the levels of mRNA for CCND1, VEGF-A, GLUT1, and PAI-1 in a concentration-dependent manner. Treatment of Hep3B cells with PT2385 reduces hypoxia-induced expression of erythropoietin (EPO) and PAI-1, both known HIF2α target genes[2].
Cell Research Cell lines 786-O cells
Concentrations 20, 6.67, 2.22, 0.74, 0.25, 0.082, 0.027, 0.009, 0.003, 0.001 μM
Incubation Time 44 h
Method

About 7500 of 786-O cells in 180 μL of growth medium are seeded into each well of a 96 well plate with white clear bottom on the first day. Four hours later, serial dilutions of 10x compound stocks are made in growth medium from 500x DMSO stocks, and 20 μL of those 10x stocks are added to each well to make final concentrations as follows (μM): 20, 6.67, 2.22, 0.74, 0.25, 0.082, 0.027, 0.009, 0.003, 0.001, and 0. Each concentration has duplicated wells. About 20 hours later, medium is removed by suction and each well is supplied with 180 μL of growth medium. About 20 μl freshly-made 10x compound stocks are added to each well. About 24 hours later, cell culture medium is removed for the determination of VEGFA concentration using an ELISA kit.
In Vivo
In vivo

PT2385 exhibits good mouse oral bioavailability (110%) and low to medium in vivo clearance. In mice administrated via intravenous injection, the t1/2 of PT2385 is 3.3 h. In rat pharmacokinetics studies, the oral bioavailability (F) when dosed at 10 mg/kg is 40% and the t1/2 is 3.3 h. In dogs, the oral bioavailability (F) is 87% and the t1/2 is 11 h[1]. Treatment of tumor-bearing mice with PT2385 causes dramatic tumor regressions (clear cell renal cell carcinomas). PT2385 exhibits no adverse effect on cardiovascular performance[2].
Animal Research Animal Models male CD1 mice
Dosages 3 mg/kg (IV) and 10 mg/kg (PO)
Administration IV or PO
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02553356 Completed
Healthy
Peloton Therapeutics Inc. a subsidiary of Merck & Co. Inc. (Rahway New Jersey USA)
 September 2015 Phase 1

Chemical Information & Solubility

Molecular Weight 383.34 Formula

C17H12F3NO4S
CAS No. 1672665-49-4 SDF --
Smiles CS(=O)(=O)C1=C2C(C(CC2=C(C=C1)OC3=CC(=CC(=C3)C#N)F)(F)F)O
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 77 mg/mL ( (200.86 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 5 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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