Name: PT2385
Brand: Selleck Chemicals
SKU: S8352
Rating: 5 (14 reviews)

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Quality Control

Batch: Purity: 99.38%

99.38

Related Targets	HDAC JAK BET Histone Methyltransferase PKC PARP PRMT EZH2 AMPK Histone Acetyltransferase
Other HIF Inhibitors	PT2399 PX-478 Dihydrochloride BAY 87-2243 KC7F2 Lificiguat (YC-1) IOX2 CAY10585 (LW 6) Molidustat (BAY 85-3934) IDF-11774 MK-8617

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	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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Chemical Information, Storage & Stability

Molecular Weight	383.34	Formula	C₁₇H₁₂F₃NO₄S	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	1672665-49-4	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CS(=O)(=O)C1=C2C(C(CC2=C(C=C1)OC3=CC(=CC(=C3)C#N)F)(F)F)O

Solubility

In vitro
Batch:

DMSO : 77 mg/mL (200.86 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 5 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.850mg/ml (10.04mM)	Taking the 1 mL working solution as an example, add 50 μL of clarified DMSO stock solution of 77 mg/ml to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	HIF-2α (Cell-free assay) 27 nM(EC50)
In vitro	PT2385 blocks HIF-2α dimerization with the HIF1α/2α transcriptional dimerization partner ARNT/HIF1β. This compound inhibits the expression of HIF2α-dependent genes, including VEGF-A, PAI-1, and cyclin D1 in ccRCC cell lines and tumour xenografts. It 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 this chemical significantly reduces the levels of mRNA for CCND1, VEGF-A, GLUT1, and PAI-1 in a concentration-dependent manner. Treatment of Hep3B cells with this agent reduces hypoxia-induced expression of erythropoietin (EPO) and PAI-1, both known HIF2α target genes.
In vivo	PT2385 exhibits good mouse oral bioavailability (110%) and low to medium in vivo clearance. In mice administrated via intravenous injection, the t_1/2 of this compound is 3.3 h. In rat pharmacokinetics studies, the oral bioavailability (F) when dosed at 10 mg/kg is 40% and the t_1/2 is 3.3 h. In dogs, the oral bioavailability (F) is 87% and the t_1/2 is 11 h. Treatment of tumour-bearing mice with this chemical causes dramatic tumour regressions (clear cell renal cell carcinomas). It exhibits no adverse effect on cardiovascular performance.
References	[1] https://pubmed.ncbi.nlm.nih.gov/30289716/ [2] https://pubmed.ncbi.nlm.nih.gov/27635045/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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PT2385 HIF-2α Inhibitor

Chemical Structure

Molecular Weight: 383.34