PT2385

Catalog No.S8352 Batch:S835202

Technical Data

Formula

C₁₇H₁₂F₃NO₄S

Molecular Weight

383.34

CAS No.

1672665-49-4

Solubility (25°C)*

In vitro

DMSO

77 mg/mL (200.86 mM)

Ethanol

19 mg/mL (49.56 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

3.85mg/ml

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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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].

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 PT2385 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^[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].

Protocol (from reference)

Cell Assay:^{^[1]}	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.
Animal Study:^{^[1]}	Animal Models male CD1 mice Dosages 3 mg/kg (IV) and 10 mg/kg (PO) Administration IV or PO

Cell Assay:^{^[1]}

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.

Animal Study:^{^[1]}

Animal Models
male CD1 mice
Dosages
3 mg/kg (IV) and 10 mg/kg (PO)
Administration
IV or PO

References

Selleck's PT2385 has been cited by 11 publications

Inhibition of OGFOD1 by FG4592 confers neuroprotection by activating unfolded protein response and autophagy after ischemic stroke [ J Transl Med, 2024, 22(1):248]	PubMed: 38454480
Microbiota-assisted iron uptake promotes immune tolerance in the intestine [ Nat Commun, 2023, 14(1):2790]	PubMed: 37188703
Spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells maintain pluripotency of stem cells by regulating hypoxia-inducible factors [ Biol Res, 2023, 56(1):17]	PubMed: 37016436
Protective effects of activated vitamin D receptor on radiation-induced intestinal injury [ J Cell Mol Med, 2023, 27(2):246-258]	PubMed: 36579449
EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50 [ Zool Res, 2023, 44(3):636-649]	PubMed: 37070589
Targeting SELPLG/P-selectin glycoprotein ligand 1 in preclinical ARDS: Genetic and epigenetic regulation of the SELPLG promoter [ Pulm Circ, 2023, 13(1):e12206]	PubMed: 36873461
ACSL4 deficiency confers protection against ferroptosis-mediated acute kidney injury [ Redox Biol, 2022, 51:102262]	PubMed: 35180475
System analysis based on the cancer-immunity cycle identifies ZNF207 as a novel immunotherapy target for hepatocellular carcinoma [ J Immunother Cancer, 2022, 10(3)e004414]	PubMed: 35246476
Differential HIF2α Protein Expression in Human Carotid Body and Adrenal Medulla under Physiologic and Tumorigenic Conditions [ Cancers (Basel), 2022, 14(12)2986]	PubMed: 35740651
The Inhibitory Effect and Mechanism of Ferula akitschkensis Volatile Oil on Gastric Cancer [ Evid Based Complement Alternat Med, 2022, 2022:5092742]	PubMed: 35392643

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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