PT2385

製品コードS8352 バッチS835202

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₁₇H₁₂F₃NO₄S

分子量

383.34

CAS No.

1672665-49-4

Solubility (25°C)*

体外

DMSO

77 mg/mL (200.86 mM)

Ethanol

19 mg/mL (49.56 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

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.

溶剤液（一定の濃度）を調合する

生物活性

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

プロトコル(参考用のみ)

細胞アッセイ	細胞株	786-O cells
	濃度	20, 6.67, 2.22, 0.74, 0.25, 0.082, 0.027, 0.009, 0.003, 0.001 μM
	反応時間	44 h
	実験の流れ	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.
動物実験	動物モデル	male CD1 mice
	投薬量	3 mg/kg (IV) and 10 mg/kg (PO)
	投与方法	IV or PO

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。