IHMT-PI3Kδ-372

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

IHMT-PI3Kδ-372 是一种有效的选择性 PI3Kδ 抑制剂，IC50 为 14 nM。IHMT-PI3Kδ-372 对 PI3Kδ 的选择性高于其他 I 类 PI3K (56-83 倍) 和其他蛋白激酶。IHMT-PI3Kδ-372 可用于慢性阻塞性肺疾病 (COPD )的研究。

IHMT-PI3Kδ-372 is a potent and selective PI3Kδ inhibitor with an IC50 of 14 nM. IHMT-PI3Kδ-372 shows high selectivity over other class I PI3Ks (56～83 fold) and other protein kinases. IHMT-PI3Kδ-372 can be uesd for chronic obstructive pulmonary disease (COPD) research.

IHMT-PI3Kδ-372 (Compound (S)-18; 0.03-3 μM; 1 hour; Raji cells) treatment inhibits PI3Kδ-mediated AKT T308 phosphorylation in Raji cells with an EC50 value of 67 nM.IHMT-PI3Kδ-372 (compound (S)-18) shows moderate inhibition of CYP2C9 (IC50 of 2.7 μM) and no apparent inhibition against CYP1A2, CYP2B6, CYP2C19, and CYP3A4 (IC50s > 10 μM).Western Blot Analysis Cell Line:Raji cells Concentration:0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Time:1 hour Result:Inhibited PI3Kδ-mediated AKT T308 phosphorylation in Raji cells with an EC50 value of 67 nM.

IHMT-PI3Kδ-372 (Compound (S)-18; 1-5 mg/kg; inhalation; daily; for 28 days) improves lung function and reduced the inflammatory patterns characteristic of COPD. The lung function parameters such as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) are improved dose-dependently. The abnormally high level of leukocytes including the alveolar macrophages, neutrophils, and lymphocytes are also reduced. IHMT-PI3Kδ-372 decreases the inflammatory cell infiltration in a dose-dependent manner.In rats, inhalation of 5 mg/kg dose of IHMT-PI3Kδ-372 (compound (S)-18) displays a half-life of 2.3 h, low exposure of 66 ng/mL, and high clearance of 348.5 mL/min/kg in plasma but high exposure of 5599 ng/g (6 h after inhalation) in lung tissue.IHMT-PI3Kδ-372 is stable in human, rat, and mouse liver microsomes, while it has moderate stability in monkey and dog liver microsomes.Animal Model:Sprague-Dawley (SD) rats (5-week-old) induced with cigarette-smoke and LPS Dosage:1 mg/kg, 3 mg/kg, and 5 mg/kg Administration: Inhalation; daily; for 28 days Result:Improved lung function and reduced the inflammatory patterns characteristic of COPD.

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PI3K/Akt/mTOR signaling

PI3K

PI3K

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2429889-62-1

503.5

C26H23F2N7O2

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 41.67 mg/mL (82.76 mM; 超声助溶 )

CC[C@H](c1nc2cccc(F)c2c(=O)n1C1CC1)n1nc(-c2ccc(OC)c(F)c2)c2c(N)ncnc12

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(-20℃)

With Ice Pack

≥ 2 years