AMG319 是一种有效的选择性 PI3Kδ 抑制剂，IC₅₀ 为 18 nM。

AMG319 is a potent and selective PI3Kδ kinase inhibitor with IC 50 of 18 nM.

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PI3Kδ 18 nM (IC50) PI3Kγ 850 nM (IC50

AMG319 inhibits PI3Kδ, PI3Kγ, PI3Kβ and PI3Kα with IC50s of 18 nM, 850 nM, 2.7 μM and 33 μM, respectively. AMG319, a compound with an IC50 of 16 nM in a human whole blood assay (HWB), excellent selectivity over a large panel of protein kinases, and a high level of in vivo efficacy as measured by two rodent disease models of inflammation. AMG319 has minimal CYP3A4/2D6 inhibition and does not inhibit CYPs (1A2, 2C8, 2C9, 2C19, 2E1, all >20 μM). There is no time dependent inhibition (TDI) against CYPs 3A4, 2D6, 1A2, and 2C9 nor CYP induction (3A4, 2D6, 1A2, 2B6) as measured in hepatocytes. AMG319 is clean in a hERG binding assay (>25 μM), and an Ames micronucleus test proved negative. AMG319 has minimal effects in a BSEP assay up to >200 μM. Additionally, AMG319 is clean in a large side effect profiling panel (CEREP) and has no activity in a large p

The study is performed to determine the correlation between biochemical coverage (i.e., pAKT) with functional activity in vivo. AMG319 achieves this coverage at the 3 mg/kg level, which also coveres the human whole blood assay (HWB) (CD-69) IC 90 at trough for a full 24 h period. The lower doses 0.1, 0.3, and 1 mg/kg cover trough concentrations between the HWB IC 50 and IC 90 and evince partial efficacy. Similarly, the plasma concentration of AMG319 covers the IC 90 at the 1 mg/kg dose of the mouse anti-IgM pAKT in vitro assay. has not independently confirmed the accuracy of these methods. They are for reference only.

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[1]. Cushing TD, et al. Discovery and in vivo evaluation of (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and related PI3Kδ inhibitors for inflammation and autoimmune disease. J Med Chem. 2015 Jan 8;58(1):480-511.

In Vitro: DMSO : 50 mg/mL (129.74 mM; Need ultrasonic)配制储备液