AMG 511

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

AMG 511 是一种有效的口服 I 类 PI3K 泛抑制剂（PI3Kα、β、δ 和 γ 的 Ki 值分别为 4 nM、6 nM、2 nM 和 1 nM）。

AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks(Kis of 4 nM, 6 nM, 2 nM and 1 nM for PI3Kα, β, δ and γ, respectively). It exhibits anti-tumor activity in mouse glioblastoma xenograft model[1]. AMG 511 significantly suppresses PI3K signaling that is indicated by p-Akt (Ser473) decrease.

AMG 511 shows the inhibition of AKT (Ser473) phosphorylation in U87 malignant glioma (MG) cells with an IC50 of 4 nM.

AMG 511 potently blocks the targeted PI3K pathway in a mouse liver pharmacodynamic model (3-30 mg/kg; p.o.) and inhibits tumor growth in a U87 MG glioblastoma xenograft model (3-30 mg/kg; p.o.; daily; for 12 days).AMG 511 shows excellent in vivo efficacy and pharmacokinetic profile. Animal Model:Female CD1 NU/NU mice, with U87 MG glioblastoma xenograft model Dosage:1 mg/kg, 3 mg/kg, 10 mg/kg Administration:Oral administration, daily, for 12 days Result:Inhibited tumor growth.Animal Model:Male Sprague-Dawley rats Dosage:1 mg/kg Administration:Oral administration (Pharmacokinetic Analysis)Result:Had a superior pharmacokinetic profile with low clearance (0.4 L/h/kg, 12% of liver blood flow), good oral bioavailability (F = 60%), and a commensurate high oral exposure (AUC = 5.0 μM·h).

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PI3K/Akt/mTOR signaling

PI3K

PI3Kα|PI3Kβ|PI3Kγ|PI3Kδ

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1253573-53-3

517.58

C22H28FN9O3S

>98% (HPLC)

DMSO:33.33 mg/mL (64.40 mM; Need ultrasonic)

C[C@H](c(cc1-c2nc(N)nc(C)n2)cnc1Nc(cc1F)cnc1OC)N(CC1)CCN1S(C)(=O)=O

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(-20℃)

With Ice Pack

≥ 2 years