AMG 511

Product NameAMG 511
CAS1253573-53-3
MFC22H28FN9O3S
MW517.58
EINECS
MOL File1253573-53-3.mol

Chemical Properties

solubility	Acetonitrile: Slightly soluble: 0.1-1 mg/ml DMSO: Sparingly soluble: 1-10 mg/ml
form	Solid
color	Light yellow to yellow

Usage And Synthesis

Uses

AMG-511 is a PI3Kα inhibitor used as a cancer therapeutic due to its effect on cell growth and cell survival.

in vivo

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)^[1].
AMG 511 shows excellent in vivo efficacy and pharmacokinetic profile^[1].

Animal Model:	Female CD1 NU/NU mice, with U87 MG glioblastoma xenograft model^[1]
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^[1]
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).

IC 50

PI3Kα: 4 nM (Ki); PI3Kβ: 6 nM (Ki); PI3Kδ: 2 nM (Ki); PI3Kγ: 1 nM (Ki)

References

[1] MARK H. NORMAN*. Selective Class I Phosphoinositide 3-Kinase Inhibitors: Optimization of a Series of Pyridyltriazines Leading to the Identification of a Clinical Candidate, AMG 511[J]. Journal of Medicinal Chemistry, 2012, 55 17: 7796-7816. DOI: 10.1021/jm300846z