PF 06463922 ((10R)-7-Amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-2H-4,8-methenopyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile) | 1454846-35-5

name

pf 06463922

chemical name

(10r)-7-amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-2h-4,8-methenopyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile

activity

high affinity and selective alk and ros1 inhibitor (ki values are <0.02, <0.07 and 0.7 nm for ros1, wild-type alk and alk-l1196m, respectively). exhibits >100-fold selectivity for ros1 over a panel of 204 other kinases. inhibits proliferation of baf3 cells containing crizotinib-resistant ros1 mutation in vitro. inhibits tumor growth in relevant mouse models. orally available and brain penetrant.

MW

406.41

Formula:

c21h19fn6o2

Solubility:

soluble to 100 mm in dmso and to 100 mm in ethanol

Purity:

>98 %

Storage:

store at -20°c

CAS No:

1454846-35-5

Johnson et al (2014) Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J.Med.Chem. 57 4720. PMID: 24819116.

Zou et al (2015) PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc.Natl.Acad.Sci.U.S.A. 112 3493. PMID: 25733882.