PF-06463922

Short Summary : ALK/ROS1 inhibitor,potent and selective

Category : Tyrosine Kinase|ALK

Purity : 0.9922

CAS Number : 1454846-35-5

Formula : C21H19FN6O2

Molecular Weight :

Molecular Weight : 406.41

SMILE : FC1=CC([C@H](OC2=C(N)N=CC(C3=C(C#N)N(C)N=C3CN4C)=C2)C)=C(C4=O)C=C1

Solubility : >20.3mg/mL in DMSO

Storage : Store at -20°C

Description : PF-06463922 is a potent and selective ALK/ROS1 inhibitor with IC50 values ranging from 0.19-0.53 nM for the kinase activity of ROS1 fusion enzymes [1].The receptor tyrosine kinase c-ros oncogene1 (ROS1) is a receptor with a kinase domain that is related to the anaplastic lymphoma kinase/lymphocyte-specific protein tyrosine kinase (ALK/LTK) and insulin receptor (INSR) RTK families [1]. Via cellular ROS1 autophosphorylation in the recombinant enzyme assay, PF-06463922 showed a 30-fold improved potency against ROS1, compared with crizotinib, ceritinib, alectinib and foretinib (XL-880). Engineered NIH 3T3 cells were expressing oncogenic human ROS1 fusions. In these cells, PF-06463922 was more potent than foretinib and crizotinib by >10 folds, more potent than alectinib and ceritinib by >100 folds against cellular ROS1 autophosphorylation [1].Oncogenic gene fusions involving the 3′ region of ROS1 kinase had been found in various human cancers [2]. Mice bearing CD74-ROS1, CD74-ROS1G2032R and FIG-ROS1(S) s.c. Tumors (250 mm3) were used. Treatments with PF-06463992 at various doses were applied consecutively for 7 or 9 d. At dosages of 0.2 to 1 mg/kg/d, PF-06463922 significantly inhibited the growth of both established FIGROS1(S) and CD74-ROS1 tumors compared with vehicle control. At 2-6 mg/kg/d, PF-06463922 significantly made tumor volumes regress (58C85%, P References: [1]. Zou HY, Li Q, Engstrom LD, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proceedings of the National Academy of Sciences, 2015, 112(11): 3493-3498.[2]. Davies KD, Le AT, Theodoro MF, et al. Identifying and targeting ROS1 gene fusions in nonCsmall cell lung cancer. Clinical Cancer Research, 2012, 18(17): 4570-4579.

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