(R)-Crizotinib

(R)-Crizotinib is a dual inhibitor of c-Met and anaplastic lymphoma kinase (ALK, IC50s = 8 and 20 nM, respectively, in a cell-based assay). It is selective for c-Met and ALK over several other receptor- and non-receptor tyrosine kinases, including Ron, Tie2, Abl, LCK, and VEGFR2 (IC50s = 0.08, 0.448, 1.159, 2.741, and >10 µM, respectively). (R)-Crizotinib selectively inhibits the proliferation of cancer cell lines with MET amplifications over cancer cell lines with MET or EGFR mutations (IC50s = 5-10, 472-1,284, and 767-787 nM, respectively). It induces apoptosis in MET-amplified EBC-1 and NCI H1993 lung cancer cells when used at a concentration of 100 nM. (R)-Crizotinib (25 mg/kg) reduces tumor volume in an EBC-1 mouse xenograft model. Formulations containing crizotinib have been used in the treatment of metastatic, relapsed, or refractory ALK-positive cancers.Formal Name: 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(4-piperidinyl)-1H-pyrazol-4-yl]-2-pyridinamine. CAS Number: 877399-52-5. Synonyms: PF 2341066. Molecular Formula: C21H22Cl2FN5O. Formula Weight: 450.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 5 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 0.5 mg/ml, Ethanol: 0.5 mg/ml. lambdamax: 206, 269, 323 nm. SMILES: NC1=C(O[C@@H](C2=C(Cl)C=CC(F)=C2Cl)C)C=C(C3=CN(C4CCNCC4)N=C3)C=N1. InChi Code: InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1. InChi Key: KTEIFNKAUNYNJU-GFCCVEGCSA-N.