Ceritinib

Ceritinib is an inhibitor of anaplastic lymphoma kinase (ALK, IC50 = 0.2 nM). It is selective for ALK over IGF-1R, InsR, STK22D, and FLT3 (IC50s = 8, 7, 23, and 60 nM, respectively) as well as a panel of 25 additional kinases (IC50s = >0.26 µM for all). Ceritinib inhibits the proliferation of Ba/F3 cells expressing the fusion protein nucleophosmin-ALK (NPM-ALK) or echinoderm microtubule-associated protein-like 4-ALK (ELM4-ALK, IC50s = 0.02 and 0.021 µM, respectively), as well as several crizotinib-resistant NPM-ALK and ELM4-ALK mutants. It reduces tumor growth in an H2228 non-small cell lung cancer (NSCLC) rat xenograft model when administered at a dose of 10 mg/kg per day and induces tumor regression at 25 mg/kg per day. Ceritinib (25 and 50 mg/kg per day) also induces tumor regression in a Karpas299 lymphoma rat xenograft model. Formulations containing ceritinib have been used in the treatment of ALK-positive metastatic NSCLC.Formal Name: 5-chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine. CAS Number: 1032900-25-6. Synonyms: LDK 378. Molecular Formula: C28H36ClN5O3S. Formula Weight: 558.1. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 12 mg/mL, DMF:PBS(pH7.2) (1:2): 0.3 mg/mL, DMSO: 1 mg/mL, Ethanol: 16 mg/mL. lambdamax: 277, 303 nm. SMILES: CC(C=C(NC1=NC=C(Cl)C(NC2=CC=CC=C2S(C(C)C)(=O)=O)=N1)C(OC(C)C)=C3)=C3C4CCNCC4. InChi Code: InChI=1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34). InChi Key: VERWOWGGCGHDQE-UHFFFAOYSA-N.