Cat No:LP000227
Product Name:LDK378;Ceritinib
CAS No:1032900-25-6
Purity: ≥99%
Solubility: In DMSO
Storage: -10°C
LDK378 (Ceritinib) also inhibits RET (IC50=400 nM), FGFR3 (IC50=430 nM), LCK (IC50=560 nM), JAK2 (IC50=610 nM), Aurora (IC50=660 nM), LYN (50=840 nM), EGFR (IC50=900 nM), and FGFR4 (IC50=950 nM)[1]. LDK378 retains high potency against the ALK enzymatic activity with an IC50 value of 200 pM and shows only strong inhibition against IGF-1R, InsR, and STK22D out of a panel of 46 kinases with a minimum selectivity of 70-fold. In Ba/F3 cells transfected with various kinases, LDK378 inhibits ALK activity with an IC50 value of 40.7 nM and had IC50 values of >100 nM against all other kinases tested. LDK378 shows potent antiproliferative activity with an IC50 value of 22.8 nM in Karpas 299 human non-Hodgkin’s Ki-positive large cell lymphoma carrying the NPM-ALK fusion gene and 26 nM in Ba/F3 cells transfected with the NPM-ALK fusion gene. LDK378 also shows good selectivity over wild-type Ba/F3 cells (IC50>2 μM) and Ba/F3 cells transfected with Tel-InsR gene (IC50=320 nM)[2].
The t1/2 of LDK378 in LDK378 mouse rat, dog, and monkey is 6.2 h, 9.1 h, 21 h, and 26 h,respectively[1]. LDK378 has an excellent pharmacokinetics profile in rodents and non-rodents with an oral bioavailability of >50%. LDK378 demonstrates dose-dependent tumor growth inhibition and achieved partial tumor regression in the Karpas 299 rat xenograft model with daily administration but is capable of achieving complete tumor regression in the H2228 NSCLC rat xenograft model, which carries the EML4-ALK fusion gene. In both models, LDK378 is well tolerated in animals. LDK378 is further assessed for its ADME profile and is found to have a relatively good metabolic stability in liver microsomes, modest CYP3A4 inhibition, some hERG inhibition with an IC50 value of 46 μM in hERG patch clamp experiments, but no evidence of QTc prolongation in both dog and monkey telemetry studies[2].
