KRCA-0008

Research use only, not for human use.

KRCA-0008 is a potent, selective ALK inhibitor with IC50 of 12 nM (wt ALK).

KRCA-0008 is a potent, selective ALK inhibitor with IC50 of 12 nM (wt ALK), also is potent against various ALK mutants, including L1196M, F1174L, R1275Q, and C1156Y (IC50=5-75 nM); weakly inhibits IR (IC50=210 nM), inhibits H3122 and BaF3 EML4-ALK L1196M cell proliferation with IC50 of 80 and 68 nM, respectively; demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice model, has drug-like properties without hERG concerns.

Cell Proliferation Assay Cell Line:H3122 and H1993 cell lines Concentration:200 nM Incubation Time:6 hours Result:Inhibited cell proliferation of H3122 and H1993 cells with IC50s of 0.08 and 3.6 nM, respectively.Cell Proliferation Assay Cell Line:NPM-ALK-positive ALCL cell lines (Karpas-299 and SU-DHL-1) and U937 NPM ALK-negative lymphoma cell line Concentration:200 nM Incubation Time:72 hoursResult:Inhibited proliferation of Karpas-299, SU-DHL-1 and U937 cells with GI50s of 12 nM, 3 nM and 3.5 μM, respectively.Western Blot Analysis Cell Line:Karpas-299 and SU-DHL-1 cell lines Concentration:0, 10, 100 and 1000 nMIncubation Time:4 hoursResult:Completely suppressed phosphorylation of ALK and its effectors at a dose of 100 nM in NPM-ALK-positive ALCL cells.Apoptosis AnalysisCell Line:SU-DHL-1 cell line Concentration:0-1 μM Incubation Time:72 hours Result:Dose-dependently increased cspase-3/7 activities and induced cell apoptosis.Cell Cycle Analysis Cell Line:Karpas-299 and SU-DHL-1 cell lines Concentration:0-100 nM Incubation Time:48 hours Result:Induced G0/G1 cell cycle arrest in ALCL cells expressing NPM-ALK.

Animal Model:NOD/SCID mice with Karpas-299 xenograftsDosage:25 and 50 mg/kg Administration:Oral gavage; 25 and 50 mg/kg twice a day; for two weeks Result:Significantly inhibited tumor growth by inhibiting NPM-ALK phosphorylation without showing overt signs of toxicity or significant compound-related body weight loss.

KRCA 0008 | KRCA0008

Angiogenesis

ALK

ACK|ALK

Cancer

——

1472795-20-2

609.119

C30H37ClN8O4

>98% (HPLC)

10 mM in DMSO

ClC1=CN=C(NC2=CC=C(N3CCN(C(C)=O)CC3)C=C2OC)N=C1NC4=CC=C(N5CCN(C(C)=O)CC5)C=C4OC

Ethanone, 1,1'-[(5-chloro-2,4-pyrimidinediyl)bis[imino(3-methoxy-4,1-phenylene)-4,1-piperazinediyl]]bis-

(-20℃)

With Ice Pack

≥ 2 years