KRCA 0008

KRCA 0008 is an inhibitor of anaplastic lymphoma kinase (ALK) and tyrosine non-receptor kinase 2 (TNK2), also known as activated Cdc42 kinase 1 (ACK1, IC50s = 12 and 4 nM, respectively). It is selective for these kinases over the insulin receptor (InsR, IC50 = 210 nM). KRCA 0008 also inhibits the ALK mutants ALKL1196M, ALKC1156Y, ALKF1174L, and ALKR1275Q (IC50s = 75, 4, 171, and 17 nM, respectively). It selectively reduces the proliferation of NCI H3122 lung cancer cells, which are driven by the EML4-ALK fusion protein, over NCI H1993 lung cancer cells, which are driven by c-Met (IC50s = 80 and 3,600 nM, respectively). KRCA 0008 (25 and 50 mg/kg) reduces tumor volume in an NCI H3122 mouse xenograft model. InChI: InChI=1S/C30H37ClN8O4/c1-20(40)36-9-13-38(14-10-36)22-5-7-25(27(17-22)42-3)33-29-24(31)19-32-30(35-29)34-26-8-6-23(18-28(26)43-4)39-15-11-37(12-16-39)21(2)41/h5-8,17-19H,9-16H2,1-4H3,(H2,32,33,34,35) InChIKey: TXDIRJCYNAWBOS-UHFFFAOYSA-N SMILES: O=C(C)N1CCN(CC1)C2=CC=C(C(OC)=C2)NC3=NC=C(C(NC(C(OC)=C4)=CC=C4N5CCN(CC5)C(C)=O)=N3)Cl