KW-2449 hydrochloride

• CAT Number: I000066
• CAS Number: 1000669-72-6
• Molecular Formula: C20H20N4O. HCl
• Molecular Weight: 368.86
• Purity: ≥95%
• Target: FLT3
• Solubility: DMSO ≥63mg/mL Water <1.2mg/mL Ethanol ≥63mg/mL
• Storage: 3 years -20C powder
• IC50: 6.6 nM
• IUPAC Name: [4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone
• InChI: InChI=1S/C20H20N4O/c25-20(24-13-11-21-12-14-24)16-8-5-15(6-9-16)7-10-19-17-3-1-2-4-18(17)22-23-19/h1-10,21H,11-14H2,(H,22,23)/b10-7+
• InChIKey: YYLKKYCXAOBSRM-JXMROGBWSA-N
• SMILES: C1CN(CCN1)C(=O)C2=CC=C(C=C2)C=CC3=NNC4=CC=CC=C43

KW-2449 hydrochloride (CAT: I000066) is a multi-targeted inhibitor with a strong affinity for FMS-like tyrosine kinase 3 (Flt3) with an IC50 of 6.6 nM. It also exhibits moderate potency against fibroblast growth factor receptor 1 (FGFR1), Bcr-Abl, and Aurora A kinases. However, it has little effect on platelet-derived growth factor receptor beta (PDGFRβ), insulin-like growth factor-1 receptor (IGF-1R), and epidermal growth factor receptor (EGFR). The broad spectrum of kinase inhibition suggests potential applications of KW-2449 in targeting multiple signaling pathways implicated in various diseases, including cancer.

Overview of Clinical Research

KW-2449 is an aurora kinase inhibitor , a Bcr-abl tyrosine kinase inhibitor, and a Fms-like tyrosine kinase 3 inhibitor. It is to treat acute myeloid leukaemia. 

Reference

1:HDAC inhibitors potentiate the activity of the BCR/ABL kinase inhibitor KW-2449 in imatinib-sensitive or -resistant BCR/ABL+ leukemia cells in vitro and in vivo. Nguyen T, Dai Y, Attkisson E, Kramer L, Jordan N, Nguyen N, Kolluri N, Muschen M, Grant S.Clin Cancer Res. 2011 May 15;17(10):3219-32. doi: 10.1158/1078-0432.CCR-11-0234. Epub 2011 Apr 7. PMID: 21474579 Free PMC Article
2:KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Shiotsu Y, Kiyoi H, Ishikawa Y, Tanizaki R, Shimizu M, Umehara H, Ishii K, Mori Y, Ozeki K, Minami Y, Abe A, Maeda H, Akiyama T, Kanda Y, Sato Y, Akinaga S, Naoe T.Blood. 2009 Aug 20;114(8):1607-17. doi: 10.1182/blood-2009-01-199307. Epub 2009 Jun 18. PMID: 19541823 Free Article
3:A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Pratz KW, Cortes J, Roboz GJ, Rao N, Arowojolu O, Stine A, Shiotsu Y, Shudo A, Akinaga S, Small D, Karp JE, Levis M.Blood. 2009 Apr 23;113(17):3938-46. doi: 10.1182/blood-2008-09-177030. Epub 2008 Nov 24. PMID: 19029442 Free PMC Article
4:[New therapeutic option for leukemia patients, with FLT3/Aurora kinase inhibitor, KW-2449: strategy and comparison with other kinase inhibitors]. Shiotsu Y.Rinsho Ketsueki. 2008 Aug;49(8):641-9. Review. Japanese. No abstract available. PMID: 18800614