Rebastinib (DCC2036)

Description: Rebastinib (formerly also known as DCC-2036), a novel, potent and orally bioavailable small-molecule inhibitor of multiple tyrosine kinases with potential antineoplastic activity, is a conformational control Bcr-Abl inhibitor for Abl1(WT) and Abl1(T315I) with IC50s of 0.8 nM and 4 nM. It also inhibits other kinases such as SRC, LYN, FGR, HCK, KDR, FLT3, and Tie-2, and has low activity towards c-Kit. DCC-2036 inhibits ABL1 through forcing the kinase domains into inhibitor-bound, inactive Type II conformations. In cellular assay, DCC-2036 inhibits the proliferation of Ba/F3 and K562 cells with IC50 values of 5.4nM and 5.5nM, respectively.

References: Cancer Cell. 2011 Apr 12; 19(4):556-68; Cancer Res. 2011 May 1; 71(9):3189-95.

Synonym: DCC-2036; DCC 2036; DCC2036; Rebastinib.

Chemical Name: N-[3-tert-Butyl-1-(quinolin-6-yl)-1H-pyrazol-5-yl]-N'-[2-fluoro-4-[(2-(methylcarbamoyl)pyridin-4-yl)oxy]phenyl]urea

InChi Key: WVXNSAVVKYZVOE-UHFFFAOYSA-N

InChi Code: InChI=1S/C30H28FN7O3/c1-30(2, 3)26-17-27(38(37-26)19-7-9-23-18(14-19)6-5-12-33-23)36-29(40)35-24-10-8-20(15-22(24)31)41-21-11-13-34-25(16-21)28(39)32-4/h5-17H, 1-4H3, (H, 32, 39)(H2, 35, 36, 40)

SMILES Code: O=C(NC1=CC=C(OC2=CC(C(NC)=O)=NC=C2)C=C1F)NC3=CC(C(C)(C)C)=NN3C4=CC=C5N=CC=CC5=C4