WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200851
Description: Rebastinib, also known as DCC-2036, is an orally bioavailable small-molecule inhibitor of multiple tyrosine kinases with potential antineoplastic activity. Multitargeted tyrosine kinase inhibitor DCC-2036 binds to and inhibits the Bcr-Abl fusion oncoprotein by changing the conformation of the folded protein to disallow ligand-dependent and ligand-independent activation; in addition, this agent binds to and inhibits Src family kinases LYN, HCK and FGR and the receptor tyrosine kinases TIE-2 and VEGFR-2. Multitargeted tyrosine kinase inhibitor DCC-2036 may exhibit more potent activity against T315I Bcr-Abl gatekeeper mutant kinases than other Bcr-Abl kinase inhibitors
MedKoo Cat#: 200851
Chemical Formula: C30H28FN7O3
Exact Mass: 553.22377
Molecular Weight: 553.59
Elemental Analysis: C, 65.09; H, 5.10; F, 3.43; N, 17.71; O, 8.67
Synonym: DCC2036; DCC2036; DCC 2036; Rebastinib.
IUPAC/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
DCC-2036 inhibits BCR-ABL kinase, an oncogenic fusion protein kinase resulting from chromosomal translocation (Philadelphia + chromosome). BCR-ABL is causative of myeloproliferative diseases, including chronic myelogenous leukemia (CML). In preclinical studies, DCC-2036 has demonstrated potent enzymatic and cellular inhibition of BCR-ABL, the T315I gatekeeper mutant, and other clinically relevant P-loop & Activation loop mutants. DCC-2036 is highly efficacious in animal models of human T315I CML. DCC-2036 is being developed as an orally administered treatment for CML. See Deciphera's webpage.
1: O'Hare T, Zabriskie MS, Eide CA, Agarwal A, Adrian LT, You H, Corbin AS, Yang F, Press RD, Rivera VM, Toplin J, Wong S, Deininger MW, Druker BJ. The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Blood. 2011 Nov 10;118(19):5250-4. Epub 2011 Sep 8. PubMed PMID: 21908430; PubMed Central PMCID: PMC3217407.
2: Eide CA, Adrian LT, Tyner JW, Mac Partlin M, Anderson DJ, Wise SC, Smith BD, Petillo PA, Flynn DL, Deininger MW, O'Hare T, Druker BJ. The ABL switch control inhibitor DCC-2036 is active against the chronic myeloid leukemia mutant BCR-ABLT315I and exhibits a narrow resistance profile. Cancer Res. 2011 May 1;71(9):3189-95. Epub 2011 Apr 19. PubMed PMID: 21505103; PubMed Central PMCID: PMC3206627.
3: Chan WW, Wise SC, Kaufman MD, Ahn YM, Ensinger CL, Haack T, Hood MM, Jones J, Lord JW, Lu WP, Miller D, Patt WC, Smith BD, Petillo PA, Rutkoski TJ, Telikepalli H, Vogeti L, Yao T, Chun L, Clark R, Evangelista P, Gavrilescu LC, Lazarides K, Zaleskas VM, Stewart LJ, Van Etten RA, Flynn DL. Conformational control inhibition of the BCR-ABL1 tyrosine kinase, including the gatekeeper T315I mutant, by the switch-control inhibitor DCC-2036. Cancer Cell. 2011 Apr 12;19(4):556-68. PubMed PMID: 21481795; PubMed Central PMCID: PMC3077923.
4: O'Hare T, Deininger MW, Eide CA, Clackson T, Druker BJ. Targeting the BCR-ABL signaling pathway in therapy-resistant Philadelphia chromosome-positive leukemia. Clin Cancer Res. 2011 Jan 15;17(2):212-21. Epub 2010 Nov 22. PubMed PMID: 21098337.