Bafetinib

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WARNING: This product is for research use only, not for human or veterinary use.

Description:Bafetinib, also known as INNO-406 and NS187, is an orally bioavailable 2-phenylaminopyrimidine derivative with potential antineoplastic activity. Bafetinib specifically binds to and inhibits the Bcr/Abl fusion protein tyrosine kinase, an abnormal enzyme produced by Philadelphia chromosomal translocation associated with chronic myeloid leukemia (CML). This agent also inhibits the Src-family member Lyn tyrosine kinase, upregulated in imatinib-resistant CML cells and in a variety of solid cancer cell types.

Price and Availability

Bafetinib, purity > 98%, is in stock. The same day shipping after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200316Name: BafetinibCAS#: 859212-16-1Chemical Formula: C30H31F3N8OExact Mass: 576.25729Molecular Weight: 576.61Elemental Analysis:C, 62.49; H, 5.42; F, 9.88; N, 19.43; O, 2.77

Related CAS #:859212-16-1887650-05-7

Synonym:INNO406; INNO-406; INNO 406; NS187; NS-187; NS 187; Bafetinib.

IUPAC/Chemical Name:(S)-N-(3-([4,5'-bipyrimidin]-2-ylamino)-4-methylphenyl)-4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)benzamide

InChi Key:ZGBAJMQHJDFTQJ-DEOSSOPVSA-N

InChi Code:InChI=1S/C30H31F3N8O/c1-19-4-7-23(13-27(19)39-29-36-10-8-26(38-29)22-14-34-18-35-15-22)37-28(42)20-5-6-21(25(12-20)30(31,32)33)16-41-11-9-24(17-41)40(2)3/h4-8,10,12-15,18,24H,9,11,16-17H2,1-3H3,(H,37,42)(H,36,38,39)/t24-/m0/s1

SMILES Code:O=C(NC1=CC=C(C)C(NC2=NC=CC(C3=CN=CN=C3)=N2)=C1)C4=CC=C(CN5C[C@@H](N(C)C)CC5)C(C(F)(F)F)=C4

Technical Data

Additional Information

The inhibitory effect of bafetinib on these specific tyrosine kinases may decrease cellular proliferation and induce apoptosis in tumor cells that overexpress these kinases. CML patients may be refractory to imatinib, which sometimes results from point mutations occurring in the kinase domain of the Bcr/Abl fusion product. Due to its dual inhibitory activity, the use of bafetinib has been shown to overcome this particular drug resistance.

References

1: Peter B, Hadzijusufovic E, Blatt K, Gleixner KV,Pickl WF, Thaiwong T, Yuzbasiyan-Gurkan V, Willmann M, Valent P. KITpolymorphisms and mutations determine responses of neoplastic mast cellsto bafetinib (INNO-406). Exp Hematol. 2010 Sep;38(9):782-91. doi:10.1016/j.exphem.2010.05.004. Epub 2010 May 26. PubMed PMID: 20685234.

2: Kantarjian H, le Coutre P, Cortes J, Pinilla-Ibarz J, Nagler A,Hochhaus A, Kimura S, Ottmann O. Phase 1 study of INNO-406, a dual Abl/Lynkinase inhibitor, in Philadelphia chromosome-positive leukemias afterimatinib resistance or intolerance. Cancer. 2010 Jun 1;116(11):2665-72.doi: 10.1002/cncr.25079. PubMed PMID: 20310049; PubMed Central PMCID:PMC2876208.

3: Rix U, Remsing Rix LL, Terker AS, Fernbach NV, Hantschel O,Planyavsky M, Breitwieser FP, Herrmann H, Colinge J, Bennett KL,Augustin M, Till JH, Heinrich MC, Valent P, Superti-Furga G. Acomprehensive target selectivity survey of the BCR-ABL kinase inhibitorINNO-406 by kinase profiling and chemical proteomics in chronic myeloidleukemia cells. Leukemia. 2010 Jan;24(1):44-50. doi:10.1038/leu.2009.228. Epub 2009 Nov 5. PubMed PMID: 19890374.

4: Kamitsuji Y, Kuroda J, Kimura S, Toyokuni S, Watanabe K, Ashihara E,Tanaka H, Yui Y, Watanabe M, Matsubara H, Mizushima Y, Hiraumi Y, KawataE, Yoshikawa T, Maekawa T, Nakahata T, Adachi S. The Bcr-Abl kinaseinhibitor INNO-406 induces autophagy and different modes of cell deathexecution in Bcr-Abl-positive leukemias. Cell Death Differ. 2008Nov;15(11):1712-22. doi: 10.1038/cdd.2008.107. Epub 2008 Jul 11. PubMedPMID: 18617896.

5: Morinaga K, Yamauchi T, Kimura S, Maekawa T, Ueda T. Overcomingimatinib resistance using Src inhibitor CGP76030, Abl inhibitornilotinib and Abl/Lyn inhibitor INNO-406 in newly established K562variants with BCR-ABL gene amplification. Int J Cancer. 2008 Jun1;122(11):2621-7. doi: 10.1002/ijc.23435. PubMed PMID: 18338755.

6: Deguchi Y, Kimura S, Ashihara E, Niwa T, Hodohara K, Fujiyama Y,Maekawa T. Comparison of imatinib, dasatinib, nilotinib and INNO-406 inimatinib-resistant cell lines. Leuk Res. 2008 Jun;32(6):980-3. doi:10.1016/j.leukres.2007.11.008. Epub 2008 Jan 8. PubMed PMID: 18191450.

7: Pan J, Quintás-Cardama A, Manshouri T, Cortes J, Kantarjian H,Verstovsek S. Sensitivity of human cells bearing oncogenic mutant kitisoforms to the novel tyrosine kinase inhibitor INNO-406. Cancer Sci.2007 Aug;98(8):1223-5. Epub 2007 May 22. PubMed PMID: 17517053.

8: Kuroda J, Kimura S, Strasser A, Andreeff M, O"Reilly LA, Ashihara E,Kamitsuji Y, Yokota A, Kawata E, Takeuchi M, Tanaka R, Tabe Y, TaniwakiM, Maekawa T. Apoptosis-based dual molecular targeting by INNO-406, asecond-generation Bcr-Abl inhibitor, and ABT-737, an inhibitor ofantiapoptotic Bcl-2 proteins, against Bcr-Abl-positive leukemia. CellDeath Differ. 2007 Sep;14(9):1667-77. Epub 2007 May 18. PubMed PMID:17510658.

9: Maekawa T. [Innovation of clinical trials for anti-cancer drugs inJapan--proposals from academia with special reference to the developmentof novel Bcr-Abl/Lyn tyrosine kinase inhibitor INNO-406 (NS-187) forimatinib-resistant chronic myelogenous leukemia]. Gan To Kagaku Ryoho.2007 Feb;34(2):301-4. Japanese. PubMed PMID: 17301549.

10: Niwa T, Asaki T, Kimura S. NS-187 (INNO-406), a Bcr-Abl/Lyn dualtyrosine kinase inhibitor. Anal Chem Insights. 2007 Nov 14;2:93-106.PubMed PMID: 19662183; PubMed Central PMCID: PMC2716809.

11: Yokota A, Kimura S, Masuda S, Ashihara E, Kuroda J, Sato K,Kamitsuji Y, Kawata E, Deguchi Y, Urasaki Y, Terui Y, Ruthardt M, UedaT, Hatake K, Inui K, Maekawa T. INNO-406, a novel BCR-ABL/Lyn dualtyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cellsin the central nervous system, and cyclosporine A augments its in vivoactivity. Blood. 2007 Jan 1;109(1):306-14. Epub 2006 Sep 5. PubMed PMID:16954504.