bosutinib   Click here for help

GtoPdb Ligand ID: 5710

Synonyms: Bosulif® | SK 606 | SK-606 | SKI 606
Approved drug PDB Ligand Immunopharmacology Ligand
bosutinib is an approved drug (FDA (2012), EMA (2013))
Compound class: Synthetic organic
Comment: Bosutinib is a Type-1 kinase inhibitor. This compound is a dual inhibitor of Src family kinases and Abl kinase activity [9]. Bosutinib has been shown to stimulate macrophage clearance of bacterial infections [3]. Although it does not have intrinsic antibacterial activity, bosutinib could be used to boost host innate immunity and delivered as part of an antibacterial drug combination for the treatment for drug-resistant bacterial infections [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 82.88
Molecular weight 529.16
XLogP 3.63
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES COc1cc2c(cc1OCCCN1CCN(CC1)C)ncc(c2Nc1cc(OC)c(cc1Cl)Cl)C#N
Isomeric SMILES COc1cc2c(cc1OCCCN1CCN(CC1)C)ncc(c2Nc1cc(OC)c(cc1Cl)Cl)C#N
InChI InChI=1S/C26H29Cl2N5O3/c1-32-6-8-33(9-7-32)5-4-10-36-25-13-21-18(11-24(25)35-3)26(17(15-29)16-30-21)31-22-14-23(34-2)20(28)12-19(22)27/h11-14,16H,4-10H2,1-3H3,(H,30,31)
InChI Key UBPYILGKFZZVDX-UHFFFAOYSA-N
References
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Bantscheff M, Eberhard D, Abraham Y, Bastuck S, Boesche M, Hobson S, Mathieson T, Perrin J, Raida M, Rau C et al.. (2007)
Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors.
Nat Biotechnol, 25 (9): 1035-44. [PMID:17721511]
3. da Silva RAG, Stocks CJ, Hu G, Kline KA, Chen J. (2024)
Bosutinib Stimulates Macrophage Survival, Phagocytosis, and Intracellular Killing of Bacteria.
ACS Infect Dis, 10 (5): 1725-1738. [PMID:38602352]
4. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
5. FDA. 
FDA grants accelerated approval to bosutinib for treatment of newly-diagnosed PH+ CML.
Accessed on 03/01/2018. Modified on 03/01/2018. fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm589856.htm?utm_campaign=Oncology%2012%2F20&utm_medium=email&utm_source=Eloqua&elqTrackId=d490fb7b300744518a65cc9c56f2db77&elq=70477587f45543ad83873a1367bab364&elqaid=1850&elqat=1&elqCampaignId=1227
6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
7. Golas JM, Arndt K, Etienne C, Lucas J, Nardin D, Gibbons J, Frost P, Ye F, Boschelli DH, Boschelli F. (2003)
SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice.
Cancer Res, 63 (2): 375-81. [PMID:12543790]
8. Ozanne J, Prescott AR, Clark K. (2015)
The clinically approved drugs dasatinib and bosutinib induce anti-inflammatory macrophages by inhibiting the salt-inducible kinases.
Biochem J, 465 (2): 271-9. [PMID:25351958]
9. Puttini M, Coluccia AM, Boschelli F, Cleris L, Marchesi E, Donella-Deana A, Ahmed S, Redaelli S, Piazza R, Magistroni V et al.. (2006)
In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells.
Cancer Res, 66 (23): 11314-22. [PMID:17114238]
10. Remsing Rix LL, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Müller A, Baumgartner C, Valent P, Augustin M et al.. (2009)
Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells.
Leukemia, 23 (3): 477-85. [PMID:19039322]
11. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]