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
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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)
Immunopharmacology Comments
Bosutinib is reported as a pan-salt inducible kinase (SIK) inhibitor [8]. Bosutinib-induced inhibition of SIK2 has anti-inflammatory action, mediated via induction of a macrophage phentoype switch to a 'regulatory'-like phenotype [8]. These 'regulatory'-like macrophages produce the anti-inflammatory cytokine IL-10 and promote the resolution of inflammation. Inhibition of SIK2 to promote macrophage switch to a 'regulatory'-like phenotype is considered a potential therapeutic strategy for the treatment of chronic inflammatory diseases.