Bosutinib (rINN/USAN; codenamed SKI-606, marketed under the trade name Bosulif) is a small molecule BCR-ABL and src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia. Originally synthesized by Wyeth, it is being developed by Pfizer. Mechanism
It is an ATP-competitive Bcr-Abl tyrosine-kinase inhibitor with an additional inhibitory effect on Src family kinases (including Src, Lyn and Hck). It has also shown activity against the receptors for platelet derived growth factor and vascular endothelial growth factor. Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines, but did not inhibit T315I and V299L mutant cells.Bosutinib is metabolized through CYP3A4. Medical uses
Bosutinib received US FDA and EU European Medicines Agency approval in September 2012, and March 2013, respectively for the treatment of adults with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy. Contraindications
Bosutinib has two known absolute contraindications, which are: known hypersensitivity to bosutinib and liver impairment. Interactions
Bosutinib is both a substrate and an inhibitor of P-glycoprotein (P-gp) and CYP3A4. Hence P-gp and CYP3A4 inhibitors may increase plasma levels of bosutinib. Likewise CYP3A4 inducers may reduce plasma concentrations of bosutinib. It may also alter the metabolism and uptake (into the GIT by means of its P-gp inhibitory effects) of other drugs that are substrates for P-gp and CYP3A4. Notes
See also
Discovery and development of Bcr-Abl tyrosine kinase inhibitors

References
External links
"Bosutinib". Drug Information Portal. U.S. National Library of Medicine.
It is important that the radioscaphocapitate ligament is left intact, because if the ligament is not preserved the capitate bone will translate to the ulnar side of the wrist and move away from the distal radius. The new formed joint between the capitate and the lunate fossa of the distal radius is not as congruent as the former scaphoid-lunate-radius joint, however the results of proximal row carpectomy are generally excellent. In patients older than 40 years proximal row carpectomy is preferred because these patients have a small chance of developing osteoarthritis in the new formed capitate-radial joint during their remaining life.Patients younger than 40 years have a big chance to develop osteoarthritis in the radiocapitate joint. These patients have longer to live, therefore the incongruence of the joint will exist for a longer time. Thus, in this patient population four-corner arthrodesis is the treatment of first choice. The capitate, lunate, hamate and triquetrum are bounded together in this procedure and the scaphoid is excised. Before the arthrodesis is executed, the lunate must be reduced out of DISI position. Because the radiolunate joint is typically preserved in stage II SLAC and SNAC wrists, this joint can be the only remaining joint of the proximal wrist. Both procedures are often combined with wrist denervation, as described in the text of treatment stage I. Stage III
The only treatment option for stage III wrist osteoarthritis is four-corner arthrodesis, as described above in stage II.