Bosutinib
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| Trade names | Bosulif |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Protein binding | 94–96% |
| Metabolism | By CYP3A4, to inactive metabolites |
| Elimination half-life | 22.5±1.7 hours |
| Excretion | Fecal (91.3%) and kidney (3%) |
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| ChEMBL | |
| ECHA InfoCard | 100.149.122 |
| Chemical and physical data | |
| Formula | C26H29Cl2N5O3 |
| Molar mass | 530.45 g·mol−1 |
| 3D model (JSmol) | |
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Bosutinib, sold under the brand name Bosulif, is a small molecule BCR-ABL and src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukemia.[medical citation needed]
Originally synthesized by Wyeth, it is being developed by Pfizer.[citation needed]
Mechanism[edit]
It is an ATP-competitive Bcr-Abl tyrosine-kinase inhibitor with an additional inhibitory effect on Src family kinases (including Src, Lyn and Hck).[2][3] It has also shown activity against the receptors for platelet derived growth factor and vascular endothelial growth factor.[4] 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.[2]
Bosutinib is metabolized through CYP3A4.
Medical uses[edit]
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.[5][6][7][8]
Contraindications[edit]
Bosutinib has two known absolute contraindications, which are: known hypersensitivity to bosutinib and liver impairment.[9][10]
Interactions[edit]
Bosutinib is both a substrate and an inhibitor of P-glycoprotein (P-gp) and CYP3A4.[2] Hence P-gp and CYP3A4 inhibitors may increase plasma levels of bosutinib.[2] Likewise CYP3A4 inducers may reduce plasma concentrations of bosutinib.[2] 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.[2]
Notes[edit]
See also[edit]
References[edit]
- ^ "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
- ^ a b c d e f "Bosulif (bosutinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 3 January 2014. Retrieved 3 January 2014.
- ^ Daud AI, Krishnamurthi SS, Saleh MN, Gitlitz BJ, Borad MJ, Gold PJ, et al. (February 2012). "Phase I study of bosutinib, a src/abl tyrosine kinase inhibitor, administered to patients with advanced solid tumors" (PDF). Clinical Cancer Research. 18 (4): 1092–100. doi:10.1158/1078-0432.CCR-11-2378. PMID 22179664.
- ^ Bosutinib. 2012. Archived from the original on 3 April 2018. Retrieved 2 April 2018.
{{cite book}}:|website=ignored (help) - ^ Cortes JE, Kantarjian HM, Brümmendorf TH, Kim DW, Turkina AG, Shen ZX, et al. (October 2011). "Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib". Blood. 118 (17): 4567–76. doi:10.1182/blood-2011-05-355594. PMC 4916618. PMID 21865346.
- ^ Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicius L, et al. (October 2012). "Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial". Journal of Clinical Oncology. 30 (28): 3486–92. doi:10.1200/JCO.2011.38.7522. PMC 4979199. PMID 22949154.
- ^ "Bosulif Approved for Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia". 5 September 2012. Archived from the original on 24 September 2015. Retrieved 6 September 2012.
- ^ "Bosulif : EPAR - Product Information" (PDF). European Medicines Agency. Pfitzer Ltd. 9 April 2013. Archived (PDF) from the original on 3 January 2014. Retrieved 3 January 2014.
- ^ "Bosulif 100mg and 500mg Tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Pfitzer Limited. 7 June 2013. Archived from the original on 3 January 2014. Retrieved 3 January 2014.
- ^ "BOSULIF (bosutinib monohydrate) tablet, film coated [Pfizer Laboratories Div Pfizer Inc]". DailyMed. Pfitzer Inc. September 2013. Archived from the original on 3 January 2014. Retrieved 3 January 2014.
External links[edit]
- "Bosutinib". Drug Information Portal. U.S. National Library of Medicine.
