Chemistry:Bosutinib
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| Trade names | Bosulif |
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| Routes of administration | By mouth |
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| 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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| Formula | C26H29Cl2N5O3 |
| Molar mass | 530.45 g·mol−1 |
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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.
Originally synthesized by Wyeth, it is being developed by Pfizer.[citation needed]
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).[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
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
Bosutinib has two known absolute contraindications, which are: known hypersensitivity to bosutinib and liver impairment.[9][10]
Interactions
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
See also
- Discovery and development of Bcr-Abl tyrosine kinase inhibitors
References
- ↑ "Prescription medicines: registration of new chemical entities in Australia, 2014". 21 June 2022. https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "Bosulif (bosutinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. http://reference.medscape.com/drug/bosulif-bosutinib-999770#showall.
- ↑ "Phase I study of bosutinib, a src/abl tyrosine kinase inhibitor, administered to patients with advanced solid tumors". Clinical Cancer Research 18 (4): 1092–100. February 2012. doi:10.1158/1078-0432.CCR-11-2378. PMID 22179664.
- ↑ Bosutinib. 2012. https://livertox.nih.gov/Bosutinib.htm. Retrieved 2 April 2018.
- ↑ "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. October 2011. doi:10.1182/blood-2011-05-355594. PMID 21865346.
- ↑ "Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial". Journal of Clinical Oncology 30 (28): 3486–92. October 2012. doi:10.1200/JCO.2011.38.7522. PMID 22949154.
- ↑ "Bosulif Approved for Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia". 5 September 2012. http://www.empr.com/bosulif-approved-for-previously-treated-philadelphia-chromosome-positive-chronic-myelogenous-leukemia/article/257548/.
- ↑ "Bosulif : EPAR - Product Information". European Medicines Agency. Pfitzer Ltd. 9 April 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002373/WC500141721.pdf.
- ↑ "Bosulif 100mg and 500mg Tablets - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Pfitzer Limited. 7 June 2013. http://www.medicines.org.uk/emc/medicine/27795/SPC/Bosulif+100mg+and+500mg+Tablets/.
- ↑ "BOSULIF (bosutinib monohydrate) tablet, film coated [Pfizer Laboratories Div Pfizer Inc"]. DailyMed. Pfitzer Inc. September 2013. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=adc84ad5-a04d-4fee-9ba8-91f7abd928e3.
External links
- "Bosutinib". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/bosutinib.
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