Bosutinib

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Bosutinib
Clinical data
Trade namesBosulif
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)[1]
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Pharmacokinetic data
Protein binding94–96%
MetabolismBy CYP3A4, to inactive metabolites
Elimination half-life22.5±1.7 hours
ExcretionFecal (91.3%) and kidney (3%)
Identifiers
  • 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
JSmol)
  • Clc1c(OC)cc(c(Cl)c1)Nc4c(C#N)cnc3cc(OCCCN2CCN(CC2)C)c(OC)cc34
  • 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) checkY
  • Key:UBPYILGKFZZVDX-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Bosutinib, sold under the brand name Bosulif, is a small molecule

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

It is an ATP-competitive

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]

WEE1
kinase domain in complex with bosutinib.

Notes

See also

  • Discovery and development of Bcr-Abl tyrosine kinase inhibitors

References

  1. ^ "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.
  2. ^ 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.
  3. PMID 22179664
    .
  4. ^ Bosutinib. 2012. Archived from the original on 3 April 2018. Retrieved 2 April 2018. {{cite book}}: |website= ignored (help)
  5. PMID 21865346
    .
  6. PMID 22949154
    .
  7. ^ "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.
  8. ^ "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.
  9. ^ "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.
  10. ^ "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

  • "Bosutinib". Drug Information Portal. U.S. National Library of Medicine.
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