Contents

Bosutinib

Bosutinib

Clinical data
Trade names	Bosulif
License data	EU EMA: by INN US DailyMed: Bosutinib
Routes of administration	By mouth
ATC code	L01EA04 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[1] UK: POM (Prescription only) US: ℞-only EU: Rx-only
Pharmacokinetic data
Protein binding	94–96%
Metabolism	ByCYP3A4, to inactive metabolites
Elimination half-life	22.5±1.7 hours
Excretion	Fecal (91.3%) and kidney (3%)
Identifiers
IUPAC name 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
CAS Number	380843-75-4 N
PubChem CID	5328940
IUPHAR/BPS	5710
DrugBank	DB06616 Y
ChemSpider	4486102 Y
UNII	5018V4AEZ0
KEGG	D03252
ChEBI	CHEBI:39112 Y
ChEMBL	ChEMBL288441 Y
CompTox Dashboard (EPA)	DTXSID10861568
ECHA InfoCard	100.149.122
Chemical and physical data
Formula	C26H29Cl2N5O3
Molar mass	530.45 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc1c(OC)cc(c(Cl)c1)Nc4c(C#N)cnc3cc(OCCCN2CCN(CC2)C)c(OC)cc34
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) Y Key:UBPYILGKFZZVDX-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

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]

• Discovery and development of Bcr-Abl tyrosine kinase inhibitors

References[edit]

External links[edit]

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