Bosutinib

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Bosutinib
Systematic (IUPAC) name
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
Clinical data
Trade namesBosulif
Licence dataUS FDA:link
Pregnancy cat.D (US)
Legal status-only (US)
RoutesOral
Pharmacokinetic data
Protein binding94–96%
MetabolismBy CYP3A4, to inactive metabolites
Half-life22.5±1.7 hours
ExcretionFecal (91.3%) and renal (3%)
Identifiers
CAS number380843-75-4 N
ATC codeL01XE14
PubChemCID 5328940
ChemSpider4486102 YesY
UNII5018V4AEZ0 YesY
ChEBICHEBI:39112 YesY
ChEMBLCHEMBL288441 YesY
Chemical data
FormulaC26H29Cl2N5O3 
Mol. mass530.446 g/mol
 N (what is this?)  (verify)
 
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Bosutinib
Systematic (IUPAC) name
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
Clinical data
Trade namesBosulif
Licence dataUS FDA:link
Pregnancy cat.D (US)
Legal status-only (US)
RoutesOral
Pharmacokinetic data
Protein binding94–96%
MetabolismBy CYP3A4, to inactive metabolites
Half-life22.5±1.7 hours
ExcretionFecal (91.3%) and renal (3%)
Identifiers
CAS number380843-75-4 N
ATC codeL01XE14
PubChemCID 5328940
ChemSpider4486102 YesY
UNII5018V4AEZ0 YesY
ChEBICHEBI:39112 YesY
ChEMBLCHEMBL288441 YesY
Chemical data
FormulaC26H29Cl2N5O3 
Mol. mass530.446 g/mol
 N (what is this?)  (verify)

Bosutinib (rINN/USAN; codenamed SKI-606, marketed under the trade name Bosulif) is a tyrosine kinase inhibitor undergoing research for use in the treatment of cancer.[1] [2] Originally synthesized by Wyeth, it is being developed by Pfizer.

Some commercial stocks of bosutinib (from sources other than the Pfizer material used for clinical trials) have recently been found to have the incorrect chemical structure, calling the biological results obtained with them into doubt.[3]

Bosutinib received US FDA approval on September 4, 2012 for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.[4][5][6]

See also[edit]

References[edit]

  1. ^ Puttini M, Coluccia AM, Boschelli F, Cleris L, Marchesi E, Donella-Deana A, Ahmed S, Redaelli S, Piazza R, Magistroni V, Andreoni F, Scapozza L, Formelli F, Gambacorti-Passerini C. In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res. 2006 Dec 1;66(23):11314-22. Epub 2006 Nov 17.
  2. ^ Vultur A, Buettner R, Kowolik C, et al. (May 2008). "SKI-606 (bosutinib), a novel Src kinase inhibitor, suppresses migration and invasion of human breast cancer cells". Mol. Cancer Ther. 7 (5): 1185–94. doi:10.1158/1535-7163.MCT-08-0126. PMC 2794837. PMID 18483306. 
  3. ^ Derek Lowe, In The Pipeline (blog), "Bosutinib: Don't Believe the Label!"
  4. ^ Cortes JE, Kantarjian HM, Brümmendorf TH, Kim DW, Turkina AG, Shen ZX, Pasquini R, Khoury HJ, Arkin S, Volkert A, Besson N, Abbas R, Wang J, Leip E, Gambacorti-Passerini C. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011 Oct 27;118(17):4567-76. Epub 2011 Aug 24.
  5. ^ Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicus L, Malhotra H, Powell C, Gogat K, Countouriotis AM, Gambacorti-Passerini C. Bosutinib Versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Results From the BELA Trial. J Clin Oncol. 2012 Sep 4. [Epub ahead of print]
  6. ^ "Bosulif Approved for Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia". 05 Sep 2012. 

External links[edit]