BOSUTINIB

 

 

BOSUTINIB

4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile

Bosutinib Monohydrate (伯舒替尼)

(Bosulif®)

Approved sept4 2012 by FDA

PMDA SEPT26 2014

EMA MAR 27 2013

A kinase inhibitor indicated for the treatment of adult patients with Ph+ chronic myelogenous leukemia (CML).
WYETH  INNOVATOR
PFIZER DEVELOPER

SKI-606; SK-606

CAS No.380843-75-4 (Free form)

 CAS  918639-08-4(Bosutinib Monohydrate)

 

 

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

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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 5, 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]

 

Article

Good News For Pfizer’s Orphan Drug Bosulif (Bosutinib) in Europe

January 18, 2013

The European Medicines Agency’s  (EMA) Committee for Medicinal Products for Human Use (CHMP) on January 17, 2013, adopts a positive opinion, recommending a conditional marketing authhorization for Pfizer’s orphan drug Bosulif (Bosutinib) for Chronic Leukemia (CML).  Bosutinib receives orphan designation from the European Commission (EC) on August 4, 2010, for CML.

https://docs.google.com/viewer?url=http%3A%2F%2Fwww.ema.europa.eu%2Fdocs%2Fen_GB%2Fdocument_library%2FSummary_of_opinion_-_Initial_authorisation%2Fhuman%2F002373%2FWC500137464.pdf

Pfizer receives FDA approval on September 4, 2012, for orphan drug Bosulif (Bosutinib) for CML. Pfizer receives on February 24, 2009, FDA Orphan Drug Designation (ODD) for Bosutinib for CML.

Per a September 2012 article in  FierceBioTech.com, a Pfizer spokesperson says that “the drug will cost less than $8,200/month”/patient in the US. In other words, treatment will cost approximately $98,400/patient/year. Also per FierceBiotech,“Bosulif is the 3^rd new medicine from Pfizer Oncology’s pipeline to be approved by the FDA in just 13 months ….”.

ARTICLE

Pfizer’s response to compound fraud spotlights quality issues

read .........http://www.rsc.org/chemistryworld/2015/12/pfizer-bogus-bosutinib-isomer-fraud-leukaemia-drug

Synthesis

REFERENCES

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.
7. P Bowles et al, Org. Process Res. Dev., 2015, DOI: 10.1021/acs.oprd.5b00244
   8  N M Levinson and S G Boxer, PLoS One, 2012, 7, e29828 (DOI: 10.1371/journal.pone.0029828)
   9 N Beeharry et al, Cell Cycle, 2014, 13, 2172 (DOI: 10.4161/cc.29214)

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