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B-1709 Bosutinib, Free Base, >99%

[SKI-606]

M.W. 530.45

C26H29Cl2N5O3

[380843-75-4]

M.I. 14:  10347

Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO at 33 mg/mL; soluble in ethanol at 10 mg/mL with warming; very poorly soluble in water; maximum solubility in plain water is estimated to be about 10-50 µM; buffers, serum, or other additives may increase or decrease the aqueous solubility.  Disposal:  A

Find and View a Certificate of Analysis for this product

View the MSDS for this product

• Scientists at our parent organization have obtained what we believe is unambiguous evidence that at least two different compounds are being offered in the research reagent marketplace under the name "bosutinib".  This is a somewhat complex problem.  Please visit this link http://www.pkcpharma.com/TwoOrMoreBosutinibs.html for details.

• To the best of our knowledge, LC Labs has never sold an incorrect compound in its entire 32-year history.  However, if the compound that LC Laboratories has been selling as "bosutinib" turns out to be incorrect, then (i) according to data in hand, some other vendors who we believe did not obtain this compound from LC Labs are also selling incorrect "bosutinib", and (ii) we will of course fully honor our warranty as always.  Shortly we will be sending more information about the "bosutinib" problem directly to all LC Labs customers who have purchased this compound from us.

• Bosutinib (SKI-606) is a novel tyrosine kinase inhibitor, more potent than imatinib.  Bosutinib can overcome not only Bcr-Abl-dependent mechanisms of resistance, but also those that are Bcr-Abl-independent.  It is used to treat patients with chronic myelogenous leukemia (CML) who demonstrate resistance to imatinib or develop resistance during treatment.  Jabbour, E., et al.  "New targeted therapies for chronic myelogenous leukemia: opportunities to overcome imatinib resistance."  Semin. Hematol. 44:  25-31 (2007).

• Bosutinib is an active inhibitor of Bcr-Abl in several chronic myelogenous leukemia cell lines and transfectants.  The IC50 values are in the low nanomolar range, which is 10- to 100-fold lower than those obtained with imatinib.  Bosutinib has activity in cells where resistance to imatinib resulted from BCR-ABL gene amplification and in three of four Bcr-Abl point mutants examined.  In in vivo experiments bosutinib retains activity in models where resistance is not caused by mutations, as well as in cells carrying the Y253F, E255K, and D276G mutations.  Bosutinib binds to a different conformation of Bcr-Abl than does imatinib.  Puttini, M., et al.  "In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells."  Cancer Res. 66:  11314-11322 (2006).

• Bosutinib inhibits tumor cell proliferation, angiogenesis, growth factor expression and Src-mediated signaling pathways in vivo.  Jallal, H., et al.  "A Src/Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth, and metastasis in vitro and in vivo."  Cancer Res. 67:  1580-1588 (2007).

• Bosutinib inhibited src-dependent activation of beta-catenin and blocked beta-catenin nuclear function by reducing its binding to the TCF4 transcription factor and its trans-activating ability in colorectal cancer cells.  Coluccia, A.M., et al.  "SKI-606 decreases growth and motility of colorectal cancer cells by preventing pp60(c-Src)-dependent tyrosine phosphorylation of beta-catenin and its nuclear signaling."  Cancer Res. 66:  2279-2286 (2006).

• Bosutinib inhibited Src autophosphorylation in HT29 cells (IC50 = 0.25 µM).  Although submicromolar concentrations of bosutinib inhibited HT29 cell colony formation in soft agar, antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC50s, 1.5 and 2.5 µM, respectively).  Golas, J.M., et al.  "SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models."  Cancer Res. 65:  5358-5364 (2005).

• We note that bosutinib is offered for sale by another vendor under the name "Bosutinib Methanoate", by which they probably mean "methanolate" ("methanoate" means "formate ester", which is definitely not correct here).  This "methanolate" nomenclature is somewhat ambiguous because "methanolate" is often taken to mean "methoxide anion" (not correct here) rather than "a molecule of neutral methanol included as solvent of crystallization with the primary compound" as presumably intended by this other vendor.  The level of solvent or water in our bosutinib product is found on the Certificate of Analysis for each lot.  Our current lot as of this writing (June 2009) is free of methanol or water of crystallization, but future lots may contain small amounts of water or other solvent of crystallization, which would affect the nominal molecular weight but not the biological properties of the bosutinib product.

• Sold for laboratory or manufacturing purposes only; not for human, medical, veterinary, food, or household use.

• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.

• Not available in some countries; not available to some institutions; not available for some uses.