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A-8644 Afatinib, Free Base, >99%      NEW!       Prices Reduced (November 2011)

Synonyms:  [BIBW-2992] [BIBW 2992] [BIBW2992]
Related Terms:  [Tomtovok] [Tovok]

M.W. 485.94

C24H25ClFN5O3

[850140-72-6]

[439081-18-2]

Storage:  Store at or below -20 ºC.  Solubility:  Soluble in DMSO at 200 mg/mL; soluble in ethanol at 25 mg/mL; very poorly soluble in water; maximum solubility in plain water is estimated to be about 50-100 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

• Afatinib, also known as BIBW-2992, is an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinases.

• Afatinib inhibits EGFR1 tyrosine kinase (IC50 = 0.5 nM) and EGFR2 (HER2) tyrosine kinase (IC50 = 14 nM).  It also suppresses EGF-induced EGFR phosphorylation and cellular proliferation in various cell lines, including EGFR-overexpressing and HER2-expressing cell lines A431, NIH-3T3-HER2, NCI-N87 and BT-474.  Oral afatinib induced tumor regression in mice carrying A431 or MDA-MB-453 xenografts.  Both xenografts are EGFR-overexpressing and HER2-expressing.  Afatinib also showed inhibitory effects in NCI-N87 gastric and SKOV-3 ovarian models.  Eskens, F.A., et al.  "A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours."  Br. J. Cancer 98:  80-85 (2008).

• Afatinib inhibits the kinase activity of wild-type and activated EGFR and HER2 mutants, including erlotinib-resistant isoforms.  Afatinib suppressed proliferation of cancer cell lines and caused tumor regression in xenograft and transgenic lung cancer models, with activity superior to that of erlotinib.  Li, D., et al.  "BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models."  Oncogene 27:  4702-4711 (2008).

• Combination treatment of HER2(YVMA) transgenic mice or H1781 xenografts with afatinib and rapamycin caused significant tumor shrinkage and was an effective treatment paradigm in the adenosquamous lung tumor model in mice.  Perera, S.A., et al.  "HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy."  Proc. Natl. Acad. Sci. USA 106:  474-479 (2009).

• The EGFR T854A mutation reduces the inhibition of tyrosine phosphorylation by erlotinib.  Afatinib overcomes the resistance.  Bean, J., et al.  "Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma."  Clin. Cancer Res. 14:  7519-7525 (2008).

• Tumors overexpressing EGFR with the secondary T790M point mutation show resistance to the first-generation EGFR inhibitors gefitinib and erlotinib.  Such resistance is overcome by afatinib.  Minkovsky, N. and Berezov, A.  "BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors."  Curr. Opin. Investig. 9:  1336-1346 (2008).

• Afatinib is the active ingredient in the drug product sold under the trade names Tovok® and Tomtovok®.  This drug is currently approved in at least one country for use in patients with non-small cell lung carcinoma.  NOTE:  THE AFATINIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT TOVOK® OR TOMTOVOK®, AND IS NOT FOR HUMAN USE.

• Chemical Abstracts Service currently has two different CAS numbers for afatinib.  One of them, 439081-18-2, is by far the most widely used, but its entry in the CAS database does not show the geometry of the double bond.  A later CAS number, 850140-72-6, is not in wide use, but its entry in the CAS database shows the trans geometry of the double bond.  It is likely that CAS will eventually cancel one of these two numbers.

• Related CAS numbers:  850140-73-7 for the afatinib dimaleate salt.

• Another CAS number previously assigned to afatinib, namely 915958-11-1, has been deleted by CAS and is no longer in use.

• Sold for laboratory or manufacturing purposes only; not for human, 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.

** Our prices are lower than other vendors', but there is no compromise in quality.  Read how we are able to accomplish this:  Product Quality Discussion.

NOTES:
1.  The purpose of our competitor price comparison tables is to enable our visitors to compare the prices and purities of products of nominally equivalent quality, for vendors whose price and purity claims are openly available from a website or catalog (without a need for the customer to contact the vendor and request a quotation in order to obtain a price and purity for a standard product size).  However, the quality comparisons in these tables are not absolute:  although our product purities are uniformly very high and are established by careful testing of every lot in our laboratories, we cannot and do not vouch for the purities claimed by other vendors in these competitor price comparison tables.  (We do carry out occasional testing of other vendors' products -- see below --  and we have found many instances where vendors' product purities are far below their claimed levels.)  Effective April 1, 2011, our price comparison tables only include products where a purity commitment is found together with sizes and prices on at least one page of the vendor's web site.

2.  Researching and compiling sizes and prices for the >160 competitive vendors and more than 175 products is an expensive and tedious task for our small company.  Thus, we typically only perform revisions of these tables annually or less frequently.  The date and source of each competitive vendor's prices is indicated at the bottom of this page.  Obviously, we make no guarantee that competitive vendor prices will remain unchanged in the interval between our annual revisions.  We may occasionally update individual competitive vendor information and add new competitive vendors as we locate them.

3.  In some circumstances we permanently remove vendors from our price comparison tables.  Circumstances that lead to permanent removal are: 

A.  If a vendor does not honor its advertised price (ignoring small price increases) for one or more products when an order is attempted.  Example:  a vendor listed a compound at $808 for 10 grams on its website price list, but quoted $4,500 per 10 grams upon our inquiry.  That vendor has been permanently removed from our price comparison tables.

B.  If, on a product-by-product basis, our analyses of a vendor's product show purities more than a few percent below the vendor's advertised purities.  Example:  a vendor advertises a purity for 97% for a compound, but repeated elemental analyses show a minimum of 9% inorganic material present, beyond any salt counterion.  Another example: an HPLC analysis at a relevant UV detector wavelength shows 92% purity for a vendor's product for which 98% purity is claimed.  We realize of course that UV absorbances for impurities can be higher than for the main compound, but our products meet our purity commitment of typically >99% irrespective of absorbance factors for impurities, and we apply that standard to products from other vendors.

C.  Again on a product-by-product basis, if a vendor makes no purity claim for a given product, then their product is not shown on that product table.

D.  If we find that, as a pattern, several of a competitive vendor's products fail to meet their advertised purity commitments by significant margins or if a vendor does not provide standard and consistent purity claims for several of its products, then that vendor is permanently removed from all of our competitor price tables.

E.  Finally, if we determine that a vendor has provided fraudulent information on its website, in its literature or on a certificate of analysis, that vendor is permanently removed from all of our price comparison tables.

4.  IMPORTANT:  The presence of a competitive vendor entry in our price comparison tables does not necessarily mean that we have analyzed any of that vendor's products for purity; indeed, in most cases we have not.

5.  Please note:  where necessary, competitor prices are rounded to the nearest whole dollar.

To the best of our knowledge, the prices listed above for our competitors' products were correct as of the dates listed below for the sources of our annual price information update process.

Pricing Sources and Dates:  LC Labs - Current, Active Biochem - website - Apr 2012, BioVision - website - Mar 2012, Cambridge BioScience - website - Mar 2012, ChemieTek - website - Dec 2011, Axon Medchem - website - Mar 2012, Wecoochem Laboratories - website - Apr 2012, ShangHai Biochempartner - website - Dec 2011, antibodies-online - website - Dec 2011, biorbyt.com - website - Mar 2012, Reagents Direct - website - Feb 2012, biokits.com - website - Dec 2011, HuoLi Biochem - website - Feb 2012, Reliable ChemTech - Google Sites - May 2012, BPS Bioscience - website - Dec 2011, AbMole BioScience - website - Mar 2012, SynChem - website - Jan 2012, Medchem Express - website - Apr 2012, AdooQ BioScience - website - Apr 2012, EMMX BioChemicals - website - May 2012.