Afatinib, Free Base (BIBW-2992, Giotrif, Gilotrif, Tovok, Tomtovok, CAS 850140-72-6, CAS 439081-18-2), >99%

LC Laboratories' Product Number A-8644 - Afatinib, Free Base (BIBW-2992, Giotrif, Gilotrif, Tovok, Tomtovok, CAS 850140-72-6, CAS 439081-18-2), >99% - for research use only. 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. 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. 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. The EGFR T854A mutation reduces the inhibition of tyrosine phosphorylation by erlotinib. Afatinib overcomes the resistance. 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. 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.

• Supplier: LC Laboratories
• Product #: A-8644
• Sku #: A-8644_5g