Research on drugs from Teva (formerly Cephalon)

This page is for tracking research by Teva (formerly Cephalon), including CEP-37440, CEP-28122, CEP-14083, CEP-14513, and compound “15”. There are several research articles by Cephalon and they refer to different drugs using different names so it is unclear when different articles are talking about the same drug or different ones.

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12 Responses to Research on drugs from Teva (formerly Cephalon)

  1. admin says:

    Here is an article about the identification and preclinical characterization of CEP-28122. The article finds that CEP-28122 is a potent and selective ALK inhibitor with a robust efficacy against ALK-positive tumors in mice. In some cases the tumors disappeared and did not return for at least 60 days after the last treatment with CEP-28122.

    http://mct.aacrjournals.org/content/early/2011/12/22/1535-7163.MCT-11-0776.abstract?cited-by=yes&legid=molcanther;1535-7163.MCT-11-0776v1

  2. admin says:

    Here is another research article by Cephalon. Compound 32 is the best performing of this bunch. It caused tumors to shrink in Mice.

    http://www.ncbi.nlm.nih.gov/m/pubmed/22141319/

  3. admin says:

    Teva Pharmaceuticals acquired Cephalon in October 2011.

  4. admin says:

    Here is a research article by Cephalon that lists three potential ALK inhibitors:

    http://pubs.acs.org/doi/abs/10.1021/jm201333e

  5. admin says:

    Cephalon appears to have changed which ALK inhibitor they are pursuing. They used to list CEP 28122 on their pipeline page. Now they list CEP 37440. They also have an asterisk next to it indicating “planned development by Cephalon Ventures”. Their investor day presentation slides indicate they plan to start a clinical trial in 3rd quarter of 2011 (so a 9-12 month delay). Hopefully the delay will be worth it and the new drug will be more effective.

  6. admin says:

    An October 2010 article by Cephalon describes yet another group of compounds they created during the course of endeavors to create Compound “15” (as described in another post). Of the 15 compounds described in this article (which are based on variations of TAE226 not TAE684) compound “18” had the best profile and was tested in mice. At 55 mg/kg it caused a substantial decrease in the size of ALCL tumors.

    You can find the abstract at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TF9-51BBKTK-4&_user=9746200&_coverDate=10%2F27%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1526091691&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=9746200&md5=488a380d6f4766755bacf4512281dd6d&searchtype=a

  7. admin says:

    A September 2009 article looks at the potential inhibitory effect of CEP-14083 and CEP-14513 in seven different Neuroblastoma cell lines that had a high level of ALK expression. The study finds that the drugs effectively inhibited growth in all seven cell lines including two cell lines that had mutated versions of the ALK gene. The tests were done in test tubes not in mice.

    A free copy of the full article can be found at http://cancerres.aacrjournals.org/content/69/18/7338.full.pdf+html

  8. admin says:

    An August 2005 article identifies several potential ALK Inhibitors and looks at the how effective they are at inhibiting growth in an ALK + lymphoma cell line. They find that two of the potential drugs (CEP-14083 and CEP-14513) successfully inhibit growth in the cell line.

    See http://www.ncbi.nlm.nih.gov/pubmed/16254137 for a copy of the abstract.

    See http://bloodjournal.hematologylibrary.org/cgi/reprint/107/4/1617 for a free copy of the full article.

  9. Kirkwood says:

    A February 2009 study by Cephalon that looks at how two potential drugs (compound 1 and compound 13) interact with the ALK enzyme and three mutated versions of the ALK enzyme (they identified 5 other potentially weak mutations but were not able to establish stable cell lines of the other mutations). They focused their mutation analysis on just two specific regions in the ALK enzyme: first the “anchor” region and second the “gatekeeper” region. They did not look at other potential mutation areas. It costs $30 to get a copy of the full article but you can read the abstract for free.

    Here is the abstract link: http://www.ncbi.nlm.nih.gov/pubmed/19249873

    Basically the article says that Compound 1 was effective against the natural form of the ALK enzyme and two of the potential mutations, but was not effective against the third mutation. Compound 13 was effective against the natural form of the ALK enzyme but not against the three mutations.

    I have read a subsequent August 2010 review of this article, which said that the “compound 1” in this article is the same as CEP14513 (which in earlier research was found to have “unfavourable physicochemical properties that precluded [its] use for in vivo studies.” See http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T54-516CHGD-1&_user=9746200&_coverDate=10%2F08%2F2010&_rdoc=1&_fmt=high&_orig=&_origin=&_zone=rslt_list_item&_cdi=4992&_sort=d&_docanchor=&view=c&_ct=1&_acct=C000050221&_version=1&_urlVersion=0&_userid=9746200&md5=977e3fbb512f67c098e007dd9cc2e006&searchtype=a .

    However, it appears that compound 15 (described in another study published in August 2010 – about the same time as the review article) is not covered by this study, so we probably do not yet know how compound 15 responds to mutated versions of the ALK enzyme.

  10. admin says:

    Here is a link to an August 2010 abstract of an article that discusses 20 different potential ALK inhibitors. Most of the potential inhibitors are created by Cephalon but several are created by others. It costs $30 to get a copy of the full article.

    http://pubs.acs.org/doi/abs/10.1021/ml100158s

    The focus of the article is on an analysis of the comparative selectivity of 14 of the potential drugs that are created by Cephalon. The researchers are trying to determine how much more likely it is that each of the drug candidates will bind with the ALK enzyme rather than with a similar enzyme (which binds with insulin). This is potentially important becuase the bigger the difference is – the more likely that a particular drug will be safe to take while still being effective.

    They find one drug (compound “15”) is 43 times more likely to bind with the ALK enzyme. “Furthermore, oral administration of compound 15 to mice bearing ALK-posistive ALCL [tumors] resulted in complete/near complete regressions. Compound 15 advanced to late preclinical candidate evaluation”

  11. admin says:

    An Italian research grant request references two Cephalon drugs (CEP-28122 and CEP-30440). According to Google’s translation of the grant request both drugs are orally available. Furthermore, “At 11 days of treatment, animals treated with [doxorubicin and CEP-28122] showed complete response and resorption of the tumor… Eight out of 10 mice treated for 14 days with CEP-28122 consecutive remain free of disease at 100 days after discontinuation of treatment, one died in the absence of cancer, one has developed a single brain metastasis 60 days after discontinuation of treatment.”

    See http://www.reteoncologica.it/allegati/news/100621/piva.pdf

  12. Kirkwood says:

    The pipeline page on Cephalon’s website lists CEP-28122 as being the drug that is in preclinical testing.
    An article says that Cephalon hopes to apply to the FDA by the end of 2010 for approval to start a Phase I study of CEP-28122. (see http://www.lcfamerica.org/blog/wp-content/uploads/ALK-Lung-Cancer-and-Personalized-Therapy-JNCI-2010.pdf ) (an “IND” is the FDA application)

    It is unclear at this time which of the many compounds described in various articles is in fact CEP-28122.

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