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Research ArticleArticle

Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft

Thomas J. Raub, Graham N. Wishart, Palaniappan Kulanthaivel, Brian A. Staton, Rose T. Ajamie, Geri A. Sawada, Lawrence M. Gelbert, Harlan E. Shannon, Concepcion Sanchez-Martinez and Alfonso De Dios
Drug Metabolism and Disposition September 2015, 43 (9) 1360-1371; DOI: https://doi.org/10.1124/dmd.114.062745
Thomas J. Raub
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Graham N. Wishart
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Palaniappan Kulanthaivel
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Brian A. Staton
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Rose T. Ajamie
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Geri A. Sawada
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Lawrence M. Gelbert
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Harlan E. Shannon
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Concepcion Sanchez-Martinez
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Alfonso De Dios
Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
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Article Information

vol. 43 no. 9 1360-1371
DOI 
https://doi.org/10.1124/dmd.114.062745
PubMed 
26149830

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0090-9556
Online ISSN 
1521-009X
History 
  • Received December 16, 2014
  • Accepted July 2, 2015
  • Published online July 27, 2015.

Article Versions

  • Earlier version (July 6, 2015 - 08:42).
  • Earlier version (July 9, 2015 - 07:08).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Thomas J. Raub,
  2. Graham N. Wishart,
  3. Palaniappan Kulanthaivel,
  4. Brian A. Staton1,
  5. Rose T. Ajamie,
  6. Geri A. Sawada,
  7. Lawrence M. Gelbert2,
  8. Harlan E. Shannon2,
  9. Concepcion Sanchez-Martinez, and
  10. Alfonso De Dios
  1. Drug Disposition, Lilly Research Laboratories (T.J.R., G.N.W., P.K., B.A.S., R.T.A., G.A.S.), Division of Cancer Research (L.M.G., H.E.S.), and Discovery Chemistry Research and Technologies (A.D.D.), Eli Lilly and Company, Indianapolis, Indiana; Discovery Chemistry Research and Technologies, Eli Lilly and Company, Alcobendas, Madrid, Spain (C.S.-M.); and Covance Laboratories, Greenfield, Indiana (H.E.S.)
  1. Address correspondence to:
    Dr. Thomas J. Raub, Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, DC 0710, Indianapolis, IN 46285. E-mail: raubtj{at}lilly.com
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Drug Metabolism and Disposition: 43 (9)
Drug Metabolism and Disposition
Vol. 43, Issue 9
1 Sep 2015
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Research ArticleArticle

CDK4 and CDK6 Inhibitor Abemaciclib Crosses the Blood–Brain Barrier

Thomas J. Raub, Graham N. Wishart, Palaniappan Kulanthaivel, Brian A. Staton, Rose T. Ajamie, Geri A. Sawada, Lawrence M. Gelbert, Harlan E. Shannon, Concepcion Sanchez-Martinez and Alfonso De Dios
Drug Metabolism and Disposition September 1, 2015, 43 (9) 1360-1371; DOI: https://doi.org/10.1124/dmd.114.062745

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Research ArticleArticle

CDK4 and CDK6 Inhibitor Abemaciclib Crosses the Blood–Brain Barrier

Thomas J. Raub, Graham N. Wishart, Palaniappan Kulanthaivel, Brian A. Staton, Rose T. Ajamie, Geri A. Sawada, Lawrence M. Gelbert, Harlan E. Shannon, Concepcion Sanchez-Martinez and Alfonso De Dios
Drug Metabolism and Disposition September 1, 2015, 43 (9) 1360-1371; DOI: https://doi.org/10.1124/dmd.114.062745
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