Pharmacokinetic drivers of toxicity for basic molecules: strategy to lower pKa results in decreased tissue exposure and toxicity for a small molecule Met inhibitor.

Diaz, Dolores; Ford, Kevin A; Hartley, Dylan P; Harstad, Eric B; Cain, Gary R; Achilles-Poon, Kirsten; Nguyen, Trung; Peng, Jing; Zheng, Zhong; Merchant, Mark; Sutherlin, Daniel P; Gaudino, John J; Kaus, Robert; Lewin-Koh, Sock C; Choo, Edna F; Liederer, Bianca M; Dambach, Donna M

Diaz, Dolores; Ford, Kevin A; Hartley, Dylan P; Harstad, Eric B; Cain, Gary R; Achilles-Poon, Kirsten; Nguyen, Trung; Peng, Jing; Zheng, Zhong; Merchant, Mark; Sutherlin, Daniel P; Gaudino, John J; Kaus, Robert; Lewin-Koh, Sock C; Choo, Edna F; Liederer, Bianca M; Dambach, Donna M.

Affiliation

Diaz D; Safety Assessment, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. diaz.dolores@gene.com

Toxicol Appl Pharmacol ; 266(1): 86-94, 2013 Jan 01.

Article in En | MEDLINE | ID: mdl-23142475

Subject(s)

Protein Kinase Inhibitors/pharmacokinetics; Protein Kinase Inhibitors/toxicity; Proto-Oncogene Proteins c-met/antagonists & inhibitors; Animals; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation/drug effects; Down-Regulation/physiology; Female; Humans; Hydrogen-Ion Concentration/drug effects; Male; Mice; Mice, Nude; Proto-Oncogene Proteins c-met/metabolism; Random Allocation; Tissue Distribution/drug effects; Tissue Distribution/physiology

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Full text: 1 Database: MEDLINE Main subject: Proto-Oncogene Proteins c-met / Protein Kinase Inhibitors Type of study: Clinical_trials Limits: Animals / Female / Humans / Male Language: En Journal: Toxicol Appl Pharmacol Year: 2013 Type: Article Affiliation country: United States

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