Pharmacological characterization of LY335979: A potent cyclopropyldibenzosuberane modulator of P-glycoprotein

James J. Starling, Robert L. Shepard, Jin Cao, Kevin L. Law, Bryan H. Norman, Julian S. Kroin, William J. Ehlhardt, Todd M. Baughman, Mark A. Winter, Michael G. Bell, Chuan Shih, Joseph Gruber, William F. Elmquist, Anne H. Dantzig

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


The above data indicate that LY335979 displays the following characteristics of an 'ideal modulator' of Pgp-mediated multidrug resistance: high affinity binding to Pgp, high potency for in vitro reversal of drug resistance, high therapeutic index (activity was demonstrated at doses ranging from 1-30 mg/kg) observed in vivo antitumor efficacy experiments, and a lack of pharmacokinetic interactions that alter the plasma concentration of coadministered oncolytic agents. These desirable features strongly suggest that LY335979 is an exciting new clinical agent to test the hypothesis that inhibition of P-glycoprotein activity will result in reversal of multidrug resistance in human tumors.

Original languageEnglish (US)
Pages (from-to)335-347
Number of pages13
JournalAdvances in Enzyme Regulation
StatePublished - 1997


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