Massachusetts Institute of Technology

Merck + Co., Inc.

Jeffrey H Toney

Stephen J Lippard

Patti Jean Kellett

John M Essigmann

Brian A Donahue

Pieter M Pil

Suzanne L Bruhn

Steven J Brown

Alex Elbrecht

Steven Joel Brown

Methods disclosed herein capitalize on the ability of DNA Structure Specific Recognition Proteins (SSRPs) to bind to genomic lesions formed by chemotherapeutic agents, particularly cisplatin-type agents. Methods are provided for predicting whether an agent that damages DNA will also be cytotoxic, and for predicting whether particular eukaryotic cells will be susceptible to killing by a genotoxic drug. A screening method is provided for identifying new genotoxic drugs that produce SSRP-recognized lesions in DNA. Methods also are provided for sensitizing particular eukaryotic cells to killing by chemotherapeutic agents, particularly cisplatin-type drugs.

Uses for DNA structure-specific recognition protein

An assay for identifying compounds with antiandrogenic activity employing a hamster ductus deferens cell line (DDT1) ATCC CRL-1701 and ATCC CRL-12051 is disclosed, as well as antiandrogenic compounds identified from this assay, particularly the nonsteroidal compound N-(4-chlorophenyl)-(Z,Z)-2,3-bis(cyclopropylmethylene)cyclopentane carboxamide of structural formula (I): ##STR1## This compound is an antiandrogen useful in the treatment and prevention of diseases of the prostate including prostatitis, benign prostatic hyperplasia (BPH) and prostatic carcinoma.

Treatment of prostate disease with a nonsteroidal anti-androgenic

DNA structure specific recognition protein of eukaryotic origin and DNA encoding such a factor, as well as probes specific for DNA structure specific recognition protein or DNA encoding it and methods of detecting DNA structure specific recognition protein in eukaryotic cells. In particular, a mammalian cellular factor that selectively recognizes and binds DNA damaged or modified by a drug (the anticancer drug, cis-diamminedichloroplatinum (II) or cisplatin) has been identified.

DNA structure specific recognition protein complexes

Nucleic acids encoding DNA structure-specific recognition protein and

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Westfield, NJ, United States of America

Jeffrey H Toney