Accession Number : ADA338786

Title :   C-7 Progesterone Analogues and MDRl in Breast Cancer

Descriptive Note : Annual rept. 1 Sep 96-31 Aug 97

Corporate Author : GEORGETOWN UNIV WASHINGTON DC

Personal Author(s) : Clarke, Robert R.

PDF Url : ADA338786

Report Date : SEP 1997

Pagination or Media Count : 15

Abstract : In the course of the past year, we have completed a meta-analysis of published studies, which confirms the expression and prognostic role of the MDR 1 mechanism of resistance in human breast cancer. In our effort to obtain effective inhibitors of this mechanism, we have synthesized some novel progesterone analogs. Among these, PgA4 is in vitro about 30-fold more potent a MDR1 inhibitor than the parental compound. Obtaining an MTD in vivo is limited by PgA4 low water solubility. We have defined a cyclodextrin-based formulation which, because of increased PgA4 solubility and decreased local tissue toxicity, will allow the in vivo administration of repeated and higher doses of PgA4.

Descriptors :   *INHIBITORS, *PROGESTERONE, *BREAST CANCER, GLYCOPROTEINS, CARBON, METABOLISM, IN VITRO ANALYSIS, CHEMICAL BONDS, OXIDATION, ANALOGS, LIVER, DRUGS, ACCUMULATION, IN VIVO ANALYSIS, ASSAYING, VACCINES, RESISTANCE(BIOLOGY).

Subject Categories : Biochemistry
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE