C-7 Progesterone Analogues and MDRl in Breast Cancer.
Abstract
We have generated novel analogs of progesterone (PgA) as more potent inhibitors of the MDR1 multidrug resistant phenotype in breast cancer. The objectives of this Research Project include the optimization of the PgA's MDR1-reversing activity through the generation of more compounds by analog design; definition of their in vivo efficacy and of the mechanism of MDR1-reversal. In the course of the second year of the Project, we have: (1) Completed the characterization of a model for the preliminary evaluation of in vivo MDR1-reversing activity (based on the doxorubicin accumulation in MDR1-positive ascites cells), defined PgA4's formulation for in vivo treatment and tested its in vivo toxicity; (2) generated novel PgA structures by stepwise analog design, obtaining data for initial structure-activity considerations and a further 3-fold increase in MDR1-reversing potency; 3. generated and started the characterization of a novel affinity chromatography column (with the MDR1 product, P-glycoprotein immobilized in the solid phase) to test the competitive nature of PgA-induced MDR1 reversal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA366652
Entities
People
- Robert R. Clarke
Organizations
- Georgetown University