Selective Inhibitors of 17beta-Hydroxysteroid Dehydrogenase

Abstract

Human Type I 17 Beta-HSD, also known as 17 Beta-estrndiol dehydrogenase, catalyzes the reduction of the weak estrogen, estrone, to the strong estrogen, 17 Beta estradiol, which is the biologically active estrogen involved in the development of human breast cancer. Type I 17Beta-HSD is therefore a very attractive target for drug development. Objectives: Recently, we developed a new class of dehydrogenase inhibitors that are targeted at the NAD(P)/NAD(P)H binding sites (Rossmann fold) of dehydrogenses. Surprisingly, these inhibitors exhibit selectivity for different dehydrogenases. The goal of this project is to develop selective inhibitors of human Type I 17 Beta-HSD as "lead compounds" for stmcture-based drug design. The crystal structure of human Type I 17 Beta-HSD is available to aid in structure-based drug design. The concept that the Rossmann fold may represent a useful drug target is a new concept in drug design.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2003
Accession Number
ADA423130

Entities

People

  • David L. Vander

Organizations

  • University of New Mexico

Tags

DTIC Thesaurus Topics

  • Algorithms
  • Biochemistry
  • Breast Cancer
  • Carrier Proteins
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Crystal Structure
  • Genetic Algorithms
  • Inhibitors
  • Lead Compounds
  • Macromolecules
  • Materials
  • Molecules
  • Neoplasms
  • Organic Chemistry
  • Proteins

Fields of Study

  • Chemistry

Readers

  • Molecular and Cellular Biochemistry