Indentification of Male Contraceptive Lead Compounds

男性避孕药中铅化合物的鉴定

• 批准号: 6485716
• 负责人: John T. Swindle
• 金额: $ 9.88万
• 依托单位: COMPLEGEN, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-05 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6485716
• 关键词: contraceptives; drug design /synthesis /production; fungal genetics; genetic manipulation; genetic recombination; genetic strain; high throughput technology; male; meiosis; spermatogenesis

DESCRIPTION: (provided by applicant) The long-term objective of this project is to identify lead compounds for the development of male contraceptive drugs. The project takes advantage of: 1) the observation that blocking meiotic recombination in spermatogenesis leads to apoptosis of the developing spermatocytes, and therefore sterility, 2) the high degree of homology of yeast and mammalian meiotic recombination proteins, 3) the observation that many mammalian genes involved in basic cellular functions can functionally substitute for the cognate yeast genes, and 4) the development of simple methods for replacement of yeast with mammalian genes, and 5) the development of simple methods for high throughput screening for interactions between small compounds and specific mammalians genes that are performing essential functions in yeast. In this Phase I applications we propose to replace five genes of yeast that are required for meiotic recombination with their human homologs. Identification of human meiotic recombination genes that can functionally replace the yeast homologs will provide a platform for a Phase II grant. In Phase II, we would perform high throughput screening to identify compounds that block function of the human meiotic genes. These compounds would be candidate male contraceptives, potentially capable of reversibly blocking spermatogenesis. PROPOSED COMMERCIAL APPLICATION: Years of research have failed to produce a male contraceptive drug. Most efforts have focused on hormone-based approaches. This project is designed to identify familes of compounds that should block spermatogenesis in ways less prone to the side effects that have thwarted the development of effective male contraceptives. One third of couples currently use male-based contraceptive approaches. Market research suggests there is broad interest in a male contraceptive drug.

描述：（由申请人提供）该项目的长期目标是 鉴定铅化合物以开发男性避孕药。这 项目利用以下优势：1）观察到阻塞减数分裂 精子发生中的重组导致发展的凋亡 精子细胞，因此不育，2）酵母的高度同源性 和哺乳动物减数分裂重组蛋白，3）观察到许多 参与基本细胞功能的哺乳动物基因可以在功能上 代替同源酵母基因，4）简单的发展 用哺乳动物基因代替酵母的方法，5） 用于高吞吐量筛选的简单方法，用于小型相互作用 执行基本功能的化合物和特定的哺乳动物基因 在酵母中。在此阶段I应用程序中，我们建议替换五个基因 减数分裂重组与人类同源物所需的酵母。 可以在功能上的人类减数分裂重组基因的鉴定 更换酵母同源物将为II期赠款提供平台。在 第二阶段，我们将执行高吞吐量筛选，以识别化合物 人类减数分裂基因的阻滞功能。这些化合物将是候选者 男性避孕药，可能能够可逆地阻塞 精子发生。 拟议的商业应用： 多年的研究未能产生男性避孕药。大多数努力都集中在基于激素的方法上。该项目旨在识别化合物的家族，这些家族应以不太容易受到挫败有效的男性避孕药的发展而阻止副作用的方式阻止精子发生。目前有三分之一的夫妇使用基于男性的避孕方法。市场研究表明，对男性避孕药有广泛的兴趣。