Interdisciplinary Center for Male Contraceptive Research and Drug Development

男性避孕研究和药物开发跨学科中心

• 批准号: 7277492
• 负责人: JOSEPH S TASH
• 金额: $ 150万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-26 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7277492
• 关键词: Address; Agreement; Area; Binding; Buffaloes; California; Cardenolides; Chemical Agents; Chemical Structure; Chemicals; Cities; Class; Collaborations; Contraceptive Agents; Contraceptive methods; Contracts; Dentistry; Development; Discipline; Doctor of Philosophy; Drug Design; Elongation Factor; Environment; Faculty; Female; Fertility; Fostering; Funding; Gene Targeting; Generations; Hormonal; Image; Institute of Medicine (U.S.); Institution; Interdisciplinary Study; Investigation; Kansas; Knowledge; Laboratories; Male Contraceptive Agents; Medical; Medical center; Medicine; Minnesota; Molecular; Morale; Na(+)-K(+)-Exchanging ATPase; National Institute of Child Health and Human Development; New Jersey; Numbers; Oral; Pharmaceutical Chemistry; Pharmacy Schools; Planned Pregnancy; Postdoctoral Fellow; Pregnancy; Program Development; Protein Isoforms; Protein Tyrosine Kinase; Proteins; Purpose; Recording of previous events; Regulation; Reproduction; Reproductive Biology; Reproductive Health; Research; Research Infrastructure; Research Institute; Research Personnel; Research Project Grants; San Francisco; Science; Scientist; Spermatogenesis; Spermiogenesis; Students; Talents; Testing; United States National Institutes of Health; Universities; Visit; Wood material; World Health Organization; abortion; concept; condoms; contraceptive target; design; drug development; drug discovery; inhibitor/antagonist; interdisciplinary approach; male; medical schools; member; novel; novel strategies; programs; protein structure; reproductive; reproductive development; research and development; small molecule; sperm cell; sperm function; sperm protein; statistics; success; unintended pregnancy

DESCRIPTION (provided by applicant): World Health Organization (WHO) statistics show that 122 million planned pregnancies occur worldwide per year. Yet, in spite of the availability of many different female contraceptive methods and condoms, an additional 87 million pregnancies are unintended (representing 42% of all pregnancies), and 46 million pregnancies terminated by abortion. Thus, the development of novel reversible oral male contraceptive agents has been identified as a major advance needed to address this worldwide reproductive health issue by the NIH, Institute of Medicine, and WHO. The purpose of the proposed multi-institutional U54 "Inter- disciplinary Center for Male Contraceptive Research and Drug Development" is to develop new non-hormonal male contraceptive agents. The Prime Objective of the research program of this center, using proven successful interdisciplinary approaches, will be to provide NIH with new and novel contraceptive agents for drug development. This will be accomplished by a highly interactive and collaborative group of research projects by 1) investigating a set of unique protein targets that are critical for spermatogenesis, spermiogenesis, and sperm function, and 2) identifying novel and alternative chemical structures that act via the newly discovered male contraceptive targets of our most promising new contraceptive agents. The specific research projects are: Research Project I: Mechanisms and novel male contraceptive agents that target Hsp90p and elongation factor-la. Joseph S. Tash, Ph.D., PI Research Project II: Cardenolides inhibition of the sperm Na,K-ATPase a4 isoform as contraceptive agent Gustavo Blanco, Ph.D., PI, Research Project III: Small molecule inhibitors of Dmrtl-regulated target genes as male contraceptive agents Leslie Heckert, Ph.D., PI, Research Project IV: Sperm protein tyrosine kinases as targets for small molecule contraceptives William Kinsey, Ph.D., PI The research program includes a New Investigator Development Program that will foster and support new scientists involved in research to develop new male contraceptive agents. The research program is supported by a strong and highly interactive set of Core Units including an Administrative Core, Drug Discovery, Design & Synthesis Core, Drug Development Core, and Imaging Core. The scientists involved in the research projects and cores of this proposed center have a record of success in providing NIH with highly promising reversible non-hormonal male contraceptive agents that are already under drug development in collaboration with NIH. The research program in this center will expand this success into new protein targets involved in regulation of male fertility that will be exploited by cutting edge drug discovery and design approaches for generation of new classes of non-hormonal chemical structures as male contraceptive agents.

说明（由申请人提供）：世界卫生组织（世卫组织）的统计数据显示，全世界每年发生1.22亿次计划怀孕。然而，尽管有许多不同的女性避孕方法和避孕套，另有8700万次意外怀孕（占所有怀孕的42%），4600万次怀孕因堕胎而终止。因此，美国国立卫生研究院、医学研究所和世卫组织已将开发新型可逆口服男性避孕药确定为解决这一全球生殖健康问题所需的一项重大进展。拟建的多机构U54“男性避孕药研究与药物开发跨学科中心”的目的是开发新的非激素男性避孕药。该中心研究项目的主要目标是使用已证明成功的跨学科方法，为美国国立卫生研究院提供用于药物开发的新型避孕药物。这将通过一个高度互动和协作的研究项目小组来完成：1)研究一组对精子发生、精子发生和精子功能至关重要的独特蛋白质靶点；2)通过我们最有前途的新型避孕药中新发现的男性避孕靶点，确定新的和替代的化学结构。研究项目一：以Hsp90p和延伸因子-la为靶点的新型男性避孕药的作用机制及研究。Joseph S. Tash，博士，PI研究项目II: Cardenolides抑制精子Na， k - atp酶a4异型作为避孕药Gustavo Blanco，博士，PI，研究项目III: dmrtl调控靶基因的小分子抑制剂作为男性避孕药Leslie Heckert，博士，PI，研究项目IV：精子蛋白酪氨酸激酶作为小分子避孕药的靶点研究项目包括一个新的研究者发展项目，该项目将培养和支持新的科学家参与研究开发新的男性避孕药。该研究项目由一系列强大且高度互动的核心单元提供支持，包括行政核心、药物发现、设计与合成核心、药物开发核心和成像核心。参与该中心研究项目和核心的科学家们在为NIH提供非常有前途的可逆非激素男性避孕药方面取得了成功，这些避孕药已经在与NIH合作进行药物开发。该中心的研究项目将把这一成功扩展到涉及男性生育能力调节的新蛋白质靶点，这些靶点将被前沿药物发现和设计方法所利用，以产生新型非激素化学结构，如男性避孕药。