FSH Receptor Antisense Strategy for Contraception

FSH 受体反义避孕策略

• 批准号: 6346469
• 负责人: JAMES P LEYDA
• 金额: $ 10万
• 依托单位: EMERGING CONCEPTS, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6346469
• 关键词: antisense nucleic acid; contraceptives; corpus luteum; dosage; drug design /synthesis /production; drug screening /evaluation; female; follicle stimulating hormone; graafian follicles; hormone inhibitor; hormone receptor; laboratory rat; ovary

DESCRIPTION (Scanned from the applicant's description): A new form of chemical contraceptive that has greater ease of use, more prolonged actions and a different profile of side effects than existing steroidal contraceptives would be welcomed by many women. A compound that specifically and reversibly inhibits development of ovarian follicles would be an ideal and radically different contraceptive. A specific inhibitor of follicle-stimulating hormone receptor (FSHR) synthesis is expected to be such a compound. The FSHR protein is required for ovarian follicular development and is present in ovarian follicular granulosa cells but not in non-reproductive tissues. The collaborator's laboratory has demonstrated that this compound inhibits synthesis of the FSHR in vitro. The goal of this six-month Phase I feasibility project is to determine if a phosphorothioated 18-mer antisense oligodeoxynucleotide (ODN) reversibly and specifically blocks follicular development in a mammalian species (rat) in a dose-dependent manner. The goal of the Phase II project will be to establish and refine the pharmaceutical and toxicological properties of the ODN in a primate species using a biodegradable, sustained-release, long acting, and injectable microsphere formulation of the compound. The long-term objective is to develop an FSHR antisense ODN as a contraceptive that would transiently block ovarian follicular development in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（根据申请人的描述进行扫描）：一种新的化学形式 具有更大用途的避孕药，延长的行动和 与现有类固醇避孕药的副作用不同的特征将 受到许多女性的欢迎。一种专门和可逆抑制的化合物 卵巢卵泡的发展将是理想的，根本不同 避孕。卵泡激素受体的特定抑制剂 （FSHR）预计合成是这样的化合物。 FSHR蛋白是 卵巢卵泡发育所需的所需，并且存在于卵巢中 卵泡颗粒细胞，但不在非生殖组织中。这 合作者的实验室表明，这种复合抑制了 FSHR在体外的合成。这个六个月的I阶段可行性的目标 项目是确定是否磷酸化的18-Mer反义 寡脱氧核苷酸（ODN）可逆地阻止卵泡 以剂量依赖性方式在哺乳动物物种（大鼠）中发育。目标 第二阶段项目将是建立和完善药物和 使用可生物降解的灵长类动物中ODN的毒理学特性 持续释放，长作用和可注射的微球公式 化合物。长期目标是将FSHR反义ODN作为一个 避孕药会暂时阻止卵巢卵泡发育 人类。 拟议的商业应用程序：不可用