权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

TREATING SELF-ABUSE IN AUTISM AND MENTAL RETARDATION

治疗自闭症和智力低下的自虐行为

基本信息

批准号：
2776073
负责人：
NEAL G SIMON
金额：
$ 10万
依托单位：
AZEVAN PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-15 至 2001-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2776073
关键词：
aggression autism cell line chemical structure function drug design /synthesis /production drug screening /evaluation mental disorder chemotherapy mental retardation self destructive behavior violence

项目摘要

Long Term Goals: Serenix Pharmaceuticals (SP) will develop drugs to treat impulsivity, violence, and self-injurious behavior in patients with autism, Tourette's syndrome, and mental retardation. These drugs, termed serenics, stop violent behavior without disrupting normal behaviors. No other products are available for these indications. Strategy: SP acquired a series of antagonists from Eli Lilly and Company that block the receptor subtype involved in aggression. These antagonists (LEAD SERIES) exhibit high affinity for the human receptor (<1.0 nM), are stable in stomach and blood, orally active, and pass into the brain. They require refinement to optimize these characteristics. The platform molecule has four essential structural zones that can be modified to improve bioavailability. Phase I objectives are (i) utilize combinatorial chemistry to modify structural zones on the LEAD SERIES to generate ca. 200 compounds, (ii) screen these for target receptor affinity and focus on those with Kds < 5 nM, (iii) test the high affinity compounds for in vitro biological activity, and (iv) test biologically active compounds for in vivo effects on an animal model of aggression. The findings will identify promising compounds for testing in Phase II for oral absorption, stability, CNS penetration, metabolism, and toxicity as well for efficacy in a primate model of self-injurious behavior. PROPOSED COMMERCIAL APPLICATION: SP will focus on the development of drugs to help in the control impulsivity, violence, and self-injurious behavior for the management of autism, Tourette' s syndrome, and mental retardation. It is estimated that more than 500,000 patients in the United States alone would have a need for these drugs. These drugs may also be used in the control of violence associated with mania, conduct disorder in a sub set of children with ADHD, and Alzheimer' s disease. There are no other products on the market for these indications.

长期目标：Serenix Pharmaceuticals (SP) 将开发药物来治疗自闭症、抽动秽语综合征和智力低下患者的冲动、暴力和自残行为。这些药物被称为 Serenics，可以在不破坏正常行为的情况下阻止暴力行为。没有其他产品可用于这些适应症。策略：SP从礼来公司获得了一系列拮抗剂，可以阻断参与攻击的受体亚型。这些拮抗剂（LEAD 系列）对人类受体表现出高亲和力（<1.0 nM），在胃和血液中稳定，口服有效，并进入大脑。它们需要细化来优化这些特性。该平台分子具有四个重要的结构区域，可以对其进行修改以提高生物利用度。第一阶段的目标是 (i) 利用组合化学来修改 LEAD SERIES 上的结构区域，以生成约200 种化合物，(ii) 筛选这些化合物的目标受体亲和力，并重点关注 Kds < 5 nM 的化合物，(iii) 测试高亲和力化合物的体外生物活性，以及 (iv) 测试生物活性化合物对攻击性动物模型的体内影响。这些发现将确定有前景的化合物，用于在第二阶段测试口服吸收、稳定性、中枢神经系统渗透、代谢和毒性以及在灵长类动物自残行为模型中的功效。拟议的商业应用：SP 将专注于开发有助于控制冲动、暴力和自残行为的药物，以治疗自闭症、抽动秽语综合症和智力迟钝。据估计，仅在美国就有超过 500,000 名患者需要这些药物。这些药物还可用于控制与躁狂症、ADHD 儿童的行为障碍和阿尔茨海默病相关的暴力。市场上没有其他产品可用于这些适应症。