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Mu Opioid Receptor Modulator Development to Treat Opioid Use Disorder

Mu 阿片受体调节剂开发用于治疗阿片类药物使用障碍

基本信息

批准号：
9904032
负责人：
YAN ZHANG
金额：
$ 99.68万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-30 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9904032
关键词：
Acute Affinity Agonist American Attenuated Binding Binding Proteins Biologic Characteristic Biological Assay Biological Availability Biological Products Buprenorphine Categories Cell Line Chemicals Chronic Clinical Computer Simulation Cyclic GMP Dependence Development Dose Drug Kinetics FDA approved Fentanyl Food Formulation G-Protein-Coupled Receptors Goals Heroin In Vitro Laboratory Research Lead Libraries Ligands Macaca mulatta Metabolic Methadone Modeling Mus Naltrexone National Institute of Drug Abuse Neuropharmacology Opioid Opioid Antagonist Opioid Receptor Opioid agonist Oral Penetration Permeability Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacology Pharmacotherapy Phase Plasma Proteins Procedures Production Property Rattus Research Self Administration Societies Stimulus Study models Tail Testing Therapeutic Therapeutic Effect Time Toxic effect United States United States Food and Drug Administration Universities Virginia Water Withdrawal Withdrawal Symptom attenuation base behavioral pharmacology clinical candidate compound 30 design drug candidate drug development drug discovery drug metabolism effective therapy in vivo molecular modeling mu opioid receptors multidisciplinary next generation novel opioid epidemic opioid overdose opioid use disorder opioid withdrawal pharmacokinetics and pharmacodynamics pre-clinical scale up small molecule libraries tool

项目摘要

Project Summary The United States is currently in an opioid crisis, and NIDA is committed to research on the mechanisms and treatment of opioid use disorder. Current Food and Drug Administration-approved pharmacotherapies for opioid use disorder include the MOR agonist methadone, the MOR partial agonist buprenorphine, and the MOR antagonist naltrexone. However, the clinical utility of all three compounds is limited for various reasons. Therefore, it is imperative to develop novel and effective drug candidates with enhanced therapeutic effects and reduced undesirable effects. Recently, we have identified several highly selective and potent MOR modulators as novel leads for opioid use disorder treatment. They all showed more promising pharmacological profiles compared to other known drugs in this category. The current proposal will focus on further development of these leads for preclinical IND-enabling studies, and dynamic drug discovery and development pipeline construct. Four integrated specific aims will be pursued in this project in two phases. In the UG3 phase, we will 1) further Validate therapeutic profiles of the current leads with self-administration and PK studies, and 2) expand the small molecule library to build a dynamic drug discovery and development pipeline. In the UH3 phase, we will 1) conduct preclinical IND-enabling studies on the lead(s) identified from UG3 phase, and 2) compare in vivo pharmacokinetics and pharmacodynamics profiles of the new hits from UG3 phase with current leads to define our next generation of lead compound(s).

项目总结