Investigation of Microglial CRAC Channels as a Novel Drug Target for Opioid Use Disorder

Vivreon生物科学-RFA-19-019 小胶质细胞CRAC通道作为阿片类药物使用障碍新靶点的研究 项目摘要 Vivreon生物科学公司很高兴申请NIDA RFA-19-019。Vivreon生物科学是一门创新的生命科学 一家正在开发治疗阿片类药物使用障碍的新型小分子钙通道抑制剂的公司 (有声)。我们的候选疗法通过一种全新的机制--抑制钙离子来靶向大脑小胶质细胞 释放激活的钙通道(CRAC)可阻断小胶质细胞增生。Vivreon寻求NIDA资金进行临床前研究 在阿片类药物使用障碍(OUD)动物模型中测试其临床前铅VV7063的概念验证研究 并验证CRAC通道作为阿片类药物戒断的治疗靶点。在成功完成此操作后 格兰特，Vivreon将为OUD确定一个新颖的非阿片类药物靶点。未来的资金将旨在改善药物- 类似于Vivreon的临床前Lead的特性，以确定有史以来第一个针对CRAC的阿片类药物临床候选药物 撤军，为与OUD的战斗提供了一个全新的工具。 Vivreon的临床前领先药物VV7063代表了一种新的化学型，具有前景看好的早期药物样特性和 对自主神经或运动功能无不良影响，提示CRAC通道是一种安全的中枢药物 目标。它通过阻断具有NM效力的CRAC通道活性，抑制M1样核因子-kB，从而抑制小胶质细胞增生 活性，同时增强类M2吞噬作用和动态平衡转录特征。我们现在就会 测定VV7063在大鼠体内的药代动力学(PK)，然后在大鼠模型中检测VV7063 奥德。最后的里程碑将是CRAC通道作为OUD的治疗靶点的验证。

Vivreon Biosciences – RFA-19-019 Investigation of Microglial CRAC Channels as a Novel Drug Target for Opioid Use Disorder Project Summary Vivreon Biosciences is pleased to apply for NIDA RFA-19-019. Vivreon Biosciences is an innovative life sciences company that is developing novel small molecule, Ca2+ channel inhibitors for the treatment of opioid use disorder (OUD). Our candidate therapeutics target brain microglial cells by an entirely new mechanism – inhibition of Ca2+ release-activated Ca2+ (CRAC) channels to block microgliosis. Vivreon seeks NIDA funding to perform preclinical proof of concept studies to test its preclinical lead, VV7063, in an animal model of opioid use disorder (OUD) and validate the CRAC channel as a therapeutic target for opioid withdrawal. Upon successful completion of this grant, Vivreon will identify a novel, non-opioid target for OUD. Future funding will be aimed at improving drug- like properties of Vivreon’s preclinical lead to identify the first ever CRAC-targeted clinical candidate for opioid withdrawal, providing an entirely new tool in the battle against OUD. Vivreon’s preclinical lead, VV7063, represents a novel chemotype with promising early drug-like properties and has no deleterious effect on autonomic or motor function, suggesting CRAC channels are a safe CNS drug target. It inhibits microgliosis by blocking CRAC channel activity with nM potency, suppressing M1-like NF-kB activity, while enhancing M2-like phagocytosis and a homeostatic transcriptional signature. We will now determine the pharmacokinetic (PK) profile of VV7063 in rats followed by testing of VV7063 in a rat model of OUD. The final milestone will be validation of the CRAC channel as a therapeutic target for OUD.