STSS Aspire Heal Task Order 10

美国每天有超过2500万人经历疼痛（2012年全国健康访谈调查数据），需要安全，无成瘾的治疗来减轻他们的痛苦。 这种临床需求非常重要，因为过量处方和滥用阿片类药物来管理急性和慢性疼痛助长了目前阿片类药物使用障碍和过量死亡的流行，阿片类药物用于长期疼痛管理的有效性受到质疑。安全、有效和非成瘾性药物（小分子和生物制剂）用于治疗疼痛、减轻成瘾和逆转过量是解决阿片类药物危机的关键，阿片类药物危机在2019冠状病毒病大流行后只会恶化。鉴于先前药物开发努力的失败和局限性，需要识别新靶点、具有新结构并且可以在基于人的生理学相关体外系统中鉴定的药物。 2018年，NCATS发布了NCATS ASPIRE设计挑战，该挑战从更广泛的科学界征集设计理念，以解决与非成瘾性疼痛治疗相关的临床前药物发现过程领域，这些领域可以通过引入与以下相关的新技术来加速： · 综合化学数据库 · 电子合成化学门户 · 预测算法 · 生物学测定 · 上述方面的综合解决方案 于二零二零年，NCATS跟进ASPIRE还原实践挑战赛，校外研究人员及创新者组成协作团队，提供非成瘾性止痛药药物发现平台的全功能原型，该平台整合了设计挑战赛的所有挑战主题（综合化学数据库、电子合成化学门户网站、预测算法、生物测定）。普渡大学团队（PI：Gaurav Chopra）和CiBots，Inc.团队（PI：Babak Esmaeli-Azad）分别获得了大奖和亚军。我们现在正在寻求利用2020年NCATS ASPIRE简化实践挑战赛期间开发的一系列技术，以建立一个非传统的、合并的、由所有必要专业知识组成的“超级团队”，以（1）完成两个互补平台的整合，（2）增强统一平台的能力，并快速提供具有安全和改进特性的新型镇痛药候选药物。

Over 25 million people in the United States experience pain every day (2012 National Health Interview Survey data) and need safe, addiction-free treatments to alleviate their suffering. This clinical demand is of tremendous importance given that overprescribing and abuse of opioids for managing acute and chronic pain has fueled the current epidemic of opioid use disorder and overdose deaths, and the effectiveness of opioids for long-term pain management is being questioned. Safe, effective, and non-addictive drugs (small molecules and biologics) to treat pain, mitigate addiction and reverse overdose are key to addressing the opioid crisis that has only worsened following the COVID-19 pandemics. Given failures and limitations of previous drug development efforts, drugs that recognize novel targets, have novel structures, and can be identified in human-based, physiologically relevant in vitro systems are needed. In 2018 NCATS by releasing NCATS ASPIRE Design Challenges, which solicited design ideas from the broader scientific community to address areas of the preclinical drug discovery process related to non-addictive pain treatment that could be accelerated by the introduction of new technologies related to: • Integrated Chemistry Databases • Electronic Synthetic Chemistry Portals • Predictive Algorithms • Biological Assays • Integrated Solutions of the above aspects In 2020, NCATS followed up with the ASPIRE Reduction-to-Practice Challenge, in which extramural researchers and innovators formed collaborative teams to deliver fully functioning prototypes of a non-addictive analgesics drug discovery platform that incorporated all the challenge topics from the design challenges (Integrated Chemistry Databases, Electronic Synthetic Chemistry Portals, Predictive Algorithms, Biological Assays). The Purdue University Team (PI: Gaurav Chopra) and the CiBots, Inc. Team (PI: Babak Esmaeli-Azad) garnered the grand prize and the runner-up prizes, respectively. We are now seeking to harness the array of technologies developed during the 2020 NCATS ASPIRE Reduction-to-Practice Challenge to build a non-traditional, merged, “super-team” of all expertise necessary to (1) complete integration of the two complementary platforms and (2) enhance the unified platform’s capability and rapidly deliver new analgesics drug candidates with safe and improved properties.