BOSTON--(BUSINESS WIRE)--DeepCure, a therapeutics company using AI to discover novel drugs for inflammation and immune diseases, today announced the selection of its first development candidate, DC-9476. DC-9476 is a third generation BRD inhibitor that is selective for the BD2 domain of Brd4, which is expected to enter clinical trials in 2025.

波士顿--（商业新闻短讯）--DeepCure是一家利用人工智能发现治疗炎症和免疫疾病新药的治疗公司，今天宣布选择其第一个开发候选者DC-9476。DC-9476是第三代BRD抑制剂，对Brd4的BD2结构域具有选择性，预计将于2025年进入临床试验。

The BD2 domain of Brd4 regulates multiple, clinically validated, cytokine-related pathways, such as TNF-alpha, IL6, IL-17, and IL-1b, that are important in a variety of autoimmune diseases..

Brd4的BD2结构域调节多种临床验证的细胞因子相关途径，例如TNF-α，IL6，IL-17和IL-1b，这些途径在多种自身免疫性疾病中很重要。。

Many autoimmune diseases have epigenetic changes, including histone modifications that alter chromatin structure and gene expression. The BET family of proteins, which includes Brd4, that “read” these histone modification can cause patterns of gene expression in innate and adaptive immune cells that persist long after the stimulus is gone.

许多自身免疫性疾病具有表观遗传变化，包括改变染色质结构和基因表达的组蛋白修饰。包括Brd4在内的BET蛋白家族可以“读取”这些组蛋白修饰，从而导致先天性和适应性免疫细胞中的基因表达模式，这些模式在刺激消失后会持续很长时间。

In addition, Brd4 BD2 activity can also directly regulate transcription factors. Inhibition of Brd4 BD2 by small molecule drugs can break a self-perpetuating cycle of gene expression that can occur across multiple pathways that is detrimental to normal tissues and reinstate self-resolving processes that should follow inflammatory triggers..

此外，Brd4 BD2活性也可以直接调节转录因子。小分子药物对Brd4 BD2的抑制作用可以打破基因表达的自我延续循环，这种循环可能发生在对正常组织有害的多种途径中，并恢复炎症触发后的自我解决过程。。

DC-9476 has shown promising efficacy in multiple preclinical models of autoimmune diseases, including rheumatoid arthritis (RA) and Still’s disease. In RA models, DC-9476 was superior to standard of care therapies, TNF-alpha inhibitors, IL-6 inhibitors, and the JAK inhibitor tofacitinib, and it also improved the effectiveness of TNF-alpha inhibitors when used in combination therapy.

DC-9476在包括类风湿性关节炎（RA）和斯蒂尔病在内的多种自身免疫性疾病的临床前模型中显示出有希望的功效。在RA模型中，DC-9476优于标准治疗，TNF-α抑制剂，IL-6抑制剂和JAK抑制剂托法替尼，并且当用于联合治疗时，它也提高了TNF-α抑制剂的有效性。

Unlike earlier generations of non-selective inhibitors, DC-9476 has an excellent safety profile and did not cause thrombocytopenia..

与早期的非选择性抑制剂不同，DC-9476具有优异的安全性，不会引起血小板减少症。。

The novel candidate was discovered using DeepCure’s proprietary AI platform by exploiting differences in the structure and function among the BET protein family and the two bromodomains (BD1 and BD2). DeepCure’s AI platform integrates advanced ML and physics-based tools to find interaction sites on the protein surface (PocketExpander™) and to design novel, diverse compounds that are synthetically feasible (MolGen™)..

通过利用BET蛋白家族和两个溴结构域（BD1和BD2）之间的结构和功能差异，使用DeepCure专有的AI平台发现了新的候选物。DeepCure的人工智能平台集成了先进的ML和基于物理的工具，以在蛋白质表面找到相互作用位点（PocketExpander™），并设计出合成可行的新颖多样的化合物（MolGen™）。。

“In the past years of translational and clinical research we have learnt that autoimmune diseases are the effect of multiple deranged pathways. Targeted therapies against specific cytokines, kinases or receptors have offered a first important boost in how we manage these conditions but patients would benefit enormously from pharmacological inhibition of multiple inflammatory pathways,” said Professor Francesco Del Galdo, M.D., Ph.D., Professor of Experimental Medicine NIHR Biomedical Research Centre and Institute of Rheumatic and Musculoskeletal Medicine University of Leeds.

“在过去几年的转化和临床研究中，我们了解到自身免疫性疾病是多种紊乱途径的影响。针对特定细胞因子，激酶或受体的靶向治疗为我们如何管理这些疾病提供了第一个重要的推动，但患者将从多种炎症途径的药理学抑制中受益匪浅，”医学博士、实验医学教授、NIHR生物医学研究中心和利兹大学风湿与肌肉骨骼医学研究所说。

“However, current attempts with simply combining clinically existing therapies that target individual pathways have shown limited success, mostly due to increased toxicity. New therapeutics such as DC-9476 that have a novel mechanism to address simultaneously multiple pathways while also having an excellent safety profile, are extremely promising for the field.”.

“然而，目前仅结合针对个体途径的临床现有疗法的尝试显示出有限的成功，主要是由于毒性增加。DC-9476等新疗法具有同时解决多种途径的新机制，同时具有优异的安全性，在该领域极具前景。”。

“We’re excited to announce our first AI-generated candidate, which we plan to advance into clinical trials next year. This validates our generative AI and physics-based drug discovery engine,” said Kfir Schreiber, CEO & Co-Founder, DeepCure. “DC-9476 is the first of many novel development candidates to emerge from our platform, with the potential to transform the treatment of inflammation and immune diseases.”.

DeepCure首席执行官兼联合创始人Kfir Schreiber说：“我们很高兴宣布我们的第一个人工智能生成的候选人，我们计划明年将其推进临床试验。这验证了我们的生成人工智能和基于物理的药物发现引擎。”。“DC-9476是我们平台上出现的许多新型开发候选者中的第一个，具有改变炎症和免疫疾病治疗的潜力。”。

About DeepCure

关于DeepCure

DeepCure was founded by researchers at MIT to accelerate breakthrough therapies using artificial intelligence (AI) and AI-enabling technologies to innovate small molecule discovery. The company is based in Boston, MA, and its engineers, chemists, and biologists collaborate on hard problems to find solutions that will have an enormous impact on patient health.

DeepCure由麻省理工学院的研究人员创立，旨在利用人工智能（AI）和人工智能技术创新小分子发现，加速突破性治疗。该公司总部位于马萨诸塞州波士顿，其工程师、化学家和生物学家合作解决棘手的问题，以找到对患者健康产生巨大影响的解决方案。

For more information, visit www.deepcure.ai..

有关更多信息，请访问www.deepcure.ai。。