Abstract：
UNASSIGNED: Histone deacetylases (HDACs) are a class of zinc-dependent enzymes. They maintain acetylation homeostasis, with numerous biological functions and are associated with many diseases. HDAC3 strictly requires multi-subunit complex formation for activity. It is associated with the progression of numerous non-communicable diseases. Its widespread involvement in diseases makes it an epigenetic drug target. Preexisting HDAC3 inhibitors have many uses, highlighting the need for continued research in the discovery of HDAC3-selective inhibitors.
UNASSIGNED: This review provides an overview of 24 patents published from 2010 to 2023, focusing on compounds that inhibit the HDAC3 isoenzyme.
UNASSIGNED: HDAC3-selective inhibitors - pivotal for pharmacological applications, as single or combination therapies - are gaining traction as a strategy to move away from complications laden pan-HDAC inhibitors. Moreover, there is an unmet need for HDAC3 inhibitors with alternative zinc-binding groups (ZBGs) because some preexisting ZBGs have limitations related to toxicity and side effects. Difficulties in achieving HDAC3 selectivity may be due to isoform selectivity. However, advancements in computer-aided drug design and experimental data of HDAC3 3D co-crystallized models could lead to the discovery of novel HDAC3-selective inhibitors, which bear alternative ZBGs with balanced selectivity for HDAC3 and potency.
UNASSIGNED: This review provides an overview of 24 patents published from 2010 to 2023, focusing on compounds that inhibit the HDAC3 isoenzyme.
UNASSIGNED: HDAC3-selective inhibitors - pivotal for pharmacological applications, as single or combination therapies - are gaining traction as a strategy to move away from complications laden pan-HDAC inhibitors. Moreover, there is an unmet need for HDAC3 inhibitors with alternative zinc-binding groups (ZBGs) because some preexisting ZBGs have limitations related to toxicity and side effects. Difficulties in achieving HDAC3 selectivity may be due to isoform selectivity. However, advancements in computer-aided drug design and experimental data of HDAC3 3D co-crystallized models could lead to the discovery of novel HDAC3-selective inhibitors, which bear alternative ZBGs with balanced selectivity for HDAC3 and potency.
摘要：
■组蛋白脱乙酰酶(HDAC)是一类锌依赖性酶。它们维持乙酰化稳态，具有许多生物学功能，并与许多疾病有关。HDAC3严格需要多亚基复合物形成以获得活性。它与许多非传染性疾病的进展有关。它在疾病中的广泛参与使其成为表观遗传药物靶标。先前存在的HDAC3抑制剂有许多用途，强调需要继续研究发现HDAC3选择性抑制剂。
■这篇综述概述了2010-2023年发布的24项专利，重点是抑制HDAC3同工酶的化合物。
■HDAC3选择性抑制剂-作为单一或联合疗法的药物应用至关重要-作为摆脱充满并发症的泛HDAC抑制剂的策略，正在获得牵引力。此外，对于具有替代锌结合基团(ZBG)的HDAC3抑制剂存在未满足的需求,因为一些先前存在的ZBG具有与毒性和副作用相关的局限性.实现HDAC3选择性的困难可能是由于同种型选择性。然而,计算机辅助药物设计和HDAC33D共结晶模型的实验数据的进步可能导致发现新型HDAC3选择性抑制剂。具有对HDAC3的选择性和效力平衡的替代ZBG。
■这篇综述概述了2010-2023年发布的24项专利，重点是抑制HDAC3同工酶的化合物。
■HDAC3选择性抑制剂-作为单一或联合疗法的药物应用至关重要-作为摆脱充满并发症的泛HDAC抑制剂的策略，正在获得牵引力。此外，对于具有替代锌结合基团(ZBG)的HDAC3抑制剂存在未满足的需求,因为一些先前存在的ZBG具有与毒性和副作用相关的局限性.实现HDAC3选择性的困难可能是由于同种型选择性。然而,计算机辅助药物设计和HDAC33D共结晶模型的实验数据的进步可能导致发现新型HDAC3选择性抑制剂。具有对HDAC3的选择性和效力平衡的替代ZBG。
