Department of Medicine (Division of Cardiology), Wilf Family Cardiovascular Research Institute, Einstein Institute for Aging Research, Albert Einstein College of Medicine, Montefiore University Hospital, New York City, USA.
Department of Molecular Pharmacology, Fleischer Institute for Diabetes and Metabolism, Einstein-Sinai Diabetes Research Center (ES-DRC), Albert Einstein College of Medicine, New York City, USA.
Expert Opin Drug Discov. 2021 Jun;16(6):709-718. doi: 10.1080/17460441.2021.1858792. Epub 2021 Jan 6.
: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular calcium (Ca) release channels located on the endoplasmic/sarcoplasmic reticulum. The availability of the structure of the ligand-binding domain of IP3Rs has enabled the design of compatible ligands, but the limiting step remains their actual effectiveness in a biological context.: This article summarizes the compelling literature on both agonists and antagonists targeting IP3Rs, emphasizing their strengths and limitations. The main challenges toward the discovery and development of IP3 receptor modulators are also described.: Despite significant progress in recent years, the pharmacology of IP3R still has major drawbacks, especially concerning the availability of specific antag onists. Moreover, drugs specifically targeting the three different subtypes of IP3R are especially needed.
三磷酸肌醇受体（IP3Rs）是位于内质网/肌浆网的细胞内钙（Ca2+）释放通道。IP3Rs 配体结合域结构的可用性使设计兼容的配体成为可能，但在生物学背景下，其实际效果仍然是一个限制步骤。本文总结了针对 IP3Rs 的激动剂和拮抗剂的相关文献，强调了它们的优势和局限性。同时还描述了发现和开发 IP3 受体调节剂所面临的主要挑战。尽管近年来取得了重大进展，但 IP3R 的药理学仍然存在重大缺陷，特别是在特异性拮抗剂的可用性方面。此外，特别需要针对三种不同亚型的 IP3R 的药物。
