Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry , Weinberg 3, D-06120 Halle (Saale) , Germany.
Department of Chemistry and Polymer Science, University of Stellenbosch , Matieland , Stellenbosch , South Africa.
Expert Opin Ther Pat. 2019 Sep;29(9):689-702. doi: 10.1080/13543776.2019.1655542. Epub 2019 Aug 14.
: Protein tyrosine phosphatase 1B (PTP1B) inhibition has been recommended as a crucial strategy to enhance insulin sensitivity in various cells and this fact is supported by human genetic data. PTP1B inhibitors improve the sensitivity of the insulin receptor and have the ability to cure insulin resistance-related diseases. In the latter years, targeting PTP1B inhibitors is being considered an attractive target to treat T2DM and therefore libraries of PTP1B inhibitors are being suggested as potent antidiabetic drugs. : This review provides an overview of published patents from January 2015 to December 2018. The review describes the effectiveness of potent PTP1B inhibitors as pharmaceutical agents to treat type 2 diabetes. : Enormous developments have been made in PTP1B drug discovery which describes progress in natural products, synthetic heterocyclic scaffolds or heterocyclic hybrid compounds. Various protocols are being followed to boost the pharmacological effects of PTP1B inhibitors. Moreover these new advancements suggest that it is possible to get small-molecule PTP1B inhibitors with the required potency and selectivity. Furthermore, future endevours via an integrated strategy of using medicinal chemistry and structural biology will hopefully result in potent and selective PTP1B inhibitors as well as safer and more effective orally available drugs.
蛋白酪氨酸磷酸酶 1B（PTP1B）抑制剂已被推荐作为提高各种细胞胰岛素敏感性的关键策略，这一事实得到了人类遗传数据的支持。PTP1B 抑制剂可提高胰岛素受体的敏感性，并具有治疗与胰岛素抵抗相关疾病的能力。近年来，靶向 PTP1B 抑制剂被认为是治疗 T2DM 的一个有吸引力的靶点，因此，PTP1B 抑制剂库被认为是有效的抗糖尿病药物。
本文综述了 2015 年 1 月至 2018 年 12 月期间发表的专利。综述描述了有效的 PTP1B 抑制剂作为治疗 2 型糖尿病的药物的有效性。
在 PTP1B 药物发现方面取得了巨大的进展，描述了天然产物、合成杂环骨架或杂环杂合化合物方面的进展。目前正在采用各种方案来提高 PTP1B 抑制剂的药理作用。此外，这些新进展表明，有可能获得具有所需效力和选择性的小分子 PTP1B 抑制剂。此外，通过将药物化学和结构生物学的综合策略进行整合，有望开发出有效的、选择性的 PTP1B 抑制剂以及更安全、更有效的口服药物。
