Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China; Medicinal Chemistry Department, Shouyao Holdings (Beijing) Co., Ltd., Beijing, China.
Medicinal Chemistry Department, Shouyao Holdings (Beijing) Co., Ltd., Beijing, China.
Bioorg Med Chem Lett. 2022 Nov 1;75:128973. doi: 10.1016/j.bmcl.2022.128973. Epub 2022 Sep 6.
In the past decade, Wee1 inhibition has received widespread attention as a cancer therapy. Our research aims to discover effective, selective and drug-like Wee1 inhibitors. Herein, a series of compounds with pyrrolo[2,3-d]pyrimidine-based heterocycles were designed, synthesized and confirmed to inhibit Wee1 kinase. The inhibitors afforded good potency in Wee1 Kinase inhibitory activity in enzymatic assays. These compounds showed strong proliferation inhibition against NCI-1299 cell lines and had acceptable pharmacokinetic properties. These derivatives are promising inhibitors that warrant further evaluation, towards the development of potential anticancer drug.
在过去的十年中，Wee1 抑制已作为癌症治疗方法受到广泛关注。我们的研究旨在发现有效、选择性和类药性的 Wee1 抑制剂。在此，我们设计、合成了一系列基于吡咯并[2,3-d]嘧啶杂环的化合物，并证实其可以抑制 Wee1 激酶。这些抑制剂在酶促测定中表现出对 Wee1 激酶的良好抑制活性。这些化合物对 NCI-1299 细胞系表现出强烈的增殖抑制作用，且具有可接受的药代动力学特性。这些衍生物是有前途的抑制剂，值得进一步评估，以开发潜在的抗癌药物。
