2. Academic Validation
  3. Discovery of pyrrolo[2,3-d]pyrimidine-based molecules as a Wee1 inhibitor template

Discovery of pyrrolo[2,3-d]pyrimidine-based molecules as a Wee1 inhibitor template

  • Bioorg Med Chem Lett. 2022 Nov 1:75:128973. doi: 10.1016/j.bmcl.2022.128973.
Changjun Chen 1,  Yeliu Wang 2,  Min-Qi Hu 2,  Hongjuan Li 3,  Xi Chen 2,  Gan Qiang 4,  Yinghui Sun 3,  Yan Zhu 5,  Binghui Li 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China; Medicinal Chemistry Department, Shouyao Holdings (Beijing) Co., Ltd., Beijing, China.
  • 2 Medicinal Chemistry Department, Shouyao Holdings (Beijing) Co., Ltd., Beijing, China.
  • 3 Discovery Biology Department, Shouyao Holdings (Beijing) Co., Ltd., Beijing, China.
  • 4 School of Mechatronical Engineering, Beijing Institute of Technology, Beijing,China.
  • 5 Medicinal Chemistry Department, Shouyao Holdings (Beijing) Co., Ltd., Beijing, China. Electronic address: yzhu@centaurusbio.com.
  • 6 Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
PMID: 36075370 DOI: 10.1016/j.bmcl.2022.128973
Abstract

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.

Keywords

3-d]pyrimidine; G1/S checkpoint; G2/M checkpoint; Pyrrolo[2; Synthetic lethality; Wee1.

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