1. Molecular modeling studies of [4-(3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine-based CDK4 inhibitors
- Author
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Yongli Du, Jingkang Shen, Xiehuang Sheng, Han Lv, and Zhipei Gao
- Subjects
Pharmacology ,endocrine system diseases ,integumentary system ,010304 chemical physics ,Molecular model ,Chemistry ,Field analysis ,01 natural sciences ,Combinatorial chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Molecular dynamics ,0302 clinical medicine ,CDK4 Inhibitor ,030220 oncology & carcinogenesis ,0103 physical sciences ,Drug Discovery ,Molecular Medicine ,Amine gas treating ,biological phenomena, cell phenomena, and immunity ,neoplasms ,Abemaciclib - Abstract
Aim: CDK4 is a promising target for breast cancer therapy. This study aimed to explore the structure–activity relationship of CDK4 inhibitor abemaciclib analogs and design potent CDK4 inhibitors for breast cancer treatment. Methods & results: A faithful 3D quantitative structure–activity relationship model was established by molecular docking, comparative molecular field analysis and comparative molecular similarity index analysis based on 56 abemaciclib analogs. Molecular dynamics simulation studies revealed the key residues of the interaction between CDK4 and inhibitors. Four novel inhibitors with satisfactory predicted binding affinity to CDK4 were designed. Conclusion: The 3D quantitative structure–activity relationship and molecular dynamics simulation studies provide valuable insight into the development of novel CDK4 inhibitors.
- Published
- 2021