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Computational study of novel natural inhibitors targeting Kirsten rat sarcoma viral oncogene homolog G12C.
Yang, Wenzhuo; Ge, Junliang; Yuan, Meng; Li, Jialin; Pan, Lin; Ren, Junan; Dou, Gaojing; Yang, Laiyu; Zhou, Yang; Xie, Haoqun; Wang, Xinhui; Hu, Hongrong.
Afiliación
  • Yang W; Neurosurgery and Neuro-Oncology Department, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou.
  • Ge J; Department of Neurology, First Hospital of Jilin University.
  • Yuan M; Department of Oncology, The Second Hospital of Jilin University.
  • Li J; Department of Oncology, The Second Hospital of Jilin University.
  • Pan L; Department of Neurology, First Hospital of Jilin University.
  • Ren J; Department of Oncology, The Second Hospital of Jilin University.
  • Dou G; Department of Breast Surgery, the First Hospital of Jilin University, Changchun.
  • Yang L; Department of Oncology, The Second Hospital of Jilin University.
  • Zhou Y; Department of Oncology, The Second Hospital of Jilin University.
  • Xie H; Department of Oncology, The Second Hospital of Jilin University.
  • Wang X; Department of Oncology, Xinxiang Medical College, Xinxiang, China.
  • Hu H; Neurosurgery and Neuro-Oncology Department, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou.
Anticancer Drugs ; 34(5): 609-619, 2023 06 01.
Article en En | MEDLINE | ID: mdl-36847041
Lung adenocarcinoma is one of the most aggressive and rapidly fatal types of malignant lung tumor. Molecular docking and virtual screening were effectively and systematically used to identify specific targets in malignant tumors and screen potential drugs. Here, we screen perfect leading compounds from a medicate library (ZINC15 database) and analyze their properties (conveyance, absorption, metabolism, excretion, and harmless forecasts) with potential inhibition of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C. Further results demonstrated that ZINC000013817014 and ZINC000004098458 were screened out from the ZINC15 database and were identified to have a much better binding affinity and more favorable interaction vitality binding with KRAS G12C and less rat carcinogenicity, Ames mutagenicity, way better dissolvability in water and noninhibition with cytochrome P-450 2D6. Molecular dynamics simulation analysis indicated that the binding capacity of these two compounds and KRAS G12C, ZINC000013817014-KRAS G12C, and ZINC000004098458-KRAS G12C is stable in the natural environment. Our findings reveal that ZINC000013817014 and ZINC000004098458 were perfect leading compounds to be inhibitors binding with KRAS G12C, which were selected as safe drug candidates and a cornerstone for KRAS G12C-related medicine plan and improvement. What is more, we have conducted a Cell Counting Kit-8 to verify the exactly inhibitory effects of the two selected drugs on Lung adenocarcinoma. This study establishes a solid framework for systematic anticancer medication research and development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenocarcinoma del Pulmón / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Anticancer Drugs Asunto de la revista: ANTINEOPLASICOS Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenocarcinoma del Pulmón / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Anticancer Drugs Asunto de la revista: ANTINEOPLASICOS Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido