Screening of 60,544 Traditional Chinese Medicine (TCM) compounds against the most oncogenic K-Ras(G12D) mutation switch-I/II allosteric pocket: a comprehensive structure-based screening and pharmacokinetics evaluation

被引：0

作者：

Kehinde, Ibrahim Oluwatobi ^{[1
]}

Rotondo, Archimede ^{[2
,3
]}

Pellicane, Giuseppe ^{[2
,3
]}

Ibrahim, Mahmoud A. A. ^{[4
,5
]}

Soliman, Mahmoud E. S. ^{[1
]}

机构：

[1] Univ KwaZulu Natal, Sch Hlth Sci, Mol Biocomputat & Drug Design Lab, Durban, South Africa

[2] Univ Messina, Dipartimento Sci Biomed Odontoiatr & Immagini Morf, Messina, Italy

[3] Univ Kwazulu Natal, Sch Chem & Phys, Pietermaritzburg, South Africa

[4] Minia Univ, Fac Sci, Chem Dept, Computat Chem Lab, Al Minya, Egypt

[5] Univ KwaZulu Natal, Sch Hlth Sci, Durban, South Africa

来源：

MOLECULAR SIMULATION | 2025年

关键词：

Cancer; K-Ras(G12D) mutation; Traditional Chinese Medicine (TCM); binding free energy; molecular dynamics; DRUG DISCOVERY; INHIBITORS; DYNAMICS; CANCER; IDENTIFICATION; MOLECULES; SOFTWARE; INSIGHTS; DOCKING;

D O I：

10.1080/08927022.2025.2481989

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Cancer remains a major global health issue, with particular difficulties in treating cancers associated with mutations. The K-Ras (G12D) mutation, a common oncogenic variant, is linked to aggressive forms of different cancers such as pancreatic ductal adenocarcinoma, non-small cell lung cancer, and colorectal cancer. This study investigates the potential of Traditional Chinese Medicine (TCM) compounds to target K-Ras(G12D) allosteric pockets. We screened a large library of TCM compounds, molecular docking, molecular dynamic (MD) simulations, and thermodynamic binding free energy calculations were performed and the compounds that outperform the reference drug, TH-Z835, were selected for further in-depth analysis. Among these, 10-hydroxycamptothecin, hypecorinine, and dehydroevodiamine showed highly promising activity with a diverse range of binding forces and interactions. This comprehensive screening study, albeit predictive, would offer a foundation for further experimental investigation and the development of new therapeutic approaches that leverage TCM compounds to tackle different cancers.

引用

页数：13