دورية أكاديمية
Identification of potential inhibitors, conformational dynamics, and mechanistic insights into mutant Kirsten rat sarcoma virus (G13D) driven cancers.
| العنوان: | Identification of potential inhibitors, conformational dynamics, and mechanistic insights into mutant Kirsten rat sarcoma virus (G13D) driven cancers. |
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| المؤلفون: | Tayubi IA; Department of Computer Science, Faculty of Computing and Information Technology, King Abdulaziz University, Rabigh, Saudi Arabia., Kumar S U; Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India., Doss C GP; Laboratory of Integrative Genomics, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India. |
| المصدر: | Journal of cellular biochemistry [J Cell Biochem] 2022 Sep; Vol. 123 (9), pp. 1467-1480. Date of Electronic Publication: 2022 Jul 17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8205768 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4644 (Electronic) Linking ISSN: 07302312 NLM ISO Abbreviation: J Cell Biochem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2004>- : Hoboken, NJ : Wiley-Liss Original Publication: New York : Liss, c1982- |
| مواضيع طبية MeSH: | Neoplasms* , Tramadol*, Humans ; Kirsten murine sarcoma virus ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Paroxetine ; Prospective Studies ; Proto-Oncogene Proteins p21(ras) |
| مستخلص: | The mutations at the hotspot region of K-Ras result in the progression of cancer types. Our study aimed to explore the small molecule inhibitors against the G13D mutant K-Ras model with anti-cancerous activity from food and drug administration (FDA)-approved drug compounds. We implemented several computational strategies such as pharmacophore-based virtual screening, molecular docking, absorption, distribution, metabolism and excretion features, and molecular simulation to ensure the identified hit compounds have potential efficacy against G13D K-Ras. We found that the FDA-approved compounds, namely, azelastine, dihydrocodeine, paroxetine, and tramadol, are potential candidates to inhibit the action of G13D mutant K-Ras. All four compounds exhibited similar binding patterns of sotorasib, and a structural binding mechanism with significant hydrophobic contacts. The descriptor features from the QikProp of all four compounds are within allowable limits compared to sotorasib drug. Consequently, a molecular simulation result emphasized that the dihydrocodeine and tramadol exhibited less fluctuation, minimal basin, significant h-bonds, and potent inhibition against G13D K-Ras. As a result, the current research identifies prospective K-Ras inhibitors that could be further improved with biochemical analysis for precision medicine against K-Ras-driven cancers. (© 2022 Wiley Periodicals LLC.) |
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| معلومات مُعتمدة: | IFPIP: 573-830-1442 King Abdulaziz University |
| فهرسة مساهمة: | Keywords: G13D; K-Ras; anticancer; cancer; inhibitors; metastasis; pharmacophore model |
| المشرفين على المادة: | 39J1LGJ30J (Tramadol) 41VRH5220H (Paroxetine) EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) |
| تواريخ الأحداث: | Date Created: 20220717 Date Completed: 20220919 Latest Revision: 20221021 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1002/jcb.30305 |
| PMID: | 35842839 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1097-4644 |
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| DOI: | 10.1002/jcb.30305 |