In silico studies on the interaction between bioactive ligands and ALK5, a biological target related to the cancer treatment

Abstract

Studies have showed that there are many biological targets related to the cancer treatment, for example, TGF type I receptor (TGF-βRI or ALK5). The ALK5 inhibition is a strategy to treat some types of cancer, such as breast, lung, and pancreas. Here, we performed CoMFA and CoMSIA studies for 70 ligands with ALK5 inhibition. The internal validation for both models (q²_LOO = 0.887 and 0.822, respectively) showed their robustness, while the external validations showed their predictive power (CoMFA: r²_test = 0.998; CoMSIA: r²_test = 0.975). After all validations, CoMFA and CoMSIA maps indicated physicochemical evidences on the main factors involved in the interaction between bioactive ligands and ALK5. Therefore, these results suggest molecular modifications to design new ALK5 inhibitors.

Keywords:

• ALK5 inhibitors
• Anticancer agents
• CoMFA
• CoMSIA
• molecular docking
• drug design

Additional information

Funding

This work was supported by the State of São Paulo Research Foundation (FAPESP); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; The National Council for Scientific and Technological Development (CNPq); L’Oreal, Brazilian Science Academy (ABC); UNESCO and Federal University of ABC (UFABC).