title: 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 (q(2)LOO = 0.887 and 0.822, respectively) showed their robustness, while the external validations showed their predictive power (CoMFA: r(2)test = 0.998; CoMSIA: r(2)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.
authors.affiliation: a Centro de Ciências Naturais e Humanas , Universidade Federal do ABC (UFABC) , Santo André , SP , Brazil.
authors.forename: Michell O
authors.initials: MO
authors.lastname: Almeida
authors.affiliation: b Departamento de Farmácia, Faculdade de Ciências Farmacêuticas , Universidade de São Paulo (USP) , São Paulo , SP , Brazil.
authors.forename: Gustavo H G
authors.initials: GH
authors.lastname: Trossini
authors.affiliation: a Centro de Ciências Naturais e Humanas , Universidade Federal do ABC (UFABC) , Santo André , SP , Brazil.|b Departamento de Farmácia, Faculdade de Ciências Farmacêuticas , Universidade de São Paulo (USP) , São Paulo , SP , Brazil.
authors.forename: Vinícius G
authors.initials: VG
authors.lastname: Maltarollo
authors.affiliation: c Instituto de Química de São Carlos , Universidade de São Paulo (USP) , São Paulo , SP , Brazil.
authors.forename: Danielle da C
authors.initials: Dda C
authors.lastname: Silva
authors.affiliation: a Centro de Ciências Naturais e Humanas , Universidade Federal do ABC (UFABC) , Santo André , SP , Brazil.|d Escola de Artes, Ciências e Humanidades , Universidade de São Paulo (USP) , São Paulo , SP , Brazil.
authors.forename: Kathia M
authors.initials: KM
authors.lastname: Honorio
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human
keywords: ALK5 inhibitors; Anticancer agents; CoMFA; CoMSIA; drug design; molecular docking