Banca de DEFESA: ROBERT MAIORY ALARCON FLORES

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : ROBERT MAIORY ALARCON FLORES
DATA : 02/12/2021
HORA: 14:00
LOCAL: https://meet.google.com/vuc-nogy-dre
TÍTULO:

Structural analysis and identification of new inhibitor candidates against FAM3C (ILEI), a potential therapeutic target for cancer treatment

PÁGINAS: 70
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Físico-Química
ESPECIALIDADE: Química Teórica
RESUMO:

Based on the knowledge about the existence of the FAM3 family, studies aimed at analyzing the four proteins (FAM3A, FAM3B, FAM3C and FAM3D) have grown considerably in recent decades. The first studies showed that these four proteins are quite distinct from any known protein, having relevant similarity only within the family itself, which aroused the need for analysis on the structure and function of the FAM3 family in the human body. The need for studies on this family of proteins has increased over time, as some of its members are involved in important processes in the body, especially FAM3B and FAM3C. FAM3B became known as pancreatic-derived factor (PANDER), and is currently studied as an effector of type 2 diabetes mellitus. FAM3C is also known to induce epithelial-mesenchymal transition (EMT), and is similar to the interleukin ILEI (interleukin-like EMT inducer). However, despite the growing studies on the role of FAM3B and FAM3C, which reveal expression in many tissues and an association with several diseases, little is known about their action and possible inhibitors. So far, only one computational study focusing on the search for possible inhibitors is presented in the literature, but only for one member of the FAM3 family (FAM3B). Therefore, this work seeks to carry out a computational study to find new possible inhibitors for the FAM3C protein, as it can be a therapeutic target for the metastasis process. In this study, a structural analysis of the target of interest (FAM3C) in its active form (monomer or dimer) was performed, as well as possible binding sites were investigated. After structural analyzes on the target, identification of possible FAM3C ligands was also performed and these candidate FAM3C ligands were submitted to pharmacokinetic property analyses. In addition, docking and molecular dynamics simulations for the selected compounds were also performed. Thus, it was possible to determine from the structural analysis the importance of dimerization for the stability of FAM3C and the most likely binding site. In addition, four substances were identified as potential inhibitors from the results of molecular docking, visual inspection of the main interactions, analysis of pharmacokinetic properties and molecular dynamics simulations. Therefore, from the results obtained in this study, it was possible to better understand the behavior of the target under study, as well as the main interactions between the substances selected as potential inhibitors and FAM3C.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 149.405.258-05 - KATHIA MARIA HONORIO - USP
Membro Titular - Examinador(a) Interno ao Programa - 1544394 - PAULA HOMEM DE MELLO
Membro Titular - Examinador(a) Externo à Instituição - KAREN CACILDA WEBER - UFPB
Membro Suplente - Examinador(a) Interno ao Programa - 1544403 - MAURICIO DOMINGUES COUTINHO NETO
Membro Suplente - Examinador(a) Externo à Instituição - GUSTAVO HENRIQUE GOULART TROSSINI - USP