1st International and 10th National Iranian Conference on Bioinformatics

Home Accepted Papers

Structure-based virtual screening of FDA-approved compounds to find potential inhibitors for human monocarboxylate transporter 1 in an open-inward conformation

Paper ID : 1280-ICB10

Authors:

Fateme Jabari, Hamid Mahdiuni *, Soraya Sajadimajd

Department of Biology, School of Sciences, Razi University, Kermanshah, Iran

Abstract:

Owing to the high rate of glycolysis, increased access to glucose is necessary for cancer cells to survive and proliferation. To adapt to the changes in the tumor microenvironment, two groups of cells develop: glycolytic and oxidative cancer cells [1]. Altered metabolism and increased glucose consumption in the glycolytic cells lead to increased intracellular lactate levels, which have to be removed from those cells and absorbed by the oxidative ones. Lactate is transported by a number of monocarboxylate transporters (MCT), which has been identified as a family of 14 members, ranging from MCT1 to MCT14 [2]. The monocarboxylate transporter 1 (MCT1) catalyzes the movement of monocarboxylates such as lactate and pyruvate across the plasma membrane of mammalian cells. The overexpression of MCT1 has been reported in several cancers including lung, colon, brain, skin and lymphoma cancers. Therefore, inhibition of MCT1 holds great promise for cancer treatment [3]. In the present study, we screened the FDA-approved compounds of the Zinc Database using structure-based virtual screening methods to find effective compounds for inhibition of the MCT1 transporter in an open-inward conformation. To this end, the resolved structure of MCT1 was downloaded from RCSB (PDB ID: 7CKO). To prepare the chemical library, FAF-drugs4 was applied on FDA-approved subset of ZINC to remove compounds having more than 10 rotatable bonds and PAINS. Next, the clean library was energy minimized using Mmff94 force field. In follow, we docked the resultant library against MCT1 using a funnel-like pattern by Autodock Vina, Molegro Virtual Docker, and DOCK6. The compounds obtained from this step were studied for further investigation.

Keywords:

Monocarboxylate Transporter1, Virtual screening, inhibitors, Cancer

Status : Paper Accepted (Poster Presentation)