Identification of small molecule inhibitors against UBE2C by using docking studies
Kesavan Sabitha1, Thangarajan Rajkumar
1Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai-600 020.
Abstract:
An increased expression of UBE2C (Ubiquitin-conjugating enzyme E2C) has been associated with high tumor grade and cancer progression. It is an essential indicator of the mitotic destruction events. Our microarray study on cervical cancers showed UBE2C to be over expressed in cervical cancer. Subsequent studies from our laboratory, showed that inhibition of UBE2C can enhance radiation and chemosensitivity. Therefore it can be an appropriate target for drug development to identify potential and specific inhibitor of cancer. To identify small molecule inhibitors, a computational approach was used to model UBE2C and further docking studies were carried out. Different ligand subsets such as ChemBank, PDB, KEGG, Drug-likeness NCI, Not annotated NCI of ligand library ligands were downloaded and docked with UBE2C. Schrodinger tools were used for identifying active sites and docking studies of ligands with UBE2C. Based on glide score, the potential ligands were screened and its interaction with UBE2C was identified. We also analyzed the drug like properties such as absorption, distribution, metabolism, excretion and toxicity (ADME/T) of docked compounds. Our results suggest that 2,4-diimino-1-methyl-1,3,5-triazepan-6-one, sulfuric acid compound with 5,6-diamino-2,4-pyrimidinediol (1:1) and 7-alpha-d-ribofuranosyl-2-aminopurine-5'-phosphate may act as best inhibitors and further in vitro studies, may lead to development of novel and best inhibitor of UBE2C.
Insights
Researchers identified potential small molecule inhibitors for UBE2C (Ubiquitin-conjugating enzyme E2C), a protein linked to cancer progression. These compounds show promise for developing new cancer drugs that enhance radiation and chemotherapy effectiveness.
Area of Science:
- Oncology
- Biochemistry
- Computational Chemistry
Background:
- Increased UBE2C (Ubiquitin-conjugating enzyme E2C) expression correlates with higher tumor grade and cancer progression.
- UBE2C is a key indicator of mitotic destruction events and is overexpressed in cervical cancer.
- Inhibiting UBE2C enhances sensitivity to radiation and chemotherapy, suggesting its potential as a drug development target.
Purpose of the Study:
- To identify potential small molecule inhibitors of UBE2C.
- To explore UBE2C as a target for novel cancer drug development.
- To computationally screen for compounds that can effectively inhibit UBE2C.
Main Methods:
- Computational modeling and docking studies were performed on UBE2C.
- Ligand libraries (ChemBank, PDB, KEGG, NCI) were docked with UBE2C using Schrodinger tools.
- Potential inhibitors were screened based on glide score, and their drug-like properties (ADME/T) were analyzed.
Main Results:
- Several compounds, including 2,4-diimino-1-methyl-1,3,5-triazepan-6-one, sulfuric acid compound with 5,6-diamino-2,4-pyrimidinediol (1:1), and 7-alpha-d-ribofuranosyl-2-aminopurine-5'-phosphate, were identified as potential UBE2C inhibitors.
- Interactions between the identified ligands and UBE2C were characterized.
- Drug-like properties of the docked compounds were assessed.
Conclusions:
- The identified compounds show promise as potential inhibitors of UBE2C.
- Further in vitro studies are warranted to validate these findings.
- These inhibitors could lead to the development of novel therapeutic strategies for cancer treatment.
