Medicine and Health Sciences Commons^™

Precise Method To Identify Kinase Drug Targets In Complex Diseases: The First Step Towards Sustainable And Effective Treatment, Hasbanny Irisson, Marzieh Ayati

Research Symposium

Background: Kinases are enzymes that have proven to be important drug targets due to their role in critical biological mechanisms such as phosphorylation. Phosphorylation happens when a kinase catalyzes the transfer of a phosphate group to a protein in a phosphorylated site, which then becomes known as the substrate of the kinase. Any dysregulation of protein phosphorylation causes a wide range of complex diseases including cancer. Thus, discovering the links between kinases and their substrates (i.e. predicting kinase-substrate associations (KSAs)) is crucial in developing effective and sustainable treatments. Presently, less than 5% of phosphorylated sites have an associated kinase, and …

Identification And Characterization Of Anticancer Potential Of A Novel Small Molecule, Mortaparibmild, Hazna Noor Meidinna, Anissa Nofita Sari, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background: The development of new anticancer drugs and treatment modalities form a priority research field. The tumor suppressor protein p53 is frequently mutated or functionally inactivated in a large variety of cancers. Its inactivation by mortalin, a member of the heat shock 70 protein family, has been shown to contribute to carcinogenesis. The small molecule inhibitors of mortalin-p53 interactions have been shown to reactivate p53 yielding apoptosis/growth arrest in cancer cells. Therefore, abrogators of mortalin-p53 interaction have emerged as possible new therapeutic anticancer reagents.

Methods: We performed chemical library screening based on the imaging of mortalin-p53 interaction, leading to the …

Mortaparibplus- A Novel Anticancer Small Molecule Abrogating Mortalin-P53 Interaction In Cancer Cells, Anissa N. Sari, Ahmed Elwakeel, Jaspreet K. Dhanjal, Vipul Kumar, Durai Sundar, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug.

Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named Mortaparib^Plus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited …