Abstract B109: Drug repurposing for T315I mutation in CML through virtual screening and md simulation

Abstract

Currently, many health incidentals are allocated to diagnosing and treating cancer. Even with the significant advancements in cancer research, there are still many challenges in treating the drug resistance issue. Drug resistance is typically the result of target molecular changes that cause non-response to recommended therapy. Drug resistance to TKIs can be increased by mutations in the kinase domain, impairing the effectiveness of treatment. In the same way, Chronic myeloid Leukemia (CML) is a tumor that obeys this rule. All relevant medicines target BCR-ABL since it has been demonstrated to play a key role in the pathogenesis of CML. Some alterations in the BCR-ABL, such as Y253H, and T315I, reduce the efficiency of treatments in patients. Therefore, more accurate and effective alternative therapies are urgently needed. To address this issue, we screened FDA-approved drugs by virtual screening, MD simulation, binding free energy calculations, ADMET assessment, and Toxicity prediction to identify new inhibitors for this mutant ABL1 protein. Research studies conclude that Tepotinib could inhibit the T315I mutant ABL1. Using this newly identified drug is not just a simple hypothesis in drug discovery. After a simple kinase selectivity assay, this drugs can be evaluated in phase 2 clinical trials. Notably, safety concerns underscore the potential of Tepotinib as a safer and potentially more effective alternative, pending successful phase 2 trial validation.

Citation Format: Nimra Zulfiqar1. Drug repurposing for T315I mutation in CML through virtual screening and md simulation [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B109.