Targeting Aurora B Kinase Enzyme in Acute Myeloid Leukemia: Design and Development of Novel Heterocyclic Therapeutics

Summary

Acute Myeloid Leukemia (AML) is a complex and fast-growing blood cancer caused by abnormal growth and impaired development of early blood-forming cells in the bone marrow. With a global incidence of approximately 145,000 cases and a poor prognosis, AML presents a significant clinical and economic burden. In Egypt, leukemia accounts for 10% of all malignancies, with AML comprising 16.9% of these cases. Current treatment options are costly and often ineffective in relapsed or refractory cases, underscoring the urgent need for novel, targeted therapies.

Aurora B kinase (AURKB), an essential enzyme for mitosis, is overexpressed in AML and contributes to leukemic cell survival and proliferation. Inhibiting AURKB has shown promising therapeutic potential, as evidenced by clinical candidates like Barasertib. Building on our previously reported compound TC11, which demonstrated strong AURKB inhibition (90% at 100 nM), we have already designed and synthesized a series of amide-indolinone-based heterocyclic derivatives for targeting Aurora B kinase. This project aims to build on that foundation by continuing the synthesis of additional analogs and conducting comprehensive biological evaluations. These efforts will support the development of more effective and targeted therapeutic candidates for AML. The proposed compounds are expected to offer a cost-effective, potent, and mechanistically targeted approach to AML therapy, contributing to both national health priorities and global drug discovery efforts.

Achievements

List of Publications from the Project

Partners

Project Members

• Nada Alaa El-din
• Eman Mahmoud Elawady Dokla
• Samaa Wael Abbas Helmy

Project Leaders