A Novel Compound for Targeted Treatment of CBF Leukemia

一种靶向治疗 CBF 白血病的新型化合物

• 批准号: 9205569
• 负责人: Anton Simeonov
• 金额: $ 200.38万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9205569
• 关键词: Novel; Compound; Targeted; Treatment; CBF

Leukemia is a bone marrow cancer involving developing white blood cells and often is associated with specific, recurrent chromosome translocations and inversions that generate fusion genes, which play critical roles in leukemogenesis. In this project, targeted treatments are being developed for a subgroup of leukemia based on current understanding of how leukemia develops at the molecular level. The core binding factor (CBF) subgroup of leukemia contains CBF fusion genes that have been shown to play critical roles in leukemia development. Current treatments for CBF leukemia are not optimal, with long-term survival at 50 percent. The research team conducted a small chemical library screen to find inhibitors that block CBF protein interactions. Through biochemical, cell culture and animal model studies, they identified three chemically related lead compounds. In particular, one of the three compounds has shown leukemia reduction capability similar to standard chemotherapy drugs in preliminary studies in a mouse CBF leukemia model. The researchers will complete efficacy studies in this mouse model, develop one or more backup compounds, optimize formulation, and perform pharmacokinetics and toxicology tests that will lead to clinical trials. TRND researchers have successfully optimized and demonstrated the utility of the animal disease model. TRND scientists are performing medicinal chemistry optimization to identify a compound suitable for formal preclinical development. Once such a compound is identified, TRND will conduct the necessary studies to support filing an Investigational New Drug (IND) Application with the U.S. Food and drug Administration.

白血病是一种涉及白细胞发育的骨髓癌，通常与特异性的、复发性的染色体易位和反转有关，这些易位和反转产生融合基因，在白血病发生中起关键作用。