The development of new methods to treat cancer is greatly needed. In this application, we have identified a macrocyclic small molecule that exhibits high differential selectivity for cancer cells vs. normal cells and aim to develop more simplified analogs of this molecule in an effort to maximize efficiency as well as to decrease the overall number of steps, which will likely lead to clinically useful molecules for the treatment of cancer. In addition, we aim to interrogate the activity manifested by these compounds in both cellular and animal models of cancer, with the goal of providing preclinical data to support the use of such compounds for translational development.
Natural products that manifest selective activities against some cancers continue to serve as leads for the development of new anti-cancer agents. However, often times such compounds are difficult to prepare or isolate, which limits their potential clinical application. In this application, macrocyclic natural products that manifest selective anti-cancer activity have been identified and a campaign to simplify their structure to enable the rapid production is proposed alongside cellular and in vivo studies, which is likely to produce compounds with clinical applications for the treatment of cancer.
|Sanchez, Jaquelyn N; Wang, Ton; Cohen, Mark S (2018) BRAF and MEK Inhibitors: Use and Resistance in BRAF-Mutated Cancers. Drugs 78:549-566|
|Subramanian, C; Kovatch, K J; Sim, M W et al. (2017) Novel C-Terminal Heat Shock Protein 90 Inhibitors (KU711 and Ku757) Are Effective in Targeting Head and Neck Squamous Cell Carcinoma Cancer Stem cells. Neoplasia 19:1003-1011|
|Lirov, Roy; Worden, Francis P; Cohen, Mark S (2017) The Treatment of Advanced Thyroid Cancer in the Age of Novel Targeted Therapies. Drugs 77:733-745|