Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2023
2289 The University of Texas at San Antonio (144177)
Principal Investigator: Frantz, Douglas
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 1,049,128
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 3/1/23 - 2/28/26
Restricted Research: YES
Academic Discipline: SCIENCES
Department, Center, School, or Institute: Cos Chemistry
Title of Contract, Award, or Gift: Rational design, synthesis and biological evaluation of simplified taccalonolide analogs for the treatment of cancer
Name of Granting or Contracting Agency/Entity:
Cancer Prevention and Research Institute of Texas
CFDA: 0
Program Title: none
Note:
SAMs 1.1.1; This research project will implement novel chemistry that allows construction of the entire carbon skeleton of the taccas from readily available steroid precursors with exquisite control of relative and absolute stereochemistry. We will incorporate parallel strategies to evaluate potency in tandem with early preclinical pharmacological evaluation (eADME and eDMPK) to prioritize novel taccalogs that will undergo a battery of biological assays to evaluate in vitro and in vivo antitumor efficacy correlated to microtubule stabilization. Additionally, we will take advantage of our previous SAR studies and advanced molecular modeling tools to rationally design taccalog small molecule probes for mechanistic studies in various models of ovarian cancer. This study is highly innovative as it will synergize a multidisciplinary approach to purposefully design highly potent and effective covalent-modifying MSAs inspired by a natural product scaffold that have a markedly distinct and clinically relevant mechanism from all other drugs of this class. This project is also significant in that the culmination of these collaborative studies at the interface of synthetic chemistry and cancer biology will provide preclinical lead candidates suitable for advanced translational investigations to provide better alternative treatments for taxane-resistant women's cancer.
Discussion: No discussion notes