Research Project Awardees - 2011 Summary
| Title | Research | Synopsis |
| Mair Churchill UC-Denver |
Pharmacological inhibition of histone chaperone activity | Recently published studies have validated the histone chaperone Asf1b as a prognostic marker in breast cancer that is highly predictive for the occurrence of metastasis. Knockdown of Asf1b results in a clear decrease of proliferative pathway markers and reduced ability of breast cancer cells to grow. In collaboration with C2D2, our goal is to develop and test new chemical entities as epigenetic tools to decrease histone acetylation levels, decrease cellular proliferation, and thus serve as lead compounds for development of new cancer chemotherapies to improve human health. |
| Steve Nordeen UC-Denver |
Non-steroidal inhibitors of progesterone receptors | Progesterone is a female sex steroid that binds to the progesterone receptor (PR) to elicit a variety of physiological and pathological actions. Inhibition of PR is an attractive therapeutic target. From initial screening studies we have identified derivatives of theophylline as non-steroidal inhibitors of steroid receptors that do not bind to the hormone binding pocket of the receptor and demonstrate specificity over related receptors. In collaboration with C2D2, we will explore compounds for anti-progestin activity, specificity, and mechanism of action. |
| Amy Brooks-Kayal and Michael Wempe UC-Denver |
Optimizing JAK/STAT inhibitors for primary prevention of epilepsy | 50 million people have epilepsy, and one-third are unresponsive to current medical therapy. Although brain injury leads to epilepsy in a substantial number of individuals, there is currently no therapy that reduces this risk, nor prevents the relentless progression of epilepsy once it begins. Our laboratories have identified changes in expression of subunits of the GABAA receptor that are associated with later development of epilepsy. In the current proposal we plan to optimize a lead compound as a novel anti-epileptic agent. The proposed studies should lead to new methods of treating and preventing epilepsy by identifying and then reversing the changes in brain cells that lead to this condition. |
| Dennis Voelker National Jewish Health |
Novel lipid antagonists of respiratory syncytial virus (RSV) | Respiratory Syncytial Virus (RSV) is a major pediatric pathogen infecting 98% of all children before the age of two and is the major cause of pediatric hospitalizations in the first year of life in the USA. RSV is also a serious pathogen in adults with chronic lung diseases, especially individuals with asthma, Chronic Obstructive Pulmonary Disease (COPD), and Interstitial Lung Disease (ILD). Currently, there is no effective therapy after infection. We recently discovered that the minor pulmonary surfactant phospholipid, palmitoyl-oleoyl-phosphatidylglycerol (POPG), exerts potent anti-RSV effects in vitro and in vivo, in mice. The focus of this proposal is to further evaluate compounds that are structurally related to POPG in which preliminary data indicates these compounds interfere with viral infection in vitro. The studies are likely to lead to a new and highly effective treatment for short-term prophylaxis against RSV, and treatment of individuals already infected with the virus. |
| Scott Pegan and Kateri Ahrendt Denver University and Regis University |
Lead Optimization of Small Molecules for Novel TB Therapeutics through inhibition of MtFBA | Tuberculosis (TB) is one of the most prevalent infections in the world and a leader among the causes of mortality in developing countries. With a rise in new cases of active TB and the emergence of the multi-drug resistant strains, there is a strong need for development of new antibiotics. An interesting drug target for TB is M. tuberculosis' class II fructose 1,6-bisphosphate aldolase (MtFBA), which is essential for bacterial survival. MtFBA differs from FBAs present in humans and other higher organisms. The intent in this proposal is to produce lead compounds that possess robust drug-like and inhibitory properties against MtFBA and M. tuberculosis. |
| Tomislav Rovis Colorado State University |
Novel Hybrid SNRI's | Antipsychotics represented one of the highest grossing class of medications sold in the United States in 2010. Despite this widespread success, there remains considerable interest in identifying new and safer serotonin and norepinephrine reuptake inhibitors (SNRI's). A key to this proposal is the utilization of novel chemistry methods that allow unprecedented access new compounds that have the potential to be novel SNRI's with improved pharmacological properties. |
Past Research Project Awardees
Research Project Awardees - 2010 Summary