Scientists could potentially uncover compounds that block CD36, which could cut fat cravings and combat obesity, says biochemist Nada Abumrad at Washington University School of Medicine in St .Louis, Missouri.
Structure activity relationship studies of the novel set of diarylisoxazoles allowed to identify new key determinants for COX-1 selectivity, and to uncover compounds appropriate for a deep pharmacokinetic and pharmacodynamic investigation.
Additionally, recent studies have uncovered compounds that inhibit OGT.
It is clear that transcription of the TTP gene ZFP36 is regulated differently from that of the other two family members, and it might be possible to uncover compounds that stimulate its biosynthesis, specifically in macrophages, that would not affect either TNF-α biosynthesis or that of the other two family members.
Dr. Duke has devoted his career to uncovering the compounds in raw ingredients that give them healing powers -- antioxidants in rosemary, thyme and marjoram; stimulants in cardamom -- and to trying to persuade the rest of us that if we ate like our ancestors, there would be far fewer diet-related illnesses.
Therefore, we adopted an orthogonal biological phenotypic screening approach to uncover candidate compounds: based on a potent cytotoxicity toward HCC-derived cell lines, and minimal toxicity toward normal liver cells.
We're optimistic that this rational approach to repellent design will uncover new compounds that are safer and more effective than those that are currently available".
Comparison of putative candidates for novel drugs indicated that drugs derived from fragment-based screens could uncover novel compounds with more drug-like properties than those derived from more conventional drug discovery techniques.
In this context, cell-based approaches involving engineered reporter genes (luciferase or EGFP) that contain artificial intronic sequences or are conjugated to FXN have been developed for four different HTS approaches aiming to uncover novel compounds capable of frataxin upregulation (Table 2).
He convincingly uncovers the compound of personal loyalty, ideological conviction and selfish calculation that motivated those at the apex of power.
