In general, molecular glues that influence the activity or fate of their assembled proteins complex, either enhance the gain-of-function effect via protein−protein interaction or induce the target protein degradation by bringing the cellular protein degradation machinery to act on the targeted ...
Structural and kinetic analyses have shown that Arl2/3 act allosterically to increase the dissociation rate constants for cargo- carrier complexes13,15,29,30. In contrast, it was shown recently by pull-down experiments with cellular extracts that Arl3 but not Arl2 can efficiently release INPP5E...
43 Depending on the expression levels of such lipid-binding proteins, they may effectively act as sinks for PDE6Di. It is plausible to assume that raising compounds with a higher affinity to a highly hydrophobic pocket will render them likewise more hydrophobic. It is possible that this trend ...
Ninety-six hours after transduction with shRNAs, cells were harvested and fixed with 70% cold ethanol overnight at −20 °C. The cell pellets were washed twice with PBS, suspended in 0.5 ml of PI/RNase Staining Buffer and subsequently incubated for 15 min at RT in the dark. The...
Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future ...
Friedrich Luft and colleagues identify missense mutations in PDE3A in six unrelated families with an autosomal dominant syndrome marked by severe hypertension and brachydactyly. They further show that the mutations result in gain of enzymatic function, l
Phosphodiesterase 4D interacting protein (PDE4DIP) is a Golgi/centrosome-associated protein that plays critical roles in the regulation of microtubule dynamics and maintenance of the Golgi structure. However, its biological role in human cancer remains l
Imidazole (36 mg, 0.53 mmol), triphenylphosphine (139 mg, 0.53 mmol) and iodine (134 mg, 0.53 mmol) were added to a solution of the compound from example 54 (200 mg, 0.4 mmol) in dichloromethane (10 ml), and the suspension stirred at room temperature for 48 hours. Sodium methylmercapt...
The ability of the compounds to act in this way may be simply determined by the tests described in the Examples hereinafter. The compounds according to the invention are thus of particular use in the prophylaxis and treatment of human diseases where an unwanted inflammatory response or muscular ...
PDE7 inhibitors will act at a different stage of the T cell signaling process compared to current immunosuppressants by inhibiting a very early stage of the T cell activation cascade. A selective inhibitor of PDE7 is also expected to have a decreased potential for clinically significant side ...