Pharmacology inhibitors

Calpain inhibition may represent an important mechanism for future drug development. Control of calpain activity may limit the invasive properties of cells and thereby provides a possible mechanism to limit the invasiveness of tumors or inhibits the development of chronic inflammation. For the moment, pharmacological inhibitors of calpains are still not capable of differentiating among different calpain isoforms in cellular systems or in vivo. The importance of calpains in diseases will continue to stimulate the development of new and better inhibitors. 

MAP Kinase Cascades. Table 1 Pharmacological Inhibitors of MAPK Cascades... 

The most extensive development of pharmacological inhibitors of MAPK cascades members has been for p38 (Table 1) [3]. Small-molecule inhibitors have been developed for two p38 isoforms (a and (3). Pyridinyl imidazole compounds have been known to block inflammation since the early 1970s. Structural analyses have revealed that p38 kinase inhibitors binds to the ATP-binding pocket of p38 thereby acting as competitive inhibitors. The p38 kinase inhibitor SB202190 is able to bind both the low-activity nonphosphorylated... 

English JM, Cobb MH (2002) Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci 23 40—45... 

LeVine H III. Screening for pharmacologic inhibitors of amyloid fibril formation. Methods Enzymol 1999 309 467 176. 

Smoking researchers may have to wait for more robust genetic assays before the issue is finally settled [30], but pharmacological inhibitors of CYP2A6 reduce smoking [31] and it seems likely that an inherited defect in nicotine metabolism would have the same effect. 

Caveolae-Mediated Endocytosis and Caveolae-Like Endocytosis Pharmacological Inhibitors... 

Keep in mind that exocytosis might occur during sample preparation (e.g., preparing cells for flow cytometric analysis). After the experiment (and prior to analysis) cells should be kept below 4°C to block all active processes (such as exocytosis). Exocytosis might also be blocked with NEM (see section Caveolae-Mediated Endocytosis and Caveolae-Like Endocytosis Pharmacological Inhibitors ). 

To remain a step ahead of life-threatening pathogens, it is essential to understand the chemical nature, structure, and diverse modes of action for bacterial toxins which represent some of the most toxic substances known today. Based upon this information, new vaccines can be created against specific domains of a toxin or perhaps cellular uptake of the toxins can be blocked by specific pharmacological inhibitors. Therefore, it will be of lasting impact to transfer our increasing knowledge of bacterial toxins from the laboratory bench into the clinic. 

Knockaert M, Greengard P, Meijer L. Pharmacological inhibitors of cydin-dependent kinases. Trends Pharmacol Sci 2002 23 417-25. 

Meijer L, Hajolet M, Greengard P. Pharmacological inhibitors of glycogen synthase kinase 3. Trends Pharmacol Sci 2004 25 471-80. 

Freemerman AJ, Turner AJ, Birrer MJ, Szabo E, Valerie K, Grant S (1996) Role of c-jun in human myeloid leukemia cell apoptosis induced by pharmacological inhibitors of protein kinase C. Mol Pharmacol 49 788-795 Freund A, Boos J, Harkin S, Schultze-Mosgau M, Veerman G, Peters GJ, Gescher A (1998) Augmentation of l-beta-D-arabinofuranosylcytosine (Ara-C) cytotoxicity... 

Jarvis, W.D., Turner, A.J., Povirk, L.F., Traylor, R.S., and Grant, S., Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C, Cancer Res., 54, 1707, 1994. 

The present chapter focuses on the physiological functions of the CaMK cascade that have been identified to date. The definition of these functions has relied heavily on the use of pharmacological inhibitors, overexpression of constitutively active or dominant/negative mutants of the various CaM kinases, and a variey of model organisms that include mice, worms and fungi null (or transgenic) for specific members of the CaMK cascade. 

Knockaert, M., Greengard, P., Meijer, L. Pharmacological inhibitors of cyclin-dependent kinases. Trends in Pharmacological Sciences 2002, 23, 417-425. 

Pharmacologic inhibitors of thrombin. Thrombin is a key enzyme in the hemostatic system in that it leads to the formation of fibrin strands and is a potent stimulus for platelet activation. Thrombin inhibitors, factor Xa inhibitors, and antiplatelet drugs act at different points in the hemostatic system to regulate the amount of thrombin that is generated. 

Sarnico, I., Boroni, F., Benarese, M., Alghisi, M., Valerio, A., Battistin, L., Spano, P., and Pizzi, M. (2008a). Targeting IKK2 by pharmacological inhibitor AS602868 prevents exdtotoxic injury to neurons and oligodendrocytes.. Neural Transm. 115, 693-701. 

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