Inhibition phosphorylation

Gleevec ) is a tyrosine kinase inhibitor used as first-line therapy in the majority of patients with CML. As a potent tyrosine kinase inhibitor, imatinib inhibits phosphorylation of various proteins involved in cell proliferation. Imatinib works by binding to the ATP-binding pocket of BCR-ABL.7 The drug induces complete hematologic responses in more than 95% of patients and complete cytogenetic responses in about 80% of patients in chronic phase.8 Most patients have traces of the disease when measured by RT-PCR and are not cured of their disease. 

Scheme 17 ADP-ribosylation of moesin inhibits phosphorylation. Moesin is phosphorylated at Thr558, but when cells are infected with Pseudomonas aeruginosa, moesin becomes ADP-ribosylated at Arg553, Arg560, and Arg563, which effectively blocks phosphorylation.

Fujimura Y, Tachibana H, Yamada K. 2004. Lipid raft-associated catechin suppresses the FceRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinasel/2. FEBS Lett 556 204-210. 

A number of substances inhibit oxidative phosphorylation at specific locations. These may be divided into agents that affect electron transport, those that affect complex V, and those that collapse proton gradients (proton ionophores). Such substances have been used as research tools to unravel the complexities of these pathways, as poisons, and as antibiotics. Inhibition of electron transport inhibits phosphorylation, the extent of which depends on the location of the inhibition site. Thus, if complex I is inactivated, electron transport can still take place using FADH2 as an electron donor. The donor P/O ratio is then 2. 

The evaluation of selected experimental agents as MEK inhibitors was performed by measuring their ability to inhibit phosphorylation of MAP kinase IRK in murine colon 26 (C26) carcinoma cells. Since ERK1 and ERK2 represent the only known substrates for MEK, measurement of ERK phosphorylation inhibition in cells provided direct readout of cellular MEK inhibition by these agents. IC50 testing results associated with cellular inhibition of ERK phosphorylation are provided for Steps 1 and 2 intermediates and phenylamino benzhydroxamic derivatives in Table 5. 

The effects of balanol and 10 -deoxybalanol on intact cells have been exmined to determine whether these compounds cross the cell membrane or if the potency and specificity observed in vitro are present in vivo. Western analysis showed that both compounds reduced phosphorylation of CREB in isoproterenol-stimulated A431 cells (ICso = 3 jM), although only balanol inhibits phosphorylation of MARCKS protein in phorbol ester-stimulated A431 cells (IC50 = 7 pM) 109],... 

Fig. 8.9 (a) Western blot of C-Kit inhibition. WBZ 4 inhibits phosphorylation of C-Kit kinase in ST-882 GIST cells. Gel bands from the western blot assays of C-Kit and its phosphorylated (P) form in GIST cells treated with WBZ 4 and imatinib. The fi-actin assay was adopted as control, (b) Western blot of Bcr-Abl inhibition. Phosphorylation of Bcr-Abl kinase is not significantly inhibited by WBZ 4 in K562 CML cells. Electrophoretic gel bands for western blots for Bcr-Abl kinase and its phosphorylated (P) form in CML cells treated with WBZ 4 and imatinib. Reprinted from the [14], copyright 2007 with permission from the American Society for Clinical Investigation... 

T3 fibroblasts stably expressing human four-repeat tau protein and endogenous levels of GSK-3 were used to evaluate whether AZl 1125357 inhibited GSK-3 mediated tau phosphorylation in cells. The effect on tau phosphorylation was determined by Western blotting. In 3T3 cells stably expressing human tau, AZl 1125357 inhibited phosphorylation on tau at a site specifically phosphorylated by GSK-3 3 (Ser396), with an IC50 of 207 nM. These data are summarised in Table 9. 

The drug inhibits phosphorylation in Ascaris mitochondria (40% inhibihon at... 

Four examples of structurally characterised, vanadate-inhibited phosphorylation enzymes working on the hydrolysis of phospho-ester bonds in nucleotides I, the vanadate-uridine complex of bovine pancreatic ribonuclease-A II, the vanadate complex of ribonuclease-Tj from the fungus Aspergillus oryzae-. III, the vanadate-uridine complex of cyclic nucleotide phosphodiesterase from the cruciferous plant Arabidopsis thaliana-, IV, human tyrosyl-DNA phosphodiesterase (Ur = uridine). 

Zidovudine Ribavirin Ribavirin inhibits phosphorylation of Avoid... 

Mishra-Gorur K, Singer HA, Castellot JJ Jr (2002) Heparin inhibits phosphorylation and autonomous activity of Ca /calmodulin-dependent protein kinase 11 in vascular smooth muscle cells. Am J Pathol 161 1893-1901... 

The selective mTOR inhibitor OSI-027 (67) from OSI Pharmaceuticals (now Astellas) is undergoing a Phase I clinical trial in patients with advanced solid tumors or lymphoma.123 A comparison study of this compound with rapamycin showed that while the mTORCl inhibitor rapamycin only partially inhibited phosphorylation of 4E-BP1, OSI-027 fully inhibited this process. OSI-027 also proved more effective than rapamycin in induction of apoptosis in a variety of tumor cell lines.124 Other studies demonstrated that OSI-027 is effective in chronic myeloid leukemia (CML) patients with a particular... 

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