Disease relevance of AG 556

• These data are consistent with the conclusion that AG 556 prevented cytokine-induced multiorgan failure and death during septic shock by inhibiting cell-signaling pathways without impairing host defenses as determined by clearance of bacteria and endotoxin [1].
• Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine Escherichia coli peritonitis [1].
• Moreover, treatment with AG 556 significantly increased the survival rate of rats after trauma-hemorrhage and induction of subsequent sepsis compared with vehicle-treated rats [2].
• In the present study, tyrphostin AG556, which is more lipophilic than those of the AG126 family, was effective in preventing LPS-induced lethal toxicity when administered 2 h after LPS [3].
• Suppression of experimental autoimmune encephalomyelitis by tyrphostin AG-556 [4].

High impact information on AG 556

• During the first 48 h after infection, AG 556 also improved mean arterial pressure, left ventricular ejection fraction, cardiac output, oxygen delivery, and alveolar-arterial oxygen gradient compared to controls (all P < or = 0.05) [1].
• Treatment with AG 556 had no effect on clearance of endotoxin or bacteria from the blood (both P = NS); however, AG 556 did significantly lower serum TNF levels (P = 0.03) [1].
• RESULTS: AG 556 treatment restored the depressed cardiovascular and hepatocellular functions after trauma-hemorrhage and resuscitation, which was associated with reduced phosphorylation of mitogen-activated protein kinases p44/42 and p38 [2].
• AG-556 does not block the activation of JNK/SAPK and of p38/HOG and therefore seems to act at a target down stream to these kinases which is activated in stress or at a target on an obligatory parallel pathway [4].
• These findings together with previous results showing inhibition of sepsis in mice and dogs suggest that protein tyrosine kinase (PTK) blockers of the AG-556 family may be considered in the management of human autoimmune disorders such as multiple sclerosis (MS) [4].

Chemical compound and disease context of AG 556

• Similarly, AG-556 administered for an additional 10 days after myosin immunization (when signs of inflammation are already present) attenuated the progression of myocarditis, though AG-126 did not [5].
• Genistein and tyrphostin AG 556 block the action potential shortening in septic shock [6].
• RESULTS: The four study groups were sham + Ringer's lactate, acute necrotising pancreatitis with Ringer's lactate, tryphostin AG 556, and dimethylsulfoxide (DMSO) [7].

Biological context of AG 556

• Two highly specific inhibitors of the epidermal growth factor receptor (EGFR) signal transduction pathway, 4,5-dianilinophthalimide (10 microM) and tyrphostin B56 (10 microM), selectively block the neurotrophic capacity of chromaffin granule protein [8].
• Tyrphostin B56 at a concentration of 10(-5) M reduced the cell number by 76%, but when incubated together with growth factors the reduction was only 44% with TGF-alpha, and 39% with EGF [9].

Anatomical context of AG 556

• Thus, AG-556 may represent a novel strategy of ameliorating the progression of myocarditis without non-selectively compromising the immune system [5].
• The reduction of myocardial damage and leukocyte polymorphonuclear accumulation following coronary artery occlusion by the tyrosine kinase inhibitor tyrphostin AG 556 [10].

Gene context of AG 556

• The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56 [11].
• TNF-alpha and IFN-gamma production by in vitro sensitized splenocytes from AG-556-treated rats was significantly diminished as compared with control cells from EAM animals [5].

Analytical, diagnostic and therapeutic context of AG 556

• Tyrphostins AG-126 and AG-556 were previously shown to reduce TNF-alpha production and its end-organ cytotoxicity, thus proving beneficial in animal models of septic shock and experimental autoimmune encephalomyelitis [5].

References