INT69322
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
Both pain states are disrupted by intrathecal CNI-1493, a p38 mitogen-activated protein (MAP) kinase inhibitor. | |||||||||||||||
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Systemic administration of CNI-1493, a p38 mitogen-activated protein kinase inhibitor, blocks intrathecal human immunodeficiency virus-1 gp120-induced enhanced pain states in rats. | |||||||||||||||
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VX-702, a novel p38 mitogen-activated protein kinase (MAPK) inhibitor, is currently under investigation in ACS patients with unstable angina to evaluate its safety and efficacy during percutaneous coronary intervention (PCI). | |||||||||||||||
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Understanding the intercellular signalling pathways involved in nociception may lead to novel drugs, such as p38 mitogen-activated protein (MAP) kinase inhibitors, being used in the treatment of cough in the future. | |||||||||||||||
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Among them, compound 4a, (S)-2-(4-fluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole (R-132811), achieved the most promising results in various in vitro and in vivo tests including several rheumatoid arthritis models ((i) inhibition of p38alpha, p38beta, p38gamma, and p38delta MAP kinases: IC(50)=0.034, 0.572, >10, and >10 microM, respectively; (ii) inhibition of TNFalpha, IL-1beta, IL-6, and IL-8 production in human whole blood: IC(50)=0.026, 0.020, 0.88, and 0.016 microM, respectively; (iii) inhibition of LPS induced TNFalpha, IL-1beta and IL-6 production in mice: ID(50)=0.93, 8.63, and 0.11 mg/kg, p.o., respectively; (iv) inhibition of anti-collagen antibody-induced arthritis in mice: ID(50)=2.22 mg/kg, p.o.; (v) inhibition of collagen-induced arthritis in mice: ID(50)=2.38 mg/kg, p.o.; (vi) prophylactic effect on adjuvant-induced arthritis in rats: ID(50)=3.1 mg/kg, p.o.; (vii) therapeutic effect on adjuvant-induced arthritis in rats: ID(50)=4.9 mg/kg, p.o.; (viii) analgesic effect on adjuvant-induced arthritic pain in rats: ID(50)=2.9 mg/kg, p.o.). | |||||||||||||||
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A number of compounds that inhibit the p38alpha MAPK have entered clinical trials for the treatment of rheumatoid arthritis and psoriasis, but side effects have prevented their progression to Phase III clinical trials. | |||||||||||||||
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SB203580, a p38 mitogen-activated protein kinase inhibitor, and RNA inhibition of p53 inhibited the sulindac-induced apoptosis. | |||||||||||||||
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Whether CNI-1493, or any other p38 MAP kinase inhibitor, can cross the blood-brain barrier to affect spinal cord function is unknown. | |||||||||||||||
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These studies provide the first evidence that systemic p38 MAP kinase inhibitors can prevent centrally mediated exaggerated pain states. | |||||||||||||||
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These studies provide the first evidence that systemic p38 MAP kinase inhibitors can prevent centrally mediated exaggerated pain states. | |||||||||||||||
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Interestingly, we show contrasting effects of p38 MAPK inhibition as compared to aspirin inhibition on platelet aggregation in response to collagen. | |||||||||||||||
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In a rodent model of inflammatory arthritis, p38-MAPK inhibition suppressed the inflammation and bone destruction [9]. | |||||||||||||||
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It is well documented that activation of the runt-related transcription factor RUNX-2 is mediated by activated p38-MAPK as inhibition of p38-MAPK abrogates its activity and the expression of cartilage degrading enzymes in chondrocytes [16]. | |||||||||||||||
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However, it is not known whether the inhibition of p38-MAPK - RUNX-2 pathway is related to the antioxidant activity of PE or one or more of the bioavailable constituents of PE exert this inhibitory effect by interfering with the kinase activity of p38-MAPK or both. | |||||||||||||||
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Inhibition of p38-MAPK with the commonly used pharmacological agent SB203580 reduces proinflammatory cytokine production in monocytes/macrophages, neutrophils, and T lymphocytes [8]. | |||||||||||||||
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Thus, our results suggest that PE or PE-derived compounds may be useful in blocking the activation of MKK3 and might provide the benefit of p38-MAPK inhibition and its downstream targets such as RUNX-2 without the direct inhibition of p38-MAPK in OA. | |||||||||||||||
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-induced DNA binding activity of RUNX-2 was also inhibited by PE in primary human OA chondrocytes and correlated with the inhibition of p38? | |||||||||||||||
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Inhibition of prostaglandin endoperoxide synthase-2 expression in stimulated human monocytes by inhibitors of p38 mitogen-activated protein kinase. | |||||||||||||||
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The inhibition of p38 kinase is associated with a suppression of the ET-1-induced stimulation of both enzymes, whereas the inhibitions of adenyl cyclase-dependent PKA kinase is associated with a partial suppression of the ET-1-induced stimulation of MMP-13 production only. | |||||||||||||||
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At this time (45 min), both p38 kinase and Akt phosphorylated forms were diminished. | |||||||||||||||
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General Comments
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