Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excessive bone resorption mediated by mature osteoclasts can cause osteoporosis, leading to fragility fractures. Therefore, an effective therapeutic strategy for anti-osteoporosis drugs is the reduction of osteoclast activity. In this study, the osteoclast inhibitory activity of a novel compound, N-phenyl-methylsulfonamido-acetamide (PMSA), was examined. PMSA treatment inhibited receptor activator of nuclear factor kappa B ligand (RNAKL)-induced osteoclast differentiation in bone marrow-derived macrophage cells (BMMs). We investigated two PMSAs, N-2-(3-acetylphenyl)-N-2-(methylsulfonyl)-N-1-[2-(phenylthio)phenyl] glycinamide (PMSA-3-Ac), and N-2-(5-chloro-2-methoxyphenyl)-N-2-(methylsulfonyl)-N-1-[2-(phenylthio)phenyl]glycinamide (PMSA-5-Cl), to determine their effects on osteoclast differentiation. PMSAs inhibited the signaling pathways at the early stage. PMSA-3-Ac inhibited tumor necrosis factor receptor-associated factor 6 (TRAF6) expression, whereas PMSA-5-Cl suppressed the mitogen-activated protein kinase (MAPK) signaling pathways. However, both PMSAs inhibited the master transcription factor, nuclear factor of activated T cell cytoplasmic-1 (NFATc1), by blocking nuclear localization. An in vivo study of PMSAs was performed in an ovariectomized (OVX) mouse model, and PMSA-5-Cl prevented bone loss in OVX mice. Therefore, our results suggested that PMSAs, specifically PMSA-5-Cl, may serve as a potential therapeutic agent for postmenopausal osteoporosis.
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PMID:PMSA prevents osteoclastogenesis and estrogen-dependent bone loss in mice. 3314 Oct 68


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