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Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase*
The compound U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene) was identified as an inhibitor of AP-1 transactivation in a cell-based reporter assay. U0126 was also shown to inhibitExpand
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Suppression of Intestinal Polyposis in ApcΔ716 Knockout Mice by Inhibition of Cyclooxygenase 2 (COX-2)
Two cyclooxygenase isozymes catalyze conversion of arachidonic acid to prostaglandin H2: constitutive COX-1 and inducible COX-2. To assess the role of COX-2 in colorectal tumorigenisis, we determinedExpand
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Multiple Female Reproductive Failures in Cyclooxygenase 2–Deficient Mice
Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In spite of long-standing speculation, definitive roles of PGsExpand
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MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products.
In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificityExpand
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Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus
Endocannabinoids form a novel class of intercellular messengers, the functions of which include retrograde signaling in the brain and mediation or modulation of several types of synaptic plasticity.Expand
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Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta.
We have demonstrated previously that cyclo-oxygenase-2 (COX2), the rate-limiting enzyme in the biosynthesis of prostaglandins (PGs), is essential for blastocyst implantation and decidualization.Expand
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Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins.
We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin andExpand
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Cloning and Characterization of ADAMTS11, an Aggrecanase from the ADAMTS Family*
Aggrecan is responsible for the mechanical properties of cartilage. One of the earliest changes observed in arthritis is the depletion of cartilage aggrecan due to increased proteolytic cleavageExpand
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Inhibition of mitogen-activated protein kinase kinase blocks T cell proliferation but does not induce or prevent anergy.
Three mitogen-activated protein kinase pathways are up-regulated during the activation of T lymphocytes, the extracellular signal-regulated kinase (ERK), Jun NH2-terminal kinase, and p38Expand
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Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II
PROSTAGLANDINS have wide-ranging effects in the body and are thought to be important mediators of inflammation. Cyclooxygen-ase (COX) plays a key regulatory role in prostaglandin synthesis, andExpand
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