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Clopidogrel is a prodrug which is metabolized by the liver into its active form. The active form specifically and irreversibly inhibits the P2Y 12 subtype of ADP receptor, which is important in activation of platelets and eventual cross-linking by the protein fibrin. [36]
1557 n/a Ensembl ENSG00000165841 n/a UniProt P33261 n/a RefSeq (mRNA) NM_000769 n/a RefSeq (protein) NP_000760 n/a Location (UCSC) Chr 10: 94.76 – 94.86 Mb n/a PubMed search n/a Wikidata View/Edit Human Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes ...
Clopidogrel, unlike prasugrel, was issued a black box warning from the FDA on 12 March 2010, as the estimated 2–14% of the US population who have low levels of the CYP2C19 liver enzyme needed to activate clopidogrel may not get the full effect. Tests are available to predict if a patient would be susceptible to this problem or not.
Unlike ticlopidine and clopidogrel, the activation of prasugrel involves hydrolysis to an intermediate thiolactone, which is then converted to the active metabolite in a single CYP-dependent step. The active metabolite, which is R-138727 (thiol intermediate), either binds irreversibly to the P2Y 12 receptor or is metabolic methylated to an ...
70839 Ensembl ENSG00000169313 ENSMUSG00000036353 UniProt Q9H244 Q9CPV9 RefSeq (mRNA) NM_176876 NM_022788 NM_027571 NM_001357007 NM_001357008 NM_001357010 RefSeq (protein) NP_073625 NP_795345 NP_081847 NP_001343936 NP_001343937 NP_001343939 Location (UCSC) Chr 3: 151.34 – 151.38 Mb Chr 3: 59.12 – 59.17 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse P2Y 12 is a chemoreceptor for ...
[2] [3] Platelet activation by ADP (blocked by clopidogrel) leads to the aforementioned conformational change in platelet gpIIb/IIIa receptors that induces binding to fibrinogen. [1] The gpIIb/IIIa receptor is a target of several drugs including abciximab, eptifibatide, and tirofiban.
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English: Clopidogrel (top left) being activated. The active metabolite (top right) has Z configuration at the double bond C3–C16 and possibly R configuration at the newly asymmetric C4. The first step is a cytochrome P450 mediated oxidation; the two structures at the bottom are tautomers of each other; and the final step is a hydrolysis.