AA74-1 is an extremely potent and selective inhibitor of the serine hydrolase acyl-peptide hydrolase (APEH) with an IC50 of 5 nM in mouse T-cell proteomes. AA74-1 potently blocked the activity of its target serine hydrolase, APEH, in mice in vivo without significantly affecting other enzymes. The APEH inhibition caused accumulation of N-acetylated proteins and stimulated cellular proliferation in T cells.
The APEH gene is deleted in some cancers, in which it has been proposed to serve as a potential tumor suppressor, and is involved in the degradation of oligomeric amyloid-beta which could make it a new target for therapy aimed at reducing neurodegeneration in Alzheimer′s disease. AA74-1 is the first selective tool for studying APEH activity.
AA74-1 is an extremely potent and selective inhibitor of the serine hydrolase acyl-peptide hydrolase (APEH).
The human malaria parasite Plasmodium falciparum causes disease as it replicates within the host's erythrocytes. We have found that an erythrocyte serine hydrolase, acylpeptide hydrolase (APEH), accumulates within developing asexual parasites. Internalization of APEH was associated with a proteolytic event
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