3-Deazaadenosine is an inhibitor of S-adenosylhomocysteine hydrolase, with a Ki of 3.9 µM, and it has anti-inflammatory, anti-proliferative and anti-HIV activity.
S-Adenosylhomocysteine (SAH) hydrolase is responsible for the reversible hydrolysis of SAH into adenosine and homocysteine. Inhibition of this enzyme leads to the accumulation of SAH within cells, thereby increasing the SAH to S-adenosylmethionine (SAM) ratio and subsequently inhibiting SAM-dependent methyltransferases. (−)-Neplanocin A, a potent and irreversible inhibitor of SAH hydrolase (Ki= 8.39 nM), exhibits significant antitumor activity against mouse leukemia L1210 cells and holds broad-spectrum antiviral properties. Its efficacy notably surpasses that of the reversible inhibitor 3-deazaneplanocin, especially in combating vesicular stomatitis, evidencing a higher potency with ID50 values of 0.07 μg/ml for Neplanocin A versus 0.3 μg/ml for 3-deazaneplanocin.
Aristeromycin diphosphate is an inhibitor of S-adenosylhomocysteine hydrolase (AHCY), inducing miR-26a and regulating oncogenic EZH2 expression, showing high inhibitory activity against AHCY, and causing growth inhibition of prostate cancer.
SAHO is a sulfoxide form of the methyl donor S-(5'-adenosyl)-L-methionine chloride and a substrate for radical SAM enzymes.1It is reductively cleaved to S-adenosylhomocysteine , 5'-deoxyadenosine , and 5'-thioadenosine sulfenic acid by the radical SAM enzymes NosL or NosN. 1.Mandalapu, D., Ji, X., and Zhang, Q.Reductive cleavage of sulfoxide and sulfone by two radical S-adenosyl-L-methionine enzymesBiochemistry58(1)36-39(2019)