S-Adenosylhomocysteine (SAH) hydrolase catalyzes the reversible hydrolysis of SAH to adenosine and homocysteine. The inhibition of SAH hydrolase causes the intracellular accumulation of SAH, elevating the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase. (−)-Neplanocin A potently and irreversibly inactivates SAH hydrolase (Ki = 8.39 nM). It has antitumor activity against mouse leukemia L1210 cells and broad-spectrum antiviral activity. Neplanocin A is more potent against vesicular stomatitis than the reversible SAH hydrolase inhibitor 3-deazaneplanocin (ID50 = 0.07 and 0.3 μg/ml, respectively).
