3-Deazaadenosine hydrochloride is an inhibitor of S-adenosylhomocysteine hydrolase (Ki: 3.9 μM). It has anti-inflammatory, anti-proliferative, and anti-HIV activity.

S-adenosylhomocysteine hydrolase:(ki)3.9 µM , HIV-1 (A012 isolate):0.15, HIV-1 (A018 isolate):0.20 µM

3-Deazaadenosine shows the anti-HIV effect and inhibits p24 antigen in peripheral blood mononuclear (PBMCs) cells infected with HIV-1 isolates (A012 and A018, IC50s: 0.15 and 0.20 μM) [1]. 3-Deazaadenosine (1-100 μM) inhibits LPS-induced expression of TNF-α mRNA, increases DNA binding activity of NF-κB, and causes proteolytic degradation of IκBα, but Not IκBβ in RAW 264.7 cells. 3-Deazaadenosine (100 μM) enhances the nuclear translocation of NF-κB but blocks LPS-induced NF-κB transcriptional activity, and such inhibition is augmented by the addition of homocysteine [2]. 3-Deazaadenosine (50, 100 μM) dose-dependently inhibits the phosphorylation of Raf and ERK, protein-dependent kinase 1, protein kinase B (Akt), and forkhead transcription factor FoxO1a. 3-Deazaadenosine (50 μM) suppresses vascular smooth muscle cell (VSMC) proliferation via interfering with Ras signaling [3].

The HIV-1 strains A012 and A018 are used in the assay. Inhibition of p24 antigen is measured. Briefly, PHA-stimulated peripheral blood mononuclear (PBMCs) are incubated with either HIV-1 strain for 1 h at 37°C at 200-fold the 50% tissue culture infectious dose (TCID50) of the virus stock per 2 × 10^5 PBMC cells. The TCID50 is defined as the amount of virus stock at which 50% of the inoculated wells are positive. Cells are then grown in microtiter plates with different drug concentrations at 2 × 10^5 cells per well. On day 4, cells are resuspended and split 1:3 with fresh media and 3-Deazaadenosine. Supernatant p24 antigen is determined on day 7 by ELISA [1].