3-Deazaadenosine

Names

[ Name ]:
3-Deazaadenosine

[Synonym ]:
1H-Imidazo[4,5-c]pyridine, 4-amino-1-β-D-ribofuranosyl-
C3-Ado
3-Deaza-D-adenosine
3-DEAZAADENOSINE
1-(β-D-Ribofuranosyl)-1H-imidazo[4,5-c]pyridin-4-amine
1H-Imidazo[4,5-c]pyridin-4-amine, 1-β-D-ribofuranosyl-

Biological Activity

[Description]:

3-Deazaadenosine is an inhibitor of S-adenosylhomocysteine hydrolase, with a Ki of 3.9 µM; 3-Deazaadenosine has anti-inflammatory, anti-proliferative and anti-HIV activity.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Inflammation/Immunology

Research Areas >> Infection

[Target]

IC50: 0.15 (HIV-1, A012 isolate), 0.20 µM (HIV-1, A018 isolate)[1] Ki: 3.9 µM (S-adenosylhomocysteine hydrolase)[1]

[In Vitro]

3-Deazaadenosine is an inhibitor of S-adenosylhomocysteine hydrolase, with a Ki of 3.9 µM. 3-Deazaadenosine shows anti-HIV effect, and inhibits p24 antigen in peripheral blood mononuclear (PBMCs) cells infected with HIV-1 isolates (A012 and A018) with IC50s of 0.15 and 0.20 µM, respectively[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 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].

[Cell Assay]

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 × 105 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 × 105 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].

[References]

[1]. Gordon RK, et al. Anti-HIV-1 activity of 3-deaza-adenosine analogs. Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners. Eur J Biochem. 2003 Sep;270(17):3507-17.

[2]. Jeong SY, et al. 3-deazaadenosine, a S-adenosylhomocysteine hydrolase inhibitor, has dual effects on NF-kappaB regulation. Inhibition of NF-kappaB transcriptional activity and promotion of IkappaBalpha degradation. J Biol Chem. 1999 Jul 2;274(27):18981-8.

[3]. Sedding DG, et al. 3-Deazaadenosine prevents smooth muscle cell proliferation and neointima formation by interfering with Ras signaling. Circ Res. 2009 May 22;104(10):1192-200.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.9±0.1 g/cm3

[ Boiling Point ]:
665.7±65.0 °C at 760 mmHg

[ Melting Point ]:
228-229ºC

[ Molecular Formula ]:
C₁₁H₁₄N₄O₄

[ Molecular Weight ]:
266.253

[ Flash Point ]:
356.4±34.3 °C

[ Exact Mass ]:
266.101501

[ PSA ]:
126.65000

[ LogP ]:
0.18

[ Vapour Pressure ]:
0.0±2.1 mmHg at 25°C

[ Index of Refraction ]:
1.834

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
H2O: 10 mg/mL with heating to 60 °C

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Safety Phrases ]:
24/25

[ RIDADR ]:
UN 2811

[ WGK Germany ]:
3

[ Packaging Group ]:
II

[ Hazard Class ]:
6.1(a)

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Disruption of choline methyl group donation for phosphatidylethanolamine methylation in hepatocarcinoma cells.

J. Biol. Chem. 277(19) , 17217-25, (2002)

Despite being widely hypothesized, the actual contribution of choline as a methyl source for phosphatidylethanolamine (PE) methylation has never been demonstrated, mainly due to the inability of conve...

Activation of caspase-8 in 3-deazaadenosine-induced apoptosis of U-937 cells occurs downstream of caspase-3 and caspase-9 without Fas receptor-ligand interaction.

Exp. Mol. Med. 33(4) , 284-92, (2001)

3-Deazaadenosine (DZA), a cellular methylation blocker was reported to induce the caspase-3-like activities-dependent apoptosis in U-937 cells. In this study, we analyzed the activation pathway of the...

Identification of A-minor tertiary interactions within a bacterial group I intron active site by 3-deazaadenosine interference mapping.

Biochemistry 41(33) , 10426-38, (2002)

The A-minor motifs appear to be the most ubiquitous helix packing elements within RNA tertiary structures. These motifs have been identified throughout the ribosome and almost every other tertiary-fol...