2',5'-dideoxy Adenosine

2',5'-dideoxy Adenosine, a nucleoside analog, is one of the first identified cell-permeable, P-site inhibitors of adenylate cyclase [1].

Adenylyl cyclase is an enzyme with key regulatory roles in almost all cells. Adenylyl cyclases have been involved in catalyzing the conversion of ATP to cAMP) and pyrophosphate [2]. 2',5'-dideoxy Adenosine inhibits forskolin-induced activation of a cAMP-dependent reporter gene in HEK293 cells with an IC50 value of 33 μM.

In vitro: In HEK293 cells expressing a cAMP response element (CRE) reporter gene, 2',5'-dideoxy Adenosine (ddAd) effectively and potently inhibited the activity of adenylate cyclase (AC). The ddAd effectively inhibited the effect of forskolin, an AC activator, with IC50 value of 33 μM [1]. Pretreatment with graded concentrations of ddAd effectively inhibited PACAP-induced reporter gene activation with IC50 value of ～35 μM [1]. The ddAd inhibited forskolin-induced Elk-1 transactivation with an IC50 of 10 μM. The ddAd at concentrations greater than 500 mM failed to completely inhibit PACAP-induced cAMP elevation[1].

References:
[1] Emery A C, Eiden M V, Eiden L E.  A new site and mechanism of action for the widely used adenylate cyclase inhibitor SQ22, 536[J]. Molecular pharmacology, 2013, 83(1): 95-105.
[2] Gilman A G.  G proteins and dual control of adenylate cyclase[J]. Cell, 1984, 36(3): 577-579.