Target intelligence / Profile preview

2'-Deoxyadenosine (dA, 2'-dA)

Target
dA, 2'-dA
Molecular classification
Purine nucleoside, Deoxyribonucleoside, Organic compound (nucleosides, nucleotides, and analogues)
01

Overview

2'-Deoxyadenosine is a naturally occurring purine nucleoside composed of adenine linked to a deoxyribose sugar. It is a DNA component and plays central roles in genetic information storage and cellular metabolism. It is not itself considered a therapeutic target, but its metabolism is clinically significant; inborn errors (especially ADA deficiency) or pharmacological ADA inhibition lead to its accumulation and resulting immune suppression or toxicity. At excessive intracellular concentrations, particularly when ADA is absent, it induces cell death in lymphocytes and can contribute to immunodeficiency syndromes. In summary, 2'-deoxyadenosine is not a canonical drug target, but a physiologically important metabolite whose dysregulation is implicated in disease. Therapies focus on its metabolic enzymes (e.g., ADA), not the nucleoside itself.

Other names
Deoxyadenosine2'-dAdAAdenyldeoxyribosideAdenine deoxyribose(2R,3S,5R)-5-(6-Amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol
02

Mechanism of action

In ADA deficiency or with ADA inhibitor treatment: accumulation of deoxyadenosine and associated metabolites is toxic to lymphocytes, primarily by interfering with DNA synthesis and repair, leading to apoptosis

03

Biological functions

Building block of DNA (transmission of genetic information)Regulation of cell growth, proliferation, differentiation, and inhibitionInvolvement in nucleotide metabolism
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Disease associations

Can accumulate to toxic levels in adenosine deaminase (ADA) deficiency, contributing to severe combined immunodeficiency (SCID)Related toxicity in the context of metabolic disorders impacting lymphocyte viability
05

Safety considerations

Cytotoxicity to lymphocytes at elevated levels, particularly in the context of ADA deficiency or ADA inhibition, causing immunodeficiencyTeratogenic and cytotoxic effects at high concentrations in developing tissues
06

Interacting drugs

Deoxycoformycin
07

Biomarkers

Elevated deoxyadenosine or dATP levels are biomarkers in diagnosing ADA deficiency/SCID

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