Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI8YQGTP0)
  Drug Name Pentostatin Drug Info Nelarabine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics Antineoplastics
  Structure

 Mechanism of Pentostatin-Nelarabine Interaction (Severity Level: Moderate)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Pentostatin Nelarabine
      Mechanism Adenosine deaminase inhibitor Adenosine deaminase substrate
      Key Mechanism Factor 1
Factor Name Adenosine deaminase
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Structure Sequence
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPDFLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQAEGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAIDLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGYHTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIFKSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAGQNL
Gene Name ADA
Uniprot ID ADA_HUMAN
KEGG Pathway hsa:100
Protein Family Metallo-dependent hydrolases superfamily
Protein Function
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:8452534, PubMed:16670267). Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4 (PubMed:20959412). Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (PubMed:20959412). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (PubMed:23193172). Stimulates plasminogen activation (PubMed:15016824). Plays a role in male fertility (PubMed:21919946, PubMed:26166670). Plays a protective role in early postimplantation embryonic development (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Nelarabine caused by Pentostatin mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Administration of nelarabine in combination with adenosine deaminase inhibitors such as pentostatin is not recommended.

References
1 Product Information. Arranon (nelarabine). GlaxoSmithKline, Research Triangle Park, NC.