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Background Information:
Extracellular Adenosine (ADO), present at high concentrations in the tumor micro-environment (TME), suppresses immune function via inhibition of T cell, natural killer (NK) cell, and dendritic cell (DC) activation. Intra-tumoral generation of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases: CD39 (ATP→AMP) and CD73 (AMP→ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression. AB-680 (AB680) is a highly potent, reversible and selective inhibitor of CD73 (Ki hCD73 = 4.9 pM on human CD8+ T-cells) and an immune-oncology modulator, highly selective against the closely-related CD39 (10,000-fold selectivity), and a large panel of unrelated enzymes, receptors, and ion channels. It potently reverses AMP and ADO-mediated suppression of immune function in vitro, robustly restores, in the presence high AMP concentration, CD25 expression, IFN-γ production and proliferation of human CD4+ and CD8+ T-cells, and reverses ADO-mediated immune suppression (ref 1). It is currently under evaluation as a cancer immunotherapy agent.
Reference:
1. K. V. Lawson, et al, Discovery and characterization of AB680, a potent and selective small-molecule CD73 inhibitor for cancer immunotherapy, In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl): Abstract nr 1756.
APIM050289: AB-680
CAS No.: 2105904-82-1.
Molecular Formula: C20H24ClFN4O9P2·2NH3·H2O.
Molecular Weight: 632.9.
Purity: >99% by Achiral and Chiral HPLCs.
QC: Achiral and Chiral HPLCs, MS, NMR, and Quantitative Elemental Analysis Report.
Solubility: Refer to Certificate of Analysis.
Storage: Refer to Certificate of Analysis.
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