compound 15 [PMID: 32045236]   Click here for help

GtoPdb Ligand ID: 10706

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 15 is a small molecule, ADP analogue-based CD73 (ecto-5'-nucleotidase) inhibitor [1]. Mechanisms to inhibit CD73 activity are being exploited for immuno-oncology potential, and are exemplified by the progress of the anti-CD73 monoclonal oleclumab and the small molecule inhibitor AB680 into clinical trials as treatments for advanced solid tumours.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 13
Hydrogen bond donors 6
Rotatable bonds 6
Topological polar surface area 242.99
Molecular weight 550.95
XLogP -2.87
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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Canonical SMILES O[C@@H]1[C@@H](COP(=O)(CP(=O)(O)O)O)O[C@H]([C@@H]1O)n1cnc2c1nc(I)nc2N
Isomeric SMILES O[C@@H]1[C@@H](COP(=O)(CP(=O)(O)O)O)O[C@H]([C@@H]1O)n1cnc2c1nc(I)nc2N
InChI InChI=1S/C11H16IN5O9P2/c12-11-15-8(13)5-9(16-11)17(2-14-5)10-7(19)6(18)4(26-10)1-25-28(23,24)3-27(20,21)22/h2,4,6-7,10,18-19H,1,3H2,(H,23,24)(H2,13,15,16)(H2,20,21,22)/t4-,6-,7-,10-/m1/s1
InChI Key OJRUSAPKCPIVBY-KQYNXXCUSA-N
Immunopharmacology Comments
CD73 hydrolyzes AMP to adenosine, and thus regulates the extracellular concentration of adenosine. It is expressed by lymphocytes, endothelial, and epithelial cells, and expression is upregulated under hypoxic or inflammatory conditions, and in various cancers. Elevated CD73 in tumours leads to increased levels of adenosine which impairs antitumour immunity and promotes tumour growth and metastasis. Mechanisms to inhibit CD73 activity are being exploited for immuno-oncology potential, and are exemplified by the progress of the anti-CD73 monoclonal oleclumab and the small molecule inhibitor AB680 into clinical trials as treatments for solid tumours.