ciforadenant   Click here for help

GtoPdb Ligand ID: 10190

Synonyms: CPI-444 | CPI444 | V-81444 | V81444
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Ciforadenant (CPI-444) is an orally active adenosine A2A receptor antagonist.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 127
Molecular weight 407.17
XLogP 0.65
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES Nc1nc(c2ccc(o2)C)c2c(n1)n(nn2)Cc1cccc(n1)COC1COCC1
Isomeric SMILES Nc1nc(c2ccc(o2)C)c2c(n1)n(nn2)Cc1cccc(n1)CO[C@@H]1COCC1
InChI InChI=1S/C20H21N7O3/c1-12-5-6-16(30-12)17-18-19(24-20(21)23-17)27(26-25-18)9-13-3-2-4-14(22-13)10-29-15-7-8-28-11-15/h2-6,15H,7-11H2,1H3,(H2,21,23,24)/t15-/m0/s1
InChI Key KURQKNMKCGYWRJ-HNNXBMFYSA-N
Immunopharmacology Comments
Adenosine suppresses the antitumour activity of T cells and other immune cells. Experimental studies are therefore evaluating the ability of adenosine receptor antagonists to abrogate adenosine-induced immunosuppression in the tumour microenvironment and to stimulate antitumour immune responses and tumour regression. Ciforadenant-mediated antagonism of the A2A receptor improves effector (T) cell function and leads to improved antitumour responses to checkpoint inhibitors in murine xenograft models [1-2]. Ciforadenant is proposed to induce systemic anti-tumour immune memory, that rejects tumour growth in re-challenged xenograft mice. These lines of evidence have led to the progression of ciforadenant to Phase 1 clinical evaluation as an adjunct to PD-L1 checkpoint blockade in advanced solid tumours.