Table 6.
Relevant statements from both, simulation and experimental results related to adenosine receptor inhibitors captured by PLIO in PubMed abstracts are listed
| Confirmatory statement | Information gain |
|---|---|
| Experiment: (i) Selective adenosine receptor agonists: CPA, CHA, CCPA, 2′Me-CCPA, NECA, IB-MECA. | Experiment: (i) Enhancers are able to increase the non-bonded interactions of the binding site with agonists as CHA, CPA, MeCPA and MeCCPA. (PMID: 12144931) |
| 2′-Me-CCPA was confirmed to be the most selective, high affinity agonist at human A(1) receptor with a Ki value of 3.3 nM and 2903- and 341-fold selective versus human A(2A) and A(3) receptors, respectively. (PMID: 15743197) | Simulation: (ii) Common binding site was found for CPA, CCPA, and NECA agonists. (PMID: 15174168) |
| Simulation: CPA CCPA Docking studies explained the lower affinity of N(6)-3-(R)-tetrahydrofur anyl-substituted compounds at bovine A(1)AR compared to that of N(6)-cyclopentyl analogues, showing that the oxygen of the tetrahydrofuranyl ring establishes unfavourable electrostatic interactions with the CO oxygen of Asn254. (PMID: 17933541) | Simulation: (iii) CPA and DPCPX show greater electrostatic similarity when the aromatic rings are superimposed according to the flipped model, in which the xanthine ring is rotated around its horizontal axis. (PMID: 7751869) |
| Simulation: (i) The binding cavity of A(1)AR is smaller than of the A(2a)AR. For this reason less bulky ligands like CPA are able to give close interactions with the A(1)AR. (PMID: 16427161) | Simulation: (iv) In the docking exploration, it was found that 2′-Me-CCPA was able to form a number of interactions with several polar residues in the transmembrane helices TM-3, TM-6, and TM-7 of bA(1)AR which were not preserved in the molecular dynamics simulation of 3′-Me-CCPA/bA(1)AR complex. (PMID: 15743197) |
| Experiment: (ii) The most active compound was found to be 3′-Me-CPA which displayed a K(i) value of 0.35 microM at A(1) receptor and a selectivity for A(1) versus A(2A) and A(3) receptors higher than 28-fold. (PMID: 15743197) |
The key statements in these publications were classified into confirmatory and information gain type of statements.