Table 5.
Docking Scores and ADME Drug-Like Properties of Cordycepin and the 31 A3AR Agonists Against ADA and A3AR
Ligand | Caco-2 | PPB (%) | CNS | HIA (%) | Docking Score | |
---|---|---|---|---|---|---|
ADA | A3AR | |||||
Cordycepin | 2 × 10−6 | 2 | −3.21 | 69 | 64.74 | 61.65 |
MRS5698 | 94 × 10−6 | 76 | −2.74 | 100 | 30.58 | 69.41 |
2-Chloroadenosine | 0.7 × 10−6 | 6 | −3.50 | 46 | 46.89 | 66.95 |
2′-Me-CCPA | 33 × 10−6 | 19 | −2.75 | 100 | 47.91 | 72.08 |
TCPA | 0.1 × 10−6 | 52 | −5.70 | 4 | 48.24 | 62.85 |
NECA | 0.4 × 10−6 | 3 | −4.28 | 31 | 50.04 | 74.43 |
MRE3008F20 | 11 × 10−6 | 97 | −5.08 | 100 | 52.32 | 54.42 |
2-Phenylethylyl-adenosine derivative | 12 × 10−6 | 47 | −3.43 | 100 | 52.91 | 86.20 |
Adenosine | 0.4 × 10−6 | 2 | −3.72 | 30 | 55.21 | 64.63 |
GS9667 | 19 × 10−6 | 13 | −2.93 | 100 | 57.20 | 79.72 |
Binodenoson | 0.6 × 10−6 | 9 | −4.13 | 34 | 58.36 | 84.77 |
(R,S)-PHPNECA | 0.7 × 10−6 | 6 | −3.50 | 46 | 59.86 | 86.73 |
N(6)-cyclohexyladenosine | 16 × 10−6 | 10 | −2.48 | 100 | 61.76 | 69.34 |
HEMADO | 19 × 10−6 | 13 | −2.93 | 100 | 63.38 | 75.65 |
Cl-IB-MECA | 54 × 10−6 | 63 | −2.98 | 100 | 64.08 | 82.17 |
Regadenoson | 0.0 × 10−6 | 2 | −5.30 | 6 | 64.31 | 80.15 |
Piclidenoson | 26 × 10−6 | 29 | −3.01 | 100 | 65.25 | 79.16 |
Cyclopentyladenosine | 10 × 10−6 | 6 | −2.66 | 100 | 65.85 | 68.79 |
PENECA | 3 × 10−6 | 34 | −3.75 | 92 | 66.75 | 87.18 |
BAY606583 | 59 × 10−6 | 81 | −2.92 | 100 | 67.84 | 82.66 |
AB-MECA | 2 × 10−6 | 6 | −3.14 | 84 | 70.23 | 73.67 |
MPC-MECA | 9 × 10−6 | 24 | −3.48 | 100 | 70.63 | 76.48 |
MRS3558 | 31 × 10−6 | 52 | −3.00 | 100 | 73.87 | 91.86 |
2-Hexynyl-NECA | 2 × 10−6 | 13 | −3.68 | 89 | 73.91 | 93.66 |
Apadenoson | 5 × 10−6 | 22 | −3.70 | 98 | 75.72 | 103.78 |
CCPA | 26 × 10−6 | 19 | −2.35 | 100 | 76.71 | 74.97 |
(S)-PIA | 35 × 10−6 | 13 | −2.19 | 100 | 77.12 | 80.90 |
CP608,039 | 35 × 10−6 | 13 | −2.19 | 100 | 77.80 | 80.02 |
CGS21680 | 0.0 × 10−6 | 45 | −6.03 | 1 | 78.86 | 108.69 |
MRS5151 | 0.4 × 10−6 | 3 | −4.28 | 31 | 79.06 | 98.80 |
I-ABA | 16 × 10−6 | 10 | −2.48 | 100 | 80.09 | 81.03 |
(R)-PIA | 35 × 10−6 | 13 | −2.19 | 100 | 81.03 | 80.12 |
Caco-2 predicts passive intestinal permeability with the unit cm/s (>7.00 is highly permeable, 1.00–7.00 is moderately permeable, ≤1.00 is poorly permeable). Plasma protein binding (PPB) estimates the overall percentage bound in blood plasma protein. Central nervous system (CNS) values of ≤−3.50 indicate nonpenetrant to CNS; −3.50 to −3.00, weak penetrant; and >−3.00, penetrant. Human intestinal absorption (HIA) values of >70% are highly absorbed; 30%–70%, moderately absorbed; and ≤30%, poorly absorbed.