Table 1.
Potencies and selectivities of natural and synthetic ligands at the human P2Y receptors (references in brackets)
| Subfamily and Pharmacologic Characteristics | Receptor Subtype | Ligands (potency and selectivity) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Native agonist | pEC50 (ref) | Synthetic agonist | pEC50 (ref) | Cross reactivity | Synthetic (or native) antagonist | pEC50 (ref) | Cross reactivity | ||
| P2Y1-like, Gq-coupled | P2Y1 | ADP 2 | 5.09 [6] | MeSADP 12 | 8.22 [6] | P2Y12,13 | A3P5P 25 | 6.08 [35] | none |
| ADP-β-Sa 8 | 7.02 [6] | P2Y12,13 | MRS2179 26 | 6.48 [36] | none | ||||
| MRS2365 24 | 9.40 [34] | none | MRS2279 29 | 7.28 [6] | none | ||||
| MRS2500 30 | 9.02 [39] | none | |||||||
| P2Y2 | UTP 3 | 8.10 [4] | UTP-γ-Sa9 | 6.62 [4] | none | Suramin 48a | 4.32 [6] | P2Y11 | |
| ATP 1 | 7.07 [4] | NS365 68c | 7.00 [4] | P2Y4 | AR-C126313 52 | 6 [4,74] | |||
| INS37217 69 | 6.66 [4] | P2Y4 | MRS2576b57 | 4.04 [81] | P2Y1,4,6 | ||||
| MRS269863b | 8.10 [64] | none | |||||||
| P2Y4 | UTP 4 | 5.60 [6] | 2'-azido-dUTP 64 | 7.14 [12] | P2Y4 | PPADS 49 | < 5.00 [6] | P2Y2 | |
| ATP 1 | 4.37 [6] | various (ago), P2Y12 | |||||||
| MRS2577b56 | 4.01 [81] | P2Y6 | |||||||
| P2Y6 | UDP 4 | 6.52 [6] | UDP-β-S 10 | 7.33 [4] | none | MRS2578b55 | 7.43 [4] | none | |
| INS48823 71 | 6.90 [4] | none | |||||||
| MRS2633 67 | 6.64 [68] | none | |||||||
| MRS2693 66 | 7.83 [68] | None | |||||||
| P2Y11 | ATP 1 | 4.77 [6] | AR-C67085 35 | 5.05 [50] | P2Y12,13 (ant) | Suramin 48a | 4.79 [6] | P2Y2 | |
| ATP-γ-Sa7 | 5.52 [6] | P2Y1,2,12 | AMP-α-Sa18 | partial agonist [50] | none | ||||
| P2Y1-like, Gi-coupled | P2Y12 | ADP 2 | 7.22 [1] | MeSADP 12 | 7.85 [1] | P2Y1,13 | MeSAMP 13 | 4.00 [82] | none |
| ADP-β-Sa8 | 6.72 [1] | P2Y1,13 | ATP 1 | 3.60 [40] | various (ago), P2Y4 | ||||
| AR-C67085 36 | 4.52 [45] | P2Y11 (ago), P2Y13 | |||||||
| AR-C69931MX 37 | 9.40 [40] | P2Y11 (ago), P2Y13 | |||||||
| AZD6140 38 | 7.90 [45] | none | |||||||
| INS50589 40 | 7.80 [41] | none | |||||||
| Clopidogrelc41 | 5.74 [42] | none | |||||||
| P2Y13 | ADP 2 | 7.94 [84] | MeSADP 12 | 7.85 [84] | P2Y1,12 | MRS2211 50 | 5.97 [83] | none | |
| AR-C67085 36 | 6.67 [50] | P2Y11 (ago), P2Y12 | |||||||
| AR-C69931MX 37 | 8.40 [83] | P2Y11 (ago), P2Y13 | |||||||
| P2Y14 | UDP-glucose 75 | 6.45 [71] | MRS2690 78 | 7.31 [71] | none | UDP 4 | 7.28 [10] | P2Y6 (ago) | |
| UDP-galactose 76 | 6.17 [71] | ||||||||
| UDP-glucosamine 77 | 5.36 [71] | ||||||||
a, unstable to oxidation.
b, an insurmountable antagonist, which is hydrophobic and reactive toward nucleophiles and aqueous medium.
c, active only in vivo, through a thiol-reactive metabolite.
ago, agonist; ant, antagonist