Table 3.
pKa distribution of compounds containing a single basic functional group.
| Dataset | pKa range (%) |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0-1 | 1-2 | 2-3 | 3-4 | 4-5 | 5-6 | 6-7 | 7-8 | 8-9 | 9-10 | 10-11 | 11-12 | |
| Drugs | 3.2 | 2.7 | 4.6 | 5.6 | 4.1 | 4.0 | 7.2 | 12.6 | 21.8 | 26.2 | 7.5 | 0.5 |
|
| ||||||||||||
| Aspartyl proteases | 16.2 | 9.6 | 12.8 | 3.4 | 4.6 | 6.8 | 11.0 | 20.1 | 9.0 | 6.0 | 0.5 | 0.1 |
| Cysteine proteases | 12.3 | 28.5 | 4.3 | 11.0 | 11.4 | 17.8 | 2.1 | 3.4 | 4.8 | 2.0 | 0.4 | 2.1 |
| GPCR amines | 0.0 | 0.2 | 0.1 | 0.4 | 1.2 | 2.0 | 12.8 | 21.2 | 29.8 | 25.9 | 5.8 | 0.5 |
| GPCR cannabinoid | 16.8 | 32.3 | 4.6 | 4.5 | 3.0 | 1.0 | 29.0 | 2.3 | 5.6 | 0.5 | 0.3 | 0.0 |
| GPCR nucleotide | 15.3 | 13.8 | 14.9 | 19.7 | 26.2 | 5.0 | 3.5 | 1.0 | 0.3 | 0.3 | 0.1 | 0.0 |
| GPCR class A other | 4.5 | 2.1 | 1.3 | 0.9 | 1.3 | 0.4 | 2.1 | 10.4 | 24.1 | 36.4 | 16.3 | 0.4 |
| GPCR peptide | 5.0 | 1.4 | 4.3 | 2.4 | 5.4 | 3.2 | 7.2 | 11.2 | 25.4 | 25.1 | 5.8 | 3.6 |
| GPCR prostaglandin | 1.5 | 0.0 | 0.0 | 3.0 | 25.8 | 3.0 | 1.5 | 10.6 | 47.0 | 4.5 | 3.0 | 0.0 |
| GPCR class B | 4.2 | 7.7 | 11.5 | 22.6 | 21.9 | 12.3 | 9.9 | 3.1 | 6.3 | 0.5 | 0.0 | 0.0 |
| GPCR class C | 8.2 | 29.7 | 3.3 | 18.6 | 13.4 | 16.0 | 0.7 | 1.1 | 2.6 | 5.9 | 0.4 | 0.0 |
| Integrins | 19.1 | 57.3 | 4.5 | 4.5 | 3.4 | 1.1 | 0.0 | 1.1 | 2.2 | 0.0 | 4.5 | 2.2 |
| Ligand-gated ion channel | 3.6 | 8.0 | 7.9 | 13.2 | 3.5 | 4.0 | 4.6 | 12.7 | 13.4 | 17.1 | 10.3 | 1.8 |
| Voltage-gated ion channel | 2.9 | 5.1 | 3.8 | 5.8 | 7.5 | 5.8 | 4.8 | 9.2 | 33.6 | 16.8 | 4.8 | 0.0 |
| Ion channel - other | 2.5 | 14.0 | 11.5 | 6.2 | 35.8 | 11.9 | 3.7 | 0.4 | 0.8 | 11.5 | 1.6 | 0.0 |
| Tyrosine kinases | 2.4 | 7.8 | 8.5 | 18.7 | 22.7 | 20.7 | 6.7 | 7.9 | 2.1 | 2.3 | 0.2 | 0.1 |
| Kinases – non tyrosine | 12.7 | 25.0 | 16.6 | 13.9 | 10.5 | 6.4 | 8.4 | 1.2 | 0.9 | 3.4 | 0.7 | 0.2 |
| Metalloproteases | 11.1 | 0.0 | 11.1 | 16.7 | 16.7 | 11.1 | 5.6 | 5.6 | 16.7 | 5.6 | 0.0 | 0.0 |
| Nuclear receptors | 6.7 | 15.9 | 6.3 | 50.8 | 10.4 | 0.9 | 0.3 | 0.1 | 7.2 | 1.5 | 0.0 | 0.0 |
| Oxido reductases | 14.6 | 4.2 | 8.8 | 6.5 | 6.2 | 7.7 | 8.8 | 27.6 | 8.2 | 4.3 | 0.8 | 2.3 |
| Oxygenases | 18.0 | 10.7 | 13.8 | 14.3 | 13.5 | 4.2 | 13.0 | 4.1 | 6.0 | 2.3 | 0.2 | 0.0 |
| Phosphodiesterases | 9.1 | 26.3 | 13.8 | 9.1 | 11.5 | 16.9 | 5.9 | 2.3 | 2.5 | 1.6 | 0.7 | 0.0 |
| Serine proteases | 8.7 | 2.1 | 3.2 | 1.9 | 3.4 | 1.4 | 5.4 | 5.7 | 28.8 | 15.1 | 4.1 | 20.3 |
| Transporters | 0.1 | 0.1 | 0.7 | 2.0 | 1.3 | 0.3 | 0.8 | 5.9 | 26.2 | 51.1 | 11.1 | 0.4 |
| Unknown targets | 8.2 | 17.3 | 11.1 | 9.9 | 9.0 | 8.9 | 9.0 | 5.7 | 10.9 | 6.9 | 2.2 | 0.8 |
|
| ||||||||||||
| Vendors – drug-like clean | 17.8 | 23.8 | 17.4 | 11.1 | 12.1 | 8.9 | 5.7 | 2.4 | 0.6 | 0.1 | 0.0 | 0.0 |
| ‘Natural’ products | 13.6 | 7.4 | 7.8 | 10.9 | 9.9 | 5.1 | 7.4 | 10.0 | 13.6 | 11.2 | 2.9 | 0.1 |
| Vendors – clean leads | 17.6 | 22.1 | 17.3 | 11.6 | 12.6 | 8.7 | 6.5 | 2.7 | 0.7 | 0.1 | 0.0 | 0.0 |