Table 1. Datasets Used for Bayesian Models Created with CDD Models Using FCFP6 Fingerprints.
| model | datasets used and refs | cutoff for active | no. of molecules | three-fold ROCa |
|---|---|---|---|---|
| malaria (Plasmodium falciparum) | CDD Public datasets (MMV, St. Jude, Novartis, and TCAMS)127−129 | 3D7 EC50 <10 nM | 184 actives, 19,824 inactives | 0.97 |
| TB (Mycobacterium tuberculosis) | CDD Public datasets from NIAID/SRI (MLSMR, CB2, kinase)138−140 | Mtb inhibition >90% | 6891 actives, 210,190 inactives | 0.88 |
| TB (Mycobacterium tuberculosis) | CDD Public datasets from NIAID/SRI (MLSMR, CB2, kinase, and ARRA)138−141 | Mtb IC50 or IC90 <10 μM | 3712 actives, 1145 inactives | 0.89 |
| TB (Mycobacterium tuberculosis) | CDD Public MLSMR single-point data | Mtb inhibition >90% | 3986 actives, 210,447 inactives | 0.87 |
| TB (Mycobacterium tuberculosis) | CDD Public MLSMR dose–response | Mtb IC50 <10 μM and classed as active | 624 actives, 1649 inactives | 0.75 |
| TB (Mycobacterium tuberculosis) efficacy in vivo mouse | CDD Public112 | described in ref (112) | 371 actives, 407 inactives | 0.73 |
| cholera | CDD Public in the TB ARRA dataset141 | IC50 <5 μM | 50 actives, 1874 inactives | 0.93 |
| Ames mutagenicity | ref (142) | Ames positive, active = 1 | 3501 actives, 3007 actives | 0.83 |
| mouse intrinsic clearance | data from ChEMBL | <10 μL/(min·g) | 52 actives, 312 inactives | 0.82 |
| human intrinsic clearance | data from ChEMBL | ≤10 μL/(min·g) | 105 actives, 638 inactives | 0.92 |
| human intrinsic clearance | AZ data from ChEMBL143 | ≤10 μL/(min·mg) | 496 actives, 604 inactives | 0.80 |
| Caco-2 | proprietary data from ADMEdata.com | pH 6.5, cutoff >1×10–5 | 181 actives, 325 inactives | 0.79 |
| Caco-2 | data from ChEMBL | cutoff >1×10–5 | 60 actives, 399 inactives | 0.89 |
| 5-HT2B | ref (144) | active = 1, described in ref (144) | 146 actives, 607 inactives | 0.89 |
| solubility | ref (145) | Log solubility = −5 | 1136 actives, 154 inactives | 0.87 |
| PXR activation | ref (146) | described in ref (146) | 174 actives, 143 inactives | 0.80 |
| maximum recommended therapeutic dose | ref (147) | >10 mg/(kg·day) | 350 actives, 813 inactives | 0.85 |
| blood brain barrier permeability | ref (28) | BBB positive, described in ref (28) | 1472 actives, 432 inactives | 0.92 |
a
ROC = receiver operator characteristic integral.