Table 1. TCP Summary of Desired Potency, Toxicity, ADME, and Physicochemical Properties.
| Desired criteria | DNDI0003363576 | ||
|---|---|---|---|
| Potency | pEC50 Leish spp | >5.3 | 5.7 |
| Leish LLEa | ≥4 | 2.1 | |
| Toxicity | PMMb pCC50 | >10 | 4.2 |
| ADME and physicochemical properties | MW | ≤360 | 350 |
| cLogP | ≤3 | 3.6 | |
| LogD7.4 | ≤2 | 3.6 | |
| MLMc Clint | ≤60 | 62 | |
| revised ADME assessment criteria | |||
| RHd Clint | ≤27 | ||
| HLMe Clint | ≤47 | ||
| Aq. Sol.f | >10 | ||
| PK exposure | free plasma concentration > EC90 | ||
a
Ligand lipophilicity efficiency pEC50 – LogD7.4.
b
Primary mouse macrophage.
c
Mouse liver microsomes μL/min/mg protein.
d
Rat hepatocyte μL/min/106 cells; 5.1 ≤ moderate ≤27.
e
Human liver microsomes μL/min/mg protein; 8.6 ≤ moderate ≤47.
f
Thermodynamic aqueous solubility μM.