Table 3.
Physicochemical and Pharmacokinetic Properties of TAM16
| MW (g/mol) | 380.4 | |
|---|---|---|
| cLogP | 1.6 | |
| logD | 1.7 | |
| Lipophilic ligand efficiency | 5.1 | |
| H-bond donors | 3 | |
| H-bond acceptors | 4 | |
| TPSA (Å2) | 86 | |
| pKa | 9.95 | |
| Kinetic solubility (μM) | 74 | |
| (phosphate buffer, pH 7.4) | ||
| Plasma protein binding (%): | Mouse | 73 |
| Human | 72 | |
| Intrinsic clearance in liver microsomes | ||
| (CLint) (mL/min/g liver): | Mouse | <0.5 |
| Human | <0.5 | |
| CYP inhibition | No significant inhibition | |
| PK parameters: | ||
| Cmax (ng/mL) in plasma | 444 | |
| Tmax (hr) | 0.5 | |
| t1/2 (hr) in plasma | 1.0 | |
| AUC0-24 (ng.min/mL) (po) | 74,940 | |
| AUC0-24 (ng.min/mL) (iv) | 79,369 | |
| Clearance (mL/min per kg) | 37 | |
| Vss (L/kg) | 4.2 | |
| Oral bioavailability (F) (%) | 28 | |
Pharmacokinetic parameters were determined after administration of single oral (po) and intravenous (iv) doses of TAM16 at 10 mg/kg and 3 mg/kg, respectively, in female BALB/c mouse. Cmax, maximum concentration; Tmax, time to reach Cmax; t1/2, half-life; AUC, area under the concentration curve; Vss, volume of distribution at steady state; cLogP, calculated log(partition coefficient); Lipophilic ligand efficiency = pIC50 − cLogP; TPSA, total polar surface area.
See also Figures S3 and S4 and Table S6.