| In
Vitro Potency |
| SARS-CoV-2
Mpro IC50 [nM] |
28.1 |
23.4 |
| HeLa-ACE2 CoV-2 EC50/90 [nM] |
70/148 |
37/90 |
| ALI-HBEC CoV-2 EC50/90 [nM] |
25.3/44.8 |
5.3/9.6 |
| HCT-8 hCoV-OC43 EC50/90 [nM] |
112/418 |
135/712 |
| MCR5 hCoV-229E EC50/90 [nM] |
353/798 |
25/146 |
| HeLa-ACE2 CoV-2 variants EC90 [nM], alpha/delta/omicron |
242/196/117 |
63/35/37 |
| Uninfected cytotoxicity
CC50 [μM], HeLa-ACE2/HCT-8/MRC5/ALI-HBEC |
>40/>30/>30/>3.3 |
>40/>30/>30/>3.3 |
| |
| ADME Properties
[Mu/Rat/Dog/Cyno/Human] |
| Microsomal/hepatocyte
stability [CLint, μL/min/mg; CLhep, μL/min/106] |
32.8/2.3 (human) |
7.5/0.2 (human) |
| Human plasma stability [% at 2 h] |
>80% |
>80% |
| PPB [%] |
73.6/58.6/98.8/70.3/54.8 |
48.1/88.8/63.6/62.3/56.3 |
| Microsomal protein binding [%] |
24.0/17.6/9.8/21.7/16.5 |
22.6/23.2/24.5/18.0/19.1 |
| B/P ratio |
0.67/0.85/0.67/0.83/1.12 |
0.89/0.94/0.74/0.88/1.15 |
|
Papp(a→b/b→a) Caco-2
[10–6 cm/s] |
0.9/9.0 |
0.6/9.3 |
| Aqueous solubility |
n.d. |
1.4–1.5 mg/mL |
| |
| In
Vivo Propertiesa [Mu/Rat/Dog/Cyno] |
| Plasma clearance |
35.8/33.5/1.9/30.0 |
125/26.3/16.5/32.9 |
| IV PK CLp [mL/min/kg] |
| IV PK Vss [L/kg] |
2.0 (Vd)/1.0/0.57/1.5 |
1.2/2.7/1.1/1.2 |
| FPO (%) |
17/44/69/3 |
14/12/53/1 |
| |
| Target Selectivity
and Tox Profiling |
| CEREP screen (10
μM, 44 targets) |
No hits |
No hits |
| hERG channel (CHO cells) IC50
|
>10 μM |
>10 μM |
| CYP inhibition IC50 (1A2, 2C19, 2C9,
2D6, 3A4) |
3A4 = 46.4 μM, |
>50 μM (all) |
| rest >50 μM |
| Ames and
MNT assay |
Negative |
Negative |
| Human peptidase selectivity panel, Cathepsin
B/K/L/L2/S
IC50 (μM) |
No significant engagement except
below cathepsins |
| >30/1.2/>30/14.6/1.8 |
4.3/0.10/1.6/0.2/0.7 |
