APH02174 |
APH02174 : Degrader (PROTAC) of IRAK4
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary
| Targets | Biochemical/Biophysical Potency | Cellular Potency |
|---|---|---|
| IRAK4 |
|
Degrader (PROTAC)
up to 100 nM
Selectivity
In Cell Selectivity Assessment
Potency Assay Off-Target:
The degradative selectivity of APH02174 was evaluated using tandem mass tag-based global discovery p ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
To determine whether APH02174 can degrade the transcription factor SALL4 and Zn-finger proteins (IKZ ...
Potency Cellular
In Vitro
IRAK4
Mode of Action: Degrader (PROTAC)
Structure-Activity-Relationship data available? No
DOI Reference: 10.1021/acs.jmedchem.5c00711
In Vivo Validations
Mouse
Dose: 2 mg/Kg
Route of delivery:
Intravenous
Plasma half life:
3.78 ± 0.09 h
Systemic clearance:
0.880 ± 0.07 mL/min/Kg
Cmax:
1867 ± 306 ng/mL
Area Under the Curve::
11671 ± 1196 h*ng/mL
Volume of Distribution at Steady-State:
1.66 ± 0.22 L/Kg
DOI Reference: 10.1021/acs.jmedchem.5c00711
Dose: 10 mg/Kg
Route of delivery:
Oral
Plasma half life:
4.34 ± 0.15 h
Cmax:
2073 ± 235 ng/mL
Tmax:
2.67 ± 1.15 h
Area Under the Curve::
23388 ± 2557 h*ng/mL
Bioavailability:
45 ± 5%
DOI Reference: 10.1021/acs.jmedchem.5c00711
Rat
Dose: 2 mg/Kg
Route of delivery:
Intravenous
Plasma half life:
4.00 ± 0.10 h
Systemic clearance:
12.8 ± 0.85 mL/min/Kg
Cmax:
1420 ± 157 ng/mL
Area Under the Curve::
2589 ± 166 h*ng/mL
Volume of Distribution at Steady-State:
2.66 ± 0.13 L/Kg
DOI Reference: 10.1021/acs.jmedchem.5c00711
Dose: 30 mg/Kg
Route of delivery:
Oral
Plasma half life:
3.43 ± 0.10 h
Cmax:
613 ± 190 ng/mL
Tmax:
6.00 h
Area Under the Curve::
7093 ± 1072 h*ng/mL
Bioavailability:
18 ± 3%
DOI Reference: 10.1021/acs.jmedchem.5c00711
Dog
Dose: 1 mg/Kg
Route of delivery:
Intravenous
Plasma half life:
8.10 ± 0.84 h
Systemic clearance:
4.75 ± 1.41 mL/min/Kg
Cmax:
599 ± 87 ng/mL
Area Under the Curve::
3669 ± 1082 h*ng/mL
Volume of Distribution at Steady-State:
2.73 ± 0.54 L/Kg
DOI Reference: 10.1021/acs.jmedchem.5c00711
Dose: 5 mg/Kg
Route of delivery:
Oral
Plasma half life:
10.6 ± 2.29 h
Cmax:
360 ± 122 ng/mL
Tmax:
4.00 h
Area Under the Curve::
6994 ± 2214 h*ng/mL
Bioavailability:
39 ± 12%
DOI Reference: 10.1021/acs.jmedchem.5c00711
Monkey (Cynomolgus)
Dose: 1 mg/Kg
Route of delivery:
Intravenous
Plasma half life:
8.67 ± 0.46 h
Systemic clearance:
9.20 ± 1.70 mL/min/Kg
Cmax:
672 ± 95 ng/Kg
Area Under the Curve::
1818 ± 299 h*ng/mL
Volume of Distribution at Steady-State:
3.85 ± 0.44 L/Kg
DOI Reference: 10.1021/acs.jmedchem.5c00711
Dose: 20 mg/Kg
Route of delivery:
Oral
Plasma half life:
9.07 ± 0.99 h
Cmax:
229 ± 33 ng/mL
Tmax:
6.00 h
Area Under the Curve::
3997 ± 461 h*ng/mL
Bioavailability:
11 ± 1%
DOI Reference: 10.1021/acs.jmedchem.5c00711
Chemical Information
| Molecular Formula | C49H55N7O8 |
| SMILEs | Cn1c(=O)n(C2CCC(=O)NC2=O)c2cccc(C#CCO[C@H]3CC[C@H](CN4CCC5(CC4)Cc4cc(NC(=O)c6coc7cccnc67)c(N6CCC(CO)CC6)cc4O5)CC3)c21 |
| InChI | InChI=1S/C49H55N7O8/c1-53-45-33(5-2-7-38(45)56(48(53)61)39-13-14-43(58)52-47(39)60)6-4-24-62-35-11-9-31(10-12-35)28-54-22-17-49(18-23-54)27-34-25-37(51-46(59)36-30-63-41-8-3-19-50-44(36)41)40(26-42(34)64-49)55-20-15-32(29-57)16-21-55/h2-3,5,7-8,19,25-26,30-32,35,39,57H,9-18,20-24,27-29H2,1H3,(H,51,59)(H,52,58,60)/t31-,35-,39? |
| Molecular weight | 869.41 Da |
| AlogP | 5.316500000000007 |
| HBond acceptors | 15 |
| HBond donors | 3 |
| Atoms | 119 |