KH1 |
KH1 : Degrader (PROTAC) of GSK3B, GSK3A
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary
| Targets | Biochemical/Biophysical Potency | Cellular Potency |
|---|---|---|
| GSK3B |
| |
| GSK3A |
|
up to 100 nM
Selectivity
In Cell Selectivity Assessment
Potency Assay Off-Target:
Proteome wide compound selectivity for compound 24 vs 27 (grey) normalised to DMSO, was perfromend f ...
Selectivity Assessment Description:
The proteomic analysis showed the GSK3A and B are the only protein degraded by KH1, and that cpd 27 ...
Potency Cellular
In Vitro
GSK3B
Mode of Action: Degrader (PROTAC)
Structure-Activity-Relationship data available? Yes
DOI Reference: 10.1038/s41467-025-63928-8
GSK3A
Mode of Action: Degrader (PROTAC)
Structure-Activity-Relationship data available? Yes
DOI Reference: 10.1038/s41467-025-63928-8
In Vivo Validations
Mouse
Dose: 0.37 mg/Kg
Route of delivery:
Intravenous
Plasma half life:
2.3 h
Systemic clearance:
10 mL/min/kg
Area Under the Curve::
34310 min*ng/mL
Volume of Distribution at Steady-State:
2.0 L/kg
DOI Reference: 10.1038/s41467-025-63928-8
Dose: 3 mg/Kg
Route of delivery:
Oral
Cmax:
19 ng/mL
Tmax:
120 min
Area Under the Curve::
4930 min*ng/mL
Bioavailability:
1.6%
DOI Reference: 10.1038/s41467-025-63928-8
Negative Control Compounds
cpd 27
Notes: negative control compound 27 is unable to engage CRBN, due to methylation of the Dihydrouracil ring therefore it shows no degradation in cells.
SMILES:
CN1C2=CC(=CC=C2C(=N1)N3CCC(=O)N(C)C3=O)CN4CCN(CC4)CC5=CN=C(C=C5)C6=CN(C7=CC=C(C=C7)C8=CN9C(=N8)C(=CC=N9)C(=O)NC%10=C(C=CN=C%10)N%11CCOCC%11)N=N6
Chemical Information
| SMILES | CN1C2=CC(=CC=C2C(=N1)N3CCC(=O)NC3=O)CN4CCN(CC4)CC5=CN=C(C=C5)C6=CN(C7=CC=C(C=C7)C8=CN9C(=N8)C(=CC=N9)C(=O)NC%10=C(C=CN=C%10)N%11CCOCC%11)N=N6 |