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Cat. No.: HY-185634

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PROTAC GSK3 degrader-1

PROTAC GSK3 degrader-1 is a potent, blood-brain barrier-permeable GSK3 PROTAC degrader, with a DC₅₀ of 1.4 nM against GSK3β. PROTAC GSK3 degrader-1 exerts equally potent degradation activity against both GSK3α and GSK3β. It inhibits the phosphorylation of CRMP2, PRKAA1 and Tau, and stabilizes β-catenin. PROTAC GSK3 degrader-1 can be used in the research of Alzheimer's disease and Parkinson's disease.
(Pink: GSK-3 ligand (HY-185635); Blue: Cereblon ligand (HY-W1137162); Black: linker).

For research use only. We do not sell to patients.

Formula: C₄₇H₄₆N₁₆O₄
Molecular Weight:898.97

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

PROTAC GSK3 degrader-1 Chemical Structure

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

PROTAC GSK3 degrader-1 is a potent, blood-brain barrier-permeable GSK3 PROTAC degrader, with a DC₅₀ of 1.4 nM against GSK3β. PROTAC GSK3 degrader-1 exerts equally potent degradation activity against both GSK3α and GSK3β. It inhibits the phosphorylation of CRMP2, PRKAA1 and Tau, and stabilizes β-catenin. PROTAC GSK3 degrader-1 can be used in the research of Alzheimer's disease and Parkinson's disease^[1]. (Pink: GSK-3 ligand (HY-185635); Blue: Cereblon ligand (HY-W1137162); Black: linker).

IC₅₀ & Target^[1]

GSK-3β

1.4 nM (DC₅₀)

GSK-3α

All PROTACs Isoforms :

All GSK-3 Isoforms :

In Vitro

PROTAC GSK3 degrader-1 (Compound KH1) (10 nM; 2 h) almost completely degrades GSK3α and GSK3β in HEK293 cells, and this degradation depends on the ubiquitin-proteasome system and binding to GSK3^[1].
PROTAC GSK3 degrader-1 (0.1-100 nM; 24 h) degrades GSK3β in differentiated SH-SY5Y neuroblastoma cells, with an onset concentration of 0.1 nM; at higher concentrations, it reduces phosphorylated CRMP2 levels and stabilizes β-catenin^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis^[1]

Cell Line:

Differentiated SH-SY5Y neuroblastoma cells
Concentration:

0.1, 1, 10 and 100 nM
Incubation Time:

24 h
Result:

Degraded GSK3β at concentrations between 0.1 and 10 nM.
Reduced phospho-CRMP2 levels concurrently with GSK3β degradation.
Stabilized β-catenin most evident at the highest tested concentration of 100 nM.

Parmacokinetics

Species	Dose	Route	Plasma Concentration	Brain Concentration	Bioavailability	Brain-to-Plasma Ratio
Mice^[1]	0.37 mg/kg	i.v.	> 65 nM	16 nM	1.6 %	0.18
Mice^[1]	3.0 mg/kg	p.o.	/	/	1.6 %	/

In Vivo

PROTAC GSK3 degrader-1 (Compound KH1) (5 mg/kg; i.v.; single bolus dose) achieves potent, specific degradation of GSK3β in female Balb/c mice, with near-complete removal in liver and significant reduction in brain following a single 5 mg/kg i.v. dose^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Balb/c (female)^[1]
Dosage:

5 mg/kg
Administration:

i.v.; single bolus dose
Result:

Reduced brain GSK3β levels to ~60% of control levels.
Reduced liver GSK3β levels to ~20% of control levels.
Achieved high proteome-wide specificity for GSK3β removal in liver tissue.
Reduced phosphorylation of GSK3α (Ser21) and AMPK alpha sub-unit (PRKAA1) in liver tissue.

Chemical Information

Molecular Weight 898.97
Formula C₄₇H₄₆N₁₆O₄
SMILES

O=C(C1=CC=NN2C1=NC(C3=CC=C(N4N=NC(C5=NC=C(CN6CCN(CC7=CC8=C(C=C7)C(N(C(N9)=O)CCC9=O)=NN8C)CC6)C=C5)=C4)C=C3)=C2)NC%10=C(N%11CCOCC%11)C=CN=C%10
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Holmqvist A, et al. Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening. Nat Commun. 2025;16(1):8857. Published 2025 Oct 6. [Content Brief]

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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100 mg

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Biological Activity
- Description
- IC₅₀ & Target
- In Vitro
- In Vivo
Chemical Information
Purity & Documentation
References

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PROTAC GSK3 degrader-1

All PROTACs Isoforms

All GSK-3 Isoforms

Biological Activity

Chemical Information

Purity & Documentation

References

Calculators

Help & FAQs

PROTAC GSK3 degrader-1 Related Classifications

HY-185634 Related Classifications