PROTAC HPK1 Degrader-5
PROTAC HPK1 Degrader-5 is a potent and orally active HPK1 PROTAC degrader (DC50 = 5.0 nM; Dmax ≥ 99%). PROTAC HPK1 Degrader-5 significantly inhibits SLP76 phosphorylation and enhanced ERK pathway activation through degrading HPK1, thereby stimulating IL-2 and IFN-γ release. PROTAC HPK1 Degrader-5 exhibits the ability to overcome the immunosuppressive effects imposed by PGE2, NECA or TGF-β. PROTAC HPK1 Degrader-5 alone efficaciously inhibits tumor growth in an MC38 syngeneic mouse model. PROTAC HPK1 Degrader-5 can be used for the study of tumor (such as colorectal cancer) immunotherapy.
(Pink: HPK1 ligand (HY-175549); Blue: Cereblon ligand (HY-W023573); Black: linker).
For research use only. We do not sell to patients.
- CAS No.: 3108744-13-1
- Formula: C43H45N11O5
- Molecular Weight:795.89
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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ERK |
IL-2 |
Cereblon |
PROTAC HPK1 Degrader-5 (Compound 10m) (30 nM, 24 h)-induced HPK1 degradation requires the ubiquitin-proteasome system (UPS), CRBN, and engagement of both HPK1 and CRBN in Jurkat cells[1].
PROTAC HPK1 Degrader-5 (10 nM) significantly and dose-dependently inhibits the phosphorylation of direct downstream SLP76 and enhances the activation of distal downstream extracellular signalregulated kinase (ERK) in both Jurkat cells and PBMCs stimulated with anti-CD3/CD28 antibodies, consistent with HPK1 degradation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Jurkat cells
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Concentration:30 nM
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Incubation Time:24 h
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Result:Degraded HPK1 and can be inhibited by MG132 (HY-13259), MLN4924 (HY-70062), and Thalidomide (HY-14658).
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:MC38 xenografts model established insix-week-old female C57BL/6 mice[1]
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Dosage:0.5, 1.5 and 3 mg/kg
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Administration:orally administration (p.o.), every other day for 14 days
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Result:Achieved a superior antitumor effect when combined with PD-1 blockade mAb
Combined with anti-PD-1 mAb achieved significantly enhanced antitumor efficacy.
Was tolerated with no significant body weight loss and mortality observed during the treatment period.
Alone or combined with anti-PD-1 induced weakened nucleus-to-cytoplasm, remarkable nuclear shrinkage and extensive tumor cell death.
Significantly increased CD8+ T cell infiltration, exceeding anti-PD-1 mAb at 1.5 mpk.
Chemical Information
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CAS No. 3108744-13-1
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Molecular Weight 795.89
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Formula C43H45N11O5
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SMILES
O=C(N)C1=NC(C2=C(C3=CC=C2)N=CN3C)=C(N=C1NC4=CC=C(C=C4)C5CCN(CC5)C[C@@H]6CCN(C6)C7=CC8=C(C=C7)C(N(C8=O)C9CCC(NC9=O)=O)=O)NC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC HPK1 Degrader-5 Related Classifications
HY-175547 Related Classifications
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