PROTAC HPK1 Degrader-4
PROTAC HPK1 Degrader-4 is an orally active HPK1 PROTAC degrader and immune activator, with DC50 values of 3.16 nM and 72.59 nM in Jurkat cells and PBMCs, respectively. PROTAC HPK1 Degrader-4 induces degradation via the ubiquitin-proteasome system, downregulates the HPK1-SLP76 signaling pathway, reduces the phosphorylation level of SLP76 (S376), and promotes immune activation. PROTAC HPK1 Degrader-4 can be used in the research of colorectal cancer and B-cell lymphoma.
(Pink: HPK1 ligand (HY-174355); Blue: Cereblon ligand (HY-45808); Black: linker (HY-174356)).
For research use only. We do not sell to patients.
- Formula: C46H46N8O5
- Molecular Weight:790.91
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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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HPK1 3.16 nM (DC50, Jurkat cells) |
HPK1 72.59 nM (DC50, PBMCs) |
SLP-76 |
PROTAC HPK1 Degrader-4 (Compound E3) (3.16-10000 nM; 24 h) degrades HPK1 protein in Jurkat cells and PBMC cells[1].
PROTAC HPK1 Degrader-4 (1 μM; 24 h) selectively downregulates HPK1 without affecting GLK protein in Jurkat cells, and degrades HPK1 protein in a ubiquitin-proteasome system-dependent manner in Jurkat cells pretreated with MG132 (HY-13259)/Thalidomide (HY-14658)/MLN4924 (HY-70062) for 8 h[1].
PROTAC HPK1 Degrader-4 (0.98-1000 nM; 24 h) downregulates the phosphorylation level of the downstream protein SLP76 in Jurkat cells[1].
PROTAC HPK1 Degrader-4 (up to 20 μM) exerts no direct cytotoxic effect on CT26 and A20 cells[1].
PROTAC HPK1 Degrader-4 (1 μM; 16 h, with 8 h of compound pre-treatment) promotes IL-2 secretion in Jurkat cells[1].
PROTAC HPK1 Degrader-4 (0.01-10000 nM) exerts a dose-dependent effect on promoting IL-2 and IFN-γ secretion in human primary T cells[1].
PROTAC HPK1 Degrader-4 (1 μM) exerts the effect of reversing the immunosuppressive microenvironment induced by NECA, PGE-2 and TGF-β in human primary T cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Jurkat and PBMC
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Concentration:0.1, 1, 10, 100, 1000, 10000 nM (Jurkat); 3.25, 16, 80, 400, 2000, 10000 nM (PBMC)
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Incubation Time:24 h
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Result:Significantly reduced the protein expression levels of HPK1 in a dose-dependent manner.
Effectively degraded HPK1 while exhibiting almost no degradation effect on the GLK protein.
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Cell Line:Jurkat
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Concentration:0.98, 3.9, 15.6, 62.5, 250, 1000 nM
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Incubation Time:24 h
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Result:Reduced the phosphorylation level of the downstream protein SLP76 in a dose-dependent manner.
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Cell Line:Jurkat
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Concentration:1 μM
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Incubation Time:Pretreatment with inhibitor, Thalidomide (2 μM), MG132 (5 μM), or MLN4924 (1 μM) for 8 h, followed by compound treatment for 24 h
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Result:The HPK1 degradation effect of the compound was effectively blocked by proteasome and ubiquitination-related inhibitors, indicating its dependence on the ubiquitin-proteasome system.
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Cell Line:Jurkat
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Concentration:1 μM or 100, 1000, 10000 nM
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Incubation Time:pretreatment for 8 h followed by stimulation for 16 h
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Result:Significantly promoted the secretion of the T cell activation-related cytokine IL-2.
PROTAC HPK1 Degrader-4 (25 or 50 mg/kg; p.o.; once daily) exerts a significant tumor growth inhibitory effect either as a monotherapy or in combination with Anti-PD-L1 in a male BALB/c mouse model of A20 xenografts implanted with B-cell lymphoma cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:3 x 105 CT26 cells were subcutaneously implanted into the right armpit of male BALB/c mice[1]
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Dosage:25, 50 mg/kg
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Administration:i.g.; once daily; treated for 18 days
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Result:The animals exhibited obvious growth inhibition in tumor volume and weight when treated with PROTAC HPK1 Degrader-4 alone.
The animals demonstrated a significantly enhanced synergistic antitumor effect when treated with PROTAC HPK1 Degrader-4 in combination with Anti-PD-L1, leading to stronger inhibition of tumor growth.
Produced no notable toxic side effects.
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Animal Model:1x106 A20 cells cells were subcutaneously implanted into the right armpit of male BALB/c mice[1]
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Dosage:25, 50 mg/kg
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Administration:i.g.; once daily; treated for 17 days
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Result:The animals exhibited obvious growth inhibition in tumor volume and weight when treated with PROTAC HPK1 Degrader-4 alone.
The animals demonstrated a significantly enhanced synergistic antitumor effect when treated with PROTAC HPK1 Degrader-4 in combination with Anti-PD-L1, leading to stronger inhibition of tumor growth.
Produced no notable toxic side effects.
Chemical Information
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Molecular Weight 790.91
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Formula C46H46N8O5
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SMILES
O=C1N(C(C2=CC(N3CC(C3)CN4CC=C(CC4)C5=C(C=C(C=C5C)C6=NC7=C(N=C6)NC=C7C8=CC(C)=C(C=C8)C(N(C)C)=O)C)=CC=C21)=O)C9C(NC(CC9)=O)=O
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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-4 Related Classifications
HY-174135 Related Classifications
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