PROTAC HPK1 Degrader-5
Based on 1 Customer Validation
PROTAC HPK1 Degrader-5 is an orally effective and selective HPK1 PROTAC degrader with a DC50 of 5.0 nM. PROTAC HPK1 Degrader-5 recruits the CRBN E3 ligase to specifically induce the degradation of HPK1 via the ubiquitin-proteasome system, which in turn significantly inhibits SLP76 phosphorylation and enhances the activation of the ERK pathway, thereby stimulating the release of IL-2 and IFN-γ. PROTAC HPK1 Degrader-5 can be used in studies related to tumor immunity (e.g., colorectal cancer).
(Pink: HPK1 ligand (HY-175549); Blue: Cereblon ligand (HY-W023573); Black: linker).
For research use only. We do not sell to patients.
- Purity: 96.67%
- CAS No.: 3108744-13-1
- Formula: C43H45N11O5
- Molecular Weight:795.89
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
HPK1 5.0 nM (DC50) |
ERK |
IL-2 |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| Jurkat | DC50 |
5.0 nM
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HPK1 protein degradation in human Jurkat cells measured by Western blotting after 24 h incubation.
HPK1 protein degradation in human Jurkat cells measured by Western blotting after 24 h incubation.
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40738757 |
In Vitro
PROTAC HPK1 Degrader-5 (Compound 10m) (0.5 nM-10 nM; 24 h) exerts potent and dose-dependent HPK1 degradation-inducing effects in Jurkat cells, with a DC50 of 5.0 nM and a Dmax ≥ 99%, and has no impact on other MAP4K family members [1].
PROTAC HPK1 Degrader-5 (500 nM; 24 h) selectively degrades HPK1 in Jurkat cells, while significantly downregulating the novel CRBN substrates IKZF1 and ZFP91, and additionally downregulating AAK1[1].
PROTAC HPK1 Degrader-5 (23.4 nM-1.5 μM) enhances the secretion of IFN-γ in a concentration-dependent manner in Jurkat cells stimulated with anti-CD3/CD28 antibodies[1].
PROTAC HPK1 Degrader-5 (23.4 nM-3 μM; 48 h) potently enhances the production of IL-2 in human PBMC and Jurkat cells, and reverses the immunosuppression mediated by PGE2 (HY-101952) and NECA (HY-103173) in Jurkat cells[1].
PROTAC HPK1 Degrader-5 (12 nM-3 μM) degrades HPK1, inhibits SLP76 phosphorylation in a dose-dependent manner, and enhances ERK activation, thereby potentiating TCR signal transduction in Jurkat cells and human PBMCs[1].
PROTAC HPK1 Degrader-5 (0.1-3.0 μM) has no effect on the protein levels of most tested kinases, and only a slight increase in the protein levels of FYN and PKCθ is observed in Jurkat cells at a concentration as high as 3.0 μM[1].
PROTAC HPK1 Degrader-5 inhibits HPK1 kinase activity in a cell-free biochemical assay, with an IC50 of 125.7 nM[1].
PROTAC HPK1 Degrader-5 (1.5 nM-10 μM) exhibits no cytotoxicity against human peripheral blood mononuclear cells (PBMCs)[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:0.5, 1.5, 4.6, 13.7, 41.1, 123, 370, 1111, 3333 nM, 10 μM
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Incubation Time:24 h
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Result:Induced the degradation of HPK1 protein in a concentration-dependent manner, achieving nearly complete elimination of HPK1.
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Cell Line:Jurkat cells
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Concentration:123, 370, 1111, 3333 nM, 10 μM
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Incubation Time:24 h
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Result:Did not cause the degradation of other MAP4K family member proteins such as GCK, GLK, and HGK.
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Cell Line:Jurkat cells
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Concentration:30 nM
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Incubation Time:3, 6, 12, 24, 48, 72, 96 h
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Result:Significantly decreased HPK1 levels within 3 h of treatment, and the degradation effect persisted for up to 72 h.
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Cell Line:PBMCs and Jurkat cells
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Concentration:23.4, 46.9, 93.8, 187.5, 375, 750, 1500, 3000 nM
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Incubation Time:48 h
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Result:Significantly promoted the release of the IL-2 cytokine under anti-CD3/CD28 antibody co-stimulation, exhibiting a bell-shaped dose-response curve.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 6 weeks old, subcutaneous injection of 5×105 MC38 cells)[1]
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Dosage:0.25 mg/kg, 0.5 mg/kg; 1.5 mg/kg; 3.0 mg/kg; 1.5 mg/kg (combination with anti-PD-1 mAb); 3.0 mg/kg (combination with anti-PD-1 mAb)
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Administration:p.o.; every other day; 14 days
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Result:Reduced tumor volume compared to the control group.
Showed greater tumor volume reduction at 3.0 mg/kg dose than at 0.25 mg/kg dose.
Achieved a tumor growth inhibition (TGI) value of 42.45% at 1.5 mg/kg monotherapy.
Achieved a TGI of 32.54% at 3.0 mg/kg monotherapy.
Achieved a TGI of 75.83% at 1.5 mg/kg in combination with anti-PD-1 mAb.
Achieved a TGI of 61.56% at 3.0 mg/kg in combination with anti-PD-1 mAb.
Significantly increased CD8+ T cell infiltration into tumor tissue at 1.5 mg/kg and 3.0 mg/kg monotherapy, with 1.5 mg/kg inducing higher infiltration than anti-PD-1 mAb alone.
Further enhanced CD8+ T cell infiltration in combination treatments.
Induced weakened nucleus-to-cytoplasm ratio, nuclear shrinkage, and extensive tumor cell death in all treatment groups.
Caused no significant lesions in major organs (heart, liver, spleen, lung, kidney), no significant body weight loss, and no mortality during treatment.
Chemical Information
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CAS No. 3108744-13-1
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Appearance Solid
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Molecular Weight 795.89
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Formula C43H45N11O5
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Color Light yellow to yellow
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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
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 2 mg/mL (2.51 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (279 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.2565 mL | 6.2823 mL | 12.5646 mL | 31.4114 mL |
PROTAC HPK1 Degrader-5 Related Classifications
HY-175547 Related Classifications
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