2. PROTAC MAPK/ERK Pathway Stem Cell/Wnt Immunology/Inflammation
  3. PROTACs MAP4K ERK Interleukin Related IFNAR
  4. 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: Target protein ligand (HY-175549); Blue: E3 ligand (HY-W023573); Black: Linker; E3 ligand + Linker (HY-175551)).

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

PROTAC HPK1 Degrader-5

PROTAC HPK1 Degrader-5 Chemical Structure

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PROTAC HPK1 Degrader-5 Related Antibodies

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MAP4K2/GCK MAP4K3/GLK MAP4K4/HGK MAP4K5/KHS1 MAP4K6/MINK1 MAP4K7/TNIK MAP4K1/HPK1

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  • Biological Activity

  • Purity & Documentation

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Description

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: Target protein ligand (HY-175549); Blue: E3 ligand (HY-W023573); Black: Linker; E3 ligand + Linker (HY-175551))[1].

IC50 & Target[1]

ERK

 

IL-2

 

Cereblon

 

In Vitro

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.

PROTAC HPK1 Degrader-5 Related Antibodies

Western Blot Analysis[1]

Cell Line: Jurkat cells
Concentration: 30 nM
Incubation Time: 24 h
Result: Degraded HPK1 and can be inhibited by MG132 (HY-13259), MLN4924 (HY-70062), and Thalidomide (HY-14658).
Parmacokinetics[1]
Species Dose Route Indicator value
Mice 2 mg/kg i.v. CL 2.40 mL/min/kg
Mice 20 mg/kg p.o. Tmax 11.7 h
Mice 2 mg/kg i.v. Vss 1.42 L/kg
Mice 20 mg/kg p.o. T1/2 18.3 h
Mice 2 mg/kg i.v. T1/2 6.81 h
Mice 20 mg/kg p.o. Cmax 1527 ng/mL
Mice 2 mg/kg i.v. AUClast 12770 ng·h/mL
Mice 20 mg/kg p.o. AUClast 26758 ng·h/mL
Mice 2 mg/kg i.v. AUCinf 14043 ng·h/mL
Mice 20 mg/kg p.o. AUCinf 48715 ng·h/mL
Mice 2 mg/kg i.v. MRT 8.95 h
Mice 20 mg/kg p.o. F 21.0 %
In Vivo

PROTAC HPK1 Degrader-5 (Compound 10m) (0.5-3 mg/kg, p.o., every other day for 14 days) significantly inhibits tumor growth in a MC38 syngeneic tumor mouse model and achieves a superior antitumor effect when combined with PD-1 blockade[1].

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

Animal Model: MC38 xenografts model established insix-week-old female C57BL/6 mice[1]
Dosage: 0.5, 1.5 and 3 mg/kg
Administration: orally administration (p.o.), every other day for 14 days
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.
Molecular Weight

795.89

Formula

C43H45N11O5
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
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
References
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PROTAC HPK1 Degrader-5 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PROTAC HPK1 Degrader-5PROTACsMAP4KERKInterleukin RelatedIFNARMAPK Kinase Kinase KinaseExtracellular signal regulated kinasesILInterferon-α/β receptorInterferon-alpha/beta receptorPROTACtumor immunotherapymice modelPD-1Jurkat cellsInhibitorinhibitorinhibit

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