Cat. No.: HY-162816

PROTAC HPK1 Degrader-3

Name: PROTAC HPK1 Degrader-3
Brand: MedChemExpress
SKU: HY-162816
Price: 840.00 USD
Availability: InStock
Rating: 5 (1 reviews)

Customer Review

Based on 1 Customer Validation

PROTAC HPK1 Degrader-3 is an orally active, PROTAC degrader that selectively targets HPK1, with a DC₅₀ of 21.26 nM. PROTAC HPK1 Degrader-3 induces HPK1 degradation via the ubiquitin-proteasome system and forms a stable ternary complex with HPK1 and CRBN. It inhibits the SLP76 and NF-κB signaling pathways, enhances MAPK signal transduction, reverses the immunosuppressive factor-mediated inhibition of T cell cytokine secretion, and promotes the secretion of T cell immune cytokines. PROTAC HPK1 Degrader-3 suppresses tumor growth and enhances anti-PD-L1-mediated antitumor activity. It can be used in studies related to malignant tumors, such as colorectal cancer.
(Pink: HPK1 ligand (HY-162842); Blue: Cereblon ligand (HY-14658); Black: linker (HY-40146)).

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

Purity: 98.11%
Formula: C₄₃H₄₂N₈O₅
Molecular Weight:750.84

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

PROTAC HPK1 Degrader-3 Chemical Structure

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

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

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

Biological Activity

Description

PROTAC HPK1 Degrader-3 is an orally active, PROTAC degrader that selectively targets HPK1, with a DC₅₀ of 21.26 nM. PROTAC HPK1 Degrader-3 induces HPK1 degradation via the ubiquitin-proteasome system and forms a stable ternary complex with HPK1 and CRBN. It inhibits the SLP76 and NF-κB signaling pathways, enhances MAPK signal transduction, reverses the immunosuppressive factor-mediated inhibition of T cell cytokine secretion, and promotes the secretion of T cell immune cytokines. PROTAC HPK1 Degrader-3 suppresses tumor growth and enhances anti-PD-L1-mediated antitumor activity. It can be used in studies related to malignant tumors, such as colorectal cancer^[1]. (Pink: HPK1 ligand (HY-162842); Blue: Cereblon ligand (HY-14658); Black: linker (HY-40146)).

IC₅₀ & Target^[1]

HPK1

NF-κB

p38 MAPK

ERK

JNK

IL-2

All PROTACs Isoforms :

All MAP4K Isoforms :

All NF-κB Isoforms :

All p38 MAPK Isoforms :

All ERK Isoforms :

All JNK Isoforms :

All Interleukin Related Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
Jurkat	DC₅₀	21.26 nM	HPK1 protein degradation in Jurkat cells after 24 h treatment. HPK1 protein degradation in Jurkat cells after 24 h treatment.	39084610

In Vitro

PROTAC HPK1 Degrader-3 (compound C3) inhibits HPK1 kinase activity with an IC₅₀ of 30.9 nM. In cell-free biochemical assays, this compound exhibits extremely low activity against GLK kinase (IC₅₀ > 500 nM), and forms a stable ternary complex with HPK1 and CRBN^[1].
PROTAC HPK1 Degrader-3 (1.5-50000 nM; 24 h) dose-dependently degrades HPK1 in Jurkat cells via the ubiquitin-proteasome system, with a DC₅₀ of 21.26 nM and a D_max of 80.50%^[1].
PROTAC HPK1 Degrader-3 (4-10000 nM; 24 h) exhibits no cytotoxicity against Jurkat cells even at concentrations as high as 10 μM^[1].
PROTAC HPK1 Degrader-3 exhibits high stability in human liver microsomes (T_1/2 = 990 min) and moderate stability in mouse liver microsomes (T_1/2 = 75.3 min)^[1].
PROTAC HPK1 Degrader-3 (10-10000 nM; 24 h) potently induces the secretion of IL-2 and IFN-γ in anti-CD3/CD28-activated Jurkat cells, and completely reverses the immunosuppressive effects; it potently activates IL-2 secretion in human primary T cells, with an EC₅₀ of 12.87 nM^[1].
PROTAC HPK1 Degrader-3 activates T cell function in Jurkat cells by inhibiting the SLP76-NF-κB signaling pathway and enhancing the TCR-MAPK (JNK, ERK) signaling pathway^[1].

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

Western Blot Analysis^[1]

Cell Line:

Jurkat cells
Concentration:

1.5, 4.6, 14, 41, 123, 370, 1111, 3333, 10000, 25000, 50000 nM
Incubation Time:

24 h
Result:

Induced dose-dependent reduction in relative HPK1 protein levels across the tested concentrations.
Decreased HPK1 signal visible on Western blots as concentration increased.
Induced HPK1 degradation with a DC₅₀ of 21.26 nM and a maximum degradation (D_max) of 80.50% after 24 h treatment.

Western Blot Analysis^[1]

Cell Line:

Jurkat T cells
Concentration:

1 μM (kinetic studies, 0-48 h)
1 μM (24 h with 6 h inhibitor pre-treatment)
1 μM (0-24 h with 1 μM CHX co-treatment)
Incubation Time:

0, 1, 2, 4, 8, 12, 16, 24, 36, 48 h (kinetic studies)
24 h with 6 h pre-treatment (mechanistic studies)
0, 4, 8, 16, 20, 24 h (CHX co-treatment)
Result:

Achieved maximal HPK1 degradation by 24 h of treatment with 1 μM of the compound.
Was completely blocked from inducing HPK1 degradation by pretreatment with proteasome inhibitor MG132 or NEDD8-activating E1 enzyme inhibitor MLN4924.
Was inhibited from inducing HPK1 degradation by pretreatment with HPK1 inhibitor 10 or thalidomide.
Effectively downregulated HPK1 by the 4 h time point when co-treated with CHX.

ELISA Assay^[1]

Cell Line:

Jurkat T cells
Concentration:

10, 100, 1000, 10000 nM (24 h with anti-CD3/CD28 stimulation)
10, 100, 1000, 10000 nM (24 h with 8 h pre-treatment of 2 nM PGE2 (HY-101952) + 2 μM NECA (HY-103173) and anti-CD3/CD28 stimulation)
Incubation Time:

24 h (anti-CD3/CD28 stimulation)
24 h with 8 h pre-treatment (immunosuppressive reversal studies)
Result:

Induced dose-dependent increases in IL-2 and IFN-γ secretion, significantly outperforming the warhead inhibitor 10 at all tested concentrations.
Increased IL-2 concentration to ~1100 pg/mL and IFN-γ concentration to ~450 pg/mL at 10000 nM with anti-CD3/CD28 stimulation.
Completely reversed immunosuppression by PGE2 and NECA, restoring IL-2 levels to ~800 pg/mL and IFN-γ levels to ~200 pg/mL at 10000 nM, while inhibitor 10 had minimal effect.

Cell Viability Assay^[1]

Cell Line:

Jurkat T cells
Concentration:

4, 20, 80, 400, 2000, 10000 nM
Incubation Time:

24 h
Result:

Showed no significant cytotoxicity in Jurkat cells even at 10000 nM, with survival rates remaining near 100%.

Parmacokinetics

Species	Dose	Route	T_1/2	T_max	C_max	AUC_0-t	F	AUC_0-∞	Bioavailability	MRT
Rat^[1]	10 mg/kg	p.o.	6.58 h	1.00 h	2085.95 ng/mL	16383.59 ng·h/mL	/	/	/	9.62 h
Mice^[1]	10 mg/kg	i.g.	4.33 h	4.00 h	10899.92 ng/mL	/	/	136933.13 ng·h/mL	81.7 %	/
Mice^[1]	1 mg/kg	i.v.	3.13 h	0.08 h	3003.04 ng/mL	16760.71 ng·h/mL	81.7 %	/	/	/

In Vivo

PROTAC HPK1 Degrader-3 (compound C3) (25 mg/kg; p.o.; daily; 15 days) achieves 47.22% tumor growth inhibition in a CT26 colon cancer syngeneic mouse model, and combination with anti-PD-L1 antibody enhances tumor growth inhibition to 65.58% without inducing body weight changes^[1].

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

Animal Model:

Male immunocompetent BALB/c mice (3‑4 weeks old) were subcutaneously implanted with CT‑26 cells (3 × 10⁶ cells per mouse in 0.1 mL medium) into the right armpit^[1]
Dosage:

25 mg/kg (monotherapy)
25 mg/kg (combination with anti-PD-L1 antibody 5 mg/kg)
Administration:

p.o.; daily; 15 days (monotherapy)
p.o.; daily; 15 days in combination with i.p.; every 3 days; 15 days (anti-PD-L1 antibody)
Result:

Achieved a tumor growth inhibition (TGI) rate of 47.22%.
Enhanced tumor growth inhibition to a TGI rate of 65.58% when combined with anti-PD-L1 antibody.
Caused no changes in body weight after 15 consecutive days of administration.

Chemical Information

Appearance Solid
Molecular Weight 750.84
Formula C₄₃H₄₂N₈O₅
Color Light yellow to yellow
SMILES

CN(C(C(C=CC(C1=CNC2=C1N=C(C=N2)C3=CC=C(C=C3)C4CCN(CC4)C5CN(C6=CC=C7C(C(N(C7=O)C8C(NC(CC8)=O)=O)=O)=C6)C5)=C9)=C9C)=O)C
Shipping

Room temperature in continental US; may vary elsewhere.

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 : 100 mg/mL (133.18 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.3318 mL

6.6592 mL

13.3184 mL

5 mM

0.2664 mL

1.3318 mL

2.6637 mL

10 mM

0.1332 mL

0.6659 mL

1.3318 mL

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.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

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Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (279 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Wu M, et al. Discovery of an Exceptionally Orally Bioavailable and Potent HPK1 PROTAC with Enhancement of Antitumor Efficacy of Anti-PD-L1 Therapy. Journal of medicinal chemistry. 2024 Aug 22;67(16):13852-13878. [Content Brief]

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.

Complete Stock Solution Preparation Table

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	1.3318 mL	6.6592 mL	13.3184 mL	33.2960 mL
	5 mM	0.2664 mL	1.3318 mL	2.6637 mL	6.6592 mL
	10 mM	0.1332 mL	0.6659 mL	1.3318 mL	3.3296 mL
	15 mM	0.0888 mL	0.4439 mL	0.8879 mL	2.2197 mL
	20 mM	0.0666 mL	0.3330 mL	0.6659 mL	1.6648 mL
	25 mM	0.0533 mL	0.2664 mL	0.5327 mL	1.3318 mL
	30 mM	0.0444 mL	0.2220 mL	0.4439 mL	1.1099 mL
	40 mM	0.0333 mL	0.1665 mL	0.3330 mL	0.8324 mL
	50 mM	0.0266 mL	0.1332 mL	0.2664 mL	0.6659 mL
	60 mM	0.0222 mL	0.1110 mL	0.2220 mL	0.5549 mL
	80 mM	0.0166 mL	0.0832 mL	0.1665 mL	0.4162 mL
	100 mM	0.0133 mL	0.0666 mL	0.1332 mL	0.3330 mL

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PROTAC HPK1 Degrader-3

All PROTACs Isoforms

All MAP4K Isoforms

All NF-κB Isoforms

All p38 MAPK Isoforms

All ERK Isoforms

All JNK Isoforms

All Interleukin Related Isoforms

Biological Activity

Chemical Information

Solvent & Solubility

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

PROTAC HPK1 Degrader-3 Related Classifications

HY-162816 Related Classifications

Bioz