| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
HPK1 (Hematopoietic Progenitor Kinase 1), also known as MAP4K1. SS47 TFA is a PROTAC degrader that targets HPK1 for ubiquitination and subsequent degradation by the proteasome. HPK1 is a negative regulator of T cell and B cell receptor signaling; its degradation enhances T cell activation and anti-tumor immune responses.
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| ln Vitro |
SS47 TFA degrades HPK1 protein in cells, leading to enhanced T cell activation. In vitro, HPK1 degradation via SS47 significantly improves T cell effector functions. The compound degrades HPK1 in a concentration-dependent manner, with a DC50 in the low nanomolar range (specific values not published). It is a potent chemical probe for HPK1 biology.
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| ln Vivo |
In vivo, degradation of HPK1 via SS47 significantly enhances the anti-tumor efficacy of BCMA CAR-T cells. SS47 treatment leads to improved CAR-T cell expansion, persistence, and anti-tumor activity in mouse xenograft models. This demonstrates that HPK1 degradation is a promising strategy for improving adoptive T cell therapies for cancer.
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| Enzyme Assay |
Non-cell-based HPK1 binding and ubiquitination assay: Recombinant HPK1 protein is incubated with increasing concentrations of SS47 TFA (0-1000 nM) and E3 ligase components (CRBN) in ubiquitination buffer containing ATP, E1, and E2 enzymes for 60 min at 37degC. Ubiquitinated HPK1 is detected by Western blotting using anti-ubiquitin antibodies. The DC50 (half-maximal degradation concentration) is determined by densitometry.
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| Cell Assay |
T cell activation assay: Human or mouse primary T cells are isolated from peripheral blood or spleen. Cells are activated with anti-CD3/anti-CD28 antibodies (1-2 ug/mL) and treated with SS47 TFA at concentrations of 0-1000 nM for 24-72 h. Cell viability is assessed by MTT. T cell activation markers (CD69, CD25) are measured by flow cytometry. Cytokine production (IL-2, IFN-gamma, TNF-alpha) is measured by ELISA or Luminex.
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| Animal Protocol |
CAR-T cell xenograft model: NSG mice are engrafted with a BCMA-positive human tumor cell line (e.g., MM.1S) intravenously or subcutaneously. After tumor engraftment, BCMA CAR-T cells are administered intravenously, alone or in combination with SS47 TFA (1-10 mg/kg, i.p., daily or every other day). Tumor growth is monitored by bioluminescence imaging, and CAR-T cell expansion and persistence are analyzed by flow cytometry.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for SS47 TFA are limited. As a PROTAC degrader (MW 1067.09), it is cell-permeable and has reasonable metabolic stability. For in vivo studies, it can be formulated using DMSO/PEG300/Tween-80/saline mixtures, achieving ≥2.5 mg/mL solubility. The TFA salt enhances stability and solubility. The compound has an alkyne group for click chemistry labeling.
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| Toxicity/Toxicokinetics |
Toxicity data for SS47 TFA are limited. As a PROTAC degrader of HPK1, the primary on-target effect is enhanced T cell activation. Potential toxicities include cytokine release syndrome (CRS) and autoimmunity at high doses. In preclinical studies, SS47 is generally well-tolerated at effective doses (1-10 mg/kg). It is intended for research use only.
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| References | |
| Additional Infomation |
SS47 TFA is a research compound that has not entered clinical trials or received regulatory approval. It is a PROTAC-based HPK1 degrader. Its molecular weight is 1067.09, and it should be stored at -20degC, protected from light and stored under nitrogen. The compound is for research use only.
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| Molecular Formula |
C51H57F3N6O14S
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|---|---|
| Molecular Weight |
1067.09
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| Related CAS # |
SS47;2636072-62-1
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO :~100 mg/mL (~93.71 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9371 mL | 4.6856 mL | 9.3713 mL | |
| 5 mM | 0.1874 mL | 0.9371 mL | 1.8743 mL | |
| 10 mM | 0.0937 mL | 0.4686 mL | 0.9371 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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