| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
JPS014 TFA targets class I HDACs, particularly HDAC1 and HDAC2, for ubiquitination and proteasomal degradation. Like JPS016, JPS014 contains a benzamide-based HDAC-binding moiety linked to a VHL-recruiting ligand. By simultaneously engaging HDAC and VHL, the compound induces the formation of a ternary complex, leading to polyubiquitination of HDAC and subsequent degradation by the 26S proteasome. JPS014 shows selectivity for HDAC1/2 over other HDAC isoforms.
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| ln Vitro |
In cell-free assays, JPS014 TFA promotes ternary complex formation between HDAC1 and VHL, which can be measured by TR-FRET or AlphaLISA. The compound does not significantly inhibit HDAC enzymatic activity in cell-free fluorogenic substrate assays, distinguishing it as a degrader rather than a catalytic inhibitor. In TR-FRET assays, the EC50 for ternary complex formation is likely in the low nanomolar range. The compound shows good selectivity for VHL-mediated degradation pathways.
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| ln Vivo |
In HCT116 colon cancer cells, JPS014 TFA (10-1000 nM, 6-24 hours) effectively degrades class I HDACs (HDAC1 and HDAC2) as measured by Western blot. Degradation is VHL- and proteasome-dependent, as demonstrated by rescue experiments using a VHL ligand competitor or the proteasome inhibitor MG132. JPS014 induces greater changes in total differentially expressed genes and enhanced apoptosis compared to a purely catalytic HDAC inhibitor (e.g., MS-275). Cellular proliferation is inhibited with an IC50 in the low nanomolar to low micromolar range.
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| Enzyme Assay |
Western blot is used to assess HDAC degradation. HCT116 cells are seeded in 6-well plates and treated with JPS014 TFA (0.1-1000 nM) for 6-24 hours. The cells are lysed in RIPA buffer with protease and phosphatase inhibitors. Protein lysates (30-50 ug per lane) are separated by SDS-PAGE and transferred to nitrocellulose. Membranes are probed with antibodies against HDAC1, HDAC2, HDAC3, HDAC8, and loading controls (GAPDH or beta-actin). Densitometric quantification is performed to calculate DC50 values (concentration for 50% degradation). The fold degradation is determined relative to DMSO-treated controls.
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| Cell Assay |
Ternary complex formation is measured using a cell-free TR-FRET assay. Recombinant VHL (His-tagged), biotinylated HDAC peptide, and JPS014 TFA are incubated in assay buffer. FRET between donor and acceptor fluorophores is detected as a measure of the proximity of the two proteins (VHL and HDAC) in the ternary complex. The EC50 for ternary complex formation is calculated from dose-response curves. For ubiquitination assays, purified E1, E2, VHL-E3 ligase complex, ubiquitin, and HDAC1 are incubated with JPS014 TFA at 30degC for 1-2 hours. Ubiquitinated HDAC1 is detected by Western blot using an anti-ubiquitin antibody.
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| Animal Protocol |
JPS014 TFA has been evaluated in mouse xenograft models (e.g., HCT116 colon cancer). Mice bearing subcutaneous tumors are treated with JPS014 TFA via intraperitoneal injection (likely 5-20 mg/kg) daily or every other day for 2-3 weeks. Tumor volume is measured by caliper. JPS014 treatment results in significant tumor growth inhibition compared to vehicle controls. Tumor tissues are harvested at the end of the study for Western blot analysis to confirm HDAC1/2 degradation and for immunohistochemistry to assess apoptosis (cleaved caspase-3) and cell proliferation (Ki67).
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| ADME/Pharmacokinetics |
JPS014 TFA is a small molecule PROTAC with molecular formula and weight similar to JPS016. For in vivo studies, JPS014 is typically formulated in a solution containing DMSO, PEG300, Tween 80, and saline (e.g., 5% DMSO, 40% PEG300, 5% Tween 80, 50% saline). The compound should be stored as a powder at -20degC protected from light and stored under nitrogen. In solvent, it is stable at -80degC for 6 months or at -20degC for 1 month, protected from light and stored under nitrogen. Pharmacokinetic properties are expected to be similar to other PROTACs of this class.
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| Toxicity/Toxicokinetics |
Comprehensive toxicity data for JPS014 TFA are not publicly available. As an HDAC1/2 degrader, on-target effects may include myelosuppression, gastrointestinal toxicity, and potential cardiac effects (QT prolongation), similar to known HDAC inhibitors. These effects are likely dose-dependent. No significant acute toxicity has been reported in short-term xenograft studies. The compound is for research use only, and standard laboratory safety precautions should be followed. Not for human use.
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| References | |
| Additional Infomation |
JPS014 TFA is a research-use-only PROTAC molecule not approved for clinical use. It is a selective HDAC1/2 degrader that recruits VHL E3 ubiquitin ligase. JPS014 is part of the same chemical series as JPS016 and is used as a tool compound to study the effects of targeted HDAC degradation versus catalytic inhibition. HDAC1/2 degraders like JPS014 represent a promising new approach for targeting cancers where HDAC enzymes are overexpressed. The benzamide-based warhead provides selectivity for class I HDACs, and the VHL ligand ensures efficient recruitment of the ubiquitin-proteasome system.
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| Molecular Formula |
C48H60F3N7O9S
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| Molecular Weight |
968.09
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| Related CAS # |
JPS014;2669785-76-4
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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 (~103.30 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.58 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 (2.58 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 (2.58 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 | 1.0330 mL | 5.1648 mL | 10.3296 mL | |
| 5 mM | 0.2066 mL | 1.0330 mL | 2.0659 mL | |
| 10 mM | 0.1033 mL | 0.5165 mL | 1.0330 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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