| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
HBX19818 targets ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme that removes ubiquitin from substrate proteins, regulating their stability and function. By inhibiting USP7, HBX19818 prevents the deubiquitination of key substrate proteins, leading to their degradation and modulation of downstream signaling pathways. The compound shows high selectivity for USP7 over other USP members.
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| ln Vitro |
HBX 19818 is an antimicrobial peptide that forms membrane channels and raises the permeability of those channels to cations. In contrast to its action on Staphylococcus aureus, gramicidin exhibits weak effectiveness against Escherichia coli and Saccharomyces cerevisiae, as evidenced by the survival rate (%) of bacteria within a specific dose range. Saccharomyces cerevisiae is not harmed by bactericidal activity, which is observed over a range of low gramicidin and DODAB concentrations [1].
In vitro, HBX19818 is a potent USP7 inhibitor with an IC₅₀ of 28.1 μM. It exhibits high selectivity over other USP members, such as USP8, USP5, USP2, and USP20 (IC₅₀ >200 μM), and no activity against UCH-L1, UCH-L3, and SENP1. HBX19818 reduces HCT116 cell proliferation, induces caspase activity and PARP cleavage, and arrests HCT116 cancer cells in G1 phase. |
| ln Vivo |
In vivo studies on HBX19818 are limited. As a USP7 inhibitor with antiproliferative effects in cancer cells, it would be expected to be evaluated in animal models of cancer. The compound's effects on tumor growth, apoptosis, and survival would be assessed in xenograft models.
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| Enzyme Assay |
Cell-free enzyme assays for HBX19818 involve measuring its inhibition of USP7 deubiquitinase activity. These assays typically use purified USP7 enzyme and a fluorogenic or ubiquitinated substrate. The enzyme is incubated with the substrate and various concentrations of HBX19818, and the deubiquitination of the substrate is detected by fluorescence or Western blot. IC₅₀ values are calculated from dose-response curves. The compound's selectivity for USP7 over other DUBs is confirmed using similar assays with different enzymes.
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| Cell Assay |
In vitro cellular assays for HBX19818 use cancer cell lines such as HCT116 to assess its antiproliferative and pro-apoptotic effects. Cells are treated with various concentrations of HBX19818, and cell viability is measured using MTT or CCK-8 assays. Apoptosis is assessed by measuring caspase activity and PARP cleavage by Western blot. Cell cycle analysis is performed by flow cytometry. The effects on USP7 substrate ubiquitination and degradation are assessed by Western blot.
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| Animal Protocol |
In vivo animal studies for HBX19818 would typically use mouse xenograft models of cancer. Immunodeficient mice are inoculated with cancer cells, and when tumors reach a certain size, animals are randomized to receive HBX19818 or vehicle control. The compound is administered via intraperitoneal injection or oral gavage. Tumor growth is monitored by caliper measurements. At the end of the study, tumors are collected for analysis of USP7 activity, substrate ubiquitination, and apoptosis.
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| ADME/Pharmacokinetics |
HBX19818 has a molecular formula of C₂₅H₂₈ClN₃O and a molecular weight of 421.96. It is soluble in DMSO (10 mM). The compound should be stored as a powder at -20°C for 3 years and in solution at -80°C for 2 years. HBX19818 is a specific USP7 inhibitor that targets the ubiquitin-proteasome system and cell cycle/DNA damage pathways.
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| Toxicity/Toxicokinetics |
HBX19818 is a potent and selective USP7 inhibitor with an IC₅₀ of 28.1 μM. It exhibits high selectivity over other USP members and no activity against UCH-L1, UCH-L3, and SENP1. The compound reduces HCT116 cell proliferation, induces caspase activity and PARP cleavage, and arrests cells in G1 phase. HBX19818 is for research use only and not for human therapeutic use. It has been studied as a tool compound for the development of USP7 inhibitors for cancer therapy.
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| References |
| Molecular Formula |
C25H28CLN3O
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|---|---|
| Molecular Weight |
421.96
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| Exact Mass |
421.192
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| Elemental Analysis |
C, 71.16; H, 6.69; Cl, 8.40; N, 9.96; O, 3.79
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| CAS # |
1426944-49-1
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| PubChem CID |
73349008
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
631.2±55.0 °C at 760 mmHg
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| Flash Point |
335.6±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.628
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
553
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C(NCCCN(C)CC2C=CC=CC=2)=O)C=C2C(Cl)=C3CCCCC3=NC2=CC=1
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| InChi Key |
ZCALMLVWZSQGGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H28ClN3O/c1-29(17-18-8-3-2-4-9-18)15-7-14-27-25(30)19-12-13-23-21(16-19)24(26)20-10-5-6-11-22(20)28-23/h2-4,8-9,12-13,16H,5-7,10-11,14-15,17H2,1H3,(H,27,30)
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| Chemical Name |
N-[3-[benzyl(methyl)amino]propyl]-9-chloro-5,6,7,8-tetrahydroacridine-2-carboxamide
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| Synonyms |
HBX 19818 HBX-19818 HBX19818
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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 |
| 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) |
1M HCl : 100 mg/mL (~236.99 mM)
DMSO : ~20 mg/mL (~47.40 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (4.74 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 20.0 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 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3699 mL | 11.8495 mL | 23.6989 mL | |
| 5 mM | 0.4740 mL | 2.3699 mL | 4.7398 mL | |
| 10 mM | 0.2370 mL | 1.1849 mL | 2.3699 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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