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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
H3B-120 targets carbamoyl phosphate synthetase 1 (CPS1), a mitochondrial enzyme that catalyzes the synthesis of carbamoyl phosphate from ammonia, bicarbonate, and ATP. CPS1 is the rate-limiting enzyme of the urea cycle, which is responsible for the detoxification of ammonia. H3B-120 is a competitive, selective, and allosteric inhibitor of CPS1. By binding to CPS1, it inhibits carbamoyl phosphate synthesis, leading to a reduction in urea production. The compound’s anti-cancer activity is thought to be related to its effects on cancer cell metabolism, as some cancers rely on the urea cycle for growth and survival.
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| ln Vitro |
H3B-120 had no inhibitory effect on the dihydroorotase, aspartyl transcarbamylase, and CPS2 activity of CAD [1]. H3B-120 binds to an allosteric pocket situated between the ATP A domain and the integration domain to cause inhibition [1]. In a dose-dependent way, H3B-120 (25, 50, 75, and 100 μM) suppresses the formation of urea, but its cellular efficacy is much lower than that of enzymatic tests [1]. H3B-120 has a short half-life of 40 minutes [1].
In vitro, H3B-120 inhibits CPS1 enzyme activity with an IC50 of 1.5 µM and a Ki of 1.4 µM. In cell-based assays, the compound inhibits urea production in a dose-dependent manner. Its intracellular efficacy is significantly lower than its potency in enzymatic assays, suggesting that cellular permeability or other factors may limit its activity. H3B-120 exhibits anti-cancer activity in cancer cell lines. These in vitro activities confirm its potential as a research tool for studying CPS1 function and cancer metabolism. |
| ln Vivo |
In vivo activity of H3B-120 has been evaluated in animal models of cancer. The compound has shown anti-tumor activity in xenograft models. Its mechanism involves inhibition of CPS1, leading to disruption of the urea cycle and metabolic stress in cancer cells. The compound’s selectivity for CPS1 over other enzymes contributes to its potential as a targeted therapy. Further in vivo studies are needed to fully characterize its efficacy and safety profile.
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| Enzyme Assay |
In vitro enzyme assays for H3B-120 involve measuring its inhibition of CPS1 activity. CPS1 is incubated with its substrates (ammonia, bicarbonate, and ATP) and varying concentrations of H3B-120. The production of carbamoyl phosphate is measured using a coupled assay. The IC50 (1.5 µM) and Ki (1.4 µM) are determined from dose-response curves. These assays confirm the compound’s mechanism as a competitive, selective, and allosteric inhibitor of CPS1.
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| Cell Assay |
In vitro cellular assays for H3B-120 are conducted in cancer cell lines. Cells are treated with the compound at various concentrations, and urea production is measured. Cell viability and proliferation are assessed using MTT or CellTiter-Glo assays. The compound’s effects on downstream metabolic pathways are also studied. These assays confirm the compound’s anti-cancer activity and its mechanism of action.
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| Animal Protocol |
In vivo animal experiments with H3B-120 are conducted in mouse xenograft models of cancer. Immunodeficient mice are engrafted with cancer cells, and H3B-120 is administered orally or by injection. Tumor growth is measured over time, and tumor tissues are harvested for analysis of CPS1 activity, urea cycle metabolites, and apoptosis markers. These studies evaluate the compound’s efficacy and its mechanism of action in vivo.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for H3B-120 have been partially characterized. The compound has a molecular weight of 372.48 and is soluble in DMSO (74 mg/mL). Its bioavailability and half-life have not been extensively reported. The compound is typically stored as a powder at -20°C (3 years) or 4°C (2 years), and in solution at -80°C (6 months) or -20°C (1 month). Further PK studies would be needed to support any potential clinical development.
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| Toxicity/Toxicokinetics |
H3B-120 is generally well-tolerated in animal studies at therapeutic doses. Its selectivity for CPS1 may contribute to a favorable safety profile. However, comprehensive toxicological evaluations have not been extensively published. The compound is intended for research use and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Carbamoyl phosphate synthase 1 inhibitors
H3B-120 is a selective, competitive, and allosteric inhibitor of carbamoyl phosphate synthetase 1 (CPS1). It has an IC50 of 1.5 µM and a Ki of 1.4 µM. The compound exhibits anti-cancer activity and is used in research to study the urea cycle and cancer metabolism. It inhibits urea production in a dose-dependent manner. Its chemical name is N1-benzyl-N1-methyl-N4-(4-methylthiazol-2-yl)piperidine-1,4-dicarboxamide. The compound is available in high purity for research applications. Its selectivity for CPS1 makes it a valuable tool for studying metabolic pathways in cancer. |
| Molecular Formula |
C19H24N4O2S
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|---|---|
| Molecular Weight |
372.4845
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| Exact Mass |
372.161
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| CAS # |
2194903-42-7
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| PubChem CID |
132355378
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| Appearance |
Off-white to yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
490
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C=C(C)N=C1NC(C1CCN(C(N(C)CC2C=CC=CC=2)=O)CC1)=O
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| InChi Key |
ZEVOZXRSCSSPAO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H24N4O2S/c1-14-13-26-18(20-14)21-17(24)16-8-10-23(11-9-16)19(25)22(2)12-15-6-4-3-5-7-15/h3-7,13,16H,8-12H2,1-2H3,(H,20,21,24)
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| Chemical Name |
1-N-benzyl-1-N-methyl-4-N-(4-methyl-1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide
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| Synonyms |
H3B120 H3B 120
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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) |
DMSO : ~62.5 mg/mL (~167.79 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.58 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 20.8 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: ≥ 2.08 mg/mL (5.58 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 20.8 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: ≥ 2.08 mg/mL (5.58 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 | 2.6847 mL | 13.4235 mL | 26.8471 mL | |
| 5 mM | 0.5369 mL | 2.6847 mL | 5.3694 mL | |
| 10 mM | 0.2685 mL | 1.3424 mL | 2.6847 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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