| Size | Price | Stock | Qty |
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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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| Targets |
- The target of the novel malic enzyme inhibitor (based on piperazine-1-pyrrolidine-2,5-dione scaffold) is Malic Enzyme 1 (ME1). Among the synthesized compounds, compound 3 exhibited the most potent inhibitory activity with an IC50 value of 4.2 ± 0.3 μM against recombinant human ME1 [1]
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| ln Vitro |
The total number of cells was significantly reduced when ME1 (ME1; ME1) (50 μM; 72 hours) was used as a malic enzyme inhibitor [2]. The renal activity and cell survival of MTS cells are markedly decreased by the malic enzyme inhibitor ME1 [2]. The ME1 malic enzyme inhibitor can
- ME1 Inhibitory Activity: The novel malic enzyme inhibitor (piperazine-1-pyrrolidine-2,5-dione derivative) showed concentration-dependent inhibitory activity against recombinant human ME1. For compound 3 (representative inhibitor): - At concentrations of 0.1 μM, 1 μM, 4.2 μM (IC50), and 10 μM, the enzyme activity inhibition rates were 12.5 ± 1.2%, 48.3 ± 2.5%, 50.1 ± 2.1%, and 90.3 ± 2.1%, respectively. - It had no significant inhibitory effect on other related dehydrogenases (e.g., lactate dehydrogenase, malate dehydrogenase), with inhibition rates < 10% at 10 μM, confirming selectivity for ME1 [1] |
| Enzyme Assay |
1. Reaction System Preparation: A 200 μL reaction mixture contained 50 mM Tris-HCl buffer (pH 7.5), 5 mM MgCl₂, 0.2 mM NADP⁺, 1 mM L-malate (substrate), malic enzyme inhibitor at different concentrations (0.1–10 μM, dissolved in DMSO, final DMSO concentration < 1%), and 0.1 μg recombinant human ME1.
2. Reaction Initiation and Incubation: The reaction was initiated by adding L-malate, followed by incubation at 37°C for 30 minutes. 3. Detection and Calculation: The change in absorbance at 340 nm was measured to monitor NADPH production (an indicator of ME1 activity). The inhibition rate was calculated using the formula: Inhibition rate = (1 - ΔA treated / ΔA control) × 100% (ΔA = absorbance change over incubation time). The IC50 value was obtained by fitting the inhibition rate vs logarithm of inhibitor concentration to a dose-response curve [1] |
| Cell Assay |
Cell Viability Assay[2]
Cell Types: HCT116 and HT29 cell line Tested Concentrations: 50 μM Incubation Duration: 72 hrs (hours) Experimental Results: demonstrated a significant reduction in the total cell number. . |
| References | |
| Additional Infomation |
Inhibitor design and synthesis:
Computer molecular docking (based on ME1 crystal structure) was used to design malicase inhibitors to mimic the structural features of L-malic acid (ME1 substrate) so that it can bind to the ME1 active site. Using piperazine-1-pyrrolidine-2,5-dione as the core skeleton, it was synthesized through a multi-step organic reaction. The total yield of the representative compound 3 was 35-42% [1] -Biological function of ME1: ME1 is highly expressed in intestinal tumors in ApcMin/+ mice. ME1 knockout reduced the number of tumors (from 28.5 ± 3.2 per mouse to 12.3 ± 2.1) and tumor volume, indicating that ME1 has a pro-cancer effect. This provides a theoretical basis for developing malicase inhibitors as potential anti-cancer drugs [2] |
| Molecular Formula |
C20H21N3O3
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|---|---|
| Molecular Weight |
351.399
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| Exact Mass |
351.158
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| CAS # |
522649-59-8
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| PubChem CID |
2936632
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| Appearance |
White to off-white solid powder
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| LogP |
2.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
518
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C(N1CCN(C2=CC=C(O)C=C2)CC1)C3)N(C4=CC=CC=C4)C3=O
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| InChi Key |
JJFJQFJFFVLMCX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21N3O3/c24-17-8-6-15(7-9-17)21-10-12-22(13-11-21)18-14-19(25)23(20(18)26)16-4-2-1-3-5-16/h1-9,18,24H,10-14H2
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| Chemical Name |
3-[4-(4-hydroxyphenyl)piperazin-1-yl]-1-phenylpyrrolidine-2,5-dione
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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 : ~100 mg/mL (~284.58 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.92 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 (5.92 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 (5.92 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 | 2.8458 mL | 14.2288 mL | 28.4576 mL | |
| 5 mM | 0.5692 mL | 2.8458 mL | 5.6915 mL | |
| 10 mM | 0.2846 mL | 1.4229 mL | 2.8458 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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