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| Targets |
MPT0B392 targets tubulin, the protein that polymerizes to form microtubules, which are essential components of the cytoskeleton and play critical roles in cell division, intracellular transport, and cell shape. The compound is a microtubule-depolymerizing agent that inhibits tubulin polymerization. By inhibiting tubulin polymerization, MPT0B392 triggers mitotic arrest, leading to the activation of c-Jun N-terminal kinase (JNK). JNK activation leads to mitochondrial membrane potential loss and caspase cleavage, ultimately resulting in apoptosis. The compound's mechanism of action involves the disruption of microtubule dynamics and the induction of apoptosis through JNK activation.
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| ln Vitro |
The cell viability of HL60, MOLT-4, and CCRF-CEM cells is inhibited by MPT0B392 (B392) (0.001-0.1 μM; 24 and 48 hours) with IC50 values of 0.02 μM, 0.03 μM, and 0.02 μM, in that order [1]. MPT0B392 (0.1 μM; 48 hours) causes HL60 cancer cells to undergo apoptosis [1]. MPT0B392 (0.1 μM, 6-48 hours; 0.01-0.1 μM, 24 and 48 hours) induces cell arrest in the G2/M phase, which is followed by a concentration- and time-dependent accumulation in the subG1 phase [1]. MPT0B392 (0.1 μM; 48 hours) decreases Mcl-1L and increases Bcl-2 and Mcl-1S phosphorylation[1].
MPT0B392 demonstrates potent in vitro activity as a microtubule-depolymerizing agent and apoptosis inducer. The compound induces apoptosis in HL60 cancer cells. It inhibits tubulin polymerization and triggers mitotic arrest, followed by mitochondrial membrane potential loss and caspase cleavage by activation of JNK, ultimately leading to apoptosis. MPT0B392 enhances the cytotoxicity of sirolimus against drug-resistant acute leukemia cells and multidrug-resistant cell lines. The compound's activity is concentration-dependent, with effects observed at appropriate concentrations (0.1 microM for 6-48 hours). MPT0B392 is an orally active compound. Comprehensive in vitro activity data have been reported in research publications. |
| ln Vivo |
In an in vivo xenograft model, MPT0B392 (oral gavage; 50 mg/kg or 100 mg/kg for 12 or 14 days) has demonstrated comparatively strong antileukemic action [1].
In vivo, MPT0B392 has been studied for its potential in cancer therapy. As an orally active quinoline derivative that induces apoptosis, the compound has potential for the treatment of leukemia and other cancers. MPT0B392 enhances the cytotoxicity of sirolimus against drug-resistant acute leukemia cells. The compound's oral bioavailability makes it suitable for convenient dosing in research settings. Comprehensive in vivo efficacy studies have been reported in research publications. The compound's ability to induce apoptosis and inhibit tumor growth in animal models supports its potential for cancer research. |
| Enzyme Assay |
In vitro tubulin polymerization assays for MPT0B392 involve measuring the inhibition of tubulin polymerization. Purified tubulin is incubated with varying concentrations of the test compound in polymerization buffer containing GTP. Tubulin polymerization is monitored by measuring the increase in absorbance at 340 nm over time using a spectrophotometer. IC50 values for inhibition of polymerization are calculated from dose-response curves. Alternatively, cell-based assays can assess the effects of the compound on the microtubule network by immunofluorescence staining of tubulin in treated cells. Each concentration is typically tested in duplicate or triplicate with appropriate positive controls (known microtubule inhibitors such as colchicine or paclitaxel) and vehicle controls.
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| Cell Assay |
Cell viability assay [1]
Cell Types: HL60 (acute promyelocytic leukemia), MOLT-4 (acute lymphoblastic leukemia), CCRF-CEM (acute lymphoblastic leukemia) Cell Tested Concentrations: 0.001, 0.003, 0.01, 0.03, 0.1 μM Incubation Duration: 24 48 hrs (hours) Experimental Results: Inhibition of cell viability. Apoptosis analysis[1] Cell Types: HL60 Cell Tested Concentrations: 0.1 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced apoptosis of cancer cells. Cell cycle analysis[1] Cell Types: HL60 Cell Tested Concentrations: 0.1 μM or 0.01, 0.03, 0.1 μM Incubation Duration: 0.1 μM, 6-48 hrs (hours); 0.01-0.1 μM, 24 and 48 hrs (hours) Experimental Results: Triggered cell arrest at G2/M phase and then accumulate in the subG1 phase in a concentration- and time-dependent manner. Western Blot Analysis [1] Cell Types: HL60 cells Tested Concentrations: 0.1 μM Incubation Duration: 48 hrs (hours) Experimental Results: Bcl-2 and Mcl-1S phosphorylation increased, and Mcl-1L phosphorylation diminished. In vitro cellular assays for MPT0B392 are performed using cancer cell lines, particularly leukemia cell lines such as HL60, and multidrug-resistant cell lines. Cells are treated with varying concentrations of the compound for defined time periods (6-48 hours). Cell viability and proliferation are measured using MTT or CellTiter-Glo assays. Apoptosis is assessed by annexin V/propidium iodide staining, caspase activity assays, or by measuring mitochondrial membrane potential using fluorescent dyes such as JC-1. JNK activation is assessed by Western blot for phosphorylated JNK. Cell cycle analysis is performed by flow cytometry following propidium iodide staining. Cytotoxicity is assessed in parallel to ensure that observed effects are not due to cell death. IC50 values for inhibition of cell proliferation are calculated from dose-response curves. |
| Animal Protocol |
Animal/Disease Models: Severe combined immunodeficiency (SCID) mice [1]
Doses: 50 mg/kg or 100 mg/kg Route of Administration: po (oral gavage); 12 or 14 days Experimental Results: Caused significant tumor growth delay (83.3% ) and tumor volume suppression without loss of body weight. In vivo animal studies for MPT0B392 are conducted using mouse xenograft models of leukemia or other cancers. Immunodeficient mice are implanted subcutaneously or intravenously with cancer cells. Once tumors are established or leukemia is engrafted, animals are randomized into treatment groups and administered MPT0B392 via oral gavage, either alone or in combination with sirolimus. Tumor growth is measured using calipers (in subcutaneous models). Survival is monitored (in systemic models). Apoptosis and signaling pathway activation are assessed in tumor tissues by immunohistochemistry or Western blot. Pharmacokinetic studies assess drug concentrations in plasma and tissues. Animals are monitored for clinical signs and body weight. Efficacy is expressed as tumor growth inhibition or survival improvement compared to vehicle-treated controls. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of MPT0B392 have been characterized in preclinical studies. The compound has a molecular formula of C19H20N2O6S and a molecular weight of 404.44 g/mol. Its chemical name is 6-methoxy-2-(3,4,5-trimethoxybenzenesulfonyl)quinolin-5-amine. MPT0B392 is orally active. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and oral bioavailability have been characterized in animal models. The compound's oral bioavailability supports its use in preclinical studies of cancer. Detailed pharmacokinetic data are available from research publications.
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| Toxicity/Toxicokinetics |
MPT0B392 is intended for laboratory research use only and has not undergone comprehensive clinical toxicology testing. As a microtubule-depolymerizing agent that induces apoptosis, the compound would be expected to have effects on dividing cells, which could include both cancer cells and normal rapidly dividing cells. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has been conducted as part of preclinical development. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
MPT0B392 is an orally active quinoline derivative that induces JNK activation and apoptosis. It is a novel microtubule-depolymerizing agent that enhances sirolimus cytotoxicity against drug-resistant leukemia cells. MPT0B392 inhibits tubulin polymerization and triggers mitotic arrest and caspase-mediated apoptosis. The compound has a molecular formula of C19H20N2O6S and a molecular weight of 404.44 g/mol. MPT0B392 has not entered clinical trials and is available for research purposes only.
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| Molecular Formula |
C19H20N2O6S
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| Molecular Weight |
404.44
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| Exact Mass |
404.104
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| CAS # |
1346169-92-3
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| PubChem CID |
56834893
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
598
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C2C(=C(N)C(OC)=CC=2)C=CC=1S(C1=CC(OC)=C(OC)C(OC)=C1)(=O)=O
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| InChi Key |
RBBRZMLZQCYQJM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H20N2O6S/c1-24-14-7-6-13-12(18(14)20)5-8-17(21-13)28(22,23)11-9-15(25-2)19(27-4)16(10-11)26-3/h5-10H,20H2,1-4H3
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| Chemical Name |
6-methoxy-2-(3,4,5-trimethoxyphenyl)sulfonylquinolin-5-amine
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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 (~247.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.18 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4726 mL | 12.3628 mL | 24.7255 mL | |
| 5 mM | 0.4945 mL | 2.4726 mL | 4.9451 mL | |
| 10 mM | 0.2473 mL | 1.2363 mL | 2.4726 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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