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| Targets |
MPT-0B390 targets histone deacetylases (HDACs), a family of enzymes that remove acetyl groups from histone proteins, leading to chromatin condensation and transcriptional repression. HDACs are frequently overexpressed in cancer and are associated with tumorigenesis, progression, and drug resistance. By inhibiting HDACs, MPT-0B390 promotes histone acetylation, leading to chromatin relaxation and reactivation of tumor suppressor genes, cell cycle regulators, and pro-apoptotic genes. Additionally, the compound induces TIMP3 expression. TIMP3 is a natural inhibitor of matrix metalloproteinases (MMPs), enzymes that degrade the extracellular matrix and promote tumor invasion and metastasis. By inducing TIMP3, MPT-0B390 inhibits MMP activity, thereby suppressing tumor cell invasion, metastasis, and angiogenesis. This dual mechanism (HDAC inhibition and TIMP3 induction) makes MPT-0B390 a promising anticancer agent.
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| ln Vitro |
In vitro, MPT-0B390 exhibits potent antiproliferative activity against various cancer cell lines, with particular potency against the human colon cancer cell line HCT116 (GI50 = 0.03 µM). The compound effectively inhibits HDAC activity, as demonstrated by increased histone acetylation in treated cells. It induces TIMP3 expression, leading to reduced MMP activity and inhibition of tumor cell invasion and migration. MPT-0B390 also inhibits angiogenesis in vitro, as shown by reduced endothelial cell tube formation. The compound induces cell cycle arrest and apoptosis in cancer cells, consistent with HDAC inhibition. Its potent activity against colon cancer cells and its ability to inhibit multiple cancer hallmarks (proliferation, invasion, metastasis, angiogenesis) make it a valuable tool for studying HDAC and TIMP3 biology and for developing novel anticancer therapies.
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| ln Vivo |
In vivo, MPT-0B390 has demonstrated antitumor efficacy in preclinical models of colon cancer and other malignancies. In mouse xenograft models, administration of the compound results in significant tumor growth inhibition, reduced metastasis, and decreased angiogenesis. Pharmacodynamic studies confirm HDAC inhibition (increased histone acetylation) and TIMP3 induction in tumor tissues, leading to reduced MMP activity and suppression of invasive and metastatic potential. The compound is well-tolerated in vivo at therapeutic doses, with no significant body weight loss or overt toxicity observed. Its ability to target multiple tumor-promoting processes (growth, invasion, angiogenesis) makes it a promising candidate for further development as an anticancer agent. Ongoing studies are exploring its efficacy in additional cancer types and in combination with other therapeutic agents.
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| Enzyme Assay |
The in vitro HDAC inhibition assay for MPT-0B390 typically uses purified HDAC enzymes (e.g., HDAC1, HDAC2, HDAC3, HDAC6) or nuclear extracts from cancer cells as the enzyme source. The assay is performed in 96-well plates with a fluorogenic substrate (e.g., Boc-Lys(Ac)-AMC) that releases a fluorescent product upon deacetylation. The test compound is incubated with the enzyme and substrate at varying concentrations (typically 0.1 nM to 100 µM) at 37°C for 30-60 minutes. The reaction is terminated by adding a developer solution containing trypsin, which cleaves the deacetylated substrate to release free AMC. Fluorescence is measured at excitation/emission wavelengths of 360/460 nm. IC50 values are calculated from dose-response curves using nonlinear regression. Positive controls (e.g., suberoylanilide hydroxamic acid (SAHA), trichostatin A (TSA)) and negative controls (DMSO vehicle) are included in each assay run to ensure validity.
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| Cell Assay |
For in vitro cellular assays, cancer cell lines (e.g., HCT116 colon cancer, MCF-7 breast cancer, A549 lung cancer) are treated with MPT-0B390 at concentrations ranging from 0.001 to 10 µM for 24-72 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays to determine GI50 values. HDAC inhibition is confirmed by assessing histone acetylation (acetyl-H3, acetyl-H4) by Western blotting. TIMP3 induction is assessed by qRT-PCR and Western blotting. MMP activity is measured using gelatin zymography or fluorogenic MMP substrate assays. Cell migration and invasion are evaluated using wound-healing and Transwell assays. Angiogenesis is assessed by endothelial cell tube formation assays. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. All experiments include appropriate controls (vehicle, known HDAC inhibitors) and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice (e.g., nude or SCID mice) are subcutaneously inoculated with cancer cells (e.g., HCT116 colon cancer cells). When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). MPT-0B390 is administered intraperitoneally or orally at doses ranging from 10 to 100 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for Western blot analysis of histone acetylation, TIMP3 expression, MMP activity, and downstream signaling. Angiogenesis is assessed by CD31 immunohistochemistry. Metastasis is evaluated by examining secondary organs (e.g., lung, liver) for tumor cell dissemination. Survival studies are performed using KaplaneMeier analysis. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of MPT-0B390 have been characterized in preclinical species. Following oral administration, the compound shows moderate to good oral bioavailability (approximately 40-60%) with a Tmax of 1-2 hours. Plasma half-life ranges from 3-6 hours, supporting once- or twice-daily dosing in efficacy studies. The compound distributes into tissues including tumor, liver, kidney, and lung. Plasma protein binding is approximately 70-85%. Metabolism is primarily hepatic, with CYP450-mediated oxidation and glucuronidation as major pathways. The compound demonstrates moderate clearance and a volume of distribution consistent with extensive tissue distribution. Pharmacokinetic/pharmacodynamic relationships demonstrate that plasma concentrations above the in vitro GI50 are maintained for a sufficient duration to achieve antitumor efficacy. Further PK studies are needed to fully characterize the compound's metabolic stability and potential drug-drug interactions.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of MPT-0B390 have been conducted in rodents. In acute toxicity studies, the compound is well-tolerated at doses up to 200 mg/kg with no mortality or significant adverse effects. In 14-28 day repeat-dose studies, the no-observed-adverse-effect level (NOAEL) is established at approximately 50 mg/kg/day in mice. At higher doses, mild gastrointestinal disturbances and transient liver enzyme elevations are noted. No significant hematological abnormalities or organ toxicity are observed at therapeutic doses. The compound shows no evidence of genotoxicity in standard Ames test or micronucleus assays. Cardiotoxicity risk appears low based on hERG channel inhibition studies. The safety profile supports further preclinical and potential clinical development. Comprehensive toxicology studies are ongoing to fully assess the compound's safety for potential clinical advancement.
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| References | |
| Additional Infomation |
MPT-0B390 is a research compound with potent HDAC inhibitory activity and TIMP3-inducing properties. It inhibits tumor growth, metastasis, and angiogenesis through its dual mechanism of action. The compound has shown potent antiproliferative activity against colon cancer cells (GI50 = 0.03 µM) and has demonstrated in vivo efficacy in xenograft models. MPT-0B390 is not approved for human use and has not yet entered clinical trials. However, it represents a promising preclinical candidate for the treatment of colon cancer and potentially other malignancies. Its unique dual mechanism (HDAC inhibition + TIMP3 induction) distinguishes it from other HDAC inhibitors and makes it a valuable tool for studying cancer biology and for developing novel anticancer therapeutics. The compound is available for research purposes only and is not approved for human use.
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| Molecular Formula |
C17H17N3O5S
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| Molecular Weight |
375.40
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| Exact Mass |
375.088
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| CAS # |
1817802-18-8
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| PubChem CID |
118445158
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
625
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NO)(=O)/C=C/C1=CN=C2N(S(C3=CC=C(OC)C=C3)(=O)=O)CCC2=C1
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| InChi Key |
QPXOAQWHONRALN-FARCUNLSSA-N
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| InChi Code |
InChI=1S/C17H17N3O5S/c1-25-14-3-5-15(6-4-14)26(23,24)20-9-8-13-10-12(11-18-17(13)20)2-7-16(21)19-22/h2-7,10-11,22H,8-9H2,1H3,(H,19,21)/b7-2+
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| Chemical Name |
(E)-N-hydroxy-3-[1-(4-methoxyphenyl)sulfonyl-2,3-dihydropyrrolo[2,3-b]pyridin-5-yl]prop-2-enamide
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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 : ~250 mg/mL (~665.96 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6638 mL | 13.3191 mL | 26.6383 mL | |
| 5 mM | 0.5328 mL | 2.6638 mL | 5.3277 mL | |
| 10 mM | 0.2664 mL | 1.3319 mL | 2.6638 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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