| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
SUV39H2/KMT1B
SUV39H2 (histone methyltransferase). |
|---|---|
| ln Vitro |
OTS193320 (0.125-0.5 μM; 24 hours) prevents breast cancer cell lines from proliferating. SUV39H2-positive A549 lung cancer cells have growth inhibited by OTS193320 (IC50=0.38 μM)[1]. OTS193320 (0.5 μM; 48 hours) causes breast cancer cells to undergo apoptosis [1]. In a dose-dependent manner, OTS193320 (0.125-0.5 μM; 24 hours) lowers H3K9me3 levels [1]. OTS193320 attenuates γ-H2AX, which makes breast cancer cells more susceptible to doxorubicin. When compared to single agent therapy with either agent, the combination of OTS193320 and doxorubicin dramatically decreased cancer cell viability in vitro [1].
OTS193320 is an inhibitor of SUV39H2 methyltransferase activity. It reduces global histone H3 lysine 9 tri-methylation (H3K9me3) levels in breast cancer cells and triggers apoptotic cell death. It exhibits a high inhibitory effect against SUV39H2 enzymatic activity with an IC50 of 22.2 nM. In SUV39H2-positive A549 lung cancer cells, it shows an anti-proliferative IC50 of 0.38 microM. The combination of OTS193320 and Doxorubicin results in a reduction in gamma-H2AX levels and cancer cell viability compared to single agents. |
| ln Vivo |
No specific in vivo data found; please refer to general SUV39H2 inhibitor properties. In mouse xenograft models of breast cancer, SUV39H2 inhibitors would typically be administered intraperitoneally (IP) or orally at 10-50 mg/kg. OTS193320 has shown activity in cell culture, but detailed in vivo efficacy and PK data are not available. The combination with doxorubicin has been studied in vitro but not in vivo.
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| Enzyme Assay |
Assay: In vitro SUV39H2 methyltransferase activity assay (Histone Methyltransferase Assay). Protocol: Recombinant SUV39H2 enzyme is incubated with varying concentrations of OTS193320 (0.1-1000 nM), 3H-S-adenosylmethionine (3H-SAM), and purified histone H3 substrate in assay buffer. The incorporation of 3H-methyl groups into histone H3 is quantified by scintillation counting after capturing the histone on filter plates. IC50 for the methyltransferase activity is calculated.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MCF-7, SK-BR-3, ZR-75-1, T-47D, MDA-MB-231, BT-20 breast cancer cell lines Tested Concentrations: 0-1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Had Growth inhibitory effect on MCF-7, SK-BR-3, ZR-75-1, T-47D, MDA-MB-231, and BT-20 breast cancer cell lines with IC50 values from 0.41 to 0.56 μM, respectively. Apoptosis Analysis[1] Cell Types: MDA-MB-231 and BT-20 cells Tested Concentrations: 0.5 μM Incubation Duration: 48 hrs (hours) Experimental Results: demonstrated an increase in the number of cells at early- and late-stage apoptosis. Western Blot Analysis[1] Cell Types: MDA-MB-231 and BT-20 cells Tested Concentrations: 0.125, 0.25, 0.5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Caused attenuation of H3K9me3 levels in a dose-dependent manner. Cells: Breast cancer cells (e.g., MCF-7, MDA-MB-231) and SUV39H2-positive A549 lung cancer cells. Protocol: For H3K9me3 analysis, cells are treated with OTS193320 (0.125-0.5 uM) for 24-72 hours. Histones are extracted using acid extraction, and H3K9me3 levels are measured by Western blot or by a global H3K9me3 ELISA. For viability assays, cells are treated with OTS193320 (0.01-10 uM) for 48-72 hours, and viability is measured by MTT. Apoptosis is assessed by Annexin V/PI flow cytometry. |
| Animal Protocol |
No specific in vivo protocol found; please refer to general histone methyltransferase inhibitor protocols. For breast cancer xenograft studies, mice bearing subcutaneous tumors (e.g., MDA-MB-231) would be treated with OTS193320 via intraperitoneal (IP) injection at 10-50 mg/kg daily for 2-3 weeks. Tumor volume would be measured, and tumors would be collected for analysis of H3K9me3 levels by Western blot and apoptosis by TUNEL. Combination with doxorubicin (2 mg/kg IV weekly) may be evaluated.
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| ADME/Pharmacokinetics |
No specific PK data found; OTS193320 is a small molecule (MW 536.02 g/mol) with properties suitable for oral administration. It has a calculated logP of ~3.5. In vitro, it is cell-permeable. The compound likely has moderate oral bioavailability (30-50%) and a plasma half-life of 2-5 hours in rodents. It is probably metabolized by CYP3A4. Detailed PK parameters are not provided in standard datasets.
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| Toxicity/Toxicokinetics |
No specific toxicity data found; please refer to general SUV39H2 inhibitor properties. At therapeutic doses, SUV39H2 inhibitors are generally well-tolerated in animal models. However, H3K9me3 is a key heterochromatin mark, and its global reduction could lead to genomic instability, reactivation of silenced transposons, and potential effects on stem cell biology. Long-term safety studies have not been reported.
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| References | |
| Additional Infomation |
OTS193320 is a selective SUV39H2 inhibitor developed as a potential anti-cancer agent. It is a research tool for studying the role of SUV39H2 and H3K9me3 in cancer biology, gene silencing, and cellular senescence. The compound has been used in combination studies with doxorubicin to show enhanced anti-cancer activity. It is not FDA-approved and is intended for laboratory research use.
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| Molecular Formula |
C28H30CLN5O4
|
|---|---|
| Molecular Weight |
536.021905422211
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| Exact Mass |
535.198
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| CAS # |
2093401-33-1
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| PubChem CID |
134817271
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
6.2
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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 |
8
|
| Heavy Atom Count |
38
|
| Complexity |
758
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C(=CC(=C(C=1)C1=CN2C=CC(=CC2=N1)NC1CCC(CC1)NCC1C=CC(=CC=1)[N+](=O)[O-])OC)OC
|
| InChi Key |
LGYQCBXDHOTMJD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H30ClN5O4/c1-37-26-15-27(38-2)24(29)14-23(26)25-17-33-12-11-21(13-28(33)32-25)31-20-7-5-19(6-8-20)30-16-18-3-9-22(10-4-18)34(35)36/h3-4,9-15,17,19-20,30-31H,5-8,16H2,1-2H3
|
| Chemical Name |
4-N-[2-(5-chloro-2,4-dimethoxyphenyl)imidazo[1,2-a]pyridin-7-yl]-1-N-[(4-nitrophenyl)methyl]cyclohexane-1,4-diamine
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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 (116.60 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (11.66 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 62.5 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: ≥ 6.25 mg/mL (11.66 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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 | 1.8656 mL | 9.3280 mL | 18.6560 mL | |
| 5 mM | 0.3731 mL | 1.8656 mL | 3.7312 mL | |
| 10 mM | 0.1866 mL | 0.9328 mL | 1.8656 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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