| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
AMPK[1]
COH-SR4 targets mitochondria by uncoupling oxidative phosphorylation. This induces energetic stress on cells, leading to indirect activation of AMPK. The compound inhibits mTOR signaling through AMPK activation. COH-SR4 does not affect ERK/MEK MAPK signaling. By activating AMPK, the compound inhibits adipocyte differentiation and suppresses adipogenesis in 3T3-L1 cells through downstream modulation of the mTORC1 signaling pathway. |
|---|---|
| ln Vitro |
In 3T3-L1 preadipocytes and cancer cells like HL-60, HeLa, and MCF-7, COH-SR4 (1–5 μM; 24 hours) causes a dose-dependent increase in the phosphorylation of AMPK and its substrate ACC[1]. Significant inhibition of 3T3-L1 adipocyte differentiation is observed in a dose-dependent manner with COH-SR4 (3-5 μM; 7 days)[1]. In a 24-hour period, COH-SR4 (1–5 μM) stimulates cell G1 cycle arrest[1]. Key transcription factors associated with adipogenesis and lipogenic proteins are downregulated when COH-SR4 is present, leading to a significant reduction in intracellular lipid accumulation[1].
In vitro studies demonstrate that COH-SR4 exhibits potent anti-proliferative activity against various cancer cell lines. It shows a strong inhibitory effect on the survival of melanoma cells with IC50 values of 5 μM for B16-F0, 6 μM for Hs600T, and 11 μM for A2058 cell lines. The compound does not cause significant cytotoxicity in normal human aortic vascular smooth muscle cells (HAVSMG). COH-SR4 prevents cell proliferation and promotes cell death in leukemia, lung cancer, melanoma, and hepatocarcinoma. It also suppresses adipogenesis in 3T3-L1 cells. |
| ln Vivo |
In obese mice fed a high-fat diet (HFD), COH-SR4 (5 mg/kg; ig; three times/week; for six weeks) decreases body weight and fat mass without changing food intake[2]. In HFD obese mice, COH-SR4 improves dyslipidemia and glycemic control[2]. In HFD obese mice, COH-SR4 reduces adipose tissue hypertrophy and modifies circulating adipokine levels[2]. In HFD obese mice, COH-SR4 prevents hepatic lipid accumulation and fatty liver[2].
In vivo, COH-SR4 prevents cell proliferation and promotes cell death in many human cancers including leukemia, lung cancer, melanoma, and hepatocarcinoma in animal models. It inhibits vemurafenib-resistant melanoma in vivo. The compound's mechanism involves inducing energetic stress on cells, leading to AMPK activation and mTOR inhibition. COH-SR4 has been studied for its potential in obesity and metabolic disorders research. |
| Enzyme Assay |
The mitochondrial uncoupling activity of COH-SR4 can be assessed using isolated mitochondria or intact cells. In a typical assay, mitochondrial membrane potential is measured using fluorescent dyes such as JC-1 or TMRE. Oxygen consumption rate (OCR) is measured using a Seahorse analyzer to assess uncoupling of oxidative phosphorylation. AMPK activation is assessed by Western blotting using phospho-specific antibodies for AMPK (Thr172) and its downstream target ACC (Ser79).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: 3T3-L1 preadipocytes, HL-60 cells, HeLa cells, MCF-7 cells Tested Concentrations: 1 μM, 3 μM, 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Indirectly activated AMPK. Cell Cycle Analysis[1] Cell Types: 3T3-L1 cells Tested Concentrations: 1 μM, 3 μM, 5 μM Incubation Duration: 24 hrs (hours) Experimental Results: Modulated the level of proteins active during S and G2 phases of the cell cycle. The cellular activity of COH-SR4 is assessed using various cancer cell lines including melanoma (B16-F0, Hs600T, A2058), leukemia, lung cancer, and hepatocarcinoma cells. Cells are seeded in 96-well plates and treated with escalating concentrations of COH-SR4. Cell viability is measured using MTT or CellTiter-Glo assays, and IC50 values are calculated. Normal human aortic vascular smooth muscle cells (HAVSMG) are used as controls to assess cytotoxicity. AMPK activation and mTOR inhibition are assessed by Western blotting. |
| Animal Protocol |
Animal/Disease Models: Nine-week old male C57BL/6J mice[2]
Doses: 5 mg/kg Route of Administration: po (oral gavage), three times a week, for 6 weeks Experimental Results: diminished body weight and fat mass in HFD obese mice. COH-SR4 has been evaluated in animal models of cancer, including vemurafenib-resistant melanoma models. In these studies, the compound is administered at various doses and schedules. Tumor volumes are measured twice weekly. The compound's ability to prevent cell proliferation and promote cell death is assessed. COH-SR4 has also been studied in models of obesity and metabolic disorders. |
| ADME/Pharmacokinetics |
No detailed pharmacokinetic data has been published for COH-SR4. The compound has a molecular weight of 350.02 g/mol and is soluble in DMSO at 125 mg/mL. It is typically stored at -20°C. The compound is a small molecule with a LogP that suggests moderate lipophilicity. Further studies would be needed to characterize its absorption, distribution, metabolism, and excretion properties, including oral bioavailability, plasma protein binding, clearance, and half-life.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for COH-SR4. In vitro studies show that the compound does not cause significant cytotoxicity in normal human aortic vascular smooth muscle cells (HAVSMG). As a mitochondrial uncoupler, the compound may have on-target toxicity in tissues with high energy demands. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound is intended for research use only.
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| References | |
| Additional Infomation |
City of Hope (COH) has anti-tumor activity.
COH-SR4 (CAS# 73439-19-7) is a mitochondrial uncoupler that induces energetic stress, leading to AMPK activation and mTOR inhibition. It exhibits potent anti-proliferative activity against leukemia, melanoma, breast cancer, and lung cancer with IC50 values of 5-11 μM in melanoma cell lines. The compound inhibits vemurafenib-resistant melanoma in vivo. It suppresses adipogenesis in 3T3-L1 cells through AMPK activation. COH-SR4 is used in obesity and metabolic disorders research. The molecular formula is C13H8Cl4N2O. |
| Molecular Formula |
C13H8CL4N2O
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|---|---|
| Molecular Weight |
350.03
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| Exact Mass |
347.939
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| CAS # |
73439-19-7
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| PubChem CID |
595311
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| Appearance |
Gray to gray purple solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
363.2±42.0 °C at 760 mmHg
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| Melting Point |
298-300 °C
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| Flash Point |
173.5±27.9 °C
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| Vapour Pressure |
0.0±0.8 mmHg at 25°C
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| Index of Refraction |
1.706
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| LogP |
7.01
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
294
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=C(C=C(C=C1Cl)Cl)NC(=O)NC2=CC(=CC(=C2)Cl)Cl
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| InChi Key |
VKVJIWVUYNTBEZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H8Cl4N2O/c14-7-1-8(15)4-11(3-7)18-13(20)19-12-5-9(16)2-10(17)6-12/h1-6H,(H2,18,19,20)
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| Chemical Name |
1,3-bis(3,5-dichlorophenyl)urea
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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 : 125 mg/mL (357.11 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.94 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 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 (5.94 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 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 | 2.8569 mL | 14.2845 mL | 28.5690 mL | |
| 5 mM | 0.5714 mL | 2.8569 mL | 5.7138 mL | |
| 10 mM | 0.2857 mL | 1.4284 mL | 2.8569 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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