| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
Natural product; pesticidal agent; mitochondria
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|---|---|
| ln Vitro |
Dihydrorotenone (DHR) Induces Apoptosis of Human Plasma Cells. DHR Induces Loss of the Mitochondrial Membrane Potential in Human Plasma Cells.
Dihydrorotenone (DHR) Induces Unfolded Protein Response and Endoplasmic Reticulum Stress in Human Plasma Cells.
DHR Activates p38 but not the c-Jun N-terminal Kinase in Human Plasma Cells.
The p38 MAP Kinase Contributes to DHR-induced Human Plasma Cell Apoptosis.[1]
Dihydrorotenone (DHR) is a natural pesticide widely used in farming industry, such as organic produces. DHR is a potent mitochondrial inhibitor and probably induces Parkinsonian syndrome, however, it is not known whether DHR is toxic to other systems. In the present study, we evaluated the cytotoxicity of DHR on human plasma cells. As predicted, DHR impaired mitochondrial function by decreasing mitochondrial membrane potential in plasma cells. Because mito-dysfunction leads to unfolded protein response (UPR) and endoplasmic reticulum (ER) stress, we examined the signature proteins in ER stress, including GRP78, ATF4, and CHOP. After DHR treatment, these proteins were significantly upregulated. It is reported that activation of the mitogen-activated protein kinases p38 and JNK are involved in endoplasmic reticulum stress. However, in the subsequent study, DHR was found to activate p38 but not the JNK signaling. When pre-treated with p38 inhibitor SB203580, activation of p38 and cell apoptosis induced by DHR was partially blocked. Thus, we found that DHR induced human plasma cell death by activating the p38 but not the JNK signaling pathway. Because plasma cells are very important in the immune system, this study provided a new insight in the safety evaluation of DHR application.[1] |
| Enzyme Assay |
Measurement of Mitochondrial Membrane Potential[1]
LP1 cells were treated with Dihydrorotenone (DHR) for 0, 10 or 20 µM for 24 h, or 10 µM for 0.5 to 24 h. Cells were then washed in phosphate buffered saline (PBS) and incubated with 25 nM tetramethylrhodamine methyl ester or co-incubated with 25 nM TMRM and 20 µg/ml Annexin V-FITC in IMDM for 15 min at 37°C. The TMRM and Annexin V-FITC fluorescence were analyzed by flow cytometry. |
| Cell Assay |
Analysis of Apoptotic Cells by Flow Cytometry[1]
Plasma cell lines LP1, KMS11, OPM2, and U266 were plated in 24-well plates, and treated with Dihydrorotenone (DHR) for 24 h followed by staining with Annexin V-fluorescein isothiocyanate (Annexin V-FITC) and propidium iodide according to the manufacturer’s instructions. Cells were then incubated for 10 min in dark before being subject to analysis on a flow cytometer as reported previously. To analyze whether caspase activation is involved in Dihydrorotenone (DHR)-induced plasma cell apoptosis, KMS11 and LP1 cells were treated in the presence of pan-caspase inhibitor, followed by evaluation on caspase-3 activation by Western blotting and plasma cell apoptosis by Annexin V/PI double staining and flow cytometry. |
| Toxicity/Toxicokinetics |
The oral LD50 in rats was 2500 mg/kg. Behavioral manifestations included seizures or impact on the epilepsy threshold; ataxia; and other changes in the lungs, pleura, or respiration. JAMA Science, 42(364), 1953. The oral LD50 in rabbits was >2 g/kg. Industrial and Engineering Chemistry, 29(429), 1937. The oral LD50 in guinea pigs was 150 mg/kg. Behavioral manifestations included tremor; seizures or impact on the epilepsy threshold; and other changes in the lungs, pleura, or respiration. Industrial and Engineering Chemistry, 29(429), 1937.
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| References | |
| Additional Infomation |
In summary, this study shows that DHR exposure leads to plasma cell death in humans, accompanied by mitochondrial dysfunction, endoplasmic reticulum stress, and p38 signaling pathway activation. Since plasma cells are an important component of the immune system, this study suggests that DHR may interfere with the immune system. With the increasing demand for organic products, DHR exposure is also increasing; therefore, the safety of DHR and other rotenone compounds should be carefully assessed. [1]
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| Molecular Formula |
C23H24O6
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|---|---|
| Molecular Weight |
396.4331
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| Exact Mass |
396.157
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| CAS # |
6659-45-6
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| PubChem CID |
243725
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
553.9±50.0 °C at 760 mmHg
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| Melting Point |
216 °C
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| Flash Point |
241.6±30.2 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.580
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| LogP |
4.82
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
29
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| Complexity |
623
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC(C)[C@H]1CC2=C(O1)C=CC3=C2O[C@@H]4COC5=CC(=C(C=C5[C@@H]4C3=O)OC)OC
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| InChi Key |
DTFARBHXORYQBF-HBGVWJBISA-N
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| InChi Code |
InChI=1S/C23H24O6/c1-11(2)16-8-14-15(28-16)6-5-12-22(24)21-13-7-18(25-3)19(26-4)9-17(13)27-10-20(21)29-23(12)14/h5-7,9,11,16,20-21H,8,10H2,1-4H3/t16-,20-,21+/m1/s1
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| Chemical Name |
(1S,6R,13S)-16,17-dimethoxy-6-propan-2-yl-2,7,20-trioxapentacyclo[11.8.0.03,11.04,8.014,19]henicosa-3(11),4(8),9,14,16,18-hexaen-12-one
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| Synonyms |
Dihydrorotenone; 1',2'-Dihydrorotenone; 6659-45-6; Rotenone, dihydro-; S,S-Dihydrorotenone; 6',7'-Dihydrorotenone; 538CX0LPPO; MLS000851173;
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~25 mg/mL (~63.06 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.31 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 25.0 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 | 2.5225 mL | 12.6126 mL | 25.2251 mL | |
| 5 mM | 0.5045 mL | 2.5225 mL | 5.0450 mL | |
| 10 mM | 0.2523 mL | 1.2613 mL | 2.5225 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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