| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
| ln Vitro |
The growth of H295R cells is considerably inhibited by mitotane (1 nM-100 μM; 6 days) [1]. In TαT1 cells, mitotane (10-100 μM; 6 or 48 hours) dramatically enhances caspase 3/7 activity in the range of 60 μM to 80 μM, while decreasing TαT1 cell viability in a time- and dose-dependent manner. Because caspase 3/7 activity was considerably raised from 40 μM to 100 μM by TSH and TSH β-subunit mRNA expression. In a dose-dependent manner, mitotane (1-30 μM; 24 hours; HepG2) stimulates the transcription of the CYP3A4 and CYP2B6 genes [3]. In HepaRG, mitotane (20 and 40 μM; 6 h) dramatically decreased the amount of neutral lipid droplets per cell and also considerably decreased triglycerol-labeled lipid droplets, which in turn decreased PLIN1 and PLIN3 expression levels [4].
|
|---|---|
| ln Vivo |
Early on after H295R cell seeding, mitotane (440 mg/kg; ip or po, 5 days per week for 7 weeks) dramatically decreases xenograft volume [1].
|
| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: H295R Cell Tested Concentrations: 1 nM-100 μM Incubation Duration: 6 days Experimental Results: H295R cells Dramatically diminished proliferation with an IC50 of 22.8 μM. Cell viability assay[2] Cell Types: TαT1 Cell Tested Concentrations: 10, 40, 60, 80 and 100 μM Incubation Duration: 6 or 48 hrs (hours) Experimental Results: No change in cell viability at 10-80 μM, but significant (P < 0.01 ), cell viability diminished (-56%) at 100 μM after 6 hrs (hours) of incubation. Cell viability was not altered at 10-60 μM, whereas at 60 μM (-31%; P < 0.05), 80 μM (-53%; P < 0.01), and 100 μM (-75.5%; P < 0.01) Dramatically diminished. P < 0.01), after 48 hrs (hours) of incubation. RT-PCR[3] Cell Types: HepaRG cells and human hepatocytes Tested Concentrations: 0.1, 1, 10, 20, 30 or 40 μM Incubation Duration: 24 or 48 hrs (hours) Experimental Results: Increased mRNA levels of CYP3A4 and CYP2B6. Western Blot Analysis[4] Cell Types: H295R Tested Concentrations: 20, 40 and 50 μM Incubation Duration: 6 hrs (hours) Experimental Results: diminished expression levels of PLIN1 and PLIN3. |
| Animal Protocol |
Animal/Disease Models: NOD/SCID/γcnull mice (4 weeks old; 6 × 106 H295R cells were inoculated subcutaneously (sc) (sc) into the right flank) [1]
Doses: 440 mg/kg Route of Administration: ip or po; 5 days a week , continued for 7 weeks. Experimental Results: At an early time point (day 13) after H295R cell seeding, xenograft volume was Dramatically diminished. The effect of oral mitotane treatment became insignificant on day 20 after H295R cell inoculation, whereas the effect of intraperitonealmitotane continued until day 34. |
| References |
[1]. Doghman M, et al. Lack of long-lasting effects of mitotane adjuvant therapy in a mouse xenograft model of adrenocortical carcinoma. Mol Cell Endocrinol. 2013 Dec 5;381(1-2):66-9.
[2]. Zatelli MC, et al. Therapeutic concentrations of mitotane (o,p'-DDD) inhibit thyrotroph cell viability and TSH expression and secretion in a mouse cell line model. Endocrinology. 2010 Jun;151(6):2453-61. [3]. Takeshita A, Igarashi-Migitaka J, Koibuchi N, Mitotane induces CYP3A4 expression via activation of the steroid and xenobiotic receptor. J Endocrinol. 2013 Feb 15;216(3):297-305. [4]. Warde KM, et al. Mitotane Targets Lipid Droplets to Induce Lipolysis in Adrenocortical Carcinoma. Endocrinology. 2022 Sep 1;163(9):bqac102. |
| Molecular Formula |
C14H10CL4
|
|---|---|
| Molecular Weight |
320.0412
|
| CAS # |
53-19-0
|
| Related CAS # |
Mitotane-13C6;1261396-21-7;Mitotane-d8;2673270-14-7
|
| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
| SMILES |
ClC([H])(C([H])(C1=C([H])C([H])=C([H])C([H])=C1Cl)C1C([H])=C([H])C(=C([H])C=1[H])Cl)Cl
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~312.46 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.81 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 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. Solubility in Formulation 2: 2.5 mg/mL (7.81 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1246 mL | 15.6230 mL | 31.2461 mL | |
| 5 mM | 0.6249 mL | 3.1246 mL | 6.2492 mL | |
| 10 mM | 0.3125 mL | 1.5623 mL | 3.1246 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
