Mitotan

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Mitotane (2,4’-DDD) 是 DDD 的同分异构体和 DDT 的衍生物，有抗癌活性，可用于研究肾上腺皮质癌。Mitotane 的肾上腺皮质溶解作用至少部分是通过细胞内游离胆固醇 (FC) 积累引起的脂毒性。Mitotane 可对促皮质激素细胞产生直接垂体作用。Mitotane 可通过类固醇和外源性受体 (SXR) 激活诱导 CYP3A4 基因表达，并存在活性分子-活性分子相互作用。

Mitotane(2,4′-DDD), an isomer of DDD and derivative of DDT, is an antineoplastic medication used in the treatment of adrenocortical carcinoma.(In Vitro):Mitotane (1 nM-100 μM; 6 days) significantly reduces H295R cell proliferation.Mitotane (10-100 μM; 6 or 48 h; TαT1 cells) reduces TαT1 cell viability in time- and dose-dependent manners; significantly and dose dependently increases caspase 3/7 activity from 60 μM to 80 μM; induced a significant and dose-dependent reduction in TSH secretion and TSH β-subunit mRNA expression from 40 μM to 100 μM.Mitotane (1-30 μM; 24 h; HepG2) increases transcription of the CYP3A4 and CYP2B6 gene in a dose-dependent manner.Mitotane (20 and 40 μM; 6 h) significantly reduces the number of neutral lipid droplets per cell in HepaRG, also induces a significant decrease in triacylglycerol-labeled lipid droplets; decreases the expression levels of PLIN1 and PLIN3.(In Vivo):Mitotane (440 mg/kg; i.p. or p.o,; 5 days a week, for 7 weeks) significantly reduces the volume of xenografts at an early time point after H295R cells inoculation.

Cell Proliferation Assay Cell Line:H295R cellsConcentration:1 nM-100 μMIncubation Time:6 days Result:Significantly reduced H295R cell proliferation with an IC50 of 22.8 μM.Cell Viability Assay Cell Line:TαT1 cellsConcentration:10, 40, 60, 80 and 100 μMIncubation Time:6 or 48 h Result:Did not modify cell viability at 10-80 μM, while significantly (P < 0.01) reduced cell viability (-56%) at 100 μM, after 6 h incubation. Did not modify cell viability at 10-60 μM, whereas cell viability was significantly reduced at 60 μM (-31%; P < 0.05), 80 μM (-53%; P < 0.01), and 100 μM (-75.5%; P < 0.01), after 48 h incubation.RT-PCR Cell Line:HepaRG cells and human hepatocytesConcentration:0.1, 1, 10, 20, 30, or 40?μM Incubation Time:24 or 48 h Result:Increased mRNA levels of CYP3A4 and CYP2B6.Western Blot Analysis Cell Line:H295R Concentration:20, 40 and 50 μM Incubation Time:6 h Result:Decreased the expression levels of PLIN1 and PLIN3.

Animal Model:NOD/SCID/γcnull mice (4-week-old; inoculated subcutaneously 6 × 106 H295R cells into the right flank)Dosage:440 mg/kg Administration:i.p. or p.o,; 5 days a week, for 7 weeks Result:Significantly reduced the volume of xenografts at an early time point (day 13) after H295R cells inoculation.The effect of oral mitotane treatment became non-significant by day 20 after H295R cells inoculation, while the effect of i.p. mitotane lasted until day 34.

o,p'-DDD | NSC 38721

Cell Cycle/DNA Damage

AChR

Adrenodoxin

Cancer

——

53-19-0

320.04

C14H10Cl4

>98% (HPLC)

Ethanol: 64 mg/mL warmed (199.97 mM); DMSO: 64 mg/mL (199.97 mM)

ClC1=CC=C(C(C2=CC=CC=C2Cl)C(Cl)Cl)C=C1

1-chloro-2-(2,2-dichloro-1-(4-chlorophenyl)ethyl)benzene

(-20℃)

With Ice Pack

≥ 2 years