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Mitotan

Pharmacological effects Chemical Properties Uses Production method Category Toxicity grading Acute toxicity Flammability and hazard properties Storage characteristics Extinguishing media

Mitotan

CAS No.53-19-0
Chemical Name:Mitotan
CBNumber:CB0392321
Molecular Formula:C14H10Cl4
Formula Weight:320.04
MOL File:53-19-0.mol

Mitotan Property

Melting point 77-78 °C(lit.)
Boiling point 405.59°C (rough estimate)
Density 1.3118 (rough estimate)
refractive index 1.6000 (estimate)
storage temp. Inert atmosphere,Room Temperature
solubility DMSO: soluble20mg/mL, clear
form powder
color white to beige
Water Solubility <0.1 g/100 mL at 24 ºC
Merck 13,6237 / 13,6237
BRN 2056007
InChI InChI=1S/C14H10Cl4/c15-10-7-5-9(6-8-10)13(14(17)18)11-3-1-2-4-12(11)16/h1-8,13-14H
InChIKey JWBOIMRXGHLCPP-UHFFFAOYSA-N
SMILES C1(Cl)=CC=CC=C1C(C1=CC=C(Cl)C=C1)C(Cl)Cl
CAS DataBase Reference 53-19-0(CAS DataBase Reference)
EWG's Food Scores 1
NCI Dictionary of Cancer Terms mitotane
FDA UNII 78E4J5IB5J
NCI Drug Dictionary Lysodren
ATC code L01XX23
NIST Chemistry Reference Mitotane(53-19-0)
EPA Substance Registry System o,p'-DDD (53-19-0)
UNSPSC Code 41116107
NACRES NA.77

Safety

Hazard Codes :Xn
Risk Statements :40
Safety Statements :36/37
RIDADR :3249
WGK Germany :3
RTECS :KH7880000
HazardClass :6.1(b)
PackingGroup :III
HS Code :2903990002
Hazardous Substances Data :53-19-0(Hazardous Substances Data)

NFPA 704:

	0
1		0

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal wordWarning
Hazard statements H351
Precautionary statements P280

Mitotan Price More Price(4)

Brand: Sigma-Aldrich(India)
Product number: SML1885
Product name : Mitotane
Purity: ≥98% (HPLC)
Packaging: 100MG
Price: ₹5260.95
Updated: 2022/06/14
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Brand: Sigma-Aldrich(India)
Product number: 35485
Product name : 2,4′-DDD
Purity: PESTANAL?, analytical standard
Packaging: 250MG
Price: ₹7838.65
Updated: 2022/06/14
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Brand: TCI Chemicals (India)
Product number: M3304
Product name : Mitotane
Purity: min. 98.0 %
Packaging: 1G
Price: ₹2400
Updated: 2022/05/26
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Brand: TCI Chemicals (India)
Product number: M3304
Product name : Mitotane
Purity: min. 98.0 %
Packaging: 5G
Price: ₹8300
Updated: 2022/05/26
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Mitotan Chemical Properties,Usage,Production

Pharmacological effects Mitotan is structurally similar with insecticide DDT and DDD and can selectively cause the atrophy and necrosis of adrenal cortex-zona fasciculata and reticularis cells but without affecting the zona, therefore the secretion of aldosterone will not affected. After the drug administration, the cortisol and its metabolites level in blood and urine decreased rapidly after treatment. At the same time, the in vivo adrenocorticotropic hormone and metabolite products level also decrease rapidly. It is suitable for the treatment of inoperable, functional and non-functional adrenal cortical carcinoma, adrenal tumor, adrenal hyperplasia-caused Klinefelter’s syndrome, adrenal hyperplasia, and the adjuvant therapy of postoperation cortical cancer and tumor-induced Cushing's syndrome.
After oral administration, about 40% of Mitotan is absorbed through the gastrointestinal tract with the remaining 60% of the prototype excreted together with the feces. At a dose of 5~10 g daily, the plasma concentration can be up to 10~90μg/ml, the concentration of metabolites can be up to 30~50μg/ml. At 6-9 weeks after discontinuation, it can be still detected of o-alkyl chloride in the plasma. Mitotan has a high fat-solubility and is mainly stored in fat. The water soluble metabolites discharged from the urine can account for about 25% of the administered dose.
The above information is edited by the chemicalbook of Dai Xiongfeng.
Chemical Properties It appears as white crystals with the melting point being 76-78 ℃. It is soluble in ethanol and carbon tetrachloride.
Uses It belongs to antineoplastic agents and can be used for the treatment of adrenal cortical carcinoma.
Production method It can be prepared from O-bromo-chlorobenzene (see 05820) by the following steps.
Category Toxic substances.
Toxicity grading Poisoning.
Acute toxicity Oral-rat; LD50> 5000 mg/kg; Oral-Mouse LD50> 4000 mg/kg.
Flammability and hazard properties Thermal decomposition can release toxic chloride fume.
Storage characteristics Low-temperature, dry and ventilated warehouse.
Extinguishing media Water, carbon dioxide, foam, powder.
Description Mitotane is an inhibitor of steroidogenesis that suppresses the growth of adrenocortical cells. It blocks the expression of several genes that encode proteins involved in steroidogenesis and disrupts mitochondrial respiratory chain activity in human adrenocortical cells. Mitotane has anti-neoplastic actions, alone or in combination with other compounds, and suppresses cortisol synthesis, although it also has significant toxicity in the gastrointestinal tract and nervous system. It is effective against adrenocortical carcinoma and Cushing’s Syndrome in clinical trials.
Chemical Properties Crystalline Solid
Uses aminobiphoshphanate for treatment of osteoporosis and Paget's bone disease
Uses An Antineoplastic. Used as an adrenolytic agent
Uses insecticide, antineoplastic
Uses Mitotane is an inhibitor of steroidogenesis that suppresses the growth of adrenocortical cells. It blocks the expression of several genes that encode proteins involved in steroidogenesis and disrupts mitochondrial respiratory chain activity in human adrenocortical cells. Mitotane has anti-neoplastic actions, alone or in combination with other compounds, and suppresses cortisol synthesis, although it also has significant toxicity in the gastrointestinal tract and nervous system. It is effective against adrenocortical carcinoma and Cushing’s Syndrome in clinical trials.
Indications Mitotane (Lysodren) produces selective atrophy of the zona fasciculata and zona reticularis, which results in a decrease in the secretion of 17-hydroxycorticosteroids. Direct inhibition of cholesterol side-chain cleavage and 11/18-hydroxylase activities has also been demonstrated.
Indications The observation that mitotane (Lysodren) could produce adrenocortical necrosis in animals led to its use in the palliation of inoperable adrenocortical adenocarcinomas. A reduction in both tumor size and adrenocortical hormone secretion can be achieved in about half of the patients taking the drug. Because normal adrenocortical cells also are affected, endogenous glucocorticoid production should be monitored and replacement therapy administered when appropriate.
Mitotane is incompletely absorbed from the gastrointestinal tract after oral administration. However, once absorbed, it tends to accumulate in adipose tissue. Mitotane is slowly excreted and will appear in the urine for several years.The major toxicities associated with its use are anorexia, nausea, diarrhea, lethargy, somnolence, dizziness, and dermatitis.
Definition ChEBI: Mitotane is a diarylmethane.
Manufacturing Process From dichloroacetaldehyde and 2-chlorphenylmagnesiumbromide was prepared 1-(2-chlorphenyl-2,2-dichloroethanol. By action of H2SO4 on 1-(2- chlorphenyl)-2,2-dichloroethanol in chlorobenzene was prepared 1,1-dichloro- 2,2-bis(2,4'-dichlorophenyl)ethane.
brand name Lysodren (Bristol-Myers Squibb).
Therapeutic Function Antineoplastic
General Description Colorless powder.
Air & Water Reactions Insoluble in water.
Reactivity Profile Mitotan dehydrohalogenates with strong alkalis. Simple aromatic halogenated organic compounds are very unreactive; halogenated aliphatic compounds are moderately or very reactive. For both subgroups, reactivity generally decreases with increased degree of substitution of halogen for hydrogen atoms. Materials in this group are incompatible with strong oxidizing and reducing agents. Also, they are incompatible with many amines, nitrides, azo/diazo compounds, alkali metals, and epoxides.
Fire Hazard Flash point data for Mitotan are not available. Mitotan is probably combustible.
Pharmacology Mitotane, a derivative of the insecticide DDT, quickly lowers the level of corticosteroids, and is metabolized in the blood and urine and used on non-operable metastatic prostate carcinomas. Synonyms of this drug are lysodren and others.
Clinical Use Mitotane is the drug of choice for the treatment of primary adrenal carcinoma when surgery or radiation therapy is not feasible. Its effectiveness in curtailing adrenal activity is due to an action on adrenocortical mitochondria to impair cytochrome P450 steps in steroid biosynthesis. Mitotane requires metabolic transformation to exert its therapeutic action, and the differential ability of tumors to metabolize the drug may determine its clinical effectiveness. It is advised to measure serum mitotane levels and urinary free cortisol excretion to ensure adequate therapeutic concentrations. Mitotane increases circulating cholesterol by inhibiting cytochrome P450–mediated reactions and therefore contributes to the cardiovascular events that are a significant cause of mortality in untreated Cushing’s syndrome.
Mitotane, being closely related to the organochlorine insecticides, shares its inductive effects on the liver microsomal drug-metabolizing enzyme system, and its use may therefore alter the requirement for concomitantly administered drugs that are also metabolized by this pathway.
Side effects Mitotane is capable of inducing remission of Cushing’s disease, but only after several weeks of therapy and at the price of severe gastrointestinal distress. Moreover, more than half of patients relapse following cessation of therapy. Other side effects include lethargy, mental confusion, skin rashes, and altered hepatic function. Being a lipid-soluble substance, mitotane remains stored in body tissues for extended periods. This may account for the marked patient-to-patient variability in its therapeutic and/or toxic effects.
Synthesis Mitotane, 1,1-dichloro-2-(o-chlorophenyl)ethane (30.5.8), is made by alkylating chlorobenzene with 1-(2-chlorophenyl)-2,2-dichloroethane (30.5.7) in the presence of sulfuric acid. The necessary 1-(2-chlorophenyl)-2,2-dichloroethanol (30.5.7) is in turn made from reacting 2-chlorophenylmagnesiumbromide with dichloroacetic aldehyde.
Veterinary Drugs and Treatments In veterinary medicine, mitotane is used primarily for the medical treatment of pituitary-dependent hyperadrenocorticism (PDH), principally in the dog. It has also been used for the palliative treatment of adrenal carcinoma in humans and dogs.
Drug interactions Potentially hazardous interactions with other drugs
Anticoagulants: possibly reduced anticoagulant effect of coumarins.
Antipsychotics: avoid with clozapine (increased risk of agranulocytosis).
Diuretics: avoid with spironolactone.
Metabolism Metabolised in the liver and other tissues and excreted as metabolites in urine and bile. From 10-25% of a dose has been recovered in the urine as a water-soluble metabolite and 1-17% in the faeces as metabolites
Purification Methods Purify Mitotane by recrystallisation from pentane, MeOH or EtOH. It is soluble in isooctane and CCl4. [Haller et al. J Am Chem Soc 67 1600 1945, Beilstein 5 IV 1883.]