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Identification
NameMitotane
Accession NumberDB00648  (APRD00494)
Typesmall molecule
Groupsapproved
Description

A derivative of the insecticide dichlorodiphenyldichloroethane that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
MitotanGermanINN
MitotaneFrenchINN
MitotanoSpanishINN
MitotanumLatinINN
Piprine-DDD, O-Not AvailableIS
SaltsNot Available
Brand names
NameCompany
LisodrenBristol-Myers Squibb
LysodrenBristol-Myers Squibb
OpeprimYakult Honsha
Brand mixturesNot Available
Categories
CAS number53-19-0
WeightAverage: 320.041
Monoisotopic: 317.953661148
Chemical FormulaC14H10Cl4
InChI KeyInChIKey=JWBOIMRXGHLCPP-UHFFFAOYSA-N
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
IUPAC Name
1-chloro-4-[2,2-dichloro-1-(2-chlorophenyl)ethyl]benzene
SMILES
ClC(Cl)C(C1=CC=C(Cl)C=C1)C1=CC=CC=C1Cl
Mass Specshow(8.84 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassDiphenylmethanes
Direct parentDiphenylmethanes
Alternative parentsChlorobenzenes; Aryl Chlorides; Polyamines; Organochlorides; Alkyl Chlorides
Substituentschlorobenzene; aryl chloride; aryl halide; polyamine; organohalogen; organochloride; alkyl halide; alkyl chloride
Classification descriptionThis compound belongs to the diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Pharmacology
IndicationFor treatment of inoperable adrenocortical tumours; Cushing's syndrome
PharmacodynamicsMitotane is an oral chemotherapeutic agent indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. Mitotane can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. The administration of Mitotane alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-B-hydroxyl cortisol.
Mechanism of actionIts biochemical mechanism of action is unknown, although data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex.
AbsorptionAbout 40% oral Lysodren is absorbed
Volume of distributionNot Available
Protein binding6%
Metabolism

Hepatic and renal

Route of eliminationA variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues.
Half life18-159 days
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9942
Blood Brain Barrier + 0.9905
Caco-2 permeable + 0.8815
P-glycoprotein substrate Non-substrate 0.8053
P-glycoprotein inhibitor I Non-inhibitor 0.9004
P-glycoprotein inhibitor II Non-inhibitor 0.988
Renal organic cation transporter Non-inhibitor 0.7959
CYP450 2C9 substrate Non-substrate 0.7899
CYP450 2D6 substrate Non-substrate 0.818
CYP450 3A4 substrate Non-substrate 0.7045
CYP450 1A2 substrate Inhibitor 0.9542
CYP450 2C9 substrate Inhibitor 0.7241
CYP450 2D6 substrate Non-inhibitor 0.9349
CYP450 2C19 substrate Inhibitor 0.8993
CYP450 3A4 substrate Non-inhibitor 0.8629
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8
Ames test Non AMES toxic 0.9751
Carcinogenicity Non-carcinogens 0.575
Biodegradation Not ready biodegradable 0.9596
Rat acute toxicity 2.1911 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9221
hERG inhibition (predictor II) Non-inhibitor 0.875
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Mitotane powder7.75USDg
Lysodren 500 mg tablet5.13USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point77 °CPhysProp
water solubility0.1 mg/L (at 25 °C)BIGGAR,JW & RIGGS,RI (1974)
logP6Not Available
logS-6.51ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility9.42e-06 g/lALOGPS
logP6.08ALOGPS
logP6.11ChemAxon
logS-7.5ALOGPS
physiological charge0ChemAxon
hydrogen acceptor count0ChemAxon
hydrogen donor count0ChemAxon
polar surface area0ChemAxon
rotatable bond count3ChemAxon
refractivity79.97ChemAxon
polarizability29.93ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00420
PubChem Compound4211
PubChem Substance46508319
ChemSpider4066
Therapeutic Targets DatabaseDAP000033
PharmGKBPA164746157
Drug Product Database463221
RxListhttp://www.rxlist.com/cgi/generic2/mitotane.htm
Drugs.comhttp://www.drugs.com/cdi/mitotane.html
WikipediaMitotane
ATC CodesL01XX23
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(57 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolMitotane may decrease the anticoagulant effect of acenocoumarol.
AnisindioneMitotane may decrease the anticoagulant effect of anisindione.
DicoumarolMitotane may decrease the anticoagulant effect of dicumarol.
SpironolactoneSpironolactone antagonizes the effect of mitotane
WarfarinMitotane may decrease the anticoagulant effect of warfarin.
Food Interactions
  • Take without regard to meals.

1. Cytochrome P450 11B1, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 11B1, mitochondrial P15538 Details

References:

  1. Lindhe O, Skogseid B, Brandt I: Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p’-DDD in human adrenal zona fasciculata/reticularis. J Clin Endocrinol Metab. 2002 Mar;87(3):1319-26. Pubmed

2. Adrenodoxin, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
Adrenodoxin, mitochondrial P10109 Details

References:

  1. Kandul SV, Iatsyk MI, Kononenko VIa: [Comparative study of the effect of chloditan on the concentration of cytochrome P-450 and adrenodoxin in various organs of the dog and rat] Fiziol Zh. 1986 Sep-Oct;32(5):579-84. Pubmed
  2. Cabrini DA, Campos MM, Tratsk KS, Merino VF, Silva JA Jr, Souza GE, Avellar MC, Pesquero JB, Calixto JB: Molecular and pharmacological evidence for modulation of kinin B(1) receptor expression by endogenous glucocorticoids hormones in rats. Br J Pharmacol. 2001 Jan;132(2):567-77. Pubmed
  3. Cai W, Counsell RE, Schteingart DE, Sinsheimer JE, Vaz AD, Wotring LL: Adrenal proteins bound by a reactive intermediate of mitotane. Cancer Chemother Pharmacol. 1997;39(6):537-40. Pubmed

1. Sex hormone-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sex hormone-binding globulin P04278 Details

References:

  1. Nader N, Raverot G, Emptoz-Bonneton A, Dechaud H, Bonnay M, Baudin E, Pugeat M: Mitotane has an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans. J Clin Endocrinol Metab. 2006 Jun;91(6):2165-70. Epub 2006 Mar 21. Pubmed
  2. van Seters AP, Moolenaar AJ: Mitotane increases the blood levels of hormone-binding proteins. Acta Endocrinol (Copenh). 1991 May;124(5):526-33. Pubmed

2. Corticosteroid-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Corticosteroid-binding globulin P08185 Details

References:

  1. Nader N, Raverot G, Emptoz-Bonneton A, Dechaud H, Bonnay M, Baudin E, Pugeat M: Mitotane has an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans. J Clin Endocrinol Metab. 2006 Jun;91(6):2165-70. Epub 2006 Mar 21. Pubmed
  2. Tron’ko MD: [Effect of chlodithane (o,p’-DDD) on transcortin binding ability in Itsenko-Cushing’s disease] Fiziol Zh. 1970 Nov-Dec;16(6):844-5. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on January 16, 2014 10:50