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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
LysodrenNot AvailableNot Available
MitotanGermanINN
MitotaneFrenchINN
MitotanoSpanishINN
MitotanumLatinINN
Piprine-DDD, O-Not AvailableIS
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Lysodrentablet500 mgoralE.R. Squibb & Sons, L.L.C.2009-06-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Lysodrentablet500 mgoralBristol Myers Squibb CanadaNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
LisodrenBristol-Myers Squibb
OpeprimYakult Honsha
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number53-19-0
WeightAverage: 320.041
Monoisotopic: 317.953661148
Chemical FormulaC14H10Cl4
InChI KeyJWBOIMRXGHLCPP-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Halobenzene
  • Chlorobenzene
  • Aryl halide
  • Aryl chloride
  • Hydrocarbon derivative
  • Organochloride
  • Organohalogen compound
  • Alkyl halide
  • Alkyl chloride
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9942
Blood Brain Barrier+0.9905
Caco-2 permeable+0.8815
P-glycoprotein substrateNon-substrate0.8053
P-glycoprotein inhibitor INon-inhibitor0.9004
P-glycoprotein inhibitor IINon-inhibitor0.988
Renal organic cation transporterNon-inhibitor0.7959
CYP450 2C9 substrateNon-substrate0.7899
CYP450 2D6 substrateNon-substrate0.818
CYP450 3A4 substrateNon-substrate0.7045
CYP450 1A2 substrateInhibitor0.9542
CYP450 2C9 substrateInhibitor0.7241
CYP450 2D6 substrateNon-inhibitor0.9349
CYP450 2C19 substrateInhibitor0.8993
CYP450 3A4 substrateNon-inhibitor0.8629
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8
Ames testNon AMES toxic0.9751
CarcinogenicityNon-carcinogens0.575
BiodegradationNot ready biodegradable0.9596
Rat acute toxicity2.1911 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9221
hERG inhibition (predictor II)Non-inhibitor0.875
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
Packagers
Dosage forms
FormRouteStrength
Tabletoral500 mg
Prices
Unit descriptionCostUnit
Mitotane powder7.75USD g
Lysodren 500 mg tablet5.13USD tablet
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 mg/mLALOGPS
logP6.08ALOGPS
logP6.11ChemAxon
logS-7.5ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity79.97 m3·mol-1ChemAxon
Polarizability29.93 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.84 KB)
SpectraMS1D NMR
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesL01XX23
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (57 KB)
Interactions
Drug Interactions
Drug
AlfuzosinMay decrease the serum concentration of CYP3A4 Substrates.
AlprazolamMay decrease the serum concentration of CYP3A4 Substrates.
AminophyllineMay decrease the serum concentration of CYP3A4 Substrates.
AmiodaroneMay decrease the serum concentration of CYP3A4 Substrates.
AmlodipineMay decrease the serum concentration of CYP3A4 Substrates.
AprepitantMay decrease the serum concentration of CYP3A4 Substrates.
AripiprazoleMay decrease the serum concentration of CYP3A4 Substrates.
armodafinilMay decrease the serum concentration of CYP3A4 Substrates.
AtazanavirMay decrease the serum concentration of CYP3A4 Substrates.
AtorvastatinMay decrease the serum concentration of CYP3A4 Substrates.
AvanafilMay decrease the serum concentration of CYP3A4 Substrates.
BenzphetamineMay decrease the serum concentration of CYP3A4 Substrates.
BiotinMay decrease the serum concentration of CYP3A4 Substrates.
BisoprololMay decrease the serum concentration of CYP3A4 Substrates.
BuprenorphineMay decrease the serum concentration of CYP3A4 Substrates.
BuspironeMay decrease the serum concentration of CYP3A4 Substrates.
CabazitaxelMay decrease the serum concentration of CYP3A4 Substrates.
CalcitriolMay decrease the serum concentration of CYP3A4 Substrates.
CarbamazepineMay decrease the serum concentration of CYP3A4 Substrates.
ChlordiazepoxideMay decrease the serum concentration of CYP3A4 Substrates.
ChloroquineMay decrease the serum concentration of CYP3A4 Substrates.
CilostazolMay decrease the serum concentration of CYP3A4 Substrates.
CitalopramMay decrease the serum concentration of CYP3A4 Substrates.
ClarithromycinMay decrease the serum concentration of CYP3A4 Substrates.
ClidiniumMay decrease the serum concentration of CYP3A4 Substrates.
ClonazepamMay decrease the serum concentration of CYP3A4 Substrates.
ConivaptanMay decrease the serum concentration of CYP3A4 Substrates.
CorticotropinMay decrease the serum concentration of Corticosteroids (Systemic).
Cortisone acetateMay decrease the serum concentration of Corticosteroids (Systemic).
Cyproterone acetateMay decrease the serum concentration of CYP3A4 Substrates.
DantroleneMay decrease the serum concentration of CYP3A4 Substrates.
DarifenacinMay decrease the serum concentration of CYP3A4 Substrates.
DarunavirMay decrease the serum concentration of CYP3A4 Substrates.
DasatinibMay decrease the serum concentration of CYP3A4 Substrates.
DelavirdineMay decrease the serum concentration of CYP3A4 Substrates.
DesogestrelMay decrease the serum concentration of CYP3A4 Substrates.
DiazepamMay decrease the serum concentration of CYP3A4 Substrates.
DiltiazemMay decrease the serum concentration of CYP3A4 Substrates.
DisopyramideMay decrease the serum concentration of CYP3A4 Substrates.
DocetaxelMay decrease the serum concentration of CYP3A4 Substrates.
DoxazosinMay decrease the serum concentration of CYP3A4 Substrates.
DrospirenoneMay decrease the serum concentration of CYP3A4 Substrates.
EplerenoneMay decrease the serum concentration of CYP3A4 Substrates.
ErlotinibMay decrease the serum concentration of CYP3A4 Substrates.
EscitalopramMay decrease the serum concentration of CYP3A4 Substrates.
EstropipateMay decrease the serum concentration of CYP3A4 Substrates.
EszopicloneMay decrease the serum concentration of CYP3A4 Substrates.
Ethinyl EstradiolMay decrease the serum concentration of CYP3A4 Substrates.
EthosuximideMay decrease the serum concentration of CYP3A4 Substrates.
EthynodiolMay decrease the serum concentration of CYP3A4 Substrates.
EtoposideMay decrease the serum concentration of CYP3A4 Substrates.
EtravirineMay decrease the serum concentration of CYP3A4 Substrates.
ExemestaneMay decrease the serum concentration of CYP3A4 Substrates.
FelbamateMay decrease the serum concentration of CYP3A4 Substrates.
FelodipineMay decrease the serum concentration of CYP3A4 Substrates.
FesoterodineMay decrease the serum concentration of CYP3A4 Substrates.
FludrocortisoneMay decrease the serum concentration of Corticosteroids (Systemic).
FlurazepamMay decrease the serum concentration of CYP3A4 Substrates.
FlutamideMay decrease the serum concentration of CYP3A4 Substrates.
FosamprenavirMay decrease the serum concentration of CYP3A4 Substrates.
FosaprepitantMay decrease the serum concentration of CYP3A4 Substrates.
GefitinibMay decrease the serum concentration of CYP3A4 Substrates.
GuanfacineMay decrease the serum concentration of CYP3A4 Substrates.
HaloperidolMay decrease the serum concentration of CYP3A4 Substrates.
HydrocodoneMay decrease the serum concentration of CYP3A4 Substrates.
IndinavirMay decrease the serum concentration of CYP3A4 Substrates.
Isosorbide DinitrateMay decrease the serum concentration of CYP3A4 Substrates.
Isosorbide MononitrateMay decrease the serum concentration of CYP3A4 Substrates.
IsradipineMay decrease the serum concentration of CYP3A4 Substrates.
IxabepiloneMay decrease the serum concentration of CYP3A4 Substrates.
LansoprazoleMay decrease the serum concentration of CYP3A4 Substrates.
LevonorgestrelMay decrease the serum concentration of CYP3A4 Substrates.
LinagliptinMay decrease the serum concentration of CYP3A4 Substrates.
LomitapideMay decrease the serum concentration of CYP3A4 Substrates.
LopinavirMay decrease the serum concentration of CYP3A4 Substrates.
LosartanMay decrease the serum concentration of CYP3A4 Substrates.
LovastatinMay decrease the serum concentration of CYP3A4 Substrates.
MaravirocMay decrease the serum concentration of CYP3A4 Substrates.
Medroxyprogesterone AcetateMay decrease the serum concentration of CYP3A4 Substrates.
MefloquineMay decrease the serum concentration of CYP3A4 Substrates.
MestranolMay decrease the serum concentration of CYP3A4 Substrates.
MethadoneMay decrease the serum concentration of CYP3A4 Substrates.
MethylprednisoloneMay decrease the serum concentration of Corticosteroids (Systemic).
MidazolamMay decrease the serum concentration of CYP3A4 Substrates.
MirtazapineMay decrease the serum concentration of CYP3A4 Substrates.
ModafinilMay decrease the serum concentration of CYP3A4 Substrates.
NateglinideMay decrease the serum concentration of CYP3A4 Substrates.
NefazodoneMay decrease the serum concentration of CYP3A4 Substrates.
NelfinavirMay decrease the serum concentration of CYP3A4 Substrates.
NevirapineMay decrease the serum concentration of CYP3A4 Substrates.
NimodipineMay decrease the serum concentration of CYP3A4 Substrates.
NorelgestrominMay decrease the serum concentration of CYP3A4 Substrates.
NorethindroneMay decrease the serum concentration of CYP3A4 Substrates.
NorgestimateMay decrease the serum concentration of CYP3A4 Substrates.
OndansetronMay decrease the serum concentration of CYP3A4 Substrates.
OspemifeneMay decrease the serum concentration of CYP3A4 Substrates.
OxycodoneMay decrease the serum concentration of CYP3A4 Substrates.
PimozideMay decrease the serum concentration of CYP3A4 Substrates.
PiperazineMay decrease the serum concentration of CYP3A4 Substrates.
PipotiazineMay decrease the serum concentration of CYP3A4 Substrates.
PomalidomideMay decrease the serum concentration of CYP3A4 Substrates.
PrednisoneMay decrease the serum concentration of Corticosteroids (Systemic).
PrimaquineMay decrease the serum concentration of CYP3A4 Substrates.
ProgesteroneMay decrease the serum concentration of CYP3A4 Substrates.
QuetiapineMay decrease the serum concentration of CYP3A4 Substrates.
QuinidineMay decrease the serum concentration of CYP3A4 Substrates.
QuinineMay decrease the serum concentration of CYP3A4 Substrates.
RabeprazoleMay decrease the serum concentration of CYP3A4 Substrates.
RepaglinideMay decrease the serum concentration of CYP3A4 Substrates.
RilpivirineMay decrease the serum concentration of CYP3A4 Substrates.
RiociguatMay decrease the serum concentration of CYP3A4 Substrates.
RitonavirMay decrease the serum concentration of CYP3A4 Substrates.
RuxolitinibMay decrease the serum concentration of CYP3A4 Substrates.
SaquinavirMay decrease the serum concentration of CYP3A4 Substrates.
SildenafilMay decrease the serum concentration of CYP3A4 Substrates.
SilodosinMay decrease the serum concentration of CYP3A4 Substrates.
SimvastatinMay decrease the serum concentration of CYP3A4 Substrates.
SirolimusMay decrease the serum concentration of CYP3A4 Substrates.
SolifenacinMay decrease the serum concentration of CYP3A4 Substrates.
SpiramycinMay decrease the serum concentration of CYP3A4 Substrates.
SpironolactoneSpironolactone may diminish the therapeutic effect of Mitotane.
SulfamethoxazoleMay decrease the serum concentration of CYP3A4 Substrates.
SulfisoxazoleMay decrease the serum concentration of CYP3A4 Substrates.
SunitinibMay decrease the serum concentration of CYP3A4 Substrates.
TamoxifenMay decrease the serum concentration of CYP3A4 Substrates.
TamsulosinMay decrease the serum concentration of CYP3A4 Substrates.
TelithromycinMay decrease the serum concentration of CYP3A4 Substrates.
TemsirolimusMay decrease the serum concentration of CYP3A4 Substrates.
TeniposideMay decrease the serum concentration of CYP3A4 Substrates.
TetracyclineMay decrease the serum concentration of CYP3A4 Substrates.
TheophyllineMay decrease the serum concentration of CYP3A4 Substrates.
TiagabineMay decrease the serum concentration of CYP3A4 Substrates.
TiclopidineMay decrease the serum concentration of CYP3A4 Substrates.
TipranavirMay decrease the serum concentration of CYP3A4 Substrates.
TolterodineMay decrease the serum concentration of CYP3A4 Substrates.
TramadolMay decrease the serum concentration of CYP3A4 Substrates.
TriazolamMay decrease the serum concentration of CYP3A4 Substrates.
TrimethoprimMay decrease the serum concentration of CYP3A4 Substrates.
TrimipramineMay decrease the serum concentration of CYP3A4 Substrates.
VenlafaxineMay decrease the serum concentration of CYP3A4 Substrates.
VilazodoneMay decrease the serum concentration of CYP3A4 Substrates.
VinblastineMay decrease the serum concentration of CYP3A4 Substrates.
VincristineMay decrease the serum concentration of CYP3A4 Substrates.
VinorelbineMay decrease the serum concentration of CYP3A4 Substrates.
ZolpidemMay decrease the serum concentration of CYP3A4 Substrates.
ZonisamideMay decrease the serum concentration of CYP3A4 Substrates.
ZopicloneMay decrease the serum concentration of CYP3A4 Substrates.
Food Interactions
  • Take without regard to meals.

Targets

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

Carriers

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