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targets (2) carriers (2)
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Identification
Name Mitotane
Accession Number DB00648 (APRD00494)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Chloditan
Chlodithan
Chlodithane
Khlodithan
Lysodren
Mitotan
Mitotanum [INN-Latin]
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
CAS number 53-19-0
Weight Average: 320.041
Monoisotopic: 317.953661148
Chemical Formula C14H10Cl4
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec show (8.84 KB)
Taxonomy
Kingdom Organic
Classes
  • Diphenylmethanes
Substructures
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Alkyl Halides
  • Diphenylmethanes
  • Aromatic compounds
Pharmacology
Indication For treatment of inoperable adrenocortical tumours; Cushing's syndrome
Pharmacodynamics Mitotane 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 action Its 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.
Absorption About 40% oral Lysodren is absorbed
Volume of distribution Not Available
Protein binding 6%
Metabolism Hepatic and renal
Route of elimination A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues.
Half life 18-159 days
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Mitotane powder 7.75 USD g
Lysodren 500 mg tablet 5.13 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 77 °C PhysProp
water solubility 0.1 mg/L (at 25 °C) BIGGAR,JW & RIGGS,RI (1974)
logP 6 Not Available
logS -6.51 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 9.42e-06 g/l ALOGPS
logP 6.08 ALOGPS
logP 6.11 ChemAxon
logS -7.5 ALOGPS
physiological charge 0 ChemAxon
hydrogen acceptor count 0 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 0 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 79.97 ChemAxon
polarizability 29.93 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00420 Link_out
PubChem Compound 4211 Link_out
PubChem Substance 46508319 Link_out
ChemSpider 4066 Link_out
Therapeutic Targets Database DAP000033 Link_out
PharmGKB PA164746157 Link_out
Drug Product Database 463221 Link_out
RxList http://www.rxlist.com/cgi/generic2/mitotane.htm Link_out
Drugs.com http://www.drugs.com/cdi/mitotane.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mitotane Link_out
ATC Codes
  • L01XX23
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label Not Available
MSDS show (57 KB)
Interactions
Drug Interactions
Drug Interaction
Acenocoumarol Mitotane may decrease the anticoagulant effect of acenocoumarol.
Anisindione Mitotane may decrease the anticoagulant effect of anisindione.
Dicumarol Mitotane may decrease the anticoagulant effect of dicumarol.
Spironolactone Spironolactone antagonizes the effect of mitotane
Warfarin Mitotane may decrease the anticoagulant effect of warfarin.
Food Interactions
  • Take without regard to meals.
Targets

1. Cytochrome P450 11B1, mitochondrial

Pharmacological action: yes
Actions: inducer

Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB

Organism class: human
UniProt ID: P15538 Link_out
Gene: CYP11B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: unknown

Participates in the synthesis of thyroid hormones. Transfers electrons from adrenodoxin reductase to the cholesterol side chain cleavage cytochrome P450

Organism class: human
UniProt ID: P10109 Link_out
Gene: FDX1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration

UniProt ID: P04278 Link_out
Gene: SHBG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species

UniProt ID: P08185 Link_out
Gene: SERPINA6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:19