Identification
- Summary
Mitotane is an adrenal cortex inhibitor used to treat adrenocortical tumors and Cushing's syndrome.
- Brand Names
- Lysodren
- Generic Name
- Mitotane
- DrugBank Accession Number
- DB00648
- Background
Mitotane is an adrenolytic isomer of the insecticide dichlorodiphenyldichloroethane (DDD) - itself a metabolite of dichlorodiphenyltrichloroethane (DDT) - that inhibits cells of the adrenal cortex and their production of hormones. It has been in use since 1959 for the treatment of inoperable adrenocortical carcinoma1 and is used off-label for the management of Cushing's syndrome.2
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Mitotane (DB00648)
- Weight
- Average: 320.041
Monoisotopic: 317.953661148 - Chemical Formula
- C14H10Cl4
- Synonyms
- 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]-benzene
- Mitotan
- Mitotane
- Mitotano
- Mitotanum
- o,p'-DDD
- External IDs
- CB 313
- CB-313
- NSC 38721
Pharmacology
- Indication
Mitotane is indicated for the treatment of inoperable, functional or nonfunctional, adrenocortical carcinoma.4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Cushing's syndrome ••• ••••• Treatment of Inoperable adrenocortical carcinoma •••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
The administration of mitotane alters the peripheral metabolism of steroids, leading to a reduction in plasma 17-hydroxycorticosteroids and an increase in 6-β-hydroxycortisol in addition to normal corticosteroid levels.4
- Mechanism of action
The mechanism of action of mitotane 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.4 The specificity of mitotane towards the adrenal cortex may derive from the metabolic transformation to its active form via an enzyme system unique to the adrenal cortex tissue.1
Target Actions Organism ACytochrome P450 11B1, mitochondrial inducerHumans UEstrogen receptor alpha Not Available Humans UProgesterone receptor Not Available Humans UAndrogen receptor antagonistHumans UAdrenodoxin, mitochondrial unknownHumans - Absorption
The bioavailability of mitotane following oral administration is 40%.4
- Volume of distribution
Mitotane is extensively distributed and found in most tissues in the body.4 Fat is the primary site of distribution.4
- Protein binding
6%
- Metabolism
Mitotane undergoes extensive metabolism - both hepatic and extrahepatic - and no unchanged parent drug is excreted in the bile or urine.4 The major circulating metabolite of mitotane is 1,1-(o,p'-dichlorodiphenyl) acetic acid (o,p’-DDA).4
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- Route of elimination
Approximately 10% of an administered dose is recovered in the urine as water-soluble metabolites, with a varying amount of metabolite (1%-17%) excreted in the bile.4
- Half-life
The plasma terminal half-life of mitotane ranges from 18 to 159 days, with a median of 53 days.4
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Overdosage with mitotane can occur when plasma levels are above 20 mg/L.4 Symptoms can include central nervous system toxicity, including sedation, lethargy, and vertigo, as well as muscular weakness and gait disturbance.4 Mitotane is lipophilic and may therefore take weeks to adequately clear from a patient. It is unlikely to be dialyzable. In the event of a suspected overdose, consider increasing the frequency of mitotane plasma level monitoring. Withhold mitotane as clinically indicated for signs or symptoms of toxicity.4
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be increased when combined with Mitotane. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Mitotane. Abiraterone The metabolism of Abiraterone can be increased when combined with Mitotane. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Mitotane. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Mitotane. - Food Interactions
- Take with food. The timing of mitotane administration relative to food intake should remain consistent. Co-administration with high-fat food enhances absorption.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Lisodren (Bristol-Myers Squibb) / Opeprim (Yakult Honsha)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lysodren Tablet 500 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2009-06-01 2021-03-31 US 
Lysodren Tablet 500 mg Oral HRA Pharma Rare Diseases 1979-12-31 Not applicable Canada 
Lysodren Tablet 500 mg/1 Oral HRA Pharma Rare Diseases 1978-10-15 Not applicable US Lysodren Tablet 500 mg Oral HRA Pharma Rare Diseases 2016-09-08 Not applicable EU 
Categories
- ATC Codes
- L01XX23 — Mitotane
- Drug Categories
- Adrenal Cytotoxic Agents
- Antineoplastic Agents
- Antineoplastic Agents, Hormonal
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inducers (strong)
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strong)
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strong)
- Cytochrome P-450 CYP3A7 Inducers
- Cytochrome P-450 CYP3A7 Inducers (strong)
- Cytochrome P-450 Enzyme Inducers
- Hydrocarbons, Chlorinated
- Hydrocarbons, Halogenated
- Narrow Therapeutic Index Drugs
- P-glycoprotein inhibitors
- Thyroxine-binding globulin inducers
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Chlorobenzenes / Aryl chlorides / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides
- Substituents
- Alkyl chloride / Alkyl halide / Aromatic homomonocyclic compound / Aryl chloride / Aryl halide / Chlorobenzene / Diphenylmethane / Halobenzene / Hydrocarbon derivative / Organochloride
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- 78E4J5IB5J
- CAS number
- 53-19-0
- InChI Key
- 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
References
- General References
- Waszut U, Szyszka P, Dworakowska D: Understanding mitotane mode of action. J Physiol Pharmacol. 2017 Feb;68(1):13-26. [Article]
- Broersen LHA, Jha M, Biermasz NR, Pereira AM, Dekkers OM: Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis. Pituitary. 2018 Dec;21(6):631-641. doi: 10.1007/s11102-018-0897-z. [Article]
- FDA Approved Drug Products: LYSODREN (mitotane) tablets [Link]
- FDA Approved Drug Products: Lysodren (mitotane) tablets for oral use (January 2024) [Link]
- Cayman Chemical: Mitotane MSDS [Link]
- External Links
- Human Metabolome Database
- HMDB0014786
- KEGG Drug
- D00420
- PubChem Compound
- 4211
- PubChem Substance
- 46508319
- ChemSpider
- 4066
- BindingDB
- 50239991
- 7004
- ChEBI
- 6954
- ChEMBL
- CHEMBL1670
- Therapeutic Targets Database
- DAP000033
- PharmGKB
- PA164746157
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Mitotane
- MSDS
- Download (57 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Adrenocortical Carcinoma 1 3 Completed Treatment Stage I Adrenal Cortical Carcinoma AJCC v7 / Stage II Adrenal Cortical Carcinoma AJCC v7 / Stage III Adrenal Cortical Carcinoma AJCC v7 / Stage IV Adrenal Cortical Carcinoma AJCC v7 1 3 Recruiting Treatment ENSAT Stage I Adrenal Cortex Carcinoma / ENSAT Stage II Adrenal Cortex Carcinoma / ENSAT Stage III Adrenal Cortex Carcinoma 1 3 Unknown Status Treatment Adrenocortical Carcinoma 1 2 Completed Treatment Adrenocortical Carcinoma 1
Pharmacoeconomics
- Manufacturers
- Bristol myers squibb
- Packagers
- B&B Pharmaceuticals
- Bristol-Myers Squibb Co.
- Mead Johnson and Co.
- Dosage Forms
Form Route Strength Tablet Oral 500 mg Tablet Oral 500 mg/1 - Prices
Unit description Cost Unit Mitotane powder 7.75USD g Lysodren 500 mg tablet 5.13USD 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 (°C) 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 mg/mL 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 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 79.97 m3·mol-1 Chemaxon Polarizability 29.93 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - 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 inhibitor Inhibitor 0.7241 CYP450 2D6 inhibitor Non-inhibitor 0.9349 CYP450 2C19 inhibitor Inhibitor 0.8993 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Download (8.84 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 152.3858332 predictedDarkChem Lite v0.1.0 [M-H]- 157.19704 predictedDeepCCS 1.0 (2019) [M+H]+ 159.55504 predictedDeepCCS 1.0 (2019) [M+Na]+ 165.64818 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Steroid 11-beta-monooxygenase activity
- Specific Function
- 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 cytochro...
- Gene Name
- CYP11B1
- Uniprot ID
- P15538
- Uniprot Name
- Cytochrome P450 11B1, mitochondrial
- Molecular Weight
- 57572.44 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G: Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. Epub 2003 Oct 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Zinc ion binding
- Specific Function
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
- Gene Name
- PGR
- Uniprot ID
- P06401
- Uniprot Name
- Progesterone receptor
- Molecular Weight
- 98979.96 Da
References
- Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G: Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. Epub 2003 Oct 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Zinc ion binding
- Specific Function
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
- Gene Name
- AR
- Uniprot ID
- P10275
- Uniprot Name
- Androgen receptor
- Molecular Weight
- 98987.9 Da
References
- Maness SC, McDonnell DP, Gaido KW: Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells. Toxicol Appl Pharmacol. 1998 Jul;151(1):135-42. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Unknown
- General Function
- Iron ion binding
- Specific Function
- Participates in the synthesis of thyroid hormones. Essential for the synthesis of various steroid hormones, participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis. Trans...
- Gene Name
- FDX1
- Uniprot ID
- P10109
- Uniprot Name
- Adrenodoxin, mitochondrial
- Molecular Weight
- 19392.475 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Lysodren (mitotane) tablets for oral use (January 2024) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- FDA Approved Drug Products: Lysodren (mitotane) tablets for oral use (January 2024) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
References
- FDA Approved Drug Products: Lysodren (mitotane) tablets for oral use (January 2024) [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Upregulator
- General Function
- Serine-type endopeptidase inhibitor activity
- Specific Function
- Major thyroid hormone transport protein in serum.
- Gene Name
- SERPINA7
- Uniprot ID
- P05543
- Uniprot Name
- Thyroxine-binding globulin
- Molecular Weight
- 46324.12 Da
References
- FDA Approved Drug Products: Cytomel (liothyronine sodium) oral tablets [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Upregulator
- General Function
- Androgen binding
- Specific Function
- 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...
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- 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. [Article]
- van Seters AP, Moolenaar AJ: Mitotane increases the blood levels of hormone-binding proteins. Acta Endocrinol (Copenh). 1991 May;124(5):526-33. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Upregulator
- General Function
- Steroid binding
- Specific Function
- Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
- Gene Name
- SERPINA6
- Uniprot ID
- P08185
- Uniprot Name
- Corticosteroid-binding globulin
- Molecular Weight
- 45140.49 Da
References
- 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. [Article]
- 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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Gagliano T, Gentilin E, Benfini K, Di Pasquale C, Tassinari M, Falletta S, Feo C, Tagliati F, Uberti ED, Zatelli MC: Mitotane enhances doxorubicin cytotoxic activity by inhibiting P-gp in human adrenocortical carcinoma cells. Endocrine. 2014 Dec;47(3):943-51. doi: 10.1007/s12020-014-0374-z. Epub 2014 Aug 6. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54