U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C14H10Cl4
Molecular Weight 320.0415
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MITOTANE

SMILES

c1ccc(c(c1)C(c2ccc(cc2)Cl)C(Cl)Cl)Cl

InChI

InChIKey=JWBOIMRXGHLCPP-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: https://www.drugs.com/cdi/mitotane.html

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. 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. Mitotane is used for treatment of inoperable adrenocortical tumours; Cushing's syndrome

Originator

Curator's Comment:: # Bristol-Myers Squibb

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LYSODREN

Approved Use

LYSODREN is indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types.

Launch Date

1057708800000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11.3 mg/L
1 g 3 times / day multiple, oral
dose: 1 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
14.3 mg/L
2 g 3 times / day multiple, oral
dose: 2 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
543 mg × day/L
1 g 3 times / day multiple, oral
dose: 1 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
790 mg × day/L
2 g 3 times / day multiple, oral
dose: 2 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Doses

Doses

DosePopulationAdverse events​
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy, 51.4+/-11.9
Health Status: unhealthy
Age Group: 51.4+/-11.9
Sex: M+F
Sources:
Disc. AE: Anorexia, Nausea...
AEs leading to
discontinuation/dose reduction:
Anorexia (grade 1-2)
Nausea (grade 1-2)
Vomiting (grade 1-2)
Diarrhea (grade 1-2)
Abdominal pain (grade 1-2)
Sources:
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy
Disc. AE: Central nervous system toxicity, Fetal damage...
AEs leading to
discontinuation/dose reduction:
Central nervous system toxicity
Fetal damage
Ovarian cyst
Adrenal insufficiency
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy, 51.4+/-11.9
Health Status: unhealthy
Age Group: 51.4+/-11.9
Sex: M+F
Sources:
Anorexia grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy, 51.4+/-11.9
Health Status: unhealthy
Age Group: 51.4+/-11.9
Sex: M+F
Sources:
Diarrhea grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy, 51.4+/-11.9
Health Status: unhealthy
Age Group: 51.4+/-11.9
Sex: M+F
Sources:
Nausea grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy, 51.4+/-11.9
Health Status: unhealthy
Age Group: 51.4+/-11.9
Sex: M+F
Sources:
Vomiting grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy, 51.4+/-11.9
Health Status: unhealthy
Age Group: 51.4+/-11.9
Sex: M+F
Sources:
Adrenal insufficiency Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy
Central nervous system toxicity Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy
Fetal damage Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy
Ovarian cyst Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
strong
likely (co-administration study)
Comment: LYSODREN’s CYP induction effect leads to an increase in dosage requirements for warfarin. Closely monitor patients for a change in anticoagulant dosage requirements when administering LYSODREN to patients receiving coumarin-type anticoagulants
Page: 4
PubMed

PubMed

TitleDatePubMed
[The effects of o,p'-DDD on human adrenal steroid synthesis].
1984 Jul 20
Primary hypogonadism associated with o,p' DDD (mitotane) therapy.
1987
[Idiopathic intracranial hypertension during treatment of Cushing's disease with mitotane].
1987 Dec 12
[Neurotoxicity of mitotane therapy of adrenocortical carcinoma (5 cases) and Cushing's syndrome (7 cases)].
1987 May 23
Comparison of the adrenalytic activity of mitotane and a methylated homolog on normal adrenal cortex and adrenal cortical carcinoma.
1993
Identification of environmental chemicals with estrogenic activity using a combination of in vitro assays.
1996 Oct
Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells.
1998 Jul
Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin.
2000 Apr
Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use.
2000 Oct
Primary culture system of adrenocortical cells from dogs to evaluate direct effects of chemicals on steroidogenesis.
2001 Aug 28
[Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels].
2001 Jul 15
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.
2003 Oct
Tailored hormonal therapy in secretory adrenocortical cancer.
2007 Jul
Mitotane increases the radiotherapy inhibitory effect and induces G2-arrest in combined treatment on both H295R and SW13 adrenocortical cell lines.
2008 Jun
Modulation of proteomic profile in H295R adrenocortical cell line induced by mitotane.
2008 Mar
A novel pretreatment approach for fast determination of organochlorine pesticides in biotic samples.
2008 May
Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells.
2010 Feb 1
Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential treatment for adrenocortical cancer.
2012 Jan
Ribonucleotide reductase large subunit (RRM1) gene expression may predict efficacy of adjuvant mitotane in adrenocortical cancer.
2012 Jun 15
The organochlorine o,p'-DDT plays a role in coactivator-mediated MAPK crosstalk in MCF-7 breast cancer cells.
2012 Sep
Influence of the CYP2B6 polymorphism on the pharmacokinetics of mitotane.
2013 Jun
Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.
2015 Feb
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Adrenal Cortical Carcinoma
Route of Administration: Oral
Mitotane (10-40uM) inhibited basal and cAMP-induced cortisol secretion in human adrenocortical cancer NCI-H295 cells.
Name Type Language
MITOTANE
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
MITOTANE [EMA EPAR]
Common Name English
MITOTANE [USAN]
Common Name English
O,P'-DDD
Common Name English
MITOTANE [MI]
Common Name English
CHLODITAN
Brand Name English
MITOTANE [ORANGE BOOK]
Common Name English
MITOTANE [USP]
Common Name English
CB-313
Code English
O,P'-TDE
Common Name English
NSC-38721
Code English
MITOTANE [INN]
Common Name English
MITOTANE [WHO-DD]
Common Name English
CB 313
Code English
MITOTANE [MART.]
Common Name English
O,P'-DDD,O P'-TDE
Common Name English
MITOTANE [HSDB]
Common Name English
MITOTAN
Common Name English
CHLODITHANE
Brand Name English
OPEPRIM
Brand Name English
MITOTANE [JAN]
Common Name English
MITOTANE [USP-RS]
Common Name English
BENZENE, 1-CHLORO-2-(2,2-DICHLORO-1-(4-CHLOROPHENYL)ETHYL)-, (+/-)-
Systematic Name English
(+/-)-1,1-DICHLORO-2-(O-CHLOROPHENYL)-2-(P-CHLOROPHENYL)ETHANE
Common Name English
LYSODREN
Brand Name English
MITOTANE [USP MONOGRAPH]
Common Name English
BENZENE, 1-CHLORO-2-(2,2-DICHLORO-1-(4-CHLOROPHENYL)ETHYL)-
Systematic Name English
MITOTANE [VANDF]
Common Name English
Classification Tree Code System Code
WHO-ATC L01XX23
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
EMA ASSESSMENT REPORTS LYSODREN (AUTHORIZED: ADRENAL CORTEX NEOPLASMS)
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
LIVERTOX 647
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
NCI_THESAURUS C2355
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
EU-Orphan Drug EU/3/02/102
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
WHO-VATC QL01XX23
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
Code System Code Type Description
DRUG CENTRAL
1820
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
IUPHAR
6957
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
EVMPD
SUB09010MIG
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
MESH
D008939
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
CAS
53-19-0
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
NCI_THESAURUS
C664
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
EPA CompTox
53-19-0
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
PUBCHEM
4211
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-166-6
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
MERCK INDEX
M7571
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB00648
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
INN
2597
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
ChEMBL
CHEMBL1670
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
WIKIPEDIA
MITOTANE
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
RXCUI
7004
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY RxNorm
FDA UNII
78E4J5IB5J
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
USP_CATALOG
1445007
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY USP-RS
HSDB
3240
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY
NDF-RT
N0000185506
Created by admin on Fri Jun 25 20:55:08 UTC 2021 , Edited by admin on Fri Jun 25 20:55:08 UTC 2021
PRIMARY Cytochrome P450 3A4 Inducers [MoA]