MITOTANE

Details

Stereochemistry	RACEMIC
Molecular Formula	C14H10Cl4
Molecular Weight	320.041
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC(Cl)C(C1=CC=C(Cl)C=C1)C2=C(Cl)C=CC=C2

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
Sources: http://www.drugbank.ca/drugs/DB00648
Curator's Comment: Description was created based on several sources, including 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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 11A1 4 Target ID: CHEMBL2033 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D00420	Inhibitor 8297
transformed cell apoptotic process 108 Target ID: GO:0006927 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23507702	Activator 1430	38.0 µM [IC50]
cortisol biosynthetic process 1 Target ID: GO:0034651 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22546480	Inhibitor 8297
Cytochrome P450 11B1 9 Target ID: CHEMBL1908 Sources: http://www.drugbank.ca/drugs/DB00648	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Adrenal cortical carcinoma 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/016885s025lbl.pdf	Primary		Approved 8429	LYSODREN Approved Use LYSODREN is indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. Launch Date 2003

C_max

Value	Dose	Co-administered	Analyte	Population
11.3 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24057287	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24057287/	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

Value	Dose	Co-administered	Analyte	Population
543 mg × day/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24057287	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24057287/	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264	unhealthy, 51.4+/-11.9 n = 12 Health Status: unhealthy Condition: Adrenal cortical carcinoma Age Group: 51.4+/-11.9 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264	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: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Adrenal cortical carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264	unhealthy, 51.4+/-11.9 n = 12 Health Status: unhealthy Condition: Adrenal cortical carcinoma Age Group: 51.4+/-11.9 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264
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: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264	unhealthy, 51.4+/-11.9 n = 12 Health Status: unhealthy Condition: Adrenal cortical carcinoma Age Group: 51.4+/-11.9 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264
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: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264	unhealthy, 51.4+/-11.9 n = 12 Health Status: unhealthy Condition: Adrenal cortical carcinoma Age Group: 51.4+/-11.9 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264
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: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264	unhealthy, 51.4+/-11.9 n = 12 Health Status: unhealthy Condition: Adrenal cortical carcinoma Age Group: 51.4+/-11.9 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264
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: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264	unhealthy, 51.4+/-11.9 n = 12 Health Status: unhealthy Condition: Adrenal cortical carcinoma Age Group: 51.4+/-11.9 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/22048971 Page: p.264
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Adrenal cortical carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Adrenal cortical carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Adrenal cortical carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Adrenal cortical carcinoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf#page=4 Page: 4.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016885s027lbl.pdf#page=4 Page: 4.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY558683	https://www.001chemical.com/chem/53-19-0
3B Scientific (Wuhan) Corp	3B3-026423	http://www.3bsc.com/index/pro_info.php?id=47662
AA Blocks	AA00ILLB	http://www.aablocks.com/goods/Goods/detail?id=AA00ILLB
AHH Chemical co.,ltd	MT-19139	http://www.ahhchemical.com/product/MT-19139.html
AK Scientific, Inc. (AKSCI)	67599	http://www.aksci.com/item_detail.php?cat=67599
Aaron Chemicals	AR00IMD3	http://www.aaronchem.com/53-19-0
AbMole Bioscience	M3425	http://www.abmole.com/products/mitotane.html
Achemtek	0104-044397	http://www.achemtek.com/53-19-0
Alfa Chemistry	AP53190-A	https://reagents.alfa-chemistry.com/product/2-4-ddd-cas-53-19-0-12645.html
Alfa Chemistry	AP53190-B	https://reagents.alfa-chemistry.com/product/mitotane-cas-53-19-0-12646.html
Alsachim	1837	http://www.alsachim.com/product-C2719-glo.bal-view.html
Ambeed	A817688	https://www.ambeed.com/products/53-19-0.html
Angene	AGN-PC-088NK5	http://www.angenechemical.com/productshow/AGN-PC-088NK5.html
Ark Pharm	AK546750	http://www.arkpharminc.com/products/53-19-0.html
Aurora Fine Chemicals LLC	K02.120.487	http://online.aurorafinechemicals.com/info?ID=K02.120.487
Aurum Pharmatech LLC	W-5031	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5031
Axon MedChem	3248	https://www.axonmedchem.com/product/3248
BLD Pharm	BD145903	http://www.bldpharm.com/products/53-19-0.html
BioChemPartner	BCP11663	http://www.biochempartner.com/53-19-0-BCP11663
BioCrick	BCC3815	http://www.biocrick.com/Mitotane-Lsodren-BCC3815.html
CSNpharm	CSN11593	https://www.csnpharm.com/products/mitotane.html
Capot Chemical	14974	http://www.capotchem.com/en/14974.htm
Capot Chemical	PubChem14974	http://www.capotchem.com/en/14974.htm
Chem Scene	CS-1500	http://www.chemscene.com/53-19-0.html
ChemMol	49425872	http://www.chemmol.com/chemmol/49425872.html
Chemenu	CM110274	http://www.chemenu.com/products/CM110274
Chemspace	CSSB00000519455	https://chem-space.com/CSSB00000519455
Clearsynth	CS-T-58863	https://www.clearsynth.com/en/CST58863.html
DC Chemicals	DCAPI1234	http://www.dcchemicals.com//product_show-Mitotane_Lysodren_.html
Enamine	Z425389592	https://www.enaminestore.com/catalog/Z425389592
Finetech	FT-0605518	http://www.finetechnology-ind.com/prod/detail/pub/53-19-0.html
Glentham Life Sciences	GL0573	http://www.glentham.com/products/product/GL0573/
Hairui	HR124477	http://www.hairuichem.com/en/product/53-19-0.html
LGC Standards	DRE-C12030000	https://www.lgcstandards.com/US/en/p/DRE-C12030000
LGC Standards	DRE-L12030000CY	https://www.lgcstandards.com/US/en/p/DRE-L12030000CY
LGC Standards	DRE-XA12030000CY	https://www.lgcstandards.com/US/en/p/DRE-XA12030000CY
Lab Network	LN01289322	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01289322
MedChem Express	HY-13690	https://www.medchemexpress.com/mitotane.html
Molcore	MC558683	https://www.molcore.com/product/53-19-0
OChem	4284	http://www.ocheminc.com/index.php?act=psearch&pid=000M850
Sigma-Aldrich	35485_SIAL	http://www.sigmaaldrich.com/catalog/product/sial/35485?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	25925_SIGMA	http://www.sigmaaldrich.com/catalog/product/sigma/25925?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	49015_SUPELCO	http://www.sigmaaldrich.com/catalog/product/supelco/49015?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	N12706_SUPELCO	http://www.sigmaaldrich.com/catalog/product/supelco/n12706?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1445007_USP	http://www.sigmaaldrich.com/catalog/product/usp/1445007?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S013106	http://www.sinfoobiotech.com/product/1016504
Smolecule	S535549	http://www.smolecule.com/products/s535549
THE BioTek	bt-276001	https://www.thebiotek.com/product/inhibitors/bt-276001
Yuhao Chemical	LQ0013	http://www.chemyuhao.com/53-19-0.html
abcr GmbH	AB509180	http://www.abcr.com/shop/en/AB509180
eNovation Chemicals	D672644	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672644
iChemical	EBD36309	http://www.ichemical.com/products/53-19-0.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-2068358149	https://mcule.com/MCULE-2068358149/

PubMed

Title	Date	PubMed
[The effects of o,p'-DDD on human adrenal steroid synthesis].	1984 Jul 20	6094274
[Neurotoxicity of mitotane therapy of adrenocortical carcinoma (5 cases) and Cushing's syndrome (7 cases)].	1987 May 23	2954144
Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas.	1991 Jul	1675220
Reversible mental deterioration and neurological disturbances with o,p'-DDD therapy.	1992	1320517
Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator.	1996 Dec	9118873
Identification of environmental chemicals with estrogenic activity using a combination of in vitro assays.	1996 Oct	8930550
A patient with adrenocortical carcinoma: characterization of its biological activity and drug resistance profile.	1997 Mar	9815696
Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells.	1998 Jul	9705896
Primary culture system of adrenocortical cells from dogs to evaluate direct effects of chemicals on steroidogenesis.	2001 Aug 28	11522375
Molecular and pharmacological evidence for modulation of kinin B(1) receptor expression by endogenous glucocorticoids hormones in rats.	2001 Jan	11159707
[Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels].	2001 Jul 15	11494911
Cytochrome P450-catalyzed binding of 3-methylsulfonyl-DDE and o,p'-DDD in human adrenal zona fasciculata/reticularis.	2002 Mar	11889204
A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist.	2002 May 1	12015757
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.	2003 Oct	14565775
Tailored hormonal therapy in secretory adrenocortical cancer.	2007 Jul	17675396
(2S)-1,1-Dichloro-2-(2-chloro-phen-yl)-2-(4-chloro-phen-yl)ethane.	2009 Jan 14	21581907
Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential treatment for adrenocortical cancer.	2012 Jan	22156929
Differential effect of DDT, DDE, and DDD on COX-2 expression in the human trophoblast derived HTR-8/SVneo cells.	2012 Nov	23132776
The effect of mitotane on viability, steroidogenesis and gene expression in NCI‑H295R adrenocortical cells.	2013 Mar	23254310
Mitotane induces CYP3A4 expression via activation of the steroid and xenobiotic receptor.	2013 Mar	23179081
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	25349334

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Adrenal Cortical Carcinoma -Initial Dose: 2 to 6 g orally per day in 3 to 4 divided doses -Maintenance Dose: 9 to 10 g orally per day in 3 to 4 divided doses -Maximum Dose: May increase up to 16 g orally per day, if tolerated, in 3 to 4 divided doses; the highest doses used in studies were 18 to 19 g per day.

Route of Administration: Oral

In Vitro Use Guide

Mitotane (10-40uM) inhibited basal and cAMP-induced cortisol secretion in human adrenocortical cancer NCI-H295 cells.

Name

Type

Language

MITOTANE

Official Name

English

Mitotane [WHO-DD]

Common 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 [USP IMPURITY]

Common Name

English

MITOTANE [ORANGE BOOK]

Common Name

English

CB-313

Code

English

O,P'-TDE

Common Name

English

NSC-38721

Code

English

mitotane [INN]

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