ETRETINATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H30O3
Molecular Weight	354.4825
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)\C=C(C)\C=C\C=C(C)\C=C\C1=C(C)C(C)=C(OC)C=C1C

InChI

InChIKey=HQMNCQVAMBCHCO-DJRRULDNSA-N

InChI=1S/C23H30O3/c1-8-26-23(24)14-17(3)11-9-10-16(2)12-13-21-18(4)15-22(25-7)20(6)19(21)5/h9-15H,8H2,1-7H3/b11-9+,13-12+,16-10+,17-14+

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB00926
Curator's Comment: description was created based on several sources, including http://www.tabletwise.com/us/tegison-capsule | https://www.ncbi.nlm.nih.gov/pubmed/12723955 | https://www.drugs.com/mmx/etretinate.html

Etretinate (trade name Tegison) is a medication developed by Hoffmann–La Roche that was approved by the FDA in 1986 to treat severe psoriasis. It is a second-generation retinoid. It was subsequently removed from the Canadian market in 1996 and the United States market in 1998 due to the high risk of birth defects. Etretinate remains on the market in Japan as Tigason. The mechanism of action of etretinate is still incompletely understood although, like retinoic acid, it is thought to interfere with the terminal differentiation of keratinocytes. Etretinate activates retinoid receptors, causing an induction of cell differentiation, inhibition of cell proliferation, and inhibition of tissue infiltration by inflammatory cells.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Retinoic acid receptor alpha 11 Target ID: CHEMBL2792 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12723955	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Psoriasis 84 Sources: http://www.tabletwise.com/us/tegison-capsule	Primary		Approved 8429	TEGISON Approved Use Unknown Launch Date 5.28422404E11

C_max

Value	Dose	Co-administered	Analyte	Population
100 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9703120	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		ETRETINATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg single, oral Studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3508553	healthy, 20-32 years n = 12 Health Status: healthy Age Group: 20-32 years Sex: M Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/3508553	Other AEs: Headache... Other AEs: Headache (mild, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3508553
50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10568486	unhealthy, 57,1 ± 14,2 years (range 23±83 years) n = 86 Health Status: unhealthy Condition: psoriasis vulgaris Age Group: 57,1 ± 14,2 years (range 23±83 years) Sex: M+F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/10568486	Disc. AE: Palpitations, Edema face... AEs leading to discontinuation/dose reduction: Palpitations (2 patients) Edema face (2 patients) Transaminases increased (3 patients) Hypertriglyceridemia (1 patient) Hyperglycaemia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/10568486
75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2244393	unhealthy, 75 years n = 1 Health Status: unhealthy Condition: psoriasis Age Group: 75 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2244393	Disc. AE: Ectropion... AEs leading to discontinuation/dose reduction: Ectropion (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/2244393

AEs

AE	Significance	Dose	Population
Headache	mild, 1 patient	100 mg single, oral Studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/3508553	healthy, 20-32 years n = 12 Health Status: healthy Age Group: 20-32 years Sex: M Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/3508553
Hyperglycaemia	1 patient Disc. AE	50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10568486	unhealthy, 57,1 ± 14,2 years (range 23±83 years) n = 86 Health Status: unhealthy Condition: psoriasis vulgaris Age Group: 57,1 ± 14,2 years (range 23±83 years) Sex: M+F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/10568486
Hypertriglyceridemia	1 patient Disc. AE	50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10568486	unhealthy, 57,1 ± 14,2 years (range 23±83 years) n = 86 Health Status: unhealthy Condition: psoriasis vulgaris Age Group: 57,1 ± 14,2 years (range 23±83 years) Sex: M+F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/10568486
Edema face	2 patients Disc. AE	50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10568486	unhealthy, 57,1 ± 14,2 years (range 23±83 years) n = 86 Health Status: unhealthy Condition: psoriasis vulgaris Age Group: 57,1 ± 14,2 years (range 23±83 years) Sex: M+F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/10568486
Palpitations	2 patients Disc. AE	50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10568486	unhealthy, 57,1 ± 14,2 years (range 23±83 years) n = 86 Health Status: unhealthy Condition: psoriasis vulgaris Age Group: 57,1 ± 14,2 years (range 23±83 years) Sex: M+F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/10568486
Transaminases increased	3 patients Disc. AE	50 mg 1 times / day multiple, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10568486	unhealthy, 57,1 ± 14,2 years (range 23±83 years) n = 86 Health Status: unhealthy Condition: psoriasis vulgaris Age Group: 57,1 ± 14,2 years (range 23±83 years) Sex: M+F Population Size: 86 Sources: https://pubmed.ncbi.nlm.nih.gov/10568486
Ectropion	1 patient Disc. AE	75 mg 1 times / day multiple, oral Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2244393	unhealthy, 75 years n = 1 Health Status: unhealthy Condition: psoriasis Age Group: 75 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2244393

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4913	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4913
ChemicalBook	CB6214647	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6214647
MolPort	MolPort-005-937-301	https://www.molport.com/shop/molecule-link/MolPort-005-937-301
ZINC	ZINC000003830820	http://zinc15.docking.org/substances/ZINC000003830820
eMolecules	17497555	https://www.emolecules.com/cgi-bin/more?vid=17497555

PubMed

Title	Date	PubMed
A rosacea-like eruption induced by Tigason (Ro 10-9359) treatment.	1982	6183905
Differential hepatotoxicity of two oral retinoids (etretinate and isotretinoin) in a patient with palmoplantar psoriasis.	1985	2413699
The effect of etretinate compared with different regimens of PUVA in the treatment of persistent palmoplantar pustulosis.	1985 Apr	3888246
Cholestatic jaundice, an unusual side effect of etretinate.	1985 Oct	4078057
Benign intracranial hypertension during etretinate therapy for mycosis fungoides.	1985 Sep	4056125
[Retinoids and lipid metabolism].	1986 Jun	3721869
Increased muscle tone during etretinate therapy.	1986 May	3711400
Etretinate-induced skeletal muscle damage.	1987 May	2954577
Hepatocanalicular injury associated with vitamin A derivative etretinate. An idiosyncratic hypersensitivity reaction.	1987 Oct	3652901
A new syndrome of axial muscle rigidity associated with etretinate therapy.	1988	3173366
Depression induced by etretinate.	1989 Apr 8	2497882
Malformations of the maxillofacial region induced by retinoids in an experimental system.	1990 Jun	2114463
Erectile dysfunction in etretinate treatment.	1991 Mar	1998382
[Successful use of isotretinoin in type Zumbusch generalized pustular psoriasis following recovered etretinate-induced hepatitis].	1991 Sep	1938411
Renal impairment probably induced by etretinate.	1992	1477420
Peripheral neuropathy during etretinate therapy for psoriasis.	1993 Feb	8381828
Joint pains with psoriasis and long-term systemic etretinate therapy: a case report and summary of 12 cases.	1993 Oct	8277044
Prevention of etretinate-induced craniofacial malformations by vitamin B6 in the rat.	1996 Oct-Dec	9021329
Teratological studies on craniofacial malformations.	1997	9200351
Severe cholestatic hepatitis in a patient taking acitretin.	2002 Mar	11922592
Dramatic improvement of psoriatic erythroderma after acute hepatitis: analysis of cytokine synthesis capability in peripheral blood T cells.	2006 Aug	16882189

Patents

Sample Use Guides

In Vivo Use Guide

Initial: 0.75 mg to 1 mg per kg of body weight per day in divided doses. Maintenance: 0.5 to 0.75 mg per kg of body weight per day may be initiated after initial response, generally after 8 to 16 weeks of therapy. Usual adult prescribing limits 1.5 mg per kg of body weight per day.

Route of Administration: Oral

In Vitro Use Guide

Erythrocytes were isolated from fresh blood by centrifugation. Etretinate (as DMSO solution) was added to the suspensions of erythrocytes. The final concentration of etretinate was 1.4nM. Erythrocyte suspensions were incubated for 30 min at 370C. After treatment with etretinate, a significant increase in erythrocyte membrane fluidity and in antioxidant activity as well as a decrease in lipid peroxidation were observed in erythrocytes from patients.

Name

Type

Language

ETRETINATE

Official Name

English

ACITRETIN IMPURITY B [EP IMPURITY]

Common Name

English

ETRETINATE [VANDF]

Common Name

English

ACITRETIN RELATED COMPOUND B [USP-RS]

Common Name

English

ACITRETIN RELATED COMPOUND B [USP IMPURITY]

Common Name

English

NSC-297936

Code

English

RO-109359

Code

English

TEGISON

Brand Name

English

Ethyl (all-E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate

Common Name

English

etretinate [INN]

Common Name

English

2,4,6,8-NONATETRAENOIC ACID, 9-(4-METHOXY-2,3,6-TRIMETHYLPHENYL)-, ETHYL ESTER, (ALL-E-)

Common Name

English

ETRETINATE [JAN]

Common Name

English

ETRETINATE [ORANGE BOOK]

Common Name

English

ETHYL ALL-TRANS-9-(4-METHOXY-2,3,6-TRIMETHYLPHENYL)-3,7-DIMETHYL-2,4,6,8-NONATETRAENOATE

Common Name

English

ETHYL ETRINOATE

Common Name

English

ETRETINATE [HSDB]

Common Name

English

RO 10-9359

Code

English

ETRETINATE [USAN]

Common Name

English

ETRETINATE [MI]

Common Name

English

Etretinate [WHO-DD]

Common Name

English

ETRETINATE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C804