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Identification
Name Isotretinoin
Accession Number DB00982 (APRD00140)
Type small molecule
Groups approved
Description

Isotretinoin is a medication used for the treatment of severe acne. It is sometimes used in prevention of certain skin cancers. It is a retinoid, meaning it derives from vitamin A and is found in small quantities naturally in the body. Isotretinoin binds to and activates nuclear retinoic acid receptors (RAR), thereby regulating cell proliferation and differentiation. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Accutane Roche
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Anti-acne Agents
  • Keratolytic Agents
  • Skin and Mucous Membrane Agents
CAS number 4759-48-2
Weight Average: 300.4351
Monoisotopic: 300.208930140
Chemical Formula C20H28O2
InChI Key InChIKey=SHGAZHPCJJPHSC-UHFFFAOYSA-N
InChI
InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)
Plain Text
IUPAC Name
3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
SMILES
CC(C=CC1=C(C)CCCC1(C)C)=CC=CC(C)=CC(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Retinoids
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Retinoids
  • Acetates
  • Carboxylic Acids and Derivatives
  • Monoterpenes
  • Isoprenes
  • Cyclohexenes and Derivatives
Pharmacology
Indication For the treatment of severe recalcitrant nodular acne
Pharmacodynamics Isotretinoin, a retinoid, is indicated in the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. "Severe," by definition, means "many" as opposed to "few or several" nodules. Clinical improvement in nodular acne patients occurs in association with a reduction in sebum secretion. The decrease in sebum secretion is temporary and is related to the dose and duration of treatment with Accutane, and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation.
Mechanism of action Isotretinoin noticeably reduces the production of sebum and shrinks the sebaceous glands. It stabilises keratinization and prevents comedones from forming. It also reduces inflammation in moderate-severe inflammatory acne. The exact mechanism of action is unknown, however it is known that it alters DNA transcription.
Absorption Not Available
Volume of distribution Not Available
Protein binding 99.9%
Metabolism
Route of elimination Isotretinoin and its metabolites are further metabolized into conjugates, which are then excreted in urine and feces. The metabolites of isotretinoin and any conjugates are ultimately excreted in the feces and urine in relatively equal amounts (total of 65% to 83%).
Half life 17-50 hours
Clearance
  • 96 +/- 6.27 L/hr [severe recalcitrant nodular acne pediatric Patients, 12 to 15 Years]
Toxicity Isotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Accutane 20 mg capsule 23.77 USD capsule
Amnesteem 40 mg capsule 22.6 USD capsule
Claravis 40 mg capsule 22.6 USD capsule
Amnesteem 20 mg capsule 19.45 USD capsule
Claravis 20 mg capsule 18.7 USD capsule
Claravis 30 mg capsule 16.45 USD capsule
Amnesteem 10 mg capsule 16.4 USD capsule
Claravis 10 mg capsule 15.77 USD capsule
Accutane 40 mg capsule 14.88 USD capsule
Accutane 10 mg capsule 10.55 USD capsule
Sotret 40 mg capsule 10.08 USD capsule
Sotret 20 mg capsule 8.67 USD capsule
Sotret 30 mg capsule 8.44 USD capsule
Sotret 10 mg capsule 7.31 USD capsule
Clarus 40 mg Capsule 2.14 USD capsule
Clarus 10 mg Capsule 1.05 USD capsule
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 4.2 PhysProp
Predicted Properties
Property Value Source
water solubility 4.77e-03 g/l ALOGPS
logP 5.66 ALOGPS
logP 5.01 ChemAxon Molconvert
logS -4.80 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 37.30 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 97.79 ChemAxon Molconvert
polarizability 36.70 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Berard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D: Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective. Br J Clin Pharmacol. 2007 Feb;63(2):196-205. Pubmed
  2. Holmes SC, Bankowska U, Mackie RM: The prescription of isotretinoin to women: is every precaution taken? Br J Dermatol. 1998 Mar;138(3):450-5. Pubmed
  3. Amichai B, Shemer A, Grunwald MH: Low-dose isotretinoin in the treatment of acne vulgaris. J Am Acad Dermatol. 2006 Apr;54(4):644-6. Pubmed
  4. Seukeran DC, Cunliffe WJ: Acne vulgaris in the elderly: the response to low-dose isotretinoin. Br J Dermatol. 1998 Jul;139(1):99-101. Pubmed
  5. Tirado Sanchez A, Leon Dorantes G: [Erectile dysfunction during isotretinoin therapy] Actas Urol Esp. 2005 Nov-Dec;29(10):974-6. Pubmed
External Links
Resource Link
KEGG Drug D00348 Link_out
PubChem Compound 444795 Link_out
PubChem Substance 46508729 Link_out
ChemSpider 5337 Link_out
ChEBI 6067 Link_out
ChEMBL 6067 Link_out
Therapeutic Targets Database DAP000009 Link_out
Drug Product Database 582344 Link_out
RxList http://www.rxlist.com/cgi/generic/isotret.htm Link_out
Drugs.com http://www.drugs.com/cdi/isotretinoin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Isotretinoin Link_out
ATC Codes
  • D10AD04
  • D10BA01
AHFS Codes
  • 84:92.00
PDB Entries Not Available
FDA label show (376.3 KB)
MSDS show (37.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water Do not take supplements containing Vitamin A.
  • Take with high-fat meal to increase absorption.
Targets

1. Retinoic acid receptor alpha

Pharmacological action: unknown
Actions: other/unknown

This is a receptor for retinoic acid. This metabolite has profound effects on vertebrate development. Retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cell function by directly regulating gene expression

Organism class: human
UniProt ID: P10276 Link_out
Gene: RARA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Dahl AR, Grossi IM, Houchens DP, Scovell LJ, Placke ME, Imondi AR, Stoner GD, De Luca LM, Wang D, Mulshine JL: Inhaled isotretinoin (13-cis retinoic acid) is an effective lung cancer chemopreventive agent in A/J mice at low doses: a pilot study. Clin Cancer Res. 2000 Aug;6(8):3015-24. Pubmed
  2. Zouboulis CC: Isotretinoin revisited: pluripotent effects on human sebaceous gland cells. J Invest Dermatol. 2006 Oct;126(10):2154-6. Pubmed
  3. Vu-Dac N, Gervois P, Torra IP, Fruchart JC, Kosykh V, Kooistra T, Princen HM, Dallongeville J, Staels B: Retinoids increase human apo C-III expression at the transcriptional level via the retinoid X receptor. Contribution to the hypertriglyceridemic action of retinoids. J Clin Invest. 1998 Aug 1;102(3):625-32. Pubmed
  4. Taylor LE, Bennett GD, Finnell RH: Altered gene expression in murine branchial arches following in utero exposure to retinoic acid. J Craniofac Genet Dev Biol. 1995 Jan-Mar;15(1):13-25. Pubmed
  5. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.