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Showing drug card for Isotretinoin (DB00982)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:48:11
Primary Accession Number DB00982
Secondary Accession Number
  • APRD00140
Name Isotretinoin
Drug Type
  • Approved
  • Small Molecule
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.
Synonyms Not Available
Brand Names
  1. Accutane Roche
Brand Mixtures Not Available
Chemical IUPAC Name 3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)nona-2,4,6,8-tetraenoic acid
Chemical Formula C20H28O2
Chemical Structure Structure
CAS Registry Number 4759-48-2
InChI Identifier InChI=1/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)/f/h21H
InChI Key SHGAZHPCJJPHSC-PKSOQXRJCZ
KEGG Drug D00348 Link Image
KEGG Compound Not Available
PubChem Compound 5538 Link Image
PubChem Substance 7847414 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00582344 Link Image
RxList Link http://www.rxlist.com/cgi/generic/isotret.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Isotretinoin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 300.4351
Monoisotopic Molecular Weight 300.2089
State Solid
Melting Point Not Available
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 4.77e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4.2 Source: PhysProp
Predicted LogP 5.66 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.80 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(\C=C\C1=C(C)CCCC1(C)C)=C/C=C/C(C)=C/C(O)=O
Canonical SMILES CC(C=CC1=C(C)CCCC1(C)C)=CC=CC(C)=CC(O)=O
Drug Category
  • Anti-acne Agents
  • Antineoplastic Agents
  • Keratolytic Agents
  • Skin and Mucous Membrane Agents
ATC Codes
AHFS Codes
  • 84:92.00
Indication For the treatment of severe recalcitrant nodular acne
Pharmacology 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. The exact mechanism of action is unknown, however it is known that it alters DNA transcription.
Absorption Not Available
Toxicity Not Available
Protein Binding 99.9%
Biotransformation Not Available
Half Life 17-50 hours
Dosage Forms
Form Route
Capsule Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Retinoids decreases the anticoagulant effect
Anisindione Retinoids decreases the anticoagulant effect
Carbamazepine Isotretinoine decreases the effect of carbamazepine
Demeclocycline Increased risk of intracranial hypertension
Dicumarol Retinoids decreases the anticoagulant effect
Doxycycline Increased risk of intracranial hypertension
Methacycline Increased risk of intracranial hypertension
Minocycline Increased risk of intracranial hypertension
Oxytetracycline Increased risk of intracranial hypertension
Rolitetracycline Increased risk of intracranial hypertension
Tetracycline Increased risk of intracranial hypertension
Warfarin Retinoids decreases the anticoagulant effect
Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water Do not take supplements containing Vitamin A.
  • Take with food to increase absorption.
Pathways Not Available
General References
  1. Tirado Sanchez A, Leon Dorantes G: [Erectile dysfunction during isotretinoin therapy] Actas Urol Esp. 2005 Nov-Dec;29(10):974-6. [PubMed Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Retinoic acid receptor alpha
Drug Target 1 [top]
Target 1 ID 730
Target 1 Name Retinoic acid receptor alpha
Target 1 Synonyms
  1. RAR-alpha
Target 1 Gene Name RARA
Target 1 Protein Sequence >Retinoic acid receptor alpha 
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT
IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM
VYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL
TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTV
EFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA
GFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK
VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGL
DTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP
Target 1 Number of Residues 469
Target 1 Molecular Weight 50772
Target 1 Theoretical pI 7.95
Target 1 GO Classification
Function
retinoic acid receptor activity
signal transducer activity
receptor activity
ligand-dependent nuclear receptor activity
steroid hormone receptor activity
binding
nucleic acid binding
DNA binding
transcription factor activity
Process
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
Component
organelle
membrane-bound organelle
intracellular membrane-bound organelle
nucleus
Target 1 General Function Involved in transcription factor activity
Target 1 Specific Function 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 36157 Link Image
Target 1 UniProtKB/Swiss-Prot ID P10276 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name RARA_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Nucleus
Target 1 Gene Sequence >1389 bp 
ATGGCCAGCAACAGCAGCTCCTGCCCGACACCTGGGGGCGGGCACCTCAATGGGTACCCG
GTGCCTCCCTACGCCTTCTTCTTCCCCCCTATGCTGGGTGGACTCTCCCCGCCAGGCGCT
CTGACCACTCTCCAGCACCAGCTTCCAGTTAGTGGATATAGCACACCATCCCCAGCCACC
ATTGAGACCCAGAGCAGCAGTTCTGAAGAGATAGTGCCCAGCCCTCCCTCGCCACCCCCT
CTACCCCGCATCTACAAGCCTTGCTTTGTCTGTCAGGACAAGTCCTCAGGCTACCACTAT
GGGGTCAGCGCCTGTGAGGGCTGCAAGGGCTTCTTCCGCCGCAGCATCCAGAAGAACATG
GTGTACACGTGTCACCGGGACAAGAACTGCATCATCAACAAGGTGACCCGGAACCGCTGC
CAGTACTGCCGACTGCAGAAGTGCTTTGAAGTGGGCATGTCCAAGGAGTCTGTGAGAAAC
GACCGAAACAAGAAGAAGAAGGAGGTGCCCAAGCCCGAGTGCTCTGAGAGCTACACGCTG
ACGCCGGAGGTGGGGGAGCTCATTGAGAAGGTGCGCAAAGCGCACCAGGAAACCTTCCCT
GCCCTCTGCCAGCTGGGCAAATACACTACGAACAACAGCTCAGAACAACGTGTCTCTCTG
GACATTGACCTCTGGGACAAGTTCAGTGAACTCTCCACCAAGTGCATCATTAAGACTGTG
GAGTTCGCCAAGCAGCTGCCCGGCTTCACCACCCTCACCATCGCCGACCAGATCACCCTC
CTCAAGGCTGCCTGCCTGGACATCCTGATCCTGCGGATCTGCACGCGGTACACGCCCGAG
CAGGACACCATGACCTTCTCGGACGGGCTGACCCTGAACCGGACCCAGATGCACAACGCT
GGCTTCGGCCCCCTCACCGACCTGGTCTTTGCCTTCGCCAACCAGCTGCTGCCCCTGGAG
ATGGATGATGCGGAGACGGGGCTGCTCAGCGCCATCTGCCTCATCTGCGGAGACCGCCAG
GACCTGGAGCAGCCGGACCGGGTGGACATGCTGCAGGAGCCGCTGCTGGAGGCGCTAAAG
GTCTACGTGCGGAAGCGGAGGCCCAGCCGCCCCCACATGTTCCCCAAGATGCTAATGAAG
ATTACTGACCTGCGAAGCATCAGCGCCAAGGGGGCTGAGCGGGTGATCACGCTGAAGATG
GAGATCCCGGGCTCCATGCCGCCTCTCATCCAGGAAATGTTGGAGAACTCAGAGGGCCTG
GACACTCTGAGCGGACAGCCGGGGGGTGGGGGGCGGGACGGGGGTGGCCTGGCCCCCCCG
CCAGGCAGCTGTAGCCCCAGCCTCAGCCCCAGCTCCAACAGAAGCAGCCCGGCCACCCAC
TCCCCGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID RARA Link Image
Target 1 GenAtlas ID RARA Link Image
Target 1 HGNC ID HGNC:9864 Link Image
Target 1 Chromosome Location 17
Target 1 Locus 17q21
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Hjalt TA, Murray JC: Genomic structure of the human retinoic acid receptor-alpha1 gene. Mamm Genome. 1999 May;10(5):528-9. [PubMed Link Image]
  2. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem. 1999 Nov 26;274(48):34283-93. [PubMed Link Image]
  3. Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. [PubMed Link Image]
  4. Brand NJ, Petkovich M, Chambon P: Characterization of a functional promoter for the human retinoic acid receptor-alpha (hRAR-alpha). Nucleic Acids Res. 1990 Dec 11;18(23):6799-806. [PubMed Link Image]
  5. Petkovich M, Brand NJ, Krust A, Chambon P: A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3-9;330(6147):444-50. [PubMed Link Image]
  6. Giguere V, Ong ES, Segui P, Evans RM: Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17-23;330(6149):624-9. [PubMed Link Image]
  7. Chen Z, Guidez F, Rousselot P, Agadir A, Chen SJ, Wang ZY, Degos L, Zelent A, Waxman S, Chomienne C: PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1178-82. [PubMed Link Image]
  8. Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ: The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion. Blood. 1996 Feb 1;87(3):882-6. [PubMed Link Image]
  9. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. [PubMed Link Image]
Target 1 Drug 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 Link Image]
  2. Zouboulis CC: Isotretinoin revisited: pluripotent effects on human sebaceous gland cells. J Invest Dermatol. 2006 Oct;126(10):2154-6. [PubMed Link Image]
  3. 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 Link Image]
  4. Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. [PubMed Link Image]
  5. 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 Link Image]

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.