DT-Web

DB00982 - Isotretinoin


Identification
Name Isotretinoin
Accession Number DB00982 (APRD00140)
Type 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 300.4351
Groups approved
Monoisotopic Weight 300.20893014
Pharmacology
Indication For the treatment of severe recalcitrant nodular acne
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
Protein binding 99.9%
Biotransformation Not Available
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%).
Toxicity Isotretinoin is teratogenic. It also causes mucocutaneous side effects suck as cheilitis, dry skin, and dry eyes.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Carbamazepine Isotretinoine decreases the effect of carbamazepine
Demeclocycline Increased risk of intracranial hypertension
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
Vitamin A Isotretinoin increases the risk of vitamin A toxicity. Avoid vitamin A supplementation while taking isotretinoin.
Food Interactions
  • Take with a full glass of water Do not take supplements containing Vitamin A.
  • Take with high-fat meal to increase absorption.
  • Avoid alcohol.

Targets


Retinoic acid receptor alpha
Name Retinoic acid receptor alpha
Gene Name RARA
Pharmacological action unknown
Actions other/unknown
References
  • 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
  • Zouboulis CC: Isotretinoin revisited: pluripotent effects on human sebaceous gland cells. J Invest Dermatol. 2006 Oct;126(10):2154-6. - Pubmed
  • 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
  • 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
  • Shroot B, Michel S: Pharmacology and chemistry of adapalene. J Am Acad Dermatol. 1997 Jun;36(6 Pt 2):S96-103. - Pubmed
DTHybrid score 0.4853

Predictions


Id Partner name Gene Name Score
229 Retinoic acid receptor beta RARB 0.2399
162 Retinoic acid receptor gamma-1 RARG 0.1187
88 Retinoic acid receptor RXR-beta RXRB 0.1099
780 Retinoic acid receptor RXR-gamma RXRG 0.0907
459 Retinoic acid receptor RXR-alpha RXRA 0.0761
5934 Cytochrome P450 26A1 CYP26A1 0.0435
564 Cellular retinoic acid-binding protein 1 CRABP1 0.0429
331 Retinol-binding protein I, cellular RBP1 0.0259
859 Cellular retinoic acid-binding protein 2 CRABP2 0.0194
4924 Cytochrome P450 2C8 CYP2C8 0.0163
3811 Cytochrome P450 19A1 CYP19A1 0.0124
587 Serum albumin ALB 0.0097
4200 Cytochrome P450 1A2 CYP1A2 0.0077
1588 Multidrug resistance protein 1 ABCB1 0.0074
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