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Identification
Name Tretinoin
Accession Number DB00755 (APRD00362, NUTR00051)
Type small molecule
Groups approved, nutraceutical
Description

Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • All Trans Retinoic Acid
  • All Trans-Retinoic Acid
  • ATRA
  • beta-Retinoic Acid
  • Retionic Acid
  • tretinoin
Brand names
  • Aberel
  • Accutane
  • Airol
  • Aknefug
  • Aknoten
  • Amnesteem
  • Atra-IV
  • Claravis
  • Dermairol
  • Eudyna
  • Lsotretinoin
  • Retisol-A
  • Solage
  • Sotret
  • Stieva-A
  • Stieva-a Forte
  • Tri-Luma
  • Vitinoin
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents
  • Keratolytic Agents
  • Cell Stimulants and Proliferants
CAS number 302-79-4
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 the induction of remission in patients with acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 (including the M3 variant); For the topical treatment of acne vulgaris, flat warts and other skin conditions (psoriasis, ichthyosis congenita, icthyosis vulgaris, lamellar icthyosis, keratosis palmaris et plantaris, epidermolytic hyperkeratosis, senile comedones, senile keratosis, keratosis follicularis (Darier's disease), and basal cell carcinomas.); For palliative therapy to improve fine wrinkling, mottled hyperpigmentation, roughness associated with photodamage.
Pharmacodynamics Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL).
Mechanism of action Tretinoin binds to alpha, beta, and gamma retinoic acid receptors (RARs). RAR-alpha and RAR-beta have been associated with the development of acute promyelocytic leukemia and squamous cell cancers, respectively. RAR-gamma is associated with retinoid effects on mucocutaneous tissues and bone. Although the exact mechanism of action of tretinoin is unknown, current evidence suggests that the effectiveness of tretinoin in acne is due primarily to its ability to modify abnormal follicular keratinization. Comedones form in follicles with an excess of keratinized epithelial cells. Tretinoin promotes detachment of cornified cells and the enhanced shedding of corneocytes from the follicle. By increasing the mitotic activity of follicular epithelia, tretinoin also increases the turnover rate of thin, loosely-adherent corneocytes. Through these actions, the comedo contents are extruded and the formation of the microcomedo, the precursor lesion of acne vulgaris, is reduced. Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of APL cells in culture and in vivo. When Tretinoin is given systemically to APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.
Absorption 1-31% (topical)
Volume of distribution Not Available
Protein binding > 95%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 4A11 4-Hydroxyretinoic acid 4-hydroxylation
Cytochrome P450 4A11 4-Oxoretinoic acid
Cytochrome P450 4A11 18-Hydroxyretinoic acid
Cytochrome P450 3A5 4-Hydroxyretinoic acid 4-hydroxylation
Cytochrome P450 3A4 4-Hydroxyretinoic acid 4-hydroxylation
Cytochrome P450 2C9 5,6-Epoxyretinoic acid
Cytochrome P450 2C8 4-Hydroxyretinoic acid 4-hydroxylation 6.1 3.22
Cytochrome P450 2C8 18-Hydroxyretinoic acid
Cytochrome P450 2C8 5,6-Epoxyretinoic acid
Cytochrome P450 1A1 4-Hydroxyretinoic acid 4-hydroxylation
Cytochrome P450 1A1 5,6-Epoxyretinoic acid
Cytochrome P450 2C18 4-Hydroxyretinoic acid 4-hydroxylation
Cytochrome P450 2C18 4-Oxoretinoic acid
Cytochrome P450 3A7 4-Hydroxyretinoic acid 4-hydroxylation
Cytochrome P450 3A7 4-Oxoretinoic acid
Cytochrome P450 3A7 18-Hydroxyretinoic acid
Route of elimination Not Available
Half life 0.5-2 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
  • Genpharm inc
  • Barr laboratories inc
  • Ranbaxy pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Mylan bertek pharmaceuticals inc
  • Ortho dermatologics
  • Johnson and johnson consumer companies inc
  • Spear pharmaceuticals inc
  • Triax pharmaceuticals llc
  • Dow pharmaceutical sciences inc
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Wockhardt eu operations (swiss) ag
  • Ranbaxy Pharmaceuticals Inc.
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Cream Topical
Gel Topical
Liquid Topical
Prices
Unit description Cost Unit
Tretinoin (Emollient) 0.05% Cream 60 gm Tube 200.07 USD tube
Tri-Luma 0.01-4-0.05% Cream 30 gm Tube 199.99 USD tube
Solage 2-0.01% Solution 30ml Bottle 168.67 USD bottle
Tretinoin (Emollient) 0.05% Cream 40 gm Tube 135.99 USD tube
Tretinoin 0.1% Cream 45 gm Tube 114.16 USD tube
Tretinoin 0.025% Gel 45 gm Tube 99.64 USD tube
Tretinoin 0.01% Gel 45 gm Tube 98.85 USD tube
Tretinoin 0.05% Cream 45 gm Tube 97.94 USD tube
Tretinoin 0.025% Cream 45 gm Tube 83.97 USD tube
Tretinoin acid powder 74.21 USD g
Tretinoin 0.1% Cream 20 gm Tube 60.96 USD tube
Tretinoin 0.05% Cream 20 gm Tube 52.23 USD tube
Tretinoin 0.025% Cream 20 gm Tube 44.36 USD tube
Tretinoin 0.025% Gel 15 gm Tube 42.26 USD tube
Tretinoin 0.01% Gel 15 gm Tube 35.99 USD tube
Vesanoid 10 mg capsule 30.32 USD capsule
Accutane 40 mg capsule 27.62 USD capsule
Tretinoin 10 mg capsule 27.29 USD capsule
Accutane 20 mg capsule 23.77 USD capsule
Amnesteem 40 mg capsule 22.6 USD capsule
Claravis 40 mg capsule 21.73 USD capsule
Accutane 10 mg capsule 20.05 USD capsule
Amnesteem 20 mg capsule 19.45 USD capsule
Claravis 20 mg capsule 18.7 USD capsule
Claravis 30 mg capsule 16.78 USD capsule
Amnesteem 10 mg capsule 16.4 USD capsule
Claravis 10 mg capsule 15.77 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
Tri-luma cream 6.4 USD g
Retin-a micro 0.04% gel 5.65 USD g
Retin-a micro 0.1% gel 5.65 USD g
Solage topical solution 5.59 USD ml
Retin-a micro pump 0.04% gel 4.74 USD g
Retin-a micro pump 0.1% gel 4.74 USD g
Retin-a 0.05% cream 4.64 USD g
Retin-a 0.1% cream 4.51 USD g
Renova 0.02% cream 4.46 USD g
Renova pump 0.02% cream 4.28 USD g
Retin-a 0.025% cream 4.14 USD g
Refissa 0.05% cream 3.6 USD g
Tretinoin 0.05% emollient crm 3.38 USD g
Avita 0.025% cream 3.19 USD g
Tretinoin 0.1% cream 2.36 USD g
Tretinoin 0.025% cream 2.17 USD g
Tretinoin 0.05% cream 2.02 USD g
Patents
Country Patent Number Approved Expires
United States 6353029 2000-08-24 2020-08-24
United States 5470567 1993-03-19 2010-03-19
Properties
State solid
Melting point 181 oC
Experimental Properties
Property Value Source
water solubility <0.1 g/100 mL PhysProp
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. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY: Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72. Pubmed
  2. Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L: All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood. 1990 Nov 1;76(9):1704-9. Pubmed
  3. Sanz MA: Treatment of acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2006;:147-55. Pubmed
  4. Mao JT, Goldin JG, Dermand J, Ibrahim G, Brown MS, Emerick A, McNitt-Gray MF, Gjertson DW, Estrada F, Tashkin DP, Roth MD: A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am J Respir Crit Care Med. 2002 Mar 1;165(5):718-23. Pubmed
  5. Roth MD, Connett JE, D’Armiento JM, Foronjy RF, Friedman PJ, Goldin JG, Louis TA, Mao JT, Muindi JR, O’Connor GT, Ramsdell JW, Ries AL, Scharf SM, Schluger NW, Sciurba FC, Skeans MA, Walter RE, Wendt CH, Wise RA: Feasibility of retinoids for the treatment of emphysema study. Chest. 2006 Nov;130(5):1334-45. Pubmed
External Links
Resource Link
KEGG Drug D00094 Link_out
KEGG Compound C00777 Link_out
PubChem Compound 444795 Link_out
PubChem Substance 46504843 Link_out
ChemSpider 5337 Link_out
ChEBI 15367 Link_out
ChEMBL 15367 Link_out
Therapeutic Targets Database DNC000117 Link_out
PharmGKB PA451746 Link_out
Drug Product Database 2243914 Link_out
RxList http://www.rxlist.com/cgi/generic/tretinoin.htm Link_out
Drugs.com http://www.drugs.com/cdi/tretinoin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tretinoin Link_out
ATC Codes
  • D10AD01
  • D10AD51
  • L01XX14
  • D10BA01
  • D10AD04
  • L01XX22
AHFS Codes
  • 92:00.00
  • 84:16.00
PDB Entries
FDA label show (42.8 KB)
MSDS show (29.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Retinoic acid receptor RXR-beta

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA)

Organism class: human
UniProt ID: P28702 Link_out
Gene: RXRB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Stafslien DK, Vedvik KL, De Rosier T, Ozers MS: Analysis of ligand-dependent recruitment of coactivator peptides to RXRbeta in a time-resolved fluorescence resonance energy transfer assay. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):82-9. Epub 2006 Dec 20. Pubmed
  2. Redfern CP: Enhancing enhancers: new complexities in the retinoid regulation of gene expression. Biochem J. 2004 Oct 1;383(Pt 1):e1-2. Pubmed
  3. Nagasawa H, Takahashi S, Kobayashi A, Tazawa H, Tashima Y, Sato K: Effect of retinoic acid on murine preosteoblastic MC3T3-E1 cells. J Nutr Sci Vitaminol (Tokyo). 2005 Oct;51(5):311-8. Pubmed
  4. Schrage K, Koopmans G, Joosten EA, Mey J: Macrophages and neurons are targets of retinoic acid signaling after spinal cord contusion injury. Eur J Neurosci. 2006 Jan;23(2):285-95. Pubmed
  5. Hoegberg P, Schmidt CK, Fletcher N, Nilsson CB, Trossvik C, Gerlienke Schuur A, Brouwer A, Nau H, Ghyselinck NB, Chambon P, Hakansson H: Retinoid status and responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking retinoid binding protein or retinoid receptor forms. Chem Biol Interact. 2005 Sep 10;156(1):25-39. Pubmed

2. Retinoic acid receptor RXR-gamma

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. Involved in the retinoic acid response pathway. Binds 9-cis retinoic acid (9C-RA)

Organism class: human
UniProt ID: P48443 Link_out
Gene: RXRG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Koda T, Imai H, Morita M: Antiestrogenic activity of vitamin A in in vivo uterotrophic assay. Life Sci. 2007 Feb 13;80(10):945-9. Epub 2006 Nov 22. Pubmed
  2. He JC, Lu TC, Fleet M, Sunamoto M, Husain M, Fang W, Neves S, Chen Y, Shankland S, Iyengar R, Klotman PE: Retinoic acid inhibits HIV-1-induced podocyte proliferation through the cAMP pathway. J Am Soc Nephrol. 2007 Jan;18(1):93-102. Epub 2006 Dec 20. Pubmed
  3. Day RM, Lee YH, Park AM, Suzuki YJ: Retinoic acid inhibits airway smooth muscle cell migration. Am J Respir Cell Mol Biol. 2006 Jun;34(6):695-703. Epub 2006 Feb 2. Pubmed
  4. Schrage K, Koopmans G, Joosten EA, Mey J: Macrophages and neurons are targets of retinoic acid signaling after spinal cord contusion injury. Eur J Neurosci. 2006 Jan;23(2):285-95. Pubmed
  5. Wang J, Yen A: A novel retinoic acid-responsive element regulates retinoic acid-induced BLR1 expression. Mol Cell Biol. 2004 Mar;24(6):2423-43. Pubmed

3. Retinoic acid receptor gamma-1

Pharmacological action: yes
Actions: agonist

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: P13631 Link_out
Gene: RARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Reddy AP, Chen JY, Zacharewski T, Gronemeyer H, Voorhees JJ, Fisher GJ: Characterization and purification of human retinoic acid receptor-gamma 1 overexpressed in the baculovirus-insect cell system. Biochem J. 1992 Nov 1;287 ( Pt 3):833-40. Pubmed
  4. Kamei Y, Kawada T, Kazuki R, Sugimoto E: Retinoic acid receptor gamma 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes. Biochem J. 1993 Aug 1;293 ( Pt 3):807-12. Pubmed
  5. Borger DR, Mi Y, Geslani G, Zyzak LL, Batova A, Engin TS, Pirisi L, Creek KE: Retinoic acid resistance at late stages of human papillomavirus type 16-mediated transformation of human keratinocytes arises despite intact retinoid signaling and is due to a loss of sensitivity to transforming growth factor-beta. Virology. 2000 May 10;270(2):397-407. Pubmed
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Retinal dehydrogenase 1

Pharmacological action: unknown

Binds free retinal and cellular retinol-binding protein- bound retinal. Can convert/oxidize retinaldehyde to retinoic acid

Organism class: human
UniProt ID: P00352 Link_out
Gene: ALDH1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mic FA, Molotkov A, Molotkova N, Duester G: Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Dev Dyn. 2004 Oct;231(2):270-7. Pubmed
  2. Everts HB, King LE Jr, Sundberg JP, Ong DE: Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes Aldh1a2 and Aldh1a3 indicate complex regulation. J Invest Dermatol. 2004 Aug;123(2):258-63. Pubmed
  3. Gidlof AC, Ocaya P, Olofsson PS, Torma H, Sirsjo A: Differences in retinol metabolism and proliferative response between neointimal and medial smooth muscle cells. J Vasc Res. 2006;43(4):392-8. Epub 2006 Jul 6. Pubmed
  4. Matt N, Dupe V, Garnier JM, Dennefeld C, Chambon P, Mark M, Ghyselinck NB: Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells. Development. 2005 Nov;132(21):4789-800. Epub 2005 Oct 5. Pubmed
  5. Kim H, Lapointe J, Kaygusuz G, Ong DE, Li C, van de Rijn M, Brooks JD, Pollack JR: The retinoic acid synthesis gene ALDH1a2 is a candidate tumor suppressor in prostate cancer. Cancer Res. 2005 Sep 15;65(18):8118-24. Pubmed

5. Retinoic acid-induced protein 3

Pharmacological action: unknown

Unknown. This G-protein coupled receptor could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. The comparable expression level in fetal lung and kidney with adult tissues suggests a possible role in embryonic development and maturation of these organs. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways

Organism class: human
UniProt ID: Q8NFJ5 Link_out
Gene: GPRC5A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Xu J, Tian J, Shapiro SD: Normal lung development in RAIG1-deficient mice despite unique lung epithelium-specific expression. Am J Respir Cell Mol Biol. 2005 May;32(5):381-7. Epub 2005 Jan 27. Pubmed
  2. Inoue S, Nambu T, Shimomura T: The RAIG family member, GPRC5D, is associated with hard-keratinized structures. J Invest Dermatol. 2004 Mar;122(3):565-73. Pubmed

6. Nuclear receptor 0B1

Pharmacological action: unknown

Receptor that may be a component of a cascade required for development of steroidogenic tissues. Acts as a dominant negative regulator of transcription mediated by the retinoic acid receptor

Organism class: human
UniProt ID: P51843 Link_out
Gene: NR0B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. Retinal dehydrogenase 2

Pharmacological action: unknown

Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Does metabolize octanal and decanal but does not metabolize citral, benzaldehyde, acetaldehyde and propanal efficiently

Organism class: human
UniProt ID: O94788 Link_out
Gene: ALDH1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mic FA, Sirbu IO, Duester G: Retinoic acid synthesis controlled by Raldh2 is required early for limb bud initiation and then later as a proximodistal signal during apical ectodermal ridge formation. J Biol Chem. 2004 Jun 18;279(25):26698-706. Epub 2004 Apr 6. Pubmed
  2. Bordelon T, Montegudo SK, Pakhomova S, Oldham ML, Newcomer ME: A disorder to order transition accompanies catalysis in retinaldehyde dehydrogenase type II. J Biol Chem. 2004 Oct 8;279(41):43085-91. Epub 2004 Aug 7. Pubmed
  3. Mic FA, Molotkov A, Molotkova N, Duester G: Raldh2 expression in optic vesicle generates a retinoic acid signal needed for invagination of retina during optic cup formation. Dev Dyn. 2004 Oct;231(2):270-7. Pubmed
  4. Doxakis E, Davies AM: Retinoic acid negatively regulates GDNF and neurturin receptor expression and responsiveness in embryonic chicken sympathetic neurons. Mol Cell Neurosci. 2005 Aug;29(4):617-27. Pubmed
  5. Everts HB, Sundberg JP, Ong DE: Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp Cell Res. 2005 Aug 15;308(2):309-19. Pubmed

8. Retinoic acid receptor responder protein 1

Pharmacological action: unknown
Actions: agonist
Organism class: human
UniProt ID: P49788 Link_out
Gene: RARRES1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Youssef EM, Chen XQ, Higuchi E, Kondo Y, Garcia-Manero G, Lotan R, Issa JP: Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers. Cancer Res. 2004 Apr 1;64(7):2411-7. Pubmed
  2. Zirn B, Samans B, Spangenberg C, Graf N, Eilers M, Gessler M: All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo. Oncogene. 2005 Aug 4;24(33):5246-51. Pubmed
Enzymes

1. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

2. Cytochrome P450 2B6

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

3. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

4. Cytochrome P450 2C9

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

5. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

6. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

7. Cytochrome P450 2A6

Actions: substrate

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

8. Cytochrome P450 2C18

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P33260 Link_out
Gene: CYP2C18 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

9. Cytochrome P450 1A1

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed

10. Cytochrome P450 4A11

Actions: substrate

Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity towards prostaglandins A1 and E1

UniProt ID: Q02928 Link_out
Gene: CYP4A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Marill J, Cresteil T, Lanotte M, Chabot GG: Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8. Pubmed
Transporters

1. Cellular retinoic acid-binding protein 1

Actions: substrate

Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors

UniProt ID: P29762 Link_out
Gene: CRABP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hoegberg P, Schmidt CK, Fletcher N, Nilsson CB, Trossvik C, Gerlienke Schuur A, Brouwer A, Nau H, Ghyselinck NB, Chambon P, Hakansson H: Retinoid status and responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking retinoid binding protein or retinoid receptor forms. Chem Biol Interact. 2005 Sep 10;156(1):25-39. Pubmed
  2. Donato LJ, Noy N: Fluorescence-based technique for analyzing retinoic acid. Methods Mol Biol. 2010;652:177-87. Pubmed

2. Cellular retinoic acid-binding protein 2

Actions: substrate

Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors. CRABP2 may participate in a regulatory feedback mechanism to control the action of retinoic acid on cell differentiation

UniProt ID: P29373 Link_out
Gene: CRABP2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hoegberg P, Schmidt CK, Fletcher N, Nilsson CB, Trossvik C, Gerlienke Schuur A, Brouwer A, Nau H, Ghyselinck NB, Chambon P, Hakansson H: Retinoid status and responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking retinoid binding protein or retinoid receptor forms. Chem Biol Interact. 2005 Sep 10;156(1):25-39. Pubmed
  2. Ohnishi K: PML-RARalpha inhibitors (ATRA, tamibaroten, arsenic troxide) for acute promyelocytic leukemia. Int J Clin Oncol. 2007 Oct;12(5):313-7. Epub 2007 Oct 22. Pubmed
  3. Donato LJ, Noy N: Fluorescence-based technique for analyzing retinoic acid. Methods Mol Biol. 2010;652:177-87. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on June 02, 2011 15:24

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.