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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
Salts Not Available
Brand names
Name Company
Aberel
Accutane
Airol
Aknefug
Aknoten
Amnesteem
Atra-IV
Claravis
Dermairol
Eudyna
Lsotretinoin
Retisol-A
Solage
Sotret
Stieva-A
Stieva-a Forte
Vitinoin
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Brand mixtures Not Available
Categories
  • Antineoplastic Agents
  • Keratolytic Agents
  • Cell Stimulants and Proliferants
CAS number 302-79-4
Weight Average: 300.4351
Monoisotopic: 300.20893014
Chemical Formula C20H28O2
InChI Key InChIKey=SHGAZHPCJJPHSC-YCNIQYBTSA-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)/b9-6+,12-11+,15-8+,16-14+
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

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Tretinoin
4-Hydroxyretinoic acid Details
Tretinoin
18-Hydroxyretinoic acid Details
Tretinoin
5,6-Epoxyretinoic acid Details
Tretinoin
4-Oxoretinoic acid Details
Tretinoin
    		Retinoyl b-glucuronide Details
    Tretinoin
      		Retinyl beta-glucuronide Details
      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
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      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents
      Country Patent Number Approved Expires (estimated)
      United States 6353029 2000-08-24 2020-08-24
      United States 5470567 1993-03-19 2010-03-19
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 181 °C PhysProp
      water solubility <0.1 g/100 mL Not Available
      logP 6.30 HANSCH,C ET AL. (1995)
      Predicted Properties
      Property Value Source
      water solubility 4.77e-03 g/l ALOGPS
      logP 5.66 ALOGPS
      logP 5.01 ChemAxon
      logS -4.8 ALOGPS
      pKa (strongest acidic) 5 ChemAxon
      physiological charge -1 ChemAxon
      hydrogen acceptor count 2 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 37.3 ChemAxon
      rotatable bond count 5 ChemAxon
      refractivity 97.79 ChemAxon
      polarizability 36.62 ChemAxon
      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
      Drug Interaction
      Atazanavir The strong CYP2C8 inhibitor, Atazanavir, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Atazanavir is initiated, discontinued to dose changed.
      Carbamazepine The strong CYP2C8 inducer, Carbamazepine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Carbamazepine is initiated, discontinued or dose changed.
      Celecoxib The moderate CYP2C8 inhibitor, Celecoxib, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Celecoxib is initiated, discontinued to dose changed.
      Demeclocycline Demeclocycline may increase the adverse effects of oral Tretinoin. Increased risk of pseudotumour cerebri. Concurrent therapy should be avoided.
      Desogestrel Oral Tretinoin may decrease the effect of oral contraceptive, Desogestrel. An alternate form of contraception should be used during concomitant therapy.
      Doxycycline Doxycycline may increase the adverse effects of oral Tretinoin. Increase risk of pseudotumour cerebri. Concurrent therapy should be avoided.
      Drospirenone Oral Tretinoin may decrease the effect of oral contraceptive, Drospirenone. An alternate form of contraception should be used during concomitant therapy.
      Eltrombopag The moderate CYP2C8 inhibitor, Eltrombopag, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Eltrombopag is initiated, discontinued or dose changed.
      Ethinyl Estradiol Oral Tretinoin may decrease the effect of the oral contraceptive, Ethinyl Estradiol. An alternate form of contraception should be used during concomitant therapy.
      Ethynodiol Diacetate Oral Tretinoin may decrease the effect of oral contraceptive, Ethynodiol Diacetate. An alternate form of contraception should be used during concomitant therapy.
      Etonogestrel Oral Tretinoin may decrease the effect of oral contraceptive, Etonogestrel. An alternate form of contraception should be used during concomitant therapy.
      Felodipine The moderate CYP2C8 inhibitor, Felopidine, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Felopidine is initiated, discontinued to dose changed.
      Fosphenytoin The strong CYP2C8 inducer, Fosphenytoin, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Fosphenytoin is initiated, discontinued or dose changed.
      Gemfibrozil The strong CYP2C8 inhibitor, Gemfibrozil, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Gemfibrozil is initiated, discontinued to dose changed.
      Irbesartan The moderate CYP2C8 inhibitor, Irbesartan, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Irbesartan is initiated, discontinued to dose changed.
      Lapatinib The moderate CYP2C8 inhibitor, Lapatinib, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Lapatinib is initiated, discontinued to dose changed.
      Levonorgestrel Oral Tretinoin may decrease the effect of oral contraceptive, Levonorgestrel. An alternate form of contraception should be used during concomitant therapy.
      Losartan The moderate CYP2C8 inhibitor, Losartan, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Losartan is initiated, discontinued to dose changed.
      Mestranol Oral Tretinoin may decrease the effect of oral contraceptive, Mestranol. An alternate form of contraception should be used during concomitant therapy.
      Minocycline Minocycline may increase the adverse effects of oral Tretinoin. Increase risk of pseudotumour cerebri. Concurrent therapy should be avoided.
      Natalizumab Oral tretinoin may increase the adverse/toxic effects of Natalizumab. Concurrent therapy should be avoided.
      Nilotinib The moderate CYP2C8 inhibitor, Nilotinib, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Nilotinib is initiated, discontinued to dose changed.
      Norethindrone Oral Tretinoin may decrease the effect of oral contraceptive, Norethindrone. An alternate form of contraception should be used during concomitant therapy.
      Norgestimate Oral Tretinoin may decrease the effect of oral contraceptive, Norgestimate. An alternate form of contraception should be used during concomitant therapy.
      Oxytetracycline Oxytetracycline may increase the adverse effects of oral Tretinoin. Increase risk of pseudotumour cerebri. Concurrent therapy should be avoided.
      Phenobarbital The strong CYP2C8 inducer, Phenobarbital, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Phenobarbital is initiated, discontinued or dose changed.
      Phenytoin The strong CYP2C8 inducer, Phenytoin, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Phenytoin is initiated, discontinued or dose changed.
      Pioglitazone The moderate CYP2C8 inhibitor, Pioglitazone, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Pioglitazone is initiated, discontinued to dose changed.
      Primidone The strong CYP2C8 inducer, Primidone, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Primidone is initiated, discontinued or dose changed.
      Quinine The moderate CYP2C8 inhibitor, Quinine, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Quinine is initiated, discontinued to dose changed.
      Rabeprazole The moderate CYP2C8 inhibitor, Rabaprazole, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rabaprazole is initiated, discontinued to dose changed.
      Rifampin The strong CYP2C8 inducer, Rifampin, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rifampin is initiated, discontinued or dose changed.
      Rifapentine The strong CYP2C8 inducer, Rifapentine, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rifapentine is initiated, discontinued or dose changed.
      Ritonavir The strong CYP2C8 inhibitor, Ritonavir, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Ritonavir is initiated, discontinued to dose changed.
      Rosiglitazone The moderate CYP2C8 inhibitor, Rosiglitazone, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Rosiglitazone is initiated, discontinued to dose changed.
      Secobarbital The strong CYP2C8 inducer, Secobarbital, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Secobarbital is initiated, discontinued or dose changed.
      Sorafenib The strong CYP2C8 inhibitor, Sorafenib, may decrease the metabolism and clearance of oral Tretinoin. Consider alternate therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Sorafenib is initiated, discontinued to dose changed.
      Tamoxifen The moderate CYP2C8 inhibitor, Tamoxifen, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Tamoxifen is initiated, discontinued to dose changed.
      Tetracycline Demeclocycline may increase the adverse effects of oral Tretinoin. Increase risk of pseudotumour cerebri. Concurrent therapy should be avoided.
      Tigecycline Demeclocycline may increase the adverse effects of oral Tretinoin. Increase risk of pseudotumour cerebri. Concurrent therapy should be avoided.
      Trastuzumab Increased risk of leukopenia and anemia due to synergistic effects. Monitor for signs and symptoms of adverse events during concomitant therapy.
      Trimethoprim The moderate CYP2C8 inhibitor, Trimethoprim, may decrease the metabolism and clearance of oral Tretinoin. Monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Trimethoprim is initiated, discontinued to dose changed.
      Vitamin A Tretinoin increases the risk of vitamin A toxicity. Avoid vitamin A supplementation while taking systemic tretinoin.
      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 February 08, 2013 16:19