DT-Web

DB00926 - Etretinate


Identification
Name Etretinate
Accession Number DB00926 (APRD00966)
Type small molecule
Description Etretinate is a medication used to treat severe psoriasis. It is a synthetic aromatic retinoid. The mechanism of action of etretinate is still incompletely understood although, like retinoic acid, it is thought to interfere with the terminal differentiation of keratinocytes. It is thought to bind to the retinoic acid receptors. Etretinate is also believed to enhance the binding of cAMP to the regulatory RI subunit of cAMP dependent protein kinases. It was removed from the United States market in 1998 and the Canadian market in 1996 as a psoriasis medication, due to the high risk of birth defects. Etretinate is now used to treat T-cell lymphomas. It also appears to inhibit NADH oxidase activity.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 354.4825
Groups withdrawn
Monoisotopic Weight 354.219494826
Pharmacology
Indication For the treatment of severe psoriasis in adults.
Mechanism of action The mechanism of action of the active metabolite, acitretin, is unknown, however it is believed to work by targeting specific receptors (retinoid receptors) in the skin which help normalize the growth cycle of skin cells.
Absorption Absorbed in the small intestine. Studies in normal volunteers indicate that the absorption of etretinate is greater in patients consuming whole milk or a high-fat diet than in patients in a fasting state.
Protein binding More than 99% bound to plasma proteins, predominantly lipoproteins, whereas its active metabolite, acetretin (etretin), is predominantly bound to albumin.
Biotransformation Extensively metabolized, with significant first-pass metabolism to the pharmacologically active acid form. Subsequent metabolism results in the inactive 13-cis acid form, chain-shortened breakdown products, and conjugates that are ultimately excreted.
Route of elimination Not Available
Toxicity Symptoms of overdose include headache and vertigo.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Demeclocycline Increased risk of intracranial hypertension
Doxycycline Increased risk of intracranial hypertension
Methacycline Increased risk of intracranial hypertension
Methotrexate Acitretin/etretinate increases the effect and toxicity of methotrexate
Minocycline Increased risk of intracranial hypertension
Oxytetracycline Increased risk of intracranial hypertension
Rolitetracycline Increased risk of intracranial hypertension
Tetracycline Increased risk of intracranial hypertension
Food Interactions
  • Avoid alcohol completely up to 2 months after discontinuation.
  • Increases absorption, take with food.

Targets


Retinoic acid receptor alpha
Name Retinoic acid receptor alpha
Gene Name RARA
Pharmacological action yes
Actions agonist
References
  • Harnish DC, Barua AB, Soprano KJ, Soprano DR: Induction of beta-retinoic acid receptor mRNA by teratogenic doses of retinoids in murine fetuses. Differentiation. 1990 Nov;45(2):103-8. - Pubmed
  • Saurat JH: Retinoids and psoriasis: novel issues in retinoid pharmacology and implications for psoriasis treatment. J Am Acad Dermatol. 1999 Sep;41(3 Pt 2):S2-6. - Pubmed
  • Zitnik RJ, Kotloff RM, Latifpour J, Zheng T, Whiting NL, Schwalb J, Elias JA: Retinoic acid inhibition of IL-1-induced IL-6 production by human lung fibroblasts. J Immunol. 1994 Feb 1;152(3):1419-27. - Pubmed
  • Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. - Pubmed
  • Billoni N, Gautier B, Mahe YF, Bernard BA: Expression of retinoid nuclear receptor superfamily members in human hair follicles and its implication in hair growth. Acta Derm Venereol. 1997 Sep;77(5):350-5. - Pubmed
DTHybrid score 1.1735
Retinoic acid receptor RXR-alpha
Name Retinoic acid receptor RXR-alpha
Gene Name RXRA
Pharmacological action yes
Actions agonist
References
  • Zitnik RJ, Kotloff RM, Latifpour J, Zheng T, Whiting NL, Schwalb J, Elias JA: Retinoic acid inhibition of IL-1-induced IL-6 production by human lung fibroblasts. J Immunol. 1994 Feb 1;152(3):1419-27. - Pubmed
  • Orfanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC: Current use and future potential role of retinoids in dermatology. Drugs. 1997 Mar;53(3):358-88. - Pubmed
  • Billoni N, Gautier B, Mahe YF, Bernard BA: Expression of retinoid nuclear receptor superfamily members in human hair follicles and its implication in hair growth. Acta Derm Venereol. 1997 Sep;77(5):350-5. - Pubmed
DTHybrid score 0.912
Retinoic acid receptor beta
Name Retinoic acid receptor beta
Gene Name RARB
Pharmacological action yes
Actions agonist
References
  • Zitnik RJ, Kotloff RM, Latifpour J, Zheng T, Whiting NL, Schwalb J, Elias JA: Retinoic acid inhibition of IL-1-induced IL-6 production by human lung fibroblasts. J Immunol. 1994 Feb 1;152(3):1419-27. - Pubmed
  • Billoni N, Gautier B, Mahe YF, Bernard BA: Expression of retinoid nuclear receptor superfamily members in human hair follicles and its implication in hair growth. Acta Derm Venereol. 1997 Sep;77(5):350-5. - Pubmed
DTHybrid score 1.1748
Retinoic acid receptor RXR-gamma
Name Retinoic acid receptor RXR-gamma
Gene Name RXRG
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Billoni N, Gautier B, Mahe YF, Bernard BA: Expression of retinoid nuclear receptor superfamily members in human hair follicles and its implication in hair growth. Acta Derm Venereol. 1997 Sep;77(5):350-5. - Pubmed
DTHybrid score 0.7705
Retinoic acid receptor RXR-beta
Name Retinoic acid receptor RXR-beta
Gene Name RXRB
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.0585
Retinoic acid receptor gamma-1
Name Retinoic acid receptor gamma-1
Gene Name RARG
Pharmacological action yes
Actions agonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
DTHybrid score 1.5506

Enzymes


Cytochrome P450 19A1
Name Cytochrome P450 19A1
Gene Name CYP19A1
Actions inhibitor
References
  • Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. - Pubmed
DTHybrid score 0.4172
Cytochrome P450 26A1
Name Cytochrome P450 26A1
Gene Name CYP26A1
Actions substrate
References
  • Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. - Pubmed
DTHybrid score 0.3867

Carriers


Predictions


Id Partner name Gene Name Score
6283 Oxysterols receptor LXR-alpha NR1H3 0.2212
331 Retinol-binding protein I, cellular RBP1 0.1894
859 Cellular retinoic acid-binding protein 2 CRABP2 0.1784
6241 Nuclear receptor coactivator 2 NCOA2 0.1746
4512 Cytochrome P450 3A4 CYP3A4 0.1115
4924 Cytochrome P450 2C8 CYP2C8 0.0922
4200 Cytochrome P450 1A2 CYP1A2 0.0829
4757 Cytochrome P450 2C9 CYP2C9 0.0816
587 Serum albumin ALB 0.0755
1588 Multidrug resistance protein 1 ABCB1 0.0746
146 Androgen receptor AR 0.0618
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0605
569 Retinal dehydrogenase 2 ALDH1A2 0.0574
770 Retinoic acid-induced protein 3 GPRC5A 0.0561
719 Retinoic acid receptor responder protein 1 RARRES1 0.0561
611 Retinal dehydrogenase 1 ALDH1A1 0.0533
84 Nuclear receptor 0B1 NR0B1 0.0459
6228 Nuclear receptor coactivator 1 NCOA1 0.0442
5718 Cytochrome P450 2A6 CYP2A6 0.0438
6350 Nuclear receptor subfamily 1 group I member 3 NR1I3 0.0432
6030 Cytochrome P450 2B6 CYP2B6 0.0408
6024 Cytochrome P450 1A1 CYP1A1 0.0401
6107 Cytochrome P450 3A7 CYP3A7 0.0344
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0342
6105 3-oxo-5-beta-steroid 4-dehydrogenase AKR1D1 0.0333
260 Cytochrome P450 51 ERG11 0.0326
761 Cytochrome P450 51 ERG11 0.0326
3163 Cytochrome P450 51 cyp51 0.0326
136 Estrogen receptor ESR1 0.0319
4118 Cytochrome P450 3A5 CYP3A5 0.0314
468 Cytochrome P450 4A11 CYP4A11 0.0305
756 Sex hormone-binding globulin SHBG 0.0274
6106 Cytochrome P450 2C18 CYP2C18 0.0256
6016 Cytochrome P450 2C19 CYP2C19 0.0245
2907 Oxysterols receptor LXR-beta NR1H2 0.0242
563 Thyroid peroxidase TPO 0.0207
4116 Dihydropteroate synthetase Not Available 0.0199
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0194
226 Gonadotropin-releasing hormone receptor GNRHR 0.0193
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0192
6013 Cytochrome P450 2E1 CYP2E1 0.0191
589 Retinoid-binding protein 7 RBP7 0.019
35 Dehydrogenase/reductase SDR family member 4 DHRS4 0.019
1097 Lecithin retinol acyltransferase LRAT 0.019
561 Retinol-binding protein II, cellular RBP2 0.019
753 Retinol-binding protein III, cellular RBP5 0.019
4073 Retinol dehydrogenase 11 RDH11 0.019
4074 Retinol dehydrogenase 14 RDH14 0.019
4075 Photoreceptor outer segment all-trans retinol dehydrogenase RDH8 0.019
863 Cellular retinaldehyde-binding protein RLBP1 0.019
651 Retinol dehydrogenase 13 RDH13 0.019
800 Retinol dehydrogenase 12 RDH12 0.019
4071 Short-chain dehydrogenase/reductase 3 DHRS3 0.019
4072 All-trans-retinol 13,14-reductase RETSAT 0.019
282 Interphotoreceptor retinoid-binding protein RBP3 0.019
1010 Cytochrome P450 51A1 CYP51A1 0.0182
148 Lutropin-choriogonadotropic hormone receptor LHCGR 0.0175
1898 Cytochrome P450 1B1 CYP1B1 0.0153
627 11-cis retinol dehydrogenase RDH5 0.015
640 Aldehyde dehydrogenase 1A3 ALDH1A3 0.015
4119 Cytochrome P450 2D6 CYP2D6 0.0139
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0138
776 Bile salt export pump ABCB11 0.0133
345 Plasma retinol-binding protein RBP4 0.0131
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0128
6044 Serum paraoxonase/lactonase 3 PON3 0.0118
290 Prostaglandin G/H synthase 2 PTGS2 0.0113
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0102
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.01
614 Progesterone receptor PGR 0.0096
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0096
20 Prostaglandin G/H synthase 1 PTGS1 0.0091
3941 Amine oxidase [flavin-containing] A MAOA 0.0081
871 Glucocorticoid receptor NR3C1 0.008
869 Estrogen receptor beta ESR2 0.0079
3957 Adenosine deaminase ADA 0.0079
596 3-oxo-5-alpha-steroid 4-dehydrogenase 1 SRD5A1 0.0078
1680 Solute carrier family 2, facilitated glucose transporter member 1 SLC2A1 0.0078
3923 Cholinesterase BCHE 0.0072
1729 Solute carrier family 22 member 6 SLC22A6 0.0072
3939 Amine oxidase [flavin-containing] B MAOB 0.007
380 Cytochrome P450 17A1 CYP17A1 0.007
1656 CYP2B protein CYP2B 0.0068
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0065
1649 Small inducible cytokine A2 CCL2 0.0062
6142 Solute carrier family 22 member 8 SLC22A8 0.0062
6078 Neuronal acetylcholine receptor subunit beta-4 CHRNB4 0.006
217 Estradiol 17-beta-dehydrogenase 1 HSD17B1 0.0057
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0057
847 Mu-type opioid receptor OPRM1 0.0056
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0054
3947 Xanthine dehydrogenase/oxidase XDH 0.005
144 Hemoglobin subunit alpha HBA1 0.0049
3809 Estrogen-related receptor gamma ESRRG 0.0048
6020 Aldehyde oxidase AOX1 0.0047
629 Alpha-2B adrenergic receptor ADRA2B 0.0047
1178 Adenosine A2a receptor ADORA2A 0.0045
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0043
634 Squalene monooxygenase SQLE 0.0043
7196 Squalene monooxygenase ERG1 0.0043
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.004
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.004
567 Receptor tyrosine-protein kinase erbB-2 ERBB2 0.0038
2782 Complement C1s subcomponent C1S 0.0037
3815 Complement C1q subcomponent subunit A C1QA 0.0034
3816 Complement C1q subcomponent subunit B C1QB 0.0034
3817 Complement C1q subcomponent subunit C C1QC 0.0034
3818 Low affinity immunoglobulin gamma Fc region receptor III-A FCGR3A 0.0034
3819 Low affinity immunoglobulin gamma Fc region receptor II-a FCGR2A 0.0034
1102 Low affinity immunoglobulin gamma Fc region receptor III-B FCGR3B 0.0034
3821 Low affinity immunoglobulin gamma Fc region receptor II-c FCGR2C 0.0034
3814 Complement C1r subcomponent C1R 0.0034
3830 Calreticulin CALR 0.0034
3820 Low affinity immunoglobulin gamma Fc region receptor II-b FCGR2B 0.0034
474 Acetylcholinesterase ACHE 0.0033
784 High affinity immunoglobulin gamma Fc receptor I FCGR1A 0.0032
6035 Nuclear receptor ROR-beta RORB 0.0032
6034 Hydroxyindole O-methyltransferase ASMT 0.0032
6036 Eosinophil peroxidase EPX 0.0032
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0029
844 Epidermal growth factor receptor EGFR 0.0028
765 Indoleamine 2,3-dioxygenase IDO1 0.0027
6031 Cytochrome P450 3A43 CYP3A43 0.0027
571 Melatonin receptor type 1A MTNR1A 0.0026
362 Melatonin receptor type 1B MTNR1B 0.0026
3810 Catechol O-methyltransferase COMT 0.0025
5923 Microtubule-associated protein tau MAPT 0.0024
5924 Microtubule-associated protein 4 MAP4 0.0024
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0023
267 Plasminogen activator inhibitor 1 SERPINE1 0.0023
1852 Microtubule-associated protein 2 MAP2 0.0023
7 Nitric oxide synthase, inducible NOS2 0.0022
6931 Calcium-activated potassium channel subunit beta-1 KCNMB1 0.0022
6933 Calcium-activated potassium channel subunit beta-4 KCNMB4 0.0022
6932 Calcium-activated potassium channel subunit beta-3 KCNMB3 0.0022
6934 Small conductance calcium-activated potassium channel protein 1 KCNN1 0.0022
6935 Small conductance calcium-activated potassium channel protein 2 KCNN2 0.0022
6936 Small conductance calcium-activated potassium channel protein 3 KCNN3 0.0022
6143 Solute carrier family 22 member 7 SLC22A7 0.0022
273 Apoptosis regulator Bcl-2 BCL2 0.0021
373 Transthyretin TTR 0.0021
6221 Steroid hormone receptor ERR1 ESRRA 0.0021
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0021
6002 Prostaglandin E2 receptor EP4 subtype PTGER4 0.002
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.002
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0019
5463 Calcium-activated potassium channel subunit beta 2 KCNMB2 0.0019
29 Tubulin beta-1 chain TUBB1 0.0019
6145 Solute carrier family 22 member 1 SLC22A1 0.0019
4131 Prostaglandin E2 receptor, EP3 subtype PTGER3 0.0018
1457 Long-chain-fatty-acid--CoA ligase 4 ACSL4 0.0018
406 Prostaglandin E2 receptor, EP2 subtype PTGER2 0.0018
469 Annexin A1 ANXA1 0.0018
6167 Organic solute transporter subunit beta OSTB 0.0018
6166 Organic solute transporter subunit alpha OSTA 0.0018
467 Delta-type opioid receptor OPRD1 0.0018
1192 Sulfotransferase 1A1 SULT1A1 0.0018
1757 Myeloperoxidase MPO 0.0017
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0017
465 Calmodulin CALM1 0.0017
6014 Cytochrome P450 2A13 CYP2A13 0.0017
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0016
6148 Multidrug resistance-associated protein 7 ABCC10 0.0016
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0016
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0016
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0015
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0015
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0015
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0015
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0014
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0014
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0014
6152 Solute carrier organic anion transporter family member 2A1 SLCO2A1 0.0014
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0014
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0014
6136 Multidrug resistance-associated protein 5 ABCC5 0.0013
6141 Sodium/bile acid cotransporter SLC10A1 0.0013
862 Multidrug resistance-associated protein 1 ABCC1 0.0013
4604 Liver carboxylesterase 1 CES1 0.0012
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0012
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0012
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0012
1024 Solute carrier family 22 member 11 SLC22A11 0.0011
2164 Multidrug resistance-associated protein 4 ABCC4 0.0011
833 Organic cation/carnitine transporter 1 SLC22A4 0.0011
6147 Solute carrier family 22 member 3 SLC22A3 0.0011
291 Nitric-oxide synthase, endothelial NOS3 0.0011
6144 Solute carrier family 22 member 2 SLC22A2 0.001
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