Identification

Name
Alitretinoin
Accession Number
DB00523  (APRD00017)
Type
Small Molecule
Groups
Approved, Investigational
Description

An important regulator of gene expression during growth and development, and in neoplasms. Tretinoin, also known as retinoic acid and derived from maternal vitamin A, is essential for normal growth; and embryonic development. An excess of tretinoin can be teratogenic. It is used in the treatment of psoriasis; acne vulgaris; and several other skin diseases. It has also been approved for use in promyelocytic leukemia (leukemia, promyelocytic, acute).

Structure
Thumb
Synonyms
  • (2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid
  • (7E,9Z,11E,13E)-retinoic acid
  • 9-cis-retinoic acid
  • 9-cis-Tretinoin
  • 9(Z)-Retinoic acid
  • Alitretinoin
  • Alitretinoína
  • Alitrétinoïne
  • Alitretinoinum
External IDs
AGN 192013 / AGN-192013 / ALRT-1057 / ALRT1057 / BAL-4079 / BAL4079 / CCRIS 7098 / LG100057 / LGD1057 / NSC-659772
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PanretinGel0.1 %TopicalEisai Limited2000-10-11Not applicableEu
PanretinGel60 mg/60gTopicalEisai Limited1999-02-03Not applicableUs
PanretinGel0.1 %TopicalLigand PharmaceuticalsNot applicableNot applicableCanada
ToctinoCapsule10 mgOralGlaxosmithkline Inc2011-01-11Not applicableCanada
ToctinoCapsule30 mgOralGlaxosmithkline Inc2010-11-19Not applicableCanada
Categories
UNII
1UA8E65KDZ
CAS number
5300-03-8
Weight
Average: 300.4351
Monoisotopic: 300.20893014
Chemical Formula
C20H28O2
InChI Key
SHGAZHPCJJPHSC-ZVCIMWCZSA-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+
IUPAC Name
(2E,4E,6Z,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
SMILES
C\C(\C=C\C1=C(C)CCCC1(C)C)=C\C=C\C(\C)=C\C(O)=O

Pharmacology

Indication

For topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma.

Structured Indications
Pharmacodynamics

Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro.

Mechanism of action

Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells.

TargetActionsOrganism
ARetinoic acid receptor alpha
agonist
Human
ARetinoic acid receptor RXR-alpha
agonist
Human
ARetinoic acid receptor beta
agonist
Human
ARetinoic acid receptor RXR-beta
agonist
Human
ARetinoic acid receptor gamma
agonist
Human
ARetinoic acid receptor RXR-gamma
agonist
Human
UInsulin-like growth factor-binding protein 3Not AvailableHuman
UPregnancy-specific beta-1-glycoprotein 5Not AvailableHuman
UCytochrome P450 26C1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Retinol MetabolismMetabolic
Vitamin A DeficiencyDisease
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Alitretinoin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Alitretinoin.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Alitretinoin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Alitretinoin.Approved
ChlorotrianiseneThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Alitretinoin.Investigational, Withdrawn
ChlortetracyclineThe risk or severity of adverse effects can be increased when Chlortetracycline is combined with Alitretinoin.Approved, Investigational, Vet Approved
Conjugated estrogensThe therapeutic efficacy of Conjugated estrogens can be decreased when used in combination with Alitretinoin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Alitretinoin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Alitretinoin.Experimental
DemeclocyclineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with Alitretinoin.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Alitretinoin.Approved
DesogestrelThe therapeutic efficacy of Desogestrel can be decreased when used in combination with Alitretinoin.Approved
DienestrolThe therapeutic efficacy of Dienestrol can be decreased when used in combination with Alitretinoin.Approved, Investigational
DienogestThe therapeutic efficacy of Dienogest can be decreased when used in combination with Alitretinoin.Approved
DiethylstilbestrolThe therapeutic efficacy of Diethylstilbestrol can be decreased when used in combination with Alitretinoin.Approved, Investigational
DigitoxinDigitoxin may decrease the cardiotoxic activities of Alitretinoin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Alitretinoin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Alitretinoin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Alitretinoin.Approved, Investigational
DoxycyclineThe risk or severity of adverse effects can be increased when Doxycycline is combined with Alitretinoin.Approved, Investigational, Vet Approved
DrospirenoneThe therapeutic efficacy of Drospirenone can be decreased when used in combination with Alitretinoin.Approved
EstradiolThe therapeutic efficacy of Estradiol can be decreased when used in combination with Alitretinoin.Approved, Investigational, Vet Approved
EstramustineThe therapeutic efficacy of Estramustine can be decreased when used in combination with Alitretinoin.Approved
Estrogens, esterifiedThe therapeutic efficacy of Estrogens, esterified can be decreased when used in combination with Alitretinoin.Approved
Estrone sulfateThe therapeutic efficacy of Estrone sulfate can be decreased when used in combination with Alitretinoin.Approved
Ethinyl EstradiolThe therapeutic efficacy of Ethinyl Estradiol can be decreased when used in combination with Alitretinoin.Approved
Ethynodiol diacetateThe therapeutic efficacy of Ethynodiol diacetate can be decreased when used in combination with Alitretinoin.Approved
EtonogestrelThe therapeutic efficacy of Etonogestrel can be decreased when used in combination with Alitretinoin.Approved, Investigational
GestodeneThe therapeutic efficacy of Gestodene can be decreased when used in combination with Alitretinoin.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Alitretinoin.Experimental
HexestrolThe therapeutic efficacy of Hexestrol can be decreased when used in combination with Alitretinoin.Withdrawn
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Alitretinoin.Experimental
LevonorgestrelThe therapeutic efficacy of Levonorgestrel can be decreased when used in combination with Alitretinoin.Approved, Investigational
LumacaftorThe serum concentration of Alitretinoin can be decreased when it is combined with Lumacaftor.Approved
LynestrenolThe therapeutic efficacy of Lynestrenol can be decreased when used in combination with Alitretinoin.Investigational
Medroxyprogesterone acetateThe therapeutic efficacy of Medroxyprogesterone acetate can be decreased when used in combination with Alitretinoin.Approved, Investigational
MestranolThe therapeutic efficacy of Mestranol can be decreased when used in combination with Alitretinoin.Approved
MethallenestrilThe therapeutic efficacy of Methallenestril can be decreased when used in combination with Alitretinoin.Experimental
MethotrexateAlitretinoin may increase the hepatotoxic activities of Methotrexate.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Alitretinoin.Experimental
MinocyclineThe risk or severity of adverse effects can be increased when Minocycline is combined with Alitretinoin.Approved, Investigational
NorelgestrominThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Alitretinoin.Approved
NorgestimateThe therapeutic efficacy of Norgestimate can be decreased when used in combination with Alitretinoin.Approved
NorgestrelThe therapeutic efficacy of Norgestrel can be decreased when used in combination with Alitretinoin.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Alitretinoin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Alitretinoin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Alitretinoin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Alitretinoin.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Alitretinoin.Experimental
RanolazineThe serum concentration of Alitretinoin can be increased when it is combined with Ranolazine.Approved, Investigational
Synthetic Conjugated Estrogens, AThe therapeutic efficacy of Synthetic Conjugated Estrogens, A can be decreased when used in combination with Alitretinoin.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Alitretinoin.Approved, Investigational
Vitamin AThe risk or severity of adverse effects can be increased when Vitamin A is combined with Alitretinoin.Approved, Nutraceutical, Vet Approved
Food Interactions
Not Available

References

Synthesis Reference

Hector F. DeLuca, Praveen K. Tadikonda, "Method of synthesis of retinoic acid." U.S. Patent US5808120, issued December, 1975.

US5808120
General References
Not Available
External Links
Human Metabolome Database
HMDB02369
KEGG Drug
D02815
KEGG Compound
C15493
PubChem Compound
449171
PubChem Substance
46507356
ChemSpider
395778
BindingDB
31892
ChEBI
50648
ChEMBL
CHEMBL705
Therapeutic Targets Database
DAP000275
PharmGKB
PA164746900
HET
9CR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alitretinoin
ATC Codes
D11AH04 — AlitretinoinL01XX22 — Alitretinoin
AHFS Codes
  • 84:92.00 — Misc. Skin and Mucous Membrane Agents
PDB Entries
1epb / 1fby / 1fm6 / 1fm9 / 1g5y / 1k74 / 1tyr / 1xdk / 1xiu / 1xls
show 11 more
FDA label
Download (21.8 KB)
MSDS
Download (37.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentCancer, Breast / Neoplasms, Breast1
1, 2CompletedNot AvailableHepatic Insufficiency1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentPsoriasis1
2TerminatedTreatmentLupus Erythematosus, Cutaneous1
2Unknown StatusTreatmentLichen Planus (LP)1
3CompletedNot AvailableHand Dermatosis1
3CompletedTreatmentDermatitis, Eczematous2
3CompletedTreatmentHand Dermatosis2
3RecruitingTreatmentHand Eczema2
4TerminatedTreatmentAtopic Dermatitis (AD)1
Not AvailableCompletedNot AvailableHepatic Insufficiency1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1

Pharmacoeconomics

Manufacturers
  • Eisai inc
Packagers
Dosage forms
FormRouteStrength
GelTopical0.1 %
GelTopical60 mg/60g
CapsuleOral10 mg
CapsuleOral30 mg
Prices
Unit descriptionCostUnit
Retin-A Micro Pump 0.04% Gel 50 gm Bottle246.73USD bottle
Retin-A Micro Pump 0.1% Gel 50 gm Bottle246.73USD bottle
Retin-A Micro 0.04% Gel 45 gm Tube212.3USD tube
Retin-A Micro 0.1% Gel 45 gm Tube212.3USD tube
Retin-A 0.1% Cream 45 gm Tube211.1USD tube
Retin-A 0.05% Cream 45 gm Tube181.16USD tube
Retin-A 0.025% Cream 45 gm Tube163.07USD tube
Retin-A 0.025% Gel 45 gm Tube162.79USD tube
Retin-A 0.01% Gel 45 gm Tube161.48USD tube
Retin-A Micro 0.04% Gel 20 gm Tube123.7USD tube
Retin-A Micro 0.1% Gel 20 gm Tube117.51USD tube
Retin-A 0.1% Cream 20 gm Tube112.51USD tube
Retin-A 0.05% Cream 20 gm Tube97.85USD tube
Retin-A 0.025% Cream 20 gm Tube85.59USD tube
Retin-A 0.01% Gel 15 gm Tube75.83USD tube
Retin-A 0.025% Gel 15 gm Tube69.01USD tube
Panretin 0.1% gel41.0USD g
Vesanoid 10 mg capsule31.54USD capsule
Retin-a micro 0.04% gel5.65USD g
Retin-a micro 0.1% gel5.65USD g
Retin-a micro pump 0.04% gel4.74USD g
Retin-a micro pump 0.1% gel4.74USD g
Retin-a 0.05% cream4.64USD g
Retin-a 0.1% cream4.51USD g
Renova 0.02% cream4.46USD g
Renova pump 0.02% cream4.28USD g
Retin-a 0.025% cream4.14USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2301907No2009-02-102018-08-18Canada
US5932622No1996-08-032016-08-03Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)189-190 °CNot Available
water solubility0.6 mg/LNot Available
logP4.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00477 mg/mLALOGPS
logP5.66ALOGPS
logP5.01ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity97.79 m3·mol-1ChemAxon
Polarizability35.95 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9925
Blood Brain Barrier+0.9311
Caco-2 permeable+0.7603
P-glycoprotein substrateNon-substrate0.6144
P-glycoprotein inhibitor INon-inhibitor0.8912
P-glycoprotein inhibitor IINon-inhibitor0.8088
Renal organic cation transporterNon-inhibitor0.8639
CYP450 2C9 substrateNon-substrate0.8221
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.6025
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.8831
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9301
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9252
Ames testNon AMES toxic0.8944
CarcinogenicityNon-carcinogens0.7081
BiodegradationReady biodegradable0.5554
Rat acute toxicity2.1455 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9562
hERG inhibition (predictor II)Non-inhibitor0.9538
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as retinoids. These are oxygenated derivatives of 3,7-dimethyl-1-(2,6,6-trimethylcyclohex-1-enyl)nona-1,3,5,7-tetraene and derivatives thereof.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Retinoids
Direct Parent
Retinoids
Alternative Parents
Diterpenoids / Medium-chain fatty acids / Methyl-branched fatty acids / Unsaturated fatty acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Retinoic acid / Diterpenoid / Retinoid skeleton / Medium-chain fatty acid / Branched fatty acid / Methyl-branched fatty acid / Fatty acyl / Unsaturated fatty acid / Fatty acid / Monocarboxylic acid or derivatives
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
retinoic acid (CHEBI:50648) / Retinoids (C15493) / Retinoids (LMPR01090022)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARA
Uniprot ID
P10276
Uniprot Name
Retinoic acid receptor alpha
Molecular Weight
50770.805 Da
References
  1. Baumann L, Vujevich J, Halem M, Martin LK, Kerdel F, Lazarus M, Pacheco H, Black L, Bryde J: Open-label pilot study of alitretinoin gel 0.1% in the treatment of photoaging. Cutis. 2005 Jul;76(1):69-73. [PubMed:16144296]
  2. Milliano MT, Luxon BA: Rat hepatic stellate cells become retinoid unresponsive during activation. Hepatol Res. 2005 Nov;33(3):225-33. Epub 2005 Oct 25. [PubMed:16253547]
  3. Rasooly R, Schuster GU, Gregg JP, Xiao JH, Chandraratna RA, Stephensen CB: Retinoid x receptor agonists increase bcl2a1 expression and decrease apoptosis of naive T lymphocytes. J Immunol. 2005 Dec 15;175(12):7916-29. [PubMed:16339527]
  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:16420438]
  5. Ritter M, Kattmann D, Teichler S, Hartmann O, Samuelsson MK, Burchert A, Bach JP, Kim TD, Berwanger B, Thiede C, Jager R, Ehninger G, Schafer H, Ueki N, Hayman MJ, Eilers M, Neubauer A: Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia. Leukemia. 2006 Mar;20(3):437-43. [PubMed:16424870]
  6. Cheng C, Michaels J, Scheinfeld N: Alitretinoin: a comprehensive review. Expert Opin Investig Drugs. 2008 Mar;17(3):437-43. doi: 10.1517/13543784.17.3.437 . [PubMed:18321241]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRA
Uniprot ID
P19793
Uniprot Name
Retinoic acid receptor RXR-alpha
Molecular Weight
50810.835 Da
References
  1. Bartholin L, Powers SE, Melhuish TA, Lasse S, Weinstein M, Wotton D: TGIF inhibits retinoid signaling. Mol Cell Biol. 2006 Feb;26(3):990-1001. [PubMed:16428452]
  2. Calleja C, Messaddeq N, Chapellier B, Yang H, Krezel W, Li M, Metzger D, Mascrez B, Ohta K, Kagechika H, Endo Y, Mark M, Ghyselinck NB, Chambon P: Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes. Genes Dev. 2006 Jun 1;20(11):1525-38. [PubMed:16751185]
  3. Zhelyaznik N, Mey J: Regulation of retinoic acid receptors alpha, beta and retinoid X receptor alpha after sciatic nerve injury. Neuroscience. 2006 Sep 15;141(4):1761-74. Epub 2006 Jun 19. [PubMed:16782282]
  4. Fukasawa H, Kagechika H, Shudo K: [Retinoid therapy for autoimmune diseases]. Nihon Rinsho Meneki Gakkai Kaishi. 2006 Jun;29(3):114-26. [PubMed:16819260]
  5. Mizuguchi Y, Wada A, Nakagawa K, Ito M, Okano T: Antitumoral activity of 13-demethyl or 13-substituted analogues of all-trans retinoic acid and 9-cis retinoic acid in the human myeloid leukemia cell line HL-60. Biol Pharm Bull. 2006 Sep;29(9):1803-9. [PubMed:16946489]
  6. Cheng C, Michaels J, Scheinfeld N: Alitretinoin: a comprehensive review. Expert Opin Investig Drugs. 2008 Mar;17(3):437-43. doi: 10.1517/13543784.17.3.437 . [PubMed:18321241]
  7. Garnock-Jones KP, Perry CM: Alitretinoin: in severe chronic hand eczema. Drugs. 2009 Aug 20;69(12):1625-34. doi: 10.2165/11202200-000000000-00000. [PubMed:19678713]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARB
Uniprot ID
P10826
Uniprot Name
Retinoic acid receptor beta
Molecular Weight
50488.63 Da
References
  1. Mizuiri H, Yoshida K, Toge T, Oue N, Aung PP, Noguchi T, Yasui W: DNA methylation of genes linked to retinoid signaling in squamous cell carcinoma of the esophagus: DNA methylation of CRBP1 and TIG1 is associated with tumor stage. Cancer Sci. 2005 Sep;96(9):571-7. [PubMed:16128742]
  2. Milliano MT, Luxon BA: Rat hepatic stellate cells become retinoid unresponsive during activation. Hepatol Res. 2005 Nov;33(3):225-33. Epub 2005 Oct 25. [PubMed:16253547]
  3. Liu Z, Zhang L, Ding F, Li J, Guo M, Li W, Wang Y, Yu Z, Zhan Q, Wu M, Liu Z: 5-Aza-2'-deoxycytidine induces retinoic acid receptor-beta(2) demethylation and growth inhibition in esophageal squamous carcinoma cells. Cancer Lett. 2005 Dec 18;230(2):271-83. [PubMed:16297713]
  4. Nalbandian A, Pang AL, Rennert OM, Chan WY, Ravindranath N, Djakiew D: A novel function of differentiation revealed by cDNA microarray profiling of p75NTR-regulated gene expression. Differentiation. 2005 Oct;73(8):385-96. [PubMed:16316409]
  5. Husson M, Enderlin V, Delacourte A, Ghenimi N, Alfos S, Pallet V, Higueret P: Retinoic acid normalizes nuclear receptor mediated hypo-expression of proteins involved in beta-amyloid deposits in the cerebral cortex of vitamin A deprived rats. Neurobiol Dis. 2006 Jul;23(1):1-10. Epub 2006 Mar 10. [PubMed:16531051]
  6. Garnock-Jones KP, Perry CM: Alitretinoin: in severe chronic hand eczema. Drugs. 2009 Aug 20;69(12):1625-34. doi: 10.2165/11202200-000000000-00000. [PubMed:19678713]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRB
Uniprot ID
P28702
Uniprot Name
Retinoic acid receptor RXR-beta
Molecular Weight
56921.38 Da
References
  1. Brtko J: Role of retinoids and their cognate nuclear receptors in breast cancer chemoprevention. Cent Eur J Public Health. 2007 Mar;15(1):3-6. [PubMed:17491551]
  2. Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H: International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol Rev. 2006 Dec;58(4):760-72. [PubMed:17132853]
  3. Bergheim I, Wolfgarten E, Bollschweiler E, Holscher AH, Bode CH, Parlesak A: Role of retinoic acid receptors in squamous-cell carcinoma in human esophagus. J Carcinog. 2005 Nov 8;4:20. [PubMed:16277658]
  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:16420438]
  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:16109390]
  6. Cheng C, Michaels J, Scheinfeld N: Alitretinoin: a comprehensive review. Expert Opin Investig Drugs. 2008 Mar;17(3):437-43. doi: 10.1517/13543784.17.3.437 . [PubMed:18321241]
  7. Garnock-Jones KP, Perry CM: Alitretinoin: in severe chronic hand eczema. Drugs. 2009 Aug 20;69(12):1625-34. doi: 10.2165/11202200-000000000-00000. [PubMed:19678713]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RARG
Uniprot ID
P13631
Uniprot Name
Retinoic acid receptor gamma
Molecular Weight
50341.405 Da
References
  1. Dzhagalov I, Chambon P, He YW: Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor gamma. J Immunol. 2007 Feb 15;178(4):2113-21. [PubMed:17277115]
  2. Parrella E, Gianni M, Fratelli M, Barzago MM, Raska I Jr, Diomede L, Kurosaki M, Pisano C, Carminati P, Merlini L, Dallavalle S, Tavecchio M, Rochette-Egly C, Terao M, Garattini E: Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamma and retinoid-independent pathways. Mol Pharmacol. 2006 Sep;70(3):909-24. Epub 2006 Jun 20. [PubMed:16788091]
  3. Li M, Hener P, Zhang Z, Kato S, Metzger D, Chambon P: Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis. Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11736-41. Epub 2006 Jul 31. [PubMed:16880407]
  4. Garnock-Jones KP, Perry CM: Alitretinoin: in severe chronic hand eczema. Drugs. 2009 Aug 20;69(12):1625-34. doi: 10.2165/11202200-000000000-00000. [PubMed:19678713]
  5. 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:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expressi...
Gene Name
RXRG
Uniprot ID
P48443
Uniprot Name
Retinoic acid receptor RXR-gamma
Molecular Weight
50870.72 Da
References
  1. Adamczewski Z, Makarewicz J, Mikosinski S, Knapska-Kucharska M, Gunerska-Szadkowska A, Oszukowska L, Karwowska A, Lewinski A: [Application of 13-cis-retinoic acid in patients with 131I scintigraphically-negative metastases of differentiated thyroid carcinoma]. Endokrynol Pol. 2006 Jul-Aug;57(4):403-6. [PubMed:17006844]
  2. Brtko J: Role of retinoids and their cognate nuclear receptors in breast cancer chemoprevention. Cent Eur J Public Health. 2007 Mar;15(1):3-6. [PubMed:17491551]
  3. Germain P, Chambon P, Eichele G, Evans RM, Lazar MA, Leid M, De Lera AR, Lotan R, Mangelsdorf DJ, Gronemeyer H: International Union of Pharmacology. LXIII. Retinoid X receptors. Pharmacol Rev. 2006 Dec;58(4):760-72. [PubMed:17132853]
  4. 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:17182884]
  5. 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:16456186]
  6. Garnock-Jones KP, Perry CM: Alitretinoin: in severe chronic hand eczema. Drugs. 2009 Aug 20;69(12):1625-34. doi: 10.2165/11202200-000000000-00000. [PubMed:19678713]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein tyrosine phosphatase activator activity
Specific Function
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGF...
Gene Name
IGFBP3
Uniprot ID
P17936
Uniprot Name
Insulin-like growth factor-binding protein 3
Molecular Weight
31673.87 Da
References
  1. Chang YS, Cho JY, Cho HA, Kim HJ, Chang J, Ahn CM, Kim SK, Kim SK: 9-cis retinoic acid induces insulin-like growth factor binding protein-3 through DR-8 retinoic acid responsive elements. Cancer Biol Ther. 2006 Jun;5(6):586-92. Epub 2006 Jun 5. [PubMed:16760641]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Not Available
Gene Name
PSG5
Uniprot ID
Q15238
Uniprot Name
Pregnancy-specific beta-1-glycoprotein 5
Molecular Weight
37712.79 Da
References
  1. Lopez-Diaz F, Nores R, Panzetta-Dutari G, Slavin D, Prieto C, Koritschoner NP, Bocco JL: RXRalpha regulates the pregnancy-specific glycoprotein 5 gene transcription through a functional retinoic acid responsive element. Placenta. 2007 Aug-Sep;28(8-9):898-906. Epub 2007 May 2. [PubMed:17475324]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Plays a role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA (preferred substrate).
Specific Function
Heme binding
Gene Name
CYP26C1
Uniprot ID
Q6V0L0
Uniprot Name
Cytochrome P450 26C1
Molecular Weight
57110.385 Da
References
  1. Helvig C, Taimi M, Cameron D, Jones G, Petkovich M: Functional properties and substrate characterization of human CYP26A1, CYP26B1, and CYP26C1 expressed by recombinant baculovirus in insect cells. J Pharmacol Toxicol Methods. 2011 Nov-Dec;64(3):258-63. doi: 10.1016/j.vascn.2011.08.005. Epub 2011 Aug 31. [PubMed:21906690]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transporter activity
Specific Function
Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors.
Gene Name
CRABP2
Uniprot ID
P29373
Uniprot Name
Cellular retinoic acid-binding protein 2
Molecular Weight
15692.925 Da
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:16109390]
  2. Donato LJ, Noy N: Suppression of mammary carcinoma growth by retinoic acid: proapoptotic genes are targets for retinoic acid receptor and cellular retinoic acid-binding protein II signaling. Cancer Res. 2005 Sep 15;65(18):8193-9. [PubMed:16166294]
  3. Bry K, Lappalainen U: Pathogenesis of bronchopulmonary dysplasia: the role of interleukin 1beta in the regulation of inflammation-mediated pulmonary retinoic acid pathways in transgenic mice. Semin Perinatol. 2006 Jun;30(3):121-8. [PubMed:16813970]
  4. Wei T, Geiser AG, Qian HR, Su C, Helvering LM, Kulkarini NH, Shou J, N'Cho M, Bryant HU, Onyia JE: DNA microarray data integration by ortholog gene analysis reveals potential molecular mechanisms of estrogen-dependent growth of human uterine fibroids. BMC Womens Health. 2007 Apr 2;7:5. [PubMed:17407572]
  5. Boorjian SA, Milowsky MI, Kaplan J, Albert M, Cobham MV, Coll DM, Mongan NP, Shelton G, Petrylak D, Gudas LJ, Nanus DM: Phase 1/2 clinical trial of interferon alpha2b and weekly liposome-encapsulated all-trans retinoic acid in patients with advanced renal cell carcinoma. J Immunother. 2007 Sep;30(6):655-62. [PubMed:17667529]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transporter activity
Specific Function
Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors.
Gene Name
CRABP1
Uniprot ID
P29762
Uniprot Name
Cellular retinoic acid-binding protein 1
Molecular Weight
15565.45 Da
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:16109390]
  2. Goelden U, Pfoertner S, Hansen W, Toepfer T, von Knobloch R, Hofmann R, Buer J, Schrader AJ: Expression and functional influence of cellular retinoic acid-binding protein II in renal cell carcinoma. Urol Int. 2005;75(3):269-76. [PubMed:16215318]
  3. Levadoux-Martin M, Li Y, Blackburn A, Chabanon H, Hesketh JE: Perinuclear localisation of cellular retinoic acid binding protein I mRNA. Biochem Biophys Res Commun. 2006 Feb 3;340(1):326-31. [PubMed:16376305]
  4. Jetten AM: Multi-stage program of differentiation in human epidermal keratinocytes: regulation by retinoids. J Invest Dermatol. 1990 Nov;95(5 Suppl):44S-46S. [PubMed:16788631]
  5. Bry K, Lappalainen U: Pathogenesis of bronchopulmonary dysplasia: the role of interleukin 1beta in the regulation of inflammation-mediated pulmonary retinoic acid pathways in transgenic mice. Semin Perinatol. 2006 Jun;30(3):121-8. [PubMed:16813970]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Schuetz EG, Yasuda K, Arimori K, Schuetz JD: Human MDR1 and mouse mdr1a P-glycoprotein alter the cellular retention and disposition of erythromycin, but not of retinoic acid or benzo(a)pyrene. Arch Biochem Biophys. 1998 Feb 15;350(2):340-7. [PubMed:9473310]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:34