Alitretinoin

Identification

Summary

Alitretinoin is a vitamin A derivative used to treat Kaposi's sarcoma and used off label to treat chronic hand eczema and psoriasis.

Brand Names
Panretin
Generic Name
Alitretinoin
DrugBank Accession Number
DB00523
Background

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).

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 300.4351
Monoisotopic: 300.20893014
Chemical Formula
C20H28O2
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

Pharmacology

Indication

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

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofChronic eczema of the hand••••••••••••
Treatment ofCutaneous lesions••••••••••••
Treatment ofRefractory eczema of the hand••••••••••••
Treatment ofSevere eczema of the hand••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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
Humans
ARetinoic acid receptor RXR-alpha
agonist
Humans
ARetinoic acid receptor beta
agonist
Humans
ARetinoic acid receptor RXR-beta
agonist
Humans
ARetinoic acid receptor gamma
agonist
Humans
ARetinoic acid receptor RXR-gamma
agonist
Humans
UInsulin-like growth factor-binding protein 3Not AvailableHumans
UPregnancy-specific beta-1-glycoprotein 5Not AvailableHumans
UCytochrome P450 26C1Not AvailableHumans
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

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
PathwayCategory
Retinol MetabolismMetabolic
Vitamin A DeficiencyDisease
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AmbroxolThe risk or severity of methemoglobinemia can be increased when Alitretinoin is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Alitretinoin is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Alitretinoin is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Alitretinoin is combined with Benzyl alcohol.
BupivacaineThe risk or severity of methemoglobinemia can be increased when Alitretinoin is combined with Bupivacaine.
Food Interactions
  • Take at the same time every day.
  • Take with food. Food increases the bioavailability of alitretinoin capsules.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HanzemaCapsule30 mgOralDr Reddy's Laboratories Inc2021-06-09Not applicableCanada flag
HanzemaCapsule10 mgOralDr Reddy's Laboratories Inc2021-06-09Not applicableCanada flag
PanretinGel1 mg/1gTopicalLigand Pharmaceuticals Incorporated2006-10-06Not applicableUS flag
PanretinGel0.1 %TopicalLigand Pharmaceuticals IncNot applicableNot applicableCanada flag
PanretinGel60 mg/60gTopicalConcordia Pharmaceuticals Inc.2019-09-10Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Clindamycin 1% / Niacinamide 4% / Tretinoin 0.05%Alitretinoin (0.05 g/100g) + Clindamycin phosphate (1 g/100g) + Nicotinamide (4 g/100g)CreamTopicalSincerus Florida, LLC2019-05-04Not applicableUS flag

Categories

ATC Codes
L01XF02 — AlitretinoinD11AH04 — Alitretinoin
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Aliphatic homomonocyclic compound / Branched fatty acid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Diterpenoid / Fatty acid / Fatty acyl / Hydrocarbon derivative / Medium-chain fatty acid
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
retinoic acid (CHEBI:50648) / Retinoids (C15493) / Retinoids (LMPR01090022)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
1UA8E65KDZ
CAS number
5300-03-8
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

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
Human Metabolome Database
HMDB0002369
KEGG Drug
D02815
KEGG Compound
C15493
PubChem Compound
449171
PubChem Substance
46507356
ChemSpider
395778
BindingDB
31892
RxNav
81864
ChEBI
50648
ChEMBL
CHEMBL705
ZINC
ZINC000012661824
Therapeutic Targets Database
DAP000275
PharmGKB
PA164746900
PDBe Ligand
9CR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alitretinoin
PDB Entries
1epb / 1fby / 1fm6 / 1fm9 / 1k74 / 1tyr / 1xdk / 1xiu / 1xls / 2nnh
show 14 more
FDA label
Download (21.8 KB)
MSDS
Download (37.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4TerminatedTreatmentAtopic Dermatitis1
3CompletedOtherHand Dermatosis1
3CompletedTreatmentAtopic Dermatitis2
3CompletedTreatmentChronic Hand Eczema (CHE)1
3CompletedTreatmentHand Dermatosis2

Pharmacoeconomics

Manufacturers
  • Eisai inc
Packagers
  • Basilea Pharmaceuticals Corp.
  • Contract Pharm
  • Eisai Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
Dosage Forms
FormRouteStrength
CapsuleOral
CreamTopical
GelCutaneous
GelCutaneous0.1 %
GelTopical0.1 %
GelTopical1 mg/1g
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)Region
CA2301907No2009-02-102018-08-18Canada flag
US5932622No1999-08-032016-08-03US flag

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
logP5.01Chemaxon
pKa (Strongest Acidic)4.76Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area37.3 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity97.79 m3·mol-1Chemaxon
Polarizability35.91 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-MSsplash10-000i-2190000000-86aaab132a5b092ebf10
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0390000000-af1a6974c2a7872f36c7
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0090000000-82a486e1feafa5cf4f1b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00lu-2970000000-05e8c3f4df3fed93b093
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0190000000-08192331c8e265ce508b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-2890000000-2b136364b4a3a972b85b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052f-4910000000-f6c3b4ffdf3dc3f695a2
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-199.0770981
predicted
DarkChem Lite v0.1.0
[M-H]-191.2097689
predicted
DarkChem Standard v0.1.0
[M-H]-195.2712981
predicted
DarkChem Lite v0.1.0
[M-H]-198.9717981
predicted
DarkChem Lite v0.1.0
[M-H]-190.23927
predicted
DeepCCS 1.0 (2019)
[M+H]+192.59727
predicted
DeepCCS 1.0 (2019)
[M+Na]+200.62029
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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 . [Article]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  4. Fukasawa H, Kagechika H, Shudo K: [Retinoid therapy for autoimmune diseases]. Nihon Rinsho Meneki Gakkai Kaishi. 2006 Jun;29(3):114-26. [Article]
  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. [Article]
  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 . [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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 . [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Transporters

Kind
Protein
Organism
Humans
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48