Bexarotene

Targets (3)Enzymes (3)Biointeractions (7)

Identification

Name
Bexarotene
Accession Number
DB00307  (APRD00114)
Type
Small Molecule
Groups
Approved, Investigational
Description

Bexarotene (Targretin) is an antineoplastic agent indicated by the FDA for Cutaneous T cell lymphoma. It has been used off-label for lung cancer, breast cancer, and Kaposi's sarcoma.

Structure
Thumb
3D
Similar Structures
Synonyms
  • 4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl]benzoic acid
  • 4-[1-(5,6,7,8,-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl)ethenyl]benzoic acid
  • Bexaroten
  • Bexarotène
  • Bexarotene
  • Bexaroteno
  • Bexarotenum
  • p-(1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl)vinyl)benzoic acid
External IDs
LG 100069 / LG-100069 / LG100069 / LGD 1069 / LGD-1069 / LGD1069
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TargretinGel1 g/100gTopicalEisai Limited2000-06-282017-04-30Us
TargretinGel10 mg/1gTopicalLigand Pharmaceuticals2006-03-28Not applicableUs
TargretinCapsule, liquid filled75 mg/1OralValeant Pharmaceuticals North America1999-12-29Not applicableUs
TargretinGel1 g/100gTopicalValeant Pharmaceuticals North America LLC2000-06-28Not applicableUs
TargretinCapsule, liquid filled75 mg/1OralEisai Limited1999-12-292014-12-01Us
TargretinCapsule75 mg/1OralCardinal Health2006-03-282006-07-18Us
TargretinCapsule75 mgOralEisai Limited2001-03-29Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BexaroteneCapsule75 mg/1OralUpsher Smith Laboratories2018-07-25Not applicableUs
BexaroteneGel1 g/100gTopicalOceanside Pharmaceuticals2000-06-282018-03-16Us
BexaroteneCapsule, liquid filled75 mg/1OralMylan Pharmaceuticals Inc.2015-07-09Not applicableUs
BexaroteneCapsule, liquid filled75 mg/1OralMylan Institutional Inc.2016-04-15Not applicableUs
BexaroteneCapsule75 mg/1OralAmneal Pharmaceuticals LLC2018-09-04Not applicableUs
BexaroteneCapsule, liquid filled75 mg/1OralAmerigen Pharmaceuticals Inc.2018-05-10Not applicableUs
BexaroteneCapsule, liquid filled75 mg/1OralOceanside Pharmaceuticals2015-12-17Not applicableUs
Categories
UNII
A61RXM4375
CAS number
153559-49-0
Weight
Average: 348.4779
Monoisotopic: 348.20893014
Chemical Formula
C24H28O2
InChI Key
NAVMQTYZDKMPEU-UHFFFAOYSA-N
InChI
InChI=1S/C24H28O2/c1-15-13-20-21(24(5,6)12-11-23(20,3)4)14-19(15)16(2)17-7-9-18(10-8-17)22(25)26/h7-10,13-14H,2,11-12H2,1,3-6H3,(H,25,26)
IUPAC Name
4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl]benzoic acid
SMILES
CC1=CC2=C(C=C1C(=C)C1=CC=C(C=C1)C(O)=O)C(C)(C)CCC2(C)C

Pharmacology

Indication

Used orally for the treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. Also used topically for the treatment of skin lesions in early (stage IA and IB) CTCL in patients who experience refractory or persistent disease with the use of other therapies or are intolerant of other therapies.

Associated Conditions
Pharmacodynamics

Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models.

Mechanism of action

Bexarotene selectively binds with and activates retinoid X receptor subtypes. There are three subtypes in total: RXRα, RXRβ, RXRγ. The exact mechanism of action of bexarotene in the treatment of CTCL is unknown but the drug has activity in all clinical stages of CTCL.

TargetActionsOrganism
ARetinoic acid receptor RXR-alpha
agonist
Humans
ARetinoic acid receptor RXR-beta
agonist
Humans
ARetinoic acid receptor RXR-gamma
agonist
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

>99%

Metabolism
Not Available
Route of elimination

Urinary elimination of bexarotene and its known metabolites is a minor excretory pathway (<1% of administered dose).

Half life

7 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Bexarotene.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Bexarotene.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Bexarotene is combined with 2-Methoxyethanol.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Bexarotene.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Bexarotene.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Bexarotene.
6-Deoxyerythronolide BThe metabolism of Bexarotene can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Bexarotene.
7-ethyl-10-hydroxycamptothecinThe metabolism of 7-ethyl-10-hydroxycamptothecin can be increased when combined with Bexarotene.
9-(N-methyl-L-isoleucine)-cyclosporin AThe risk or severity of adverse effects can be increased when Bexarotene is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
Food Interactions
Not Available

References

Synthesis Reference
US5466861
General References
  1. Gniadecki R, Assaf C, Bagot M, Dummer R, Duvic M, Knobler R, Ranki A, Schwandt P, Whittaker S: The optimal use of bexarotene in cutaneous T-cell lymphoma. Br J Dermatol. 2007 Sep;157(3):433-40. Epub 2007 Jun 6. [PubMed:17553039]
  2. Dragnev KH, Petty WJ, Shah SJ, Lewis LD, Black CC, Memoli V, Nugent WC, Hermann T, Negro-Vilar A, Rigas JR, Dmitrovsky E: A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer. Clin Cancer Res. 2007 Mar 15;13(6):1794-800. [PubMed:17363535]
  3. Smit JW, Stokkel MP, Pereira AM, Romijn JA, Visser TJ: Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones. J Clin Endocrinol Metab. 2007 Jul;92(7):2496-9. Epub 2007 Apr 17. [PubMed:17440015]
  4. Lowe MN, Plosker GL: Bexarotene. Am J Clin Dermatol. 2000 Jul-Aug;1(4):245-50; discussion 251-2. [PubMed:11702369]
  5. Yen WC, Prudente RY, Corpuz MR, Negro-Vilar A, Lamph WW: A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br J Cancer. 2006 Mar 13;94(5):654-60. [PubMed:16495926]
  6. Farol LT, Hymes KB: Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004 Apr;4(2):180-8. [PubMed:15056048]
External Links
Human Metabolome Database
HMDB0014452
KEGG Drug
D03106
PubChem Compound
82146
PubChem Substance
46509119
ChemSpider
74139
BindingDB
50032675
ChEBI
50859
ChEMBL
CHEMBL1023
Therapeutic Targets Database
DAP000276
PharmGKB
PA164752250
IUPHAR
2807
Guide to Pharmacology
GtP Drug Page
HET
9RA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Bexarotene
ATC Codes
L01XX25 — Bexarotene
PDB Entries
3h0a / 4k6i
FDA label
Download (40.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentThyroid Cancers1
1CompletedNot AvailableAlzheimer's Disease (AD)1
1CompletedPreventionCancer, Breast1
1CompletedTreatmentAdvanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus)1
1CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Mycosis Fungoides (MF) / Primary Cutaneous Anaplastic Large Cell Lymphoma / Sezary Syndrome1
1CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)2
1RecruitingPreventionAtypical Ductal Breast Hyperplasia / Atypical Lobular Breast Hyperplasia / BRCA1 Gene Mutation / Brca2 Gene Mutation / Ductal Breast Carcinoma In Situ / Invasive Breast Carcinoma / Lobular Breast Carcinoma In Situ / No Evidence of Disease1
1TerminatedTreatmentMalignant Lymphomas1
1TerminatedTreatmentMalignant Lymphomas / Multiple Myeloma (MM) / Tumors, Solid1
1, 2CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL)1
1, 2CompletedTreatmentLung Cancers1
1, 2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Unknown StatusNot AvailableCushing's Disease1
2Active Not RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Mycosis Fungoides (MF) / Sezary Syndrome1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Diseases1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentMalignant Lymphomas3
2TerminatedTreatmentParapsoriasis1
2Unknown StatusTreatmentLung Cancers1
2Unknown StatusTreatmentMalignant Lymphomas1
2, 3CompletedTreatmentAlopecia Areata (AA)1
3CompletedPreventionSchizophrenic Disorders1
3CompletedTreatmentCutaneous T-Cell Lymphoma (CTCL) / Mycosis Fungoides (MF) / Primary Cutaneous Anaplastic Large Cell Lymphoma1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3TerminatedTreatmentMalignant Lymphomas1
3Unknown StatusTreatmentSchizophrenic Disorders1
3WithdrawnTreatmentCognition / Schizoaffective Disorders / Schizophrenic Disorders1
4CompletedTreatmentRefractory peripheral cutaneous T-cell lymphoma1
Not AvailableCompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
  • Eisai inc
Packagers
  • Catalent Pharma Solutions
  • Contract Pharm
  • Eisai Inc.
Dosage forms
FormRouteStrength
Capsule, liquid filledOral75 mg/1
CapsuleOral75 mg/1
CapsuleOral75 mg
GelTopical1 g/100g
GelTopical10 mg/1g
Prices
Unit descriptionCostUnit
Targretin 75 mg capsule38.0USD capsule
Targretin 75 mg softgel36.54USD softget capsule
Targretin 1% gel30.08USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6043279No2000-03-282012-04-22Us
US5780676No1998-07-142015-07-14Us
US5962731No1999-10-052016-10-05Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP6.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000149 mg/mLALOGPS
logP6.86ALOGPS
logP6.94ChemAxon
logS-6.4ALOGPS
pKa (Strongest Acidic)4.07ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity117.12 m3·mol-1ChemAxon
Polarizability40.89 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9954
Blood Brain Barrier+0.9022
Caco-2 permeable+0.794
P-glycoprotein substrateSubstrate0.6283
P-glycoprotein inhibitor INon-inhibitor0.5369
P-glycoprotein inhibitor IINon-inhibitor0.7182
Renal organic cation transporterNon-inhibitor0.8496
CYP450 2C9 substrateNon-substrate0.7722
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6786
CYP450 1A2 substrateNon-inhibitor0.8171
CYP450 2C9 inhibitorNon-inhibitor0.8724
CYP450 2D6 inhibitorInhibitor0.5589
CYP450 2C19 inhibitorInhibitor0.8351
CYP450 3A4 inhibitorNon-inhibitor0.8138
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6458
Ames testNon AMES toxic0.8592
CarcinogenicityNon-carcinogens0.7898
BiodegradationNot ready biodegradable0.933
Rat acute toxicity2.2119 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9703
hERG inhibition (predictor II)Non-inhibitor0.9034
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
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0002-0009000000-f46ef667393584a6300e
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udj-0009000000-9b87e4750a290eb82a7e
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0009000000-3ce7b47cafecba720b63
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0009000000-91e32292babb45759b5d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0009000000-885779b7401a85dbf649
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0029000000-e65f7a4f9e6ecad40c0b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00os-1594000000-b4c3e389bf263ae949a1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kb-1941000000-7e96ac6cea878d4fd773
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f6w-1920000000-ca6fbe2847a1daae3bd0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f97-1920000000-f8a80e931ae20d42408c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0239000000-3289f3a345e8948cb1c5

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
Sesquiterpenoids / Tetralins / Benzoic acids / Styrenes / Benzoyl derivatives / Monocarboxylic acids and derivatives / Carboxylic acids / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Bexarotene / Sesquiterpenoid / Bisabolane sesquiterpenoid / Tetralin / Benzoic acid / Benzoic acid or derivatives / Styrene / Benzoyl / Monocyclic benzene moiety / Benzenoid
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
retinoid, naphthalenes, benzoic acids (CHEBI:50859)

Targets

Details1. Retinoic acid receptor RXR-alpha
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. Lowe MN, Plosker GL: Bexarotene. Am J Clin Dermatol. 2000 Jul-Aug;1(4):245-50; discussion 251-2. [PubMed:11702369]
  2. Tsai DE, Luger SM, Andreadis C, Vogl DT, Kemner A, Potuzak M, Goradia A, Loren AW, Perl AE, Schuster SJ, Porter DL, Stadtmauer EA, Goldstein SC, Thompson JE, Swider C, Bagg A, Mato AR, Carroll M: A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia. Clin Cancer Res. 2008 Sep 1;14(17):5619-25. doi: 10.1158/1078-0432.CCR-07-5185. [PubMed:18765556]
  3. Tooker P, Yen WC, Ng SC, Negro-Vilar A, Hermann TW: Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification. Cancer Res. 2007 May 1;67(9):4425-33. [PubMed:17483357]
  4. Lalloyer F, Fievet C, Lestavel S, Torpier G, van der Veen J, Touche V, Bultel S, Yous S, Kuipers F, Paumelle R, Fruchart JC, Staels B, Tailleux A: The RXR agonist bexarotene improves cholesterol homeostasis and inhibits atherosclerosis progression in a mouse model of mixed dyslipidemia. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2731-7. Epub 2006 Sep 28. [PubMed:17008586]
  5. Yen WC, Lamph WW: The selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced breast carcinoma. Mol Cancer Ther. 2005 May;4(5):824-34. [PubMed:15897247]
  6. Yen WC, Prudente RY, Corpuz MR, Negro-Vilar A, Lamph WW: A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br J Cancer. 2006 Mar 13;94(5):654-60. [PubMed:16495926]
  7. Rizvi N, Hawkins MJ, Eisenberg PD, Yocum RC, Reich SD: Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as maintenance therapy for patients treated with chemotherapy for advanced non-small-cell lung cancer. Clin Lung Cancer. 2001 Feb;2(3):210-5. [PubMed:14700480]
  8. Rigas JR, Dragnev KH: Emerging role of rexinoids in non-small cell lung cancer: focus on bexarotene. Oncologist. 2005 Jan;10(1):22-33. [PubMed:15632250]
  9. Farol LT, Hymes KB: Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004 Apr;4(2):180-8. [PubMed:15056048]
Details2. Retinoic acid receptor RXR-beta
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  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:17016423]
  3. Tsai DE, Luger SM, Andreadis C, Vogl DT, Kemner A, Potuzak M, Goradia A, Loren AW, Perl AE, Schuster SJ, Porter DL, Stadtmauer EA, Goldstein SC, Thompson JE, Swider C, Bagg A, Mato AR, Carroll M: A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia. Clin Cancer Res. 2008 Sep 1;14(17):5619-25. doi: 10.1158/1078-0432.CCR-07-5185. [PubMed:18765556]
  4. Tooker P, Yen WC, Ng SC, Negro-Vilar A, Hermann TW: Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification. Cancer Res. 2007 May 1;67(9):4425-33. [PubMed:17483357]
  5. Lalloyer F, Fievet C, Lestavel S, Torpier G, van der Veen J, Touche V, Bultel S, Yous S, Kuipers F, Paumelle R, Fruchart JC, Staels B, Tailleux A: The RXR agonist bexarotene improves cholesterol homeostasis and inhibits atherosclerosis progression in a mouse model of mixed dyslipidemia. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2731-7. Epub 2006 Sep 28. [PubMed:17008586]
  6. Yen WC, Lamph WW: The selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced breast carcinoma. Mol Cancer Ther. 2005 May;4(5):824-34. [PubMed:15897247]
  7. Yen WC, Prudente RY, Corpuz MR, Negro-Vilar A, Lamph WW: A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br J Cancer. 2006 Mar 13;94(5):654-60. [PubMed:16495926]
  8. Rizvi N, Hawkins MJ, Eisenberg PD, Yocum RC, Reich SD: Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as maintenance therapy for patients treated with chemotherapy for advanced non-small-cell lung cancer. Clin Lung Cancer. 2001 Feb;2(3):210-5. [PubMed:14700480]
  9. Rigas JR, Dragnev KH: Emerging role of rexinoids in non-small cell lung cancer: focus on bexarotene. Oncologist. 2005 Jan;10(1):22-33. [PubMed:15632250]
  10. Farol LT, Hymes KB: Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004 Apr;4(2):180-8. [PubMed:15056048]
  11. Lowe MN, Plosker GL: Bexarotene. Am J Clin Dermatol. 2000 Jul-Aug;1(4):245-50; discussion 251-2. [PubMed:11702369]
Details3. Retinoic acid receptor RXR-gamma
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. Lowe MN, Plosker GL: Bexarotene. Am J Clin Dermatol. 2000 Jul-Aug;1(4):245-50; discussion 251-2. [PubMed:11702369]
  2. Tsai DE, Luger SM, Andreadis C, Vogl DT, Kemner A, Potuzak M, Goradia A, Loren AW, Perl AE, Schuster SJ, Porter DL, Stadtmauer EA, Goldstein SC, Thompson JE, Swider C, Bagg A, Mato AR, Carroll M: A phase I study of bexarotene, a retinoic X receptor agonist, in non-M3 acute myeloid leukemia. Clin Cancer Res. 2008 Sep 1;14(17):5619-25. doi: 10.1158/1078-0432.CCR-07-5185. [PubMed:18765556]
  3. Tooker P, Yen WC, Ng SC, Negro-Vilar A, Hermann TW: Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification. Cancer Res. 2007 May 1;67(9):4425-33. [PubMed:17483357]
  4. Lalloyer F, Fievet C, Lestavel S, Torpier G, van der Veen J, Touche V, Bultel S, Yous S, Kuipers F, Paumelle R, Fruchart JC, Staels B, Tailleux A: The RXR agonist bexarotene improves cholesterol homeostasis and inhibits atherosclerosis progression in a mouse model of mixed dyslipidemia. Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2731-7. Epub 2006 Sep 28. [PubMed:17008586]
  5. Yen WC, Lamph WW: The selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced breast carcinoma. Mol Cancer Ther. 2005 May;4(5):824-34. [PubMed:15897247]
  6. Yen WC, Prudente RY, Corpuz MR, Negro-Vilar A, Lamph WW: A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br J Cancer. 2006 Mar 13;94(5):654-60. [PubMed:16495926]
  7. Rizvi N, Hawkins MJ, Eisenberg PD, Yocum RC, Reich SD: Placebo-controlled trial of bexarotene, a retinoid x receptor agonist, as maintenance therapy for patients treated with chemotherapy for advanced non-small-cell lung cancer. Clin Lung Cancer. 2001 Feb;2(3):210-5. [PubMed:14700480]
  8. Rigas JR, Dragnev KH: Emerging role of rexinoids in non-small cell lung cancer: focus on bexarotene. Oncologist. 2005 Jan;10(1):22-33. [PubMed:15632250]
  9. Farol LT, Hymes KB: Bexarotene: a clinical review. Expert Rev Anticancer Ther. 2004 Apr;4(2):180-8. [PubMed:15056048]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 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]
Details2. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 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]
Details3. Cytochrome P450 2C8
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
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
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da

Drug created on June 13, 2005 07:24 / Updated on January 02, 2019 21:26