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. [Wikipedia]

Structure
Thumb
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
  • p-[1-(5,6,7,8,-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl)vinyl]benzoic acid
  • Targretyn
  • Targrexin
External IDs
LG 100069 / LG-100069 / LG100069 / LGD 1069 / LGD-1069 / LGD1069
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BexaroteneGel1 g/100gTopicalOceanside Pharmaceuticals2000-06-28Not applicableUs
BexaroteneCapsule, liquid filled75 mg/1OralOceanside Pharmaceuticals1999-12-29Not applicableUs
TargretinCapsule, liquid filled75 mg/1OralEisai Limited1999-12-292017-02-11Us
TargretinCapsule, liquid filled75 mg/1OralValeant Pharmaceuticals North America1999-12-29Not applicableUs
TargretinCapsule75 mgOralEisai Limited2001-03-29Not applicableEu
TargretinGel1 g/100gTopicalEisai Limited2000-06-282017-04-30Us
TargretinGel1 g/100gTopicalValeant Pharmaceuticals North America2000-06-28Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BexaroteneCapsule, liquid filled75 mg/1OralMylan Institutional2016-04-15Not applicableUs
BexaroteneCapsule, liquid filled75 mg/1OralMylan Pharmaceuticals2015-07-09Not 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.

Structured Indications
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
Human
ARetinoic acid receptor RXR-beta
agonist
Human
ARetinoic acid receptor RXR-gamma
agonist
Human
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
DrugInteractionDrug group
AbirateroneThe metabolism of Bexarotene can be decreased when combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Bexarotene.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Bexarotene.Experimental
AmiodaroneThe metabolism of Bexarotene can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Bexarotene can be increased when it is combined with Aprepitant.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Bexarotene.Approved, Investigational
AtazanavirThe metabolism of Bexarotene can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Bexarotene can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Atorvastatin can be decreased when it is combined with Bexarotene.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Bexarotene.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Bexarotene.Approved, Investigational
BoceprevirThe metabolism of Bexarotene can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Bexarotene can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Bexarotene can be decreased when it is combined with Bosentan.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Bexarotene.Approved
CapecitabineThe metabolism of Bexarotene can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Bexarotene can be increased when combined with Carbamazepine.Approved, Investigational
CarboplatinThe serum concentration of Bexarotene can be increased when it is combined with Carboplatin.Approved
CeritinibThe serum concentration of Bexarotene can be increased when it is combined with Ceritinib.Approved
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Bexarotene.Investigational, Withdrawn
ChlortetracyclineThe risk or severity of adverse effects can be increased when Chlortetracycline is combined with Bexarotene.Approved, Investigational, Vet Approved
CholecalciferolThe metabolism of Bexarotene can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
ClemastineThe metabolism of Bexarotene can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Bexarotene can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Bexarotene is combined with Clozapine.Approved
CobicistatThe metabolism of Bexarotene can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Bexarotene can be increased when it is combined with Conivaptan.Approved, Investigational
Conjugated estrogensThe serum concentration of Conjugated estrogens can be decreased when it is combined with Bexarotene.Approved
CrisaboroleThe metabolism of Bexarotene can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Bexarotene can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Bexarotene.Approved, Investigational
CyclosporineThe metabolism of Bexarotene can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Bexarotene.Experimental
DabrafenibThe serum concentration of Bexarotene can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Bexarotene can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Bexarotene can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Bexarotene can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Bexarotene can be decreased when combined with Delavirdine.Approved
DemeclocyclineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with Bexarotene.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Bexarotene.Approved
DesogestrelThe serum concentration of Desogestrel can be decreased when it is combined with Bexarotene.Approved
DienestrolThe serum concentration of Dienestrol can be decreased when it is combined with Bexarotene.Approved, Investigational
DienogestThe serum concentration of Dienogest can be decreased when it is combined with Bexarotene.Approved
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Bexarotene.Approved, Investigational
DigitoxinDigitoxin may decrease the cardiotoxic activities of Bexarotene.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Bexarotene.Approved
DihydroergotamineThe metabolism of Bexarotene can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Bexarotene can be decreased when combined with Diltiazem.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Bexarotene.Approved, Investigational
DosulepinThe metabolism of Bexarotene can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Bexarotene can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Bexarotene can be decreased when combined with Dronedarone.Approved
DrospirenoneThe serum concentration of Drospirenone can be decreased when it is combined with Bexarotene.Approved
EfavirenzThe metabolism of Bexarotene can be decreased when combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Bexarotene can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Bexarotene can be decreased when combined with Erythromycin.Approved, Vet Approved
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Bexarotene.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Estramustine can be decreased when it is combined with Bexarotene.Approved
Estrogens, esterifiedThe serum concentration of Estrogens, esterified can be decreased when it is combined with Bexarotene.Approved
Estrone sulfateThe serum concentration of Estrone sulfate can be decreased when it is combined with Bexarotene.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Bexarotene.Approved
Ethynodiol diacetateThe serum concentration of Ethynodiol diacetate can be decreased when it is combined with Bexarotene.Approved
EtonogestrelThe serum concentration of Etonogestrel can be decreased when it is combined with Bexarotene.Approved, Investigational
EtravirineThe metabolism of Bexarotene can be decreased when combined with Etravirine.Approved
FloxuridineThe metabolism of Bexarotene can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Bexarotene can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Bexarotene can be decreased when combined with Fluorouracil.Approved
FluvastatinThe metabolism of Bexarotene can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Bexarotene can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Bexarotene can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Bexarotene can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Bexarotene can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Bexarotene can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe serum concentration of Bexarotene can be increased when it is combined with Gemfibrozil.Approved
GestodeneThe serum concentration of Gestodene can be decreased when it is combined with Bexarotene.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Bexarotene.Experimental
HexestrolThe serum concentration of Hexestrol can be decreased when it is combined with Bexarotene.Withdrawn
IdelalisibThe serum concentration of Bexarotene can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Bexarotene can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Bexarotene can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Bexarotene can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Bexarotene can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Bexarotene can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Bexarotene can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Bexarotene can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Bexarotene can be decreased when combined with Ketoconazole.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Bexarotene.Experimental
LeflunomideThe metabolism of Bexarotene can be decreased when combined with Leflunomide.Approved, Investigational
LevonorgestrelThe serum concentration of Levonorgestrel can be decreased when it is combined with Bexarotene.Approved, Investigational
LobeglitazoneThe metabolism of Bexarotene can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Bexarotene can be decreased when combined with Lopinavir.Approved
LosartanThe metabolism of Bexarotene can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Bexarotene can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Bexarotene can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Bexarotene can be decreased when it is combined with Lumacaftor.Approved
LynestrenolThe serum concentration of Lynestrenol can be decreased when it is combined with Bexarotene.Investigational
ManidipineThe metabolism of Bexarotene can be decreased when combined with Manidipine.Approved, Investigational
Medroxyprogesterone acetateThe serum concentration of Medroxyprogesterone acetate can be decreased when it is combined with Bexarotene.Approved, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Bexarotene.Approved
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Bexarotene.Investigational, Withdrawn
MethallenestrilThe serum concentration of Methallenestril can be decreased when it is combined with Bexarotene.Experimental
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Bexarotene.Experimental
MidostaurinThe metabolism of Bexarotene can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Bexarotene can be increased when it is combined with Mifepristone.Approved, Investigational
MinocyclineThe risk or severity of adverse effects can be increased when Minocycline is combined with Bexarotene.Approved, Investigational
MitotaneThe serum concentration of Bexarotene can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Bexarotene can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Bexarotene can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Bexarotene can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Bexarotene can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Bexarotene can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Bexarotene can be decreased when combined with Nilotinib.Approved, Investigational
NorelgestrominThe serum concentration of Norelgestromin can be decreased when it is combined with Bexarotene.Approved
NorgestimateThe serum concentration of Norgestimate can be decreased when it is combined with Bexarotene.Approved
NorgestrelThe serum concentration of Norgestrel can be decreased when it is combined with Bexarotene.Approved
OlaparibThe metabolism of Bexarotene can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Bexarotene.Experimental, Investigational
OmeprazoleThe metabolism of Bexarotene can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Bexarotene can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Bexarotene.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Bexarotene.Approved, Vet Approved
PaclitaxelThe serum concentration of Bexarotene can be increased when it is combined with Paclitaxel.Approved, Vet Approved
PalbociclibThe serum concentration of Bexarotene can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Bexarotene can be increased when combined with Pentobarbital.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Bexarotene.Experimental
PhenobarbitalThe metabolism of Bexarotene can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Bexarotene can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Bexarotene can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Bexarotene can be increased when combined with Primidone.Approved, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Bexarotene.Experimental
PyrimethamineThe metabolism of Bexarotene can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuinineThe metabolism of Bexarotene can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Bexarotene can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Bexarotene can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Bexarotene can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Bexarotene can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Bexarotene can be decreased when combined with Ritonavir.Approved, Investigational
SaquinavirThe metabolism of Bexarotene can be decreased when combined with Saquinavir.Approved, Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Bexarotene.Approved
SecobarbitalThe metabolism of Bexarotene can be increased when combined with Secobarbital.Approved, Vet Approved
SildenafilThe metabolism of Bexarotene can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Bexarotene can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Bexarotene can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Bexarotene can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Bexarotene can be decreased when it is combined with St. John&#39;s Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Bexarotene can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Bexarotene can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Bexarotene can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Bexarotene can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
Synthetic Conjugated Estrogens, AThe serum concentration of Synthetic Conjugated Estrogens, A can be decreased when it is combined with Bexarotene.Approved
TamoxifenThe serum concentration of Tamoxifen can be decreased when it is combined with Bexarotene.Approved
TelaprevirThe metabolism of Bexarotene can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Bexarotene can be decreased when combined with Telithromycin.Approved
TicagrelorThe metabolism of Bexarotene can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Bexarotene can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Bexarotene can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Bexarotene can be decreased when combined with Tolbutamide.Approved
TopiroxostatThe metabolism of Bexarotene can be decreased when combined with Topiroxostat.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Bexarotene.Approved, Investigational
TrimethoprimThe metabolism of Bexarotene can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Bexarotene can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Bexarotene can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe metabolism of Bexarotene can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Bexarotene can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Bexarotene can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Bexarotene can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Bexarotene can be decreased when combined with Ziprasidone.Approved
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
HMDB14452
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
1Not Yet RecruitingPreventionAtypical 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
2Active Not RecruitingTreatmentLeukemias / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Diseases1
2Active Not RecruitingTreatmentLung Cancers1
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
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2CompletedTreatmentMalignant Lymphomas3
2TerminatedTreatmentParapsoriasis1
2Unknown StatusTreatmentLung Cancers1
2Unknown StatusTreatmentMalignant Lymphomas1
2, 3CompletedTreatmentAlopecia Areata (AA)1
3CompletedPreventionSchizophrenic Disorders1
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
Dosage forms
FormRouteStrength
GelTopical1 g/100g
CapsuleOral75 mg
Capsule, liquid filledOral75 mg/1
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)
US6043279No1995-04-222012-04-22Us
US5780676No1995-07-142015-07-14Us
US5962731No1996-10-052016-10-05Us

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

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. 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]
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. 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]
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. 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

Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
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]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:35