BEXAROTENE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H28O2
Molecular Weight	348.4779
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC2=C(C=C1C(=C)C3=CC=C(C=C3)C(O)=O)C(C)(C)CCC2(C)C

InChI

InChIKey=NAVMQTYZDKMPEU-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C24H28O2
Molecular Weight	348.4779
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21055lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15056048

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. 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 selectively binds and activates retinoid X receptor subtypes (RXRa, RXRb, RXRg). 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. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Retinoid X receptor 4 Target ID: CHEMBL2363070 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16495926	Agonist 2662

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cutaneous T-cell lymphoma 9 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21055lbl.pdf	Primary		Approved 8360	TARGRETIN Approved Use TARGRETIN® (bexarotene) Capsules are indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. TARGRETIN (bexarotene) is a retinoid indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. (1) Launch Date 9.4642563E11

C_max

Value	Dose	Co-administered	Analyte	Population
652.44 ng/mL EXPERIMENT https://www.researchgate.net/publication/286658511_Pharmacokinetics_of_bexarotene_soft_capsules_in_patients_with_relapsed_or_refractory_cutaneous_T-cell_lymphoma	300 mg/m² 1 times / day multiple, oral dose: 300 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		BEXAROTENE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
2133.34 ng × h/mL EXPERIMENT https://www.researchgate.net/publication/286658511_Pharmacokinetics_of_bexarotene_soft_capsules_in_patients_with_relapsed_or_refractory_cutaneous_T-cell_lymphoma	300 mg/m² 1 times / day multiple, oral dose: 300 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		BEXAROTENE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.18 h EXPERIMENT https://www.researchgate.net/publication/286658511_Pharmacokinetics_of_bexarotene_soft_capsules_in_patients_with_relapsed_or_refractory_cutaneous_T-cell_lymphoma	300 mg/m² 1 times / day multiple, oral dose: 300 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		BEXAROTENE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg/m2 1 times / day multiple, oral Studied dose Dose: 500 mg/m2, 1 times / day Route: oral Route: multiple Dose: 500 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12637463 Page: p.1003	unhealthy, 56 n = 45 Health Status: unhealthy Condition: Breast Cancer Age Group: 56 Sex: F Population Size: 45 Sources: https://pubmed.ncbi.nlm.nih.gov/12637463 Page: p.1003	Disc. AE: Granulocytopenia... AEs leading to discontinuation/dose reduction: Granulocytopenia (severe, 2.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/12637463 Page: p.1003
500 mg/m2 1 times / day multiple, oral Studied dose Dose: 500 mg/m2, 1 times / day Route: oral Route: multiple Dose: 500 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12637463 Page: p.1004	unhealthy, 56 n = 45 Health Status: unhealthy Condition: Breast Cancer Age Group: 56 Sex: F Population Size: 45 Sources: https://pubmed.ncbi.nlm.nih.gov/12637463 Page: p.1004	Disc. AE: Erythema, Triglyceride increased... AEs leading to discontinuation/dose reduction: Erythema (grade 2, 2.2%) Triglyceride increased (grade 2, 2.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/12637463 Page: p.1004
400 mg/m2 1 times / day multiple, oral MTD Dose: 400 mg/m2, 1 times / day Route: oral Route: multiple Dose: 400 mg/m2, 1 times / day Co-administed with:: Vinorelbine, i.v(15-30 mg/m2; once in 2 weeks) cisplatin, i.v(100 mg/m2; once in 6 weeks) Sources: https://pubmed.ncbi.nlm.nih.gov/11352954 Page: p.2629, 2632	unhealthy, 59 n = 28 Health Status: unhealthy Condition: Non-small-cell lung cancer Age Group: 59 Sex: M+F Population Size: 28 Sources: https://pubmed.ncbi.nlm.nih.gov/11352954 Page: p.2629, 2632	DLT: Pancreatitis... Dose limiting toxicities: Pancreatitis (grade 2, 3.57%) Sources: https://pubmed.ncbi.nlm.nih.gov/11352954 Page: p.2629, 2632
1000 mg/m2 1 times / day multiple, oral Highest studied dose Dose: 1000 mg/m2, 1 times / day Route: oral Route: multiple Dose: 1000 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10430065 Page: p.1660	unhealthy n = 6 Health Status: unhealthy Condition: Cancer Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/10430065 Page: p.1660	DLT: Transaminitis, Hyperbilirubinemia... Dose limiting toxicities: Transaminitis (grade 3, 16.7%) Hyperbilirubinemia (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/10430065 Page: p.1660
300 mg/m2 1 times / day multiple, oral Recommended Dose: 300 mg/m2, 1 times / day Route: oral Route: multiple Dose: 300 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021055s010lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Cutaneous T-cell lymphoma Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021055s010lbl.pdf Page: p.1	Disc. AE: Birth defects, Hyperlipidemia... AEs leading to discontinuation/dose reduction: Birth defects Hyperlipidemia Pancreatitis Hepatotoxicity Cholestasis Hepatic failure Hypothyroidism Neutropenia Photosensitivity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021055s010lbl.pdf Page: p.1

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50859	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50859
ChemicalBook	CB6506670	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6506670
MolPort	MolPort-003-845-030	https://www.molport.com/shop/molecule-link/MolPort-003-845-030
Selleck Chemicals	bexarotene	http://www.selleckchem.com/products/bexarotene.html
ZINC	ZINC000001539579	http://zinc15.docking.org/substances/ZINC000001539579
eMolecules	2794932	https://www.emolecules.com/cgi-bin/more?vid=2794932

PubMed

Title	Date	PubMed



Therapeutic advances in biological response modifiers in the treatment of cutaneous T-cell lymphoma.	2001	11520254
Abrogation of transforming growth factor-alpha/epidermal growth factor receptor autocrine signaling by an RXR-selective retinoid (LGD1069, Targretin) in head and neck cancer cell lines.	2001 Aug 1	11479234
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.	2001 Feb	14700480
Bexarotene metabolism in rat, dog, and human, synthesis of oxidative metabolites, and in vitro activity at retinoid receptors.	2001 Jul	11408365
Therapy options in cutaneous T-cell lymphoma.	2001 Oct	12113107
Cutaneous T-cell lymphoma. New immunomodulators.	2001 Oct	11705358
Where to next with retinoids for cancer therapy?	2001 Oct	11595682
Oral bexarotene in the treatment of cutaneous T-cell lymphoma.	2001 Sep	11573857
A review of cancer chemopreventive agents.	2001 Sep	11562271
Retinoids--which dermatological indications will benefit in the near future?	2001 Sep-Oct	11586072
Retinoid signalling and gene expression in neuroblastoma cells: RXR agonist and antagonist effects on CRABP-II and RARbeta expression.	2002	12397610
Risk management strategies in the Physicians' Desk Reference product labels for pregnancy category X drugs.	2002	12241129
Treatment of cutaneous T cell lymphoma: 2001.	2002	12079229
Treatment of cutaneous T cell lymphoma: current status and future directions.	2002	11978140
Mechanism of selective retinoid X receptor agonist-induced hypothyroidism in the rat.	2002 Aug	12130551
Immunomodulatory effects of RXR rexinoids: modulation of high-affinity IL-2R expression enhances susceptibility to denileukin diftitox.	2002 Aug 15	12149223
Validated liquid chromatographic method for the determination of bexarotene in human plasma.	2002 Aug 5	12113985
Novel multimodality biologic response modifier therapy, including bexarotene and long-wave ultraviolet A for a patient with refractory stage IVa cutaneous T-cell lymphoma.	2002 Dec	12451388
A pharmacophore for human pregnane X receptor ligands.	2002 Jan	11744617
Bexarotene gel: a Food and Drug Administration-approved skin-directed therapy for early-stage cutaneous T-cell lymphoma.	2002 Mar	11902993
Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action.	2002 May	12006543
T0070907, a selective ligand for peroxisome proliferator-activated receptor gamma, functions as an antagonist of biochemical and cellular activities.	2002 May 31	11877444
Treatment of mycosis fungoides with oral bexarotene combined with PUVA.	2002 Sep	12847736
Overview of cutaneous T-cell lymphoma: prognostic factors and novel therapeutic approaches.	2003	15202526
Treatment planning in cutaneous T-cell lymphoma.	2003	14686969
Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas.	2003 Apr	12852367
Therapy of cutaneous lymphoma--current practice and future developments.	2003 Aug	12972705
[Standard and experimental therapy of cutaneous T-cell lymphoma].	2003 Dec	14634747
Effects of oral bexarotene (targretin) on the minimal erythema dose for broadspectrum UVB light.	2003 Jul-Aug	12784063
Gateways to clinical trials.	2003 Jun	12851663
Psoralen plus long-wave UV-A (PUVA) and bexarotene therapy: An effective and synergistic combined adjunct to therapy for patients with advanced cutaneous T-cell lymphoma.	2003 Jun	12810509
Etiology, diagnosis, and treatment recommendations for central hypothyroidism associated with bexarotene therapy for cutaneous T-cell lymphoma.	2003 Mar	12672276
Long-term control of mycosis fungoides of the hands with topical bexarotene.	2003 Mar	12653924
Topical bexarotene therapy for patients with refractory or persistent early-stage cutaneous T-cell lymphoma: results of the phase III clinical trial.	2003 Nov	14576658
Current status of cutaneous T-cell lymphoma: molecular diagnosis, pathogenesis, therapy and future directions.	2003 Oct	14605466
Experiences with monolithic LC phases in quantitative bioanalysis.	2003 Oct 15	14550867
Responsiveness to the retinoic acid receptor-selective retinoid LGD1550 correlates with abrogation of transforming growth factor alpha/epidermal growth factor receptor autocrine signaling in head and neck squamous carcinoma cells.	2003 Sep 15	14519647
A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands.	2004	15318936
Combination of bexarotene and psoralen-UVA therapy in a patient with Mycosis fungoides.	2004	15237276
The novel synthetic oleanane triterpenoid CDDO (2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid) induces apoptosis in Mycosis fungoides/Sézary syndrome cells.	2004 Aug	15245439
Comparison of selective retinoic acid receptor- and retinoic X receptor-mediated efficacy, tolerance, and survival in cutaneous t-cell lymphoma.	2004 Jul	15243520
Bexarotene: new preparation. Cutaneous lymphoma: too many adverse effects.	2004 Jun	15233146
How retinoids regulate breast cancer cell proliferation and apoptosis.	2004 Jun	15197471
Therapy for mycosis fungoides.	2004 Jun	15115649
Potentiation of the teratogenic effects induced by coadministration of retinoic acid or phytanic acid/phytol with synthetic retinoid receptor ligands.	2004 Nov	15558240
Cutaneous T-cell lymphoma treatment using bexarotene and PUVA: a case series.	2004 Oct	15389192
Optimizing bexarotene therapy for cutaneous T-cell lymphoma.	2004 Sep	15338005

Patents

Sample Use Guides

In Vivo Use Guide

The recommended initial dose of Targretin (bexarotene) capsules is 300 mg/m2 /day. Capsules should be taken as a single oral daily dose with a meal.

Route of Administration: Oral

In Vitro Use Guide

Bexarotene (10−6 mol/L) inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of 300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:04:12 UTC 2023` Edited by `admin` on `Wed Jul 05 23:04:12 UTC 2023`
Record UNII	A61RXM4375
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BEXAROTENE

Official Name

English

BEXAROTENE [EMA EPAR]

Common Name

English

Bexarotene [WHO-DD]

Common Name

English

BEXAROTENE [MART.]

Common Name

English

BEXAROTENE [VANDF]

Common Name

English

BEXAROTENE [ORANGE BOOK]

Common Name

English

LGD-1069

Code

English

LGD1069

Code

English

bexarotene [INN]

Common Name

English

P-(1-(5,6,7,8-TETRAHYDRO-3,5,5,8,8-PENTAMETHYL-2-NAPHTHYL)VINYL)BENZOIC ACID

Common Name

English

BEXAROTENE [USAN]

Common Name

English

LG-100069

Code

English

LG100069

Code

English

TARGRETIN

Brand Name

English

4-(1-(5,6,7,8-TETRAHYDRO-3,5,5,8,8-PENTAMETHYL-2-NAPHTHALENYL)ETHENYL)BENZOIC ACID

Systematic Name

English

BEXAROTENE [HSDB]

Common Name

English

BEXAROTENE [MI]

Common Name

English

BEXAROTENE [JAN]

Common Name

English

NSC-747528

Code

English

Classification Tree Code System Code

NDF-RT

N0000007700