Bexarotene

Systematic (IUPAC) name
4-[1-(3,5,5,8,8-pentamethyltetralin-2-yl)ethenyl] benzoic acid
Identifiers
CAS number	153559-49-0
ATC code	L01XX25
PubChem	82146
DrugBank	APRD00114
ChemSpider	74139
Chemical data
Formula	C24H28O2
Mol. mass	348.478 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	?
Protein binding	>99%
Metabolism	Bexarotene undergoes oxidative metabolism via CYP450 3A4 and its metabolites are then glucuronidated. Four bexarotene metabolites have been identified in the plasma: 6- and 7- hydroxy-bexarotene and 6-and 7-oxo-bexarotene. All of the metabolites are active in vitro, but their clinical significance is not known.
Half life	7 hours
Excretion	Parent drug and metabolites are eliminated primarily through the hepatobiliary system. Less than 1% is excreted in the urine unchanged.
Therapeutic considerations
Pregnancy cat.	X
Legal status
Routes	Oral and Topical
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Bexarotene (Targretin) is an oral antineoplastic agent indicated by the FDA (in 2000) for cutaneous T cell lymphoma.^[1] It has been used off-label for lung cancer,^[2] breast cancer, and Kaposi's sarcoma.

[edit] Mechanism

Bexarotene is a retinoid specifically selective for retinoid X receptors, as opposed to the retinoic acid receptors.

RXRs are located primarily in visceral organs such as the liver and kidney. Activated RXRs form homodimers or heterodimers with RAR (retinoic acid receptors), vitamin D receptors, thyroid receptors or peroxisome proliferator activator receptors. Once activated, these retinoid receptor dimers bind to DNA at retinoic acid response elements and act as transcription factors that regulate the expression of genes which control cellular differentiation and proliferation. Retinoid agonists can activate the expression of retinoid regulated genes by removing negative transcription control or by facilitating positive transcriptional activity. They exert anticancer action by interfering with the growth of cells of the tumor.

[edit] Physical Properties

Bexarotene is a solid, white powder. It is poorly soluble in water; the solubility is estimated to be about 10-50 µM. It is soluble in DMSO at 65 mg/mL and in ethanol at 10 mg/mL with warming.^[3]

[edit] Clinical uses

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 (oral) and for the topical treatment of cutaneous lesions in patients with CTCL (Stage IA and IB) who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).

[edit] External links

• Targretin prescribing information (capsules)
• Targretin prescribing information (topical gel)
• Bexarotene Material Safety Data Sheet (MSDS) from LC Labs

[edit] References

1. ^ Gniadecki R, Assaf C, Bagot M, et al. (2007). "The optimal use of bexarotene in cutaneous T-cell lymphoma". Br. J. Dermatol. 157 (3): 433–40. doi:10.1111/j.1365-2133.2007.07975.x. PMID 17553039. 
2. ^ Dragnev KH, Petty WJ, Shah SJ, et al. (2007). "A proof-of-principle clinical trial of bexarotene in patients with non-small cell lung cancer". Clin. Cancer Res. 13 (6): 1794–800. doi:10.1158/1078-0432.CCR-06-1836. PMID 17363535. 
3. ^ Bexarotene MSDS (LC Labs) http://www.lclabs.com/printableMSDS/B-2422MSDSprintable.html