Bexarotene
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| Systematic (IUPAC) name | |
| 4‑[1‑(3,5,5,8,8‑pentamethyltetralin-2‑yl)ethenyl] benzoic acid | |
| Clinical data | |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a608006 |
| Pregnancy cat. | X |
| Legal status | ? |
| Routes | Oral and topical |
| Pharmacokinetic data | |
| 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. |
| Identifiers | |
| CAS number | 153559-49-0  |
| ATC code | L01XX25 |
| PubChem | CID 82146 |
| IUPHAR ligand | 2807 |
| DrugBank | DB00307 |
| ChemSpider | 74139 |
| UNII | A61RXM4375 |
| ChEBI | CHEBI:50859 |
| ChEMBL | CHEMBL1023 |
| Chemical data | |
| Formula | C24H28O2 |
| Mol. mass | 348.478 g/mol |
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Bexarotene (tradenamed Targretin) is an oral antineoplastic agent indicated by the U.S. Food and Drug Administration (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.
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Medical uses [edit]
Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in people who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).
Mechanism [edit]
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 retinoic acid receptors, vitamin D receptors, thyroid receptors or peroxisome proliferator-activated 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.
Physical properties [edit]
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]
Origin and development [edit]
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History [edit]
The developer of bexarotene (brand name Targretin) was Ligand Pharmaceuticals, a San Diego biotech company which received FDA approval for the drug in 1999.[4] Japanese pharmaceutical Eisai bought the rights to Targretin and three other anti-cancer products from Ligand in 2006.[4]
In the United States, patents on the drug expire in 2016.[4]
Alzheimer's disease [edit]
In 2012 it was announced in an epub ahead of print[5] that researchers had discovered that bexarotene reduced amyloid plaque and improved mental functioning in a small sample of mice engineered to exhibit Alzheimer's symptoms. Three different mouse models (APP/PS1, APPPS1-21, Tg2576) were used. It is thought that bexarotene stimulates expression of apolipoprotein E (ApoE), which leads to intracellular clearance of β-Amyloid.[6] The authors of the research article said, "We've fixed Alzheimer's in mice lots of times, so we need to move forward expeditiously but cautiously", and expect to start a safety study with healthy human subjects by February 2013.[7] The chief executive of the Alzheimer's Foundation of America said that people desperate to find a treatment for Alzheimer's should not take matters into "their own hands" or rush to take the medication.[8]
Chemical synthesis [edit]
M. F. Boehm, R. A. Heyman, L. Zhi, C. K. Hwang, S. White, A. Nadzan, U.S. Patent 5,780,676 (1998).
External links [edit]
References [edit]
- ^ 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.
- ^ 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.
- ^ Bexarotene MSDS (LC Labs) http://www.lclabs.com/printableMSDS/B-2422MSDSprintable.html
- ^ a b c Vinluan, Frank (2011-10-12). "Generic cancer drug from Banner aims to take on Eisai's Targretin". MedCity News. Retrieved 2012-02-11.
- ^ MedicalXpress (9 February 2012). "FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice". MedicalXpress. Retrieved 14 February 2012.
- ^ Cramer PE, Cirrito JR, Wesson DW, Lee CY, Karlo JC, Zinn AE, Casali BT, Restivo JL, Goebel WD, James MJ, Brunden KR, Wilson DA, Landreth GE (9 February 2012). "ApoE-directed therapeutics rapidly clear β‑amyloid and reverse deficits in AD mouse models" (epub ahead of print). Science Express 335 (6075): 1503–6. doi:10.1126/science.1217697. PMID 22323736.
- ^ Jaslow, Ryan (10 February 2012). "Cancer drug reverses Alzheimer's disease in mice: Hope for humans?". Retrieved 10 February 2012.
- ^ Shirley S. Wang (11 February 2012). "Alzheimer's Families Clamor for Drug". The Wall Street Journal. Retrieved 11 February 2012.
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