Bexarotene
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| Clinical data | |
|---|---|
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a608006 |
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| Routes of administration | Oral and Topical |
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| 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. |
| Elimination 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. |
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| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.206.790 |
| Chemical and physical data | |
| Formula | C24H28O2 |
| Molar mass | 348.478 g/mol g·mol−1 |
| 3D model (JSmol) | |
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Bexarotene (Targretin) is an oral antineoplastic agent indicated by the FDA (in 2000) for cutaneous T cell lymphoma.[2] It has been used off-label for lung cancer,[3] breast cancer, and Kaposi's sarcoma.
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 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
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.[4]
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 who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical). New research indicates it may have a role in the treatment of Alzheimer's dementia[5]
Chem
M.F. Boehm, R.A. Heyman, L. Zhi, C.K. Hwang, S. White, A. Nadzan, U.S. patent 5,780,676 (1998).
External links
References
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ 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.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Bexarotene MSDS (LC Labs) http://www.lclabs.com/printableMSDS/B-2422MSDSprintable.html
- ^ http://medicalxpress.com/news/2012-02-fda-approved-drug-rapidly-amyloid-brain.html