Bexarotene

Bexarotene is an agonist of retinoid X receptors (RXRs; EC₅₀s = 28, 25, and 20 nM for RXRα, RXRβ, and RXRγ, respectively, in reporter assays).¹ It is selective for RXRs over retinoic acid receptors (RARs; EC₅₀s = >10 µM for RARα, RARβ, and RARγ). Bexarotene (10 µM) induces apoptosis in MJ, HuT 78, and HH cutaneous T cell lymphoma (CTCL) cells, as well as inhibits lung metastasis and angiogenesis in A549 and MDA-MB-231 mouse xenograft models when administered at a dose of 100 mg/kg per day.^2,3 It reduces increased brain interstitial fluid levels of amyloid-β (1-40) (Aβ40) and Aβ42 in the APP/PS1 transgenic mouse model of Alzheimer’s disease.⁴ It also reduces viral load in the culture supernatant of Vero E6 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; EC₉₀ = 9.4 µM) and inhibits SARS-CoV-2 replication in a plaque reduction assay (EC₅₀ = 2.01 µM).⁵ Formulations containing bexarotene have been used in the treatment of CTCL.

WARNING This product is not for human or veterinary use.

1. Boehm, M.F., Zhang, L., Zhi, L., et al. Design and synthesis of potent retinoid X receptor selective ligands that induce apoptosis in leukemia cells. J. Med. Chem. 38(16), 3146-3155 (1995).

2. Zhang, C., Hazarika, P., Ni, X., et al. Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. Clin. Cancer Res. 8(5), 1234-1240 (2002).

3. Yen, W.-C., Prudente, R.Y., Corpuz, M.R., et al. A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours. Br. J. Cancer 94(5), 654-660 (2006).

4. Cramer, P.E., Cirrito, J.R., Wesson, D.W., et al. ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science 335(6057), 1503-1506 (2012).

5. Yuan, S., Chan, J.F.W., Chik, K.K.H., et al. Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system. Pharmacol. Res. 159, 104960 (2020).