Acitretin-d3 (Synonyms: Ro 10-1670-d3)

Acitretin-d3 is intended for use as an internal standard for the quantification of acitretin by GC- or LC-MS. Acitretin is a retinoid and an active metabolite of the retinoid etretinate that has antiproliferative activities.1,2 It binds to cellular retinoic acid binding protein I (CRABP-I) and CRABP-II (Kds = 3 and 15 nM, respectively, for the mouse recombinant proteins) but has low affinity for human recombinant retinoic acid receptor-retinoid X receptor (RAR-RXR) heterocomplexes.3,4 Acitretin inhibits proliferation (IC50 = 6.6 μM) and suppresses TNF-α- and IFN-γ-induced protein levels of STAT1, NF-•B, and RANTES in HaCaT keratinocytes when used at concentrations up to 50 μM.5 It inhibits proliferation of HL-60, SCC-4, SCC-15, and A431, but not MCF-7, cancer cells, when used at a concentration of 30 μM.1 Acitretin (20 μg per mouse) decreases the severity of psoriatic-like skin lesions in K14-VEGF transgenic mice.2 Formulations containing acitretin have been used in the treatment of psoriasis.

|1. Frey, J.R., Peck, R., and Bollag, W. Antiproliferative activity of retinoids, interferon α and their combination in five human transformed cell lines. Cancer Lett. 57(3), 223-227 (1991).|2. An, J., Zhang, D., Wu, J., et al. The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis. Pharmacol. Res. 121, 158-168 (2017).|3. Norris, A.W., Cheng, L., GiguÈre, V., et al. Measurement of subnanomolar retinoic acid binding affinities for cellular retinoic acid binding proteins by fluorometric titration. Biochim. Biophys. Acta. 1209(1), 10-18 (1994).|4. Tian, K., Norris, A.W., Lin, C.L., et al. The isolation and characterization of purified heterocomplexes of recombinant retinoic acid receptor and retinoid X receptor ligand binding domains. Biochemistry 36(19), 5669-5676 (1997).|5. Zhang, M., Zhu, L., Feng, Y., et al. Effects of acitretin on proliferative inhibition and RANTES production of HaCaT cells. Arch. Dermatol. Res. 300(10), 575-581 (2008).