4-Hydroxytamoxifen

RTECS: SL1210000 Source/Host Chemicals: Synthetic. Appearance: White to yellow powder. Solubility: Soluble in ethanol or methanol (both 5mg/ml). Identity: Determined by 1H-NMR. InChi Key: TXUZVZSFRXZGTL-QPLCGJKRSA-N Smiles: CC/C(C1=CC=CC=C1)=C(C2=CC=C(O)C=C2)/C3=CC=C(OCCN(C)C)C=C3 4-Hydroxytamoxifen is an active metabolite of the chemotherapeutic drug tamoxifen, a selective estrogen receptor modulator (SERM) that acts as an agonist or antagonist in various tissues. 4-Hydroxytamoxifen acts as a tissue-selective agonist-antagonist of the estrogen receptors ERalpha and ERbeta. 4-Hydroxytamoxifen is an isoform-specific inhibitor of orphan estrogen-receptor-related (ERR) nuclear receptors beta and gamma. 4-Hydroxytamoxifen exhibits anticancer chemotherapeutic activity, inducing autophagy and vacuole formation as well as KRAS degradation in various cancer cell lines. In cardiac myocytes, 4-hydroxytamoxifen decreases Ca2+ amplitude, slowing relaxation and decreasing contractility. 4-Hydroxytamoxifen has also shown to be a potent inhibitor of the mitochondrial permeability transition (MPT). Product References: [1] N. Terakawa, et al., Cancer 61, 1312 (1988) , [2] H. Wiseman, et al., FEBS Lett. 274, 107 (1990) , [3] G. Freiss, et al., BBRC 173, 919 (1990) , [4] H. Wiseman, et al., Biochem J. 292, 635 (1993) , [5] A.M. Davies, et al., Biochem. Soc. Trans. 23, 439S (1995) , [6] S.T. Willard, et al., Endocrine 14, 247 (2001) , [7] P. Coward, et al., PNAS 98, 8880 (2001) , [8] G.B. Tremblay, et al., Endocrinology 142, 4572 (2001) , [9] H.K. Crewe, et al., Drug Metab. Dispos. 30, 869 (2002) , [10] C.M. Cardoso, et al., Mitochondrion 1, 485 (2002) , [11] J.P. Monteiro, et al., Toxicol. In Vitro 17, 629 (2003) , [12] Z. Desta, et al., J. Pharmacol. Exp. Ther. 310, 1062 (2004) , [13] H. Seeger, et al., Horm. Metab. Res. 36, 277 (2004) , [14] E.A. Ariazi & V.C. Jordan, Curr. Top. Med. Chem. 6, 203 (2006) (Review) , [15] M.L. Asp, et al., PLoS One 8, e78768 (2013) , [16] L. Kohli, et al., Cancer Res. 73, 4395 (2013) , [17] L. Duan, et al., Cancer Lett. 353, 290 (2014)