LG 100268

LG 100268 is a highly potent and selective retinoid X receptor (RXR) agonist which strongly activates RXR homodimers with EC₅₀ value of 4nM^[1].

In vitro, LG 100268 (0.1-10µM) treatment on human normal mammary epithelial cells for 10 days significantly suppressed cell growth at 10µM, uprelgated the expression of pro-apoptotic BAX and E-cadherin and repressed the expression of cell division cycle 42 (CDC42) and collagen type VI α3^[2]. LG 100268 (1μM) incubation on human leukemia cells (HL-60 cells) for 72h significantly elevated tissue transglutaminase (TGase) activity without inducing apoptosis^[3]. LG 100268 (1μM) incubated mouse meibomian gland epithelial cells for three days after latanoprost pre-treatment. LG 100268 exerted anti-inflammatory effect by significantly suppressing IL-6 secretion induced by latanoprost and down-regulating the expression of hyperkeratinization marker Keratin-17^[4].

In vivo, LG 100268 (10mg/kg or 100mg/kg) was administrated into MMTV-erbB2 transgenic mice daily with gastric gavage for 4 months or a long term of 18 months. Short-term treatment of LG 100268 significantly prevented the development of preinvasive mammary lesions including hyperplasia and ductal carcinoma in situ. Long-term treatment with LG 100268 significantly prevented invasive mammary tumor development^[5]. LG 100268 (100mg/kg) was fed to MMTV-Neu mice of breast cancer for 5 days. LG 100268 reduced tumor burden, down-regulated the tumor-promoting macrophage marker CD206 and increased the percentage of naive and central memory CD8 T cells^[6]. LG 100268 (100mg/kg or 40mg/kg) was fed to vinyl carbamate induced lung cancer mice model for 16 weeks. LG 100268 reduced tumor number, shrinked average tumor size and altered lipid levels by decreasing plasma triglycerides levels and free glycerol content^[7].

References:
[1] Lala D S, Mukherjee R, Schulman G, et al. Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature. 1996 Oct 3;383(6599):450-3.
[2] Seo H S, Woo J K, Shin Y C, Ko S G. Identification of biomarkers regulated by rexinoids (LGD1069, LG100268 and Ro25-7386) in human breast cells using Affymetrix microarray. Mol Med Rep. 2015 Jul;12(1):800-18.
[3] 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. 1995 Aug 4;38(16):3146-55.
[4] Jiang X Y, Yang P S, Xiao O, et al. Effects of PPAR-γ and RXR-α on mouse meibomian gland epithelial cells during inflammation induced by latanoprost. Exp Eye Res.2022 Nov:224:109251.
[5] Li Y X, Zhang Y, Hill J, et al. The Rexinoid LG100268 prevents the development of preinvasive and invasive estrogen receptor negative tumors in MMTV-erbB2 mice. Clin Cancer Res. 2007 Oct 15;13(20):6224-31.
[6] Leal A S, Zydeck K, Carapellucci S,et al. Retinoid X receptor agonist LG100268 modulates the immune microenvironment in preclinical breast cancer models. NPJ Breast Cancer. 2019 Nov 1:5:39.
[7] Cao M, Royce D B, Risingsong R,et al. The Rexinoids LG100268 and LG101506 Inhibit Inflammation and Suppress Lung Carcinogenesis in A/J Mice. Cancer Prev Res (Phila). 2016 Jan;9(1):105-14.

LG 100268 是一种高效、选择性的视黄醇X受体(RXR)激动剂，EC₅₀值为4nM，可强力激活RXR同源二聚体^[1]。

在体外模型中，LG 100268（10µM）处理人正常乳腺上皮细胞10天，显著抑制细胞生长，上调促凋亡BAX和E-cadherin表达，并下调细胞分裂周期相关蛋白42（CDC42）及胶原蛋白VI α3的表达^[2]。 LG 100268（1µM）孵育人白血病HL-60细胞72小时，显著升高组织转谷氨酰胺酶（TGase）活性，但不诱导凋亡^[3]。LG 100268（1µM）孵育拉坦前列素预处理的小鼠睑板腺上皮细胞3天，显著抑制IL-6分泌并下调角化过度标志物Keratin-17^[4]。

LG 100268（10mg/kg或100mg/kg）经胃管每日给药MMTV-erbB2转基因小鼠4个月，短期给药显著阻止乳腺前侵袭性病变的形成，长期连续给药18个月显著阻止侵袭性肿瘤的发生^[5]。LG 100268（100mg/kg）饲喂MMTV-Neu乳腺癌小鼠5天，减少肿瘤负荷，下调促瘤巨噬细胞标志CD206并提高初始和中央记忆CD8 T细胞比例^[6]。LG 100268（100mg/kg或40mg/kg）饲喂乙烯基氨基甲酸酯诱导的肺癌小鼠16周，减少肿瘤数量、缩小平均肿瘤体积，并降低血浆甘油三酯及游离甘油水平^[7]。