SR 11302

SR 11302 is a retinoid-based, AP-1-selective transcription factor inhibitor that blocks AP-1 activity without activating retinoic acid response element (RARE)-mediated transcription^[1]. AP-1 is a transcription factor dimer composed of proteins such as Jun/Fos, which regulates the expression of genes such as inflammation and proliferation by binding to the TRE sequence^[2]. RARE serves as the cognate DNA element for the retinoic acid receptor (RAR)/retinoid X receptor (RXR) heterodimer, propagating classic retinoid signaling^[3]. By silencing AP-1 while remaining inert toward RAR/RXR, SR 11302 retains anti-inflammatory and anti-proliferative efficacy yet avoids the dermal toxicity, teratogenicity, and resistance associated with conventional retinoids^[4]. SR 11302 is commonly used in studies of inflammation, oncology, and AP-1–mediated signaling pathways^[5-7].

In vitro, pretreating AGS gastric epithelial cells with SR 11302 (2μM; 2h) and then infecting cells with H. pylori for 24 or 48h suppressed both cell proliferation and expression of oncogene proteins β-catenin and c-Myc^[7]. In hypoxia-treated human pulmonary artery endothelial cells (HPAECs), SR 11302(1μM; 1h) abolished the hypoxia-evoked rise in aldosterone by blocking c-Fos/c-Jun–driven StAR transcription^[8].

In vivo, oral administration of SR 11302 (o.5 or 1mg/kg/day) for 11 days in Vldlr^−/− mice reduced the total vascular lesion number by 48% and decreased the lesion size by 40%, without detectable signs of toxicity in mice, including no change in body weight^[5].

References:
[1] Fanjul A, Dawson MI, Hobbs PD, et al. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature. 1994;372(6501):107-111.
[2] Karin M, Liu Zg, Zandi E. AP-1 function and regulation. Curr Opin Cell Biol. 1997;9(2):240-246.
[3] Cunningham TJ, Duester G. Mechanisms of retinoic acid signalling and its roles in organ and limb development. Nat Rev Mol Cell Biol. 2015;16(2):110-123.
[4] Huang C, Ma WY, Dawson MI, Rincon M, Flavell RA, Dong Z. Blocking activator protein-1 activity, but not activating retinoic acid response element, is required for the antitumor promotion effect of retinoic acid. Proc Natl Acad Sci U S A. 1997;94(11):5826-5830.
[5] Sun Y, Lin Z, Liu CH, et al. Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos. J Exp Med. 2017;214(6):1753-1767.
[6] Shiohara M, Dawson MI, Hobbs PD, et al. Effects of novel RAR- and RXR-selective retinoids on myeloid leukemic proliferation and differentiation in vitro. Blood. 1999;93(6):2057-2066.
[7] Byun E, Park B, Lim JW, Kim H. Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells. Yonsei Med J. 2016;57(3):647-651.
[8] Maron BA, Oldham WM, Chan SY, et al. Upregulation of steroidogenic acute regulatory protein by hypoxia stimulates aldosterone synthesis in pulmonary artery endothelial cells to promote pulmonary vascular fibrosis. Circulation. 2014;130(2):168-179.