RGX-104 Hydrochloride

RGX-104 Hydrochloride is an orally active liver X receptor (LXR) agonist that modulates innate immunity by activating the transcription of the apolipoprotein E (ApoE) gene^{[1, 2]}. Up-regulation of ApoE promotes the clearance of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), thereby reversing the immunosuppressive state of the tumor microenvironment and enhancing antitumor immune responses^[3]. RGX-104 Hydrochloride also exhibits antitumor activity and induces cell pyroptosis^{[4, 5]}.

References:
[1] Tavazoie M F, Pollack I, Tanqueco R, et al. LXR/ApoE activation restricts innate immune suppression in cancer[J]. Cell, 2018, 172(4): 825-840. e18.
[2] Mita M, Mita A, Chmielowski B, et al. Abstract B001: A phase 1 trial of RGX-104, a first-in-class immunotherapy targeting the liver-X nuclear hormone receptor (LXR), in patients with refractory malignancies[J]. Molecular Cancer Therapeutics, 2018, 17(1_Supplement): B001-B001.
[3] Zhang J, Zhu X, Han L, et al. Cholesterol Metabolism-Mediated Immune Regulation and Cancer Immunotherapy[J]. Available at SSRN 4760648.
[4] Liang H, Shen X. LXR activation radiosensitizes non-small cell lung cancer by restricting myeloid-derived suppressor cells[J]. Biochemical and Biophysical Research Communications, 2020, 528(2): 330-335.
[5] Qiu W, Su W, Xu J, et al. Immunomodulatory‐Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy[J]. Advanced Healthcare Materials, 2022, 11(21): 2201233.