lxrα

Compound 10, Aminooxy CatB-LXR, constitutes an agent-linker conjugate for antibody-drug conjugates (ADC) [1].

LXR antagonist 2 (compound 10rr) is a potent LXR (liver X receptor) inverse agonist, acting on LXRβ (IC50: 0.36 μM) and LXRα (IC50: 2.25 μM). LXR antagonist 2 is an adipogenesis inhibitor that downregulates LXR target genes SREBP-1c, ACC, FAS and SCD-1. LXR antagonist 2 exhibits hypolipidemic activity in Triton WR-1339-induced hyperlipidemic mice.

LXR-623 (WAY 252623) is an orally bioavailable and highly specifical synthetic modulator of LXR.

LXR (Liver X receptor) agonist 1 is a potent agonist of LXR, capable of acting on LXR-α (AC50: 1.5 nM) and LXR-β (AC50: 12 nM). LXR agonist 1 has shown research potential in atherosclerosis.

LXR agonist 2 is a potent agonist of the LXR (liver X receptor). LXR agonist 2 stabilises NCOA1 (coactivator), which in turn agonises the LXR.

LXRβ agonist-3 is a potent and selective LXRβ (liver X receptor β) agonist (EC50: 0.095 μM). LXRβ agonist-3 effectively inhibits U87EGFRvIII cells (IC50: 3.75 μM). .

GSK2033 is an antagonist of LXR (pIC50s: 7 and 7.4 for LXRα or LXRβ, respectively).

T0901317 is a potent and selective agonist for both LXR and FXR, with EC50 of ~50 nM and 5 μM, respectively; it inhibits nuclear factor κB (NF κB).

TUG-1375 is an Agonist of Thiazolidine Free Fatty Acid Receptor 2

GW3965 hydrochloride (GW3965 HCl) is an effective and specific LXR agonist for hLXRα/β (EC50: 190/30 nM).

Gymnestrogenin has a dual LXRα±/α2 antagonistic profile.

Bacterial type II fatty acid synthesis (FAS-II) is mediated by a series of enzymes, each of which may be targeted by potential antibiotics. Bischloroanthrabenzoxocinone (BABX) is an inhibitor of FAS-II, blocking fatty acid synthesis in S. aureus and E. coli with IC50 values of 11.4 and 35.3 μg/ml, respectively. It inhibits the growth of S. aureus and permeable E. coli strains with minimum inhibitory concentrations ranging from 0.2-0.4 μg/ml. BABX also displays binding to liver X receptors (LXRs), inhibiting agonist binding in an LXRα-scintillation proximity assay (IC50 = 10 μM).

IMB-808 is an effective partial dual agonist of liver X receptor α and β (LXRα/β) that promotes the expression of genes related to reverse cholesterol transport (including ABCA1 and ABCG1).

(20S)-Protopanaxatriol (g-PPT)(g-PPT), a metabolite of ginsenoside, could regulate endothelial cell functions through the estrogen receptor and glucocorticoid receptor.

GSK3987 is an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC50s of 40 nM.

AZ-2 is an inducer of ABCA1 and apoE. It enhances ABCA1 activity and decreases P2X7 receptor activity. AZ-2 activates endogenous LXR signaling but shows no direct LXRα or LXRβ agonist activity.

Dendrogenin A (DDA) is a compound acting as a selective liver X receptor (LXR) modulator, cholesterol epoxide hydrolase inhibitor (Ki = 120 nM), and a metabolic product of cholesterol, originating from 5,6α-epoxy cholesterol through histamine conjugation via DDA synthase. This compound is present in non-cancerous human mammary epithelial cells and melanocytes, but absent or minimally present in various breast carcinoma, melanoma cells, and isolated human breast tumor tissues. DDA impedes the activation of LXRβ and LXRα induced by 22(R)-hydroxy cholesterol (IC50s = 76 and 362 nM, respectively), yet it also functions as a partial LXR agonist, boosting the protein levels of Nur77, NOR-1, LC3-I, and LC3-II in B16/F10 murine melanoma cells. It shows a preference for LXRα and LXRβ modulation while displaying selectivity over other receptors including pregnane X receptor (PXR), and various others at a concentration of 2.5 µM. Moreover, DDA enhances LC3-II protein levels in cancer cells and prompts autophagic cell death at specific concentrations. Notably, DDA (0.37 µg/kg) has been shown to diminish tumor growth in melanoma and mammary cancer murine models and promotes cancer cell differentiation both in vitro and in vivo.

LXRβ agonist-2 is a highly potent and β-selective liver X receptor (LXRβ) agonist with EC50 of 7 nM.

Saikosaponin A has a variety of pharmacological benefits, including antiepileptic, anti-osteoporosis, antioxidant, anti-in ammatory, immunomodulatory, and anti-bacterial activities. It can effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38 MAPK and NF-κB signaling pathways in spinal cord. It can inhibit NMDA receptor current and persistent sodium current, and inhibit the TNF-α level, the IL-1β production, and cysteine-aspartic acid protease (caspase)-1 activity.

AZ-1 is an inducer of ABCA1 and apoE. It enhances ABCA1 activity and decreases P2X7 receptor activity. AZ-1 activates endogenous LXR signaling but shows no direct LXRα or LXRβ agonist activity.

CAY10771 is a dual agonist of farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor δ (PPARδ).1It activates FXR and PPARδ in reporter assays using HEK293T cells (EC50s = 0.94 and 1.5 μM, respectively) and is selective for these receptors over retinoic acid receptor α (RARα), retinoid X receptor α (RXRα), PPARα, PPARγ, and liver X receptor α (LXRα) at 10 μM. 1.Schierle, S., Neumann, S., Heitel, P., et al.Design and structural optimization of dual FXR/PPARδ activatorsJ. Med. Chem.63(15)8369-8379(2020)

22(S)-hydroxy Cholesterol is a synthetic oxysterol and a modulator of the liver X receptor (LXR). [1] t prevents monocyte chemoattractant protein 1 (MCP-1) expression induced by the LXR agonist GW 3965 in primary hepatocytes and downregulates mRNA expression of the LXR target genes CD36, ACSL1, and SCD-1 in human myotubes. It decreases triacylglycerol and diacylglycerol synthesis from labeled palmitate and acetate, respectively, in human myoblasts by 50% when used at a concentration of 10 uM. 22(S)-hydroxy Cholesterol also reduces fatty acid synthase (FAS) reporter activity through an LXR response element in the promoter region in COS-1 cells transfected with RXRα and LXRα and decreases the expression of MCP-1 and CCR2 in a mouse model of chronic ethanol consumption.[1] [2] Dietary supplementation of 22(S)-hydroxy cholesterol (30 mg/kg per day) leads to less body weight gain and lower liver triacylglycerol levels in rats when fed either a regular chow or high-fat diet as well as prevents an increase in plasma triacylglycerol levels resulting from a high-fat diet.[3]

6-Thioinosine (6TI) is a purine antimetabolite, acts as an anti-adipogenesis agent.

SR9238 is a synthetic agonist of liver X receptor inverse (IC50s: 214 nM and 43 nM for LXRα and LXRβ, respectively).

AZ876 is a potent, highly selective LXR agonist with Ki EC50 of 7 6 nM and 11 73 nM for hLXRα and hLXRβ respectively.

Ibrolipim (NO-1886) attenuates high glucose-induced endothelial dysfunction in cultured human umbilical vein endothelial cells via PI3K Akt pathway.

BE1218 is a liver X receptor (LXR) inverse agonist active on LXRα and LXRβ with an IC50 of 9 nM and 7 nM, respectively.

BMS-779788 (XL-652) is an LXRα/β partial agonist (IC50: 68/14 nM).