hepatic gene

SBI993 is an analog of SBI-477 and can be used as a biomarker to confirm the expected action of MondoA target gene expression in vivo. SBI993 reduces muscle TAG levels and hepatic steatosis.

GSK4112 (SR6452) is a Rev-erbα agonist with EC50 of 0.4 μM, also is a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα.

Lumasiran (ALN-G01), a siRNA product, inhibits hepatic oxalate production by targeting glycolate oxidase. By silencing the gene encoding glycolate oxidase, Lumasiran depletes this enzyme and thereby prevents the synthesis of oxalate, the toxic metabolite directly linked to the clinical manifestations of Primary hyperoxaluria type 1 (PH1).

3,7-Dimethylfumarate (3,7-DMF) serves as an oral inhibitor of transforming growth factor-beta 1 (TGF-β1)-mediated hepatic stellate cell (HSC) activation. By inducing antioxidant gene expression and scavenging reactive oxygen species (ROS), 3,7-DMF is useful for researching liver fibrosis [1].

Givinostat (ITF-2357) is a HDAC inhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg/kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg/kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg/kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg/kg), there is a 22% reduction for 1 mg/kg and 40% for 5 mg/kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.

Hexafluoropropylene oxide dimer acid (HFPO-DA), a perfluoroalkyl ether carboxylic acid (PFECA), shows diverse biological impacts across species. At 250 µM, it triggers apoptosis and enhances reactive oxygen species (ROS) levels in HepG2 cells. In hatchling chickens, HFPO-DA at a dosage of 4 mg/kg per egg notably decreases right ventricular wall thickness, accelerates heart rate, and promotes hepatic lipid accumulation, though these effects are mitigable by silencing the Ppara gene. It significantly reduces zebrafish embryo survival (LC50 = 7,651 mg/L). Additionally, when administered to pregnant dams at 250 mg/kg, it results in reduced average birthweight, decreased survival time, and lowered serum glucose levels, alongside increased serum cholesterol and triglyceride levels in neonatal rats. HFPO-DA has also been identified as a contaminant in sea and river water.