LBA-3 is a selective, orally active inhibitor for sodium-coupled citrate transporter SLC13A5, with an IC50 of 67 nM. LBA-3 decreases levels of triglyceride and total cholesterol in oleic and palmitic acid (OPA)-stimulated AML12 cells, PCN-stimulated primary mouse hepatocytes and in mouse models, without detectable toxicity. LBA-3 is blood-brain barrier permeable[1].
in vivo
LBA-3 (50 mg/kg, po, single dose) exhibits a pharmacokinetic profil in Sprague Dawley rats, with peak plasma concentration Cmax of 288?262.00 μg/L, AUC of 704?570.43 h/μg–1·L and an oral bioavailability of 48.67%[1].
References
[1] Zhang L, et al., Discovery of Highly Potent Solute Carrier 13 Member 5 (SLC13A5) Inhibitors for the Treatment of Hyperlipidemia. J Med Chem. 2024 Apr 25;67(8):6687-6704. DOI:10.1021/acs.jmedchem.4c00260
