PCSK9 Inhibitor

PCSK9-IN-32 (compund 8) is a PCSK9[1:33]-GFP translation inhibitor.

R-IMPP hydrochloride (PF-00932239 hydrochloride) is a PCSK9 translation inhibitor and a selective 80S ribosome binder. R-IMPP hydrochloride inhibits the KRAS/MEK/ERK signaling cascade. R-IMPP hydrochloride reduces LPS-induced nuclear translocation of NFkB P65. R-IMPP hydrochloride increases LDL-R levels in cells, promotes LDL-C uptake, and does not alter the secretion of transferrin or albumin. R-IMPP hydrochloride inhibits the growth of colorectal cancer (CRC) cells, organoids and xenografts carrying APC/KRAS mutations, as well as the number and burden of spontaneous mouse tumors. R-IMPP hydrochloride can be used in research related to colorectal cancer with APC/KRAS mutations, hepatic ischemia-reperfusion injury and hypercholesterolemia.

BRD8518 is a PCSK9 inhibitor (EC₅₀=0.23 μM). BRD8518 lowers blood lipids by upregulating LDLR expression and stimulating LDL uptake. BRD8518 can be used in the study of cardiovascular diseases.

Obicetrapib hemicalcium (TA-8995 hemicalcium) is an orally active cholesteryl ester transfer protein (CETP) inhibitor. Obicetrapib hemicalcium shifts the plasma lipoprotein profile toward more HDL-C particles, reduces circulating PCSK9 levels, increases hepatic LDLR expression and LDLR mRNA levels, and promotes hepatic clearance of VLDL remnants. Obicetrapib hemicalcium increases the number of large HDL particles, reduces the number and area of atherosclerotic lesions and alleviates lesion severity, increases the proportion of unaffected arterial segments, improves lesion stability, and promotes regression of aortic root lesions. Obicetrapib hemicalcium also exerts a synergistic effect with Ezetimibe (HY-17376) to reduce non-HDL-C levels and improve atherosclerosis. Obicetrapib hemicalcium can be used in studies related to atherosclerosis and dyslipidemia.

Dim16 hydrochloride is a dual PCSK9 inhibitor and HMG-CoAR inhibitor, with an IC₅₀ of 0.8 nM against human PCSK9 and an IC₅₀ of 146.8 μM against HMG-CoAR. Dim16 hydrochloride disrupts the PCSK9-LDLR protein-protein interaction, inhibits the catalytic activity of HMG-CoAR, enhances cellular uptake of extracellular LDL, and suppresses PCSK9-induced platelet aggregation. Dim16 hydrochloride can be used in research related to hypercholesterolemia.