United Kingdom (UK)
Recombinant monoclonal antibody to PCSK9. Manufactured using AbAb’s Recombinant Platform with variable regions (i.e. specificity) from the human B cell clone mAb1.
UniProt Accession Number of Target Protein: Q8NBP7
Alternative Name(s) of Target: NARC1; NARC-1; PC9; Proprotein convertase subtilisin/kexin type; Neural apoptosis-regulated convertase 1; Proprotein convertase 9; Subtilisin/kexin-like protease PC9
Specificity: This antibody binds module 1 of the C-terminal domain (CTD) of PCSK9. It was reported to interact with amino acid residues R469, R496 and F515 of the human PCSK9. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease enzyme encoded by the PCSK9 gene in humans and it plays a role in regulation of circulating cholesterol. It is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of LDL (low-density lipoprotein) cholesterol. Autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease.
Application Notes: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. This antibody blocks access to an area bearing several naturally occurring gain-of-function and loss-of-function mutations. This antibody does not completely inhibit binding of PCSK9 to epidermal growth factor-like repeat A, it partially reverses PCSK9-induced reduction of the LDLR and LDL cholesterol uptake in a cellular assay. This antibody was also reported to be effective in lowering serum levels of LDL cholesterol in cynomolgus monkeys in vivo (PMID: 24252255).
Antibody first published in:
Schiele et al. An antibody against the C-terminal domain of PCSK9 lowers LDL cholesterol levels in vivo. J Mol Biol. 2014 Feb 20;426(4):843-52. PMID:24252255
Note on publication:
Describes the generation, structural and biophysical characterization and in vitro and in vivo pharmacology of an anti-PCSK9 antibody (mAb1).