Cat. No.
MABL-2623
Application
antagonist, functional assay, therapeutic, Block, ELISA
Isotype
Engineer antibody
Species Reactivity
cynomolgus monkeys, Rat, Human, Rhesus Monkey, Mouse
Clone No.
508.20.33b (Fab33)
From
Recombinant Antibody
Specificity
This antibody binds 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.
Alternative Names
NARC1; NARC-1; PC9; Proprotein convertase subtilisin/kexin type; Neural apoptosis-regulated convertase 1; Proprotein convertase 9; Subtilisin/kexin-like protease PC9
UniProt
Q8NBP7
Immunogen
The original antibody was isolated from a phage display library by panning against biotinylated human PCSK9.
Application Notes
The binding affinity of this antibody towards PCSK9 protein from human, murine, rhesus, and cynomolgus monkey was done using surface plasmon resonance. This antibody was found to inhibit binding of PCSK9 to LDLR in a competition binding ELISA. This antibody plays a role in effective prevention of LDLR downregulation in HepG2 cells in vitro. When administered in vivo, this antibody prevented LDLR downregulation in mouse liver. This antibody showed a reduction in total serum cholesterol levels in mice when a single dose of 10 mg/kg was administered. It was also found that a combination of this antibody and statin results in a greater reduction in total cholesterol level compared to anti-PCSK9 antibody alone or statin alone treatments (US9266961). A randomized, double-blind, placebo-controlled, single and multiple dose study was conducted to evaluate, primarily, the safety and tolerability of single and multiple (four weekly) doses of reformatted IgG1 version of this antibody when administered by subcutaneous (SC) injection to healthy volunteers with elevated serum low-density lipoprotein cholesterol (LDL-c)concentration. It was found that there were no serious or severe adverse events, no discontinuations for adverse events, and no dose-limiting toxicities (US9266961).
Antibody First Published
Zhang et al. Discovery of a cryptic peptide-binding site on PCSK9 and design of antagonists. Nat Struct Mol Biol. 2017 Oct;24(10):848-856. PMID:28825733
Note on publication
Describes the generation of antagonistic antibodies that encroach on the EGF(A)- binding site and inhibit LDLR binding.
Size
100 μg Purified antibody.
Concentration
1 mg/ml.
Purification
Protein A affinity purified
Buffer
PBS with 0.02% Proclin 300.
Storage Recommendation
Store at 4⁰C for up to 3 months. For longer storage, aliquot and store at - 20⁰C.
