PCSK9 Monoclonal Antibody (Evolocumab)

Proprotein convertase subtilisin kexin 9 (PCSK9) is a zymogen and member of the subtilisin serine protease family that reduces protein levels of LDL receptors (LDLRs), the receptor for LDL-cholesterol (LDL-C).^1,2 It is primarily expressed in the liver and is composed of an N-terminal prodomain that regulates PCSK9 maturation, a catalytic domain containing a catalytic aspartic acid-histidine-serine triad, and a C-terminal domain that contains the LDLR binding site.^2,3,4 PCSK9 is synthesized as a proprotein that is autocatalytically cleaved to generate the 63 kDa mature protein in which the N-terminal prodomain remains non-covalently bound to the catalytic domain to inhibit further activity.⁴ The mature PCSK9 is secreted and circulates in the plasma, where it binds to cell surface-expressed LDLRs, triggering endocytosis and lysosomal degradation of the PCSK9-LDLR complex.² This action decreases LDLR expression and reduces cellular LDL-C uptake. Gain-of-function and loss-of-function PCSK9 mutations have been associated with autosomal dominant hypercholesterolemia and decreased plasma LDL-C levels, respectively, in humans.² Formulations containing monoclonal antibodies targeting PCSK9 have been used in the treatment of hyperlipidemia, familial hypercholesterolemia, and cardiovascular disease. Cayman's PCSK9 Monoclonal Antibody (Evolocumab) was produced recombinantly from the original PCSK9 antibody sequence and can be used for ELISA and surface plasmon resonance (SPR) applications.

WARNING This product is not for human or veterinary use.

1. Maxwell, K.N., Fisher, E.A., and Breslow, J.L. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc. Natl. Acad. Sci. USA 102(6), 2069-2074 (2005).

2. Schulz, R., Schlüter, K.-D., and Laufs, U. Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9). Basic Res. Cardiol. 110(2), 4 (2015).

3. Seidah, N.G., Benjannet, S., Wickham, L., et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. USA 100(3), 928-933 (2003).

4. Burke, A.C., Dron, J.S., Hegele, R.A., et al. PCSK9: Regulation and target for drug development for dyslipidemia. Annu. Rev. Pharmacol. Toxicol. 57, 223-244 (2017).