| Description |
Frovocimab (LY 3015014) is a humanized IgG4 monoclonal antibody (mAb) that neutralizes PCSK9. Frovocimab inhibits PCSK9 binding to LDL receptor (LDLR) while permitting the normal proteolytic cleavage of the bound intact PCSK9[1].
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| Related Catalog |
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| In Vitro |
Frovocimab (LY 3015014) binds to intact but not truncated PCSK9. The selective binding of Frovocimab to intact PCSK9 is related to its binding epitope, the linear sequence of amino acids 160-181 of the catalytic domain of human PCSK9, which is absent in truncated PCSK9. Frovocimab inhibits PCSK9 binding to LDLR while permitting the normal proteolytic cleavage of the bound intact PCSK9. Additionally, upon cleavage, truncated inactive PCSK9 is released from Frovocimab[1].
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| In Vivo |
Frovocimab (LY 3015014; 10 mg/kg; i.v; once) causes significant PCSK9 accumulation, its duration of LDL lowering is reduced, and its clearance (CL) from serum is accelerated in mice expressing a noncleavable variant of human PCSK9[1]. Frovocimab (LY 3015014; 5 mg/kg; i.v; once) decreases LDL cholesterol in monkeys and, unlike other PCSK9 mAbs, does not cause an accumulation of intact PCSK9 in serum[1]. Animal Model: Male C57BL/6NTac mice injected with vector containing the NC R215A/R218A variant[1] Dosage: 10 mg/kg Administration: i.v; once Result: Caused significant PCSK9 accumulation. Animal Model: Cynomolgus monkeys[1] Dosage: 5 mg/kg Administration: i.v; once Result: Decreased LDL cholesterol in monkeys.
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| References |
[1]. Krista M Schroeder, et al. Proteolytic cleavage of antigen extends the durability of an anti-PCSK9 monoclonal antibody. J Lipid Res. 2015 Nov;56(11):2124-32.
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