Encilitide 2407527-16-4

English synonyms :Encilitide

English synonyms:L-Proline, L-alanyl-3-[[1-oxo-6-(trimethylammonio)hexyl]amino]-D-alanyl-3-[[(2-hydroxyacetyl)amino]methyl]-L-phenylalanyl-1-[6-[[[4-(2-aminoethyl)phenyl]methyl](3-carboxy-1-oxopropyl)amino]hexyl]-5-fluoro-L-tryptophyl-(3S)-3-hydroxy-L-prolyl-L-threonyl-O-methyl-L-tyrosyl-2-methyl-, (4→1),(8→4)-dilac…

L-Proline, L-alanyl-3-[[1-oxo-6-(trimethylammonio)hexyl]amino]-D-alanyl-3-[[(2-hydroxyacetyl)amino]methyl]-L-phenylalanyl-1-[6-[[[4-(2-aminoethyl)phenyl]methyl](3-carboxy-1-oxopropyl)amino]hexyl]-5-fluoro-L-tryptophyl-(3S)-3-hydroxy-L-prolyl-L-threonyl-O-methyl-L-tyrosyl-2-methyl-, (4→1),(8→4)-dilactam, cyclic (3→5)-ether, chloride (1:1)

EnlicitideDecanoate (MK-0616)

Enlicitide chloride, Enlicitide,Enlicitide (MK-0616)

CAS number :2407527-16-4

Molecular formula : C₈₂H₁₁₀FN₁₄O₁₅

Molecular weight :1586.28

Properties: White to off-white

Content: ≥98%(HPLC) Professional scientific accurate detection

Function: Used in foreign trade export, scientific research and chemical reagents and other fields

Packing: 1MG 5MG 10MG 50MG 100MG 1G

Storage: Dry sealed with dark light -20℃ storage period of 1 years

Structural formula:

Intro

Enlicitide is the first approved oral PCSK9 inhibitor. It works by blocking the binding of PCSK9 protein to low-density lipoprotein receptors on the surface of liver cells, increasing the number of receptors available to clear low-density lipoprotein cholesterol (LDL-C) from the blood, thereby lowering LDL-C levels. The U.S. Food and Drug Administration (FDA) has approved enlicitide for the treatment of adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH), as an adjunct to diet and exercise.

Peculiarity

Enlicitide is a macrocyclic peptide PCSK9 inhibitor. Its molecule has been modified with multiple covalent bridge rings to form a highly rigid three-dimensional structure. This design enables it to resist degradation by gastrointestinal proteases after oral administration, thereby conferring oral bioavailability.

In terms of target selectivity, enlicitide binds to PCSK9 in the bloodstream and blocks its interaction with low-density lipoprotein receptors on the surface of liver cells. Its mechanism of action is consistent with that of injectable anti-PCSK9 monoclonal antibodies, but the route of administration is oral. Preclinical studies show that enlicitide was discovered from a precursor peptide screened by mRNA display technology, and was subsequently chemically optimized to form a stable cross-linked macrocyclic structure.

In direct comparisons with other oral non-statin lipid-lowering drugs, enlicitide has demonstrated significant advantages. A Phase III randomized trial showed that enlicitide reduced LDL-C by 64.6%, significantly superior to ezetimibe (27.8%), bempedoic acid (6.3%), and the combination of both (36.5%). In terms of adherence, the dosing regimen adherence rate in the enlicitide group in the CORALreef Lipids trial reached over 97%.

bioactivity

Enlicitide is an oral macrocyclic peptide PCSK9 inhibitor. Its core structure is a tricyclic peptide that has been modified with covalent bridge rings to form a highly rigid three-dimensional structure. Its mechanism of action involves binding to PCSK9 in the bloodstream and blocking its interaction with low-density lipoprotein receptors on the surface of liver cells. In vitro binding assays (TR-FRET) show that enlicitide has a pKi value of 11.3 for PCSK9 (Ki ≈ 5×10⁻¹² M), indicating extremely high binding affinity for PCSK9.

In vivo research

Enlicitide has demonstrated significant lipid-lowering efficacy in multiple clinical trials.

Animal model: Enlicitide has demonstrated significant lipid-lowering efficacy in multiple clinical trials.

Dosage: 20 mg once daily, orally

Administration: Oral tablet

Results: In the Phase III CORALreef Lipids trial, at Week 24, LDL-C in the enlicitide group decreased by an average of 57.1% from baseline, while the placebo group increased by 3.0%, with a between-group difference of −55.8 percentage points (P<0.001). Enlicitide also significantly reduced non-HDL-C, apolipoprotein B, and lipoprotein(a) levels (P<0.001). In the CORALreef AddOn trial, enlicitide reduced LDL-C by 64.6%, significantly superior to ezetimibe (27.8%) and bempedoic acid (6.3%).

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