Repositioning Candidate Details
| Candidate ID: | R1559 |
| Source ID: | DB15354 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Evinacumab |
| Synonyms: | Evinacumab; evinacumab-dgnb |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Evinacumab is a recombinant human IgG4 monoclonal antibody targeted against angiopoietin-like protein 3 (ANGPTL3) and the first drug of its kind. The ANGPTL family of proteins serve a number of physiologic functions - including involvement in the regulation of lipid metabolism - which have made them desirable therapeutic targets in recent years. Loss-of-function mutations in _ANGPTL3_ have been noted to result in hypolipidemia and subsequent reductions in cardiovascular risk, whereas increases in function appear to be associated with cardiovascular risk, and it was these observations that provided a rationale for the development of a therapy targeted against ANGPTL3. In February 2021, evinacumab became the first-and-only inhibitor of ANGPTL3 to receive FDA approval after it was granted approval for the adjunctive treatment of homozygous familial hypercholesterolemia (HoFH) under the brand name "Evkeeza". Evinacumab is novel in its mechanism of action compared with other lipid-lowering therapies and therefore provides a unique and synergistic therapeutic option in the treatment of HoFH. |
| CAS Number: | 1446419-85-7 |
| Molecular Weight: | |
| DrugBank Indication: | Evinacumab is indicated, as an adjunct with other lipid-lowering therapies, for the treatment of familial homozygous hypercholesterolemia (HoFH) in patients 12 years of age and older. |
| DrugBank Pharmacology: | Evinacumab exerts its hypolipidemic and antiatherogenic effects via decreasing circulating levels of triglycerides, HDL-C, and LDL-C, apolipoprotein B, and total cholesterol. It is has a relatively long duration of action that allows for its administration via intravenous injection once-monthly. Animal studies have demonstrated embryo-fetal toxicity - administration to pregnant rabbits during organogenesis resulted in increases in fetal malformations at concentrations lower than those used in humans. For this reason, patients receiving therapy with evinacumab should obtain a pregnancy test prior to beginning therapy and use effective contraception throughout the duration of therapy and for 5 months following the administration of the last dose. |
| DrugBank MoA: | Angiopoetin-like proteins (ANGPTL) are a diverse group of proteins involved in a number of physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in _ANGPTL3_ and _ANGPTL4_ have been shown to result in hypolipidemia and a reduced risk of coronary artery disease, while increased levels of these proteins appear to be associated with cardiovascular risk. While these observations have made ANGPTLs as a class a desirable target in the treatment of hyperlipidemic disorders, ANGPTL3 is the first to be pharmacologically targeted for the purposes of lipid-lowering therapy. ANGPTL3 is expressed primarily in the liver and acts as an endogenous inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL) which are responsible, in part, for metabolizing triglycerides (TG) and HDL-C, respectively. Evinacumab is monoclonal antibody that binds to and inhibits ANGPTL3, with the resulting disinhibition of LPL and EL reducing the levels of circulating TG and HDL-C. While the mechanism through which evinacumab reduces LDL-C is not entirely clear, this effect is independent of LDL receptor density and is therefore most likely due to the promotion of VLDL processing and upstream clearance of LDL formation. |
| Targets: | Angiopoietin-related protein 3 inhibitor&binder&antibody |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|