ANGPTL3 Antibodies

Background

ANGPTL3 is a secretory glycoprotein mainly synthesized in the liver and serves as a key member of the angiopoietin-like protein family. The protein encoded by this gene directly participates in lipid metabolism regulation by inhibiting the activities of lipoprotein lipase (LPL) and endodermal lipase (EL), and affects the levels of triglycerides and cholesterol in plasma. Its loin-function mutation is associated with familial combined hypolipidemia. This discovery has prompted the development of monoclonal antibody drugs targeting ANGPTL3, such as evinacumab, for the treatment of refractory hypercholesterolemia. Due to its core position in metabolic regulation, ANGPTL3 has become an important target for the development of cardiovascular disease drugs, and related research continues to deepen the understanding of lipid metabolism networks.

Structure Function Application Advantage Our Products

Structure of ANGPTL3

ANGPTL3 is a secretory glycoprotein with a molecular weight of approximately 50-55 kDa, and its precise molecular weight varies depending on the degree of glycosylation modification.

Species	Human	Mouse	Rhesus monkey
Molecular Weight (kDa)	~52	~50	~53
Primary Structural Differences	Contains N end coiled coil and fibrous protein C end the same domains	High homology with human and conserved key functional domains	Highly similar to human sequences, it is often used in preclinical research

This protein is composed of 460 amino acids, and its primary structure can be divided into two key functional domains: the coiled helical domain at the N-terminal is responsible for oligomerization and inhibits the activity of lipoprotein lipase (LPL); The fibrin-like domain at the C-terminal is related to the function of inhibiting endrodermal lipase (EL). Its secondary structure is mainly α -helical, which is crucial for the formation of stable homologous oligomers. In the spatial conformation, the two domains act together to achieve a synergistic inhibition of key lipid metabolism enzymes through reversible steric hindrance effects.

Fig. 1 The structural features of ANGPTL3 protein.¹

Key structural properties of ANGPTL3:

Unique dual-domain architecture
Oligomerization-dependent functional regulation
Isolation of key functional sites

Functions of ANGPTL3

The core function of the protein encoded by the ANGPTL3 gene is to regulate lipid metabolism, and it is also involved in multiple metabolism-related physiological processes.

Function	Description
Lipoprotein lipase inhibition	Through N-terminal domain structure are activated to restrain activity of lipoprotein lipase (LPL), slow down the hydrolysis of triglycerides (TG) in plasma and cleared, is its main function.
Inhibition of endothelial lipase	Inhibiting the activity of endoderma lipase (EL) through the C-terminal domain affects the metabolism and remodeling of high-density lipoprotein (HDL).
Dual lipase synergistic regulation	By simultaneously inhibiting LPL and EL, it achieves dual regulation of triglyceride and cholesterol metabolism, which is the key to its becoming a popular drug target.
Phenotypic association of hypolipidemia	Loss-of-function mutations cause familial combined hypolipidemia, which is characterized by a global reduction in plasma levels of TG, LDL-C, and HDL-C.
Potential energy steady-state effect	Research has found that it may exceed lipid metabolism and be involved in the regulation of overall energy homeostasis, but the specific mechanism is still under in-depth exploration.

Unlike single-acting lipid metabolism factors, ANGPTL3, through its unique dual-domain architecture, synergistically regulates the levels of multiple lipoproteins in plasma in a "one cause, multiple effects" manner. This characteristic has made it highly regarded in the development of drugs for metabolic diseases.

Applications of ANGPTL3 and ANGPTL3 Antibody in Literature

1. Kersten, Sander. "ANGPTL3 as therapeutic target." Current opinion in lipidology 32.6 (2021): 335-341. https://doi.org/10.1097/MOL.0000000000000789

The article indicates that ANGPTL3 is a new target for lipid-lowering treatment. Inactivated mutations can lower cholesterol and triglycerides and reduce cardiovascular risk. Inhibiting its function through monoclonal antibodies or antisense oligonucleotides can effectively lower blood lipid levels and provide a new therapy for patients with abnormal lipid metabolism.

2. Watts, Gerald F., et al. "RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts." Nature Medicine 29.9 (2023): 2216-2223. https://doi.org/10.1038/s41591-023-02494-2

The article indicates that the RNAi therapy ARO-ANG3, by targeting ANGPTL3, has demonstrated good safety in early clinical trials and can effectively reduce triglycerides and non-high-density lipoprotein cholesterol in healthy subjects, confirming its potential as a new target for cardiovascular disease treatment.

3. Sosnowska, Bożena, et al. "Evinacumab, an ANGPTL3 inhibitor, in the treatment of dyslipidemia." Journal of Clinical Medicine 12.1 (2022): 168. https://doi.org/10.3390/jcm12010168

The article indicates that the ANGPTL3 inhibitor Evinacumab (Evkeeza®) can provide effective treatment for patients with homozygous familial hypercholesterolemia, significantly reducing LDL-C and triglyceride levels, and is an important new option in lipid-lowering therapy.

4. Yang, Longyan, et al. "ANGPTL3 is a novel HDL component that regulates HDL function." Journal of Translational Medicine 22.1 (2024): 263. https://doi.org/10.1186/s12967-024-05032-x

Research has found that ANGPTL3 is a component of high-density lipoprotein (HDL). In the diabetes model, the level of ANGPTL3 in HDL decreases, leading to impaired cholesterol excretion and anti-inflammatory function of HDL, indicating that it affects function by regulating the protein composition of HDL.

5. Chen, Pei-Yi, et al. "Angiopoietin-like protein 3 (ANGPTL3) modulates lipoprotein metabolism and dyslipidemia." International journal of molecular sciences 22.14 (2021): 7310. https://doi.org/10.3390/ijms22147310

Research has found that ANGPTL3 is a key regulatory factor for lipid metabolism secreted by the liver. Inhibiting its function can significantly lower triglyceride and low-density lipoprotein cholesterol levels, thereby reducing the risk of cardiovascular diseases, and has become a new target for lipid-lowering therapy.

Creative Biolabs: ANGPTL3 Antibodies for Research

Creative Biolabs specializes in the production of high-quality myoglobin antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom Myoglobin Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our ANGPTL3 antibodies, custom preparations, or technical support, contact us at email.

Reference

Chen, Pei-Yi, et al. "Angiopoietin-like protein 3 (ANGPTL3) modulates lipoprotein metabolism and dyslipidemia." International journal of molecular sciences 22.14 (2021): 7310. https://doi.org/10.3390/ijms22147310