GLP4 Antibody

Definition and Mechanism of Action

GLP-1R antibodies are monoclonal or engineered antibodies designed to modulate GLP-1 receptor activity. These antibodies function as either antagonists (blocking receptor signaling) or agonists (activating receptor pathways), depending on therapeutic goals.

• Antagonists: Used to study GLP-1R's physiological roles or treat conditions like congenital hyperinsulinism by preventing hypoglycemia .

• Agonists: Mimic GLP-1's effects to enhance insulin secretion and promote weight loss .

Key structural features include:

• Fab-arm specificity: Enables high-affinity binding to extracellular GLP-1R domains .

• Cross-species reactivity: Some antibodies (e.g., Glp1R0017) target human, mouse, rat, and primate receptors .

Antagonistic Antibodies

Agonistic Antibodies

• In vivo antibody painting: A novel delivery method covalently links GLP-1 agonists to IgGs, extending half-life and efficacy in diabetic mice .

• TB59-2: Demonstrated comparable cAMP activation to native GLP-1, with a 2-day half-life in preclinical models .

Type 2 Diabetes and Obesity

• Glucose control: Antagonists like TB-222-023 improved glucose tolerance in hyperinsulinemic models .

• Weight loss: Agonist-linked antibodies reduced body weight in obese mice at lower doses than standard therapies .

Neurological and Cardiovascular Diseases

• GLP-1R antibodies show neuroprotective effects by reducing neuroinflammation and enhancing synaptic plasticity .

• Vascular benefits include improved endothelial function and reduced cardiovascular risk .

Oncology

• Preclinical studies suggest GLP-1R antibodies inhibit tumor growth (e.g., pancreatic, prostate) via PI3K/AKT pathway suppression .

Future Directions

• Bias signaling: Developing antibodies that selectively inhibit G protein vs. β-arrestin pathways to minimize side effects .

• Multispecific antibodies: Combining GLP-1R targeting with other metabolic receptors (e.g., GIPR) for enhanced efficacy .