Ecnoglutide

Product Name: Ecnoglutide

Form: Acetate salt

CAS No: 2459531-73-6

Molar Mass: 4284.76

Chemical Formula: C194H304N48O61

Synonyms: XW003, KM6YM7L8LH

Storage: Store at -20℃

Sequence: HVEGTFTSDVSSYLEEQAAREFIK-(AEEA-AEEA-{γ-Glu}-C18 diacid)-WLVRGRG

Target: GLP-1 RA

Application:

Ecnoglutide (CAS: 2459531-73-6) is a novel GLP-1 peptide analog developed with the aim of improving stability, efficacy, and manufacturing feasibility. Through modifications to the GLP-1 peptide, particularly acylation at lysine position 30, Ecnoglutide was chosen for further development due to its favorable properties. Unlike semaglutide, it encodes valine at position 8, promoting cAMP bias and simplifying manufacturing processes by allowing synthesis from recombinant DNA without chemical conjugation. In preclinical studies, Ecnoglutide demonstrated similar potency to semaglutide in inducing cAMP and β-arrestin recruitment but exhibited more bias towards cAMP signaling, potentially enhancing its efficacy. Ecnoglutide showed significantly higher efficacy compared to semaglutide in preclinical models, particularly in blood glucose control and weight loss. Phase 1 studies in healthy volunteers confirmed its safety and tolerability with once-weekly subcutaneous dosing, and its pharmacokinetics were similar to semaglutide. Notably, Ecnoglutide displayed improved stability in simulated gastrointestinal fluid, suggesting potential for oral formulation development. Overall, Ecnoglutide shows promise as a therapeutic option for type 2 diabetes mellitus (T2DM) and obesity, with ongoing clinical trials supporting its continued development and evaluation.

Current Research:

Ecnoglutide is a novel, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) developed for the treatment of type 2 diabetes (T2D) and obesity. Designed to activate cAMP signaling pathways while minimizing β-arrestin-mediated internalization and desensitization, it holds the potential to provide better glycemic control and weight loss compared to traditional GLP-1 RAs.

Mechanism of Action
Ecnoglutide works by binding to GLP-1 receptors, which leads to increased insulin secretion in response to meals, inhibition of glucagon release, and delayed gastric emptying. These combined actions contribute to enhanced blood glucose regulation and appetite suppression. Ecnoglutide’s selective activation of cAMP signaling pathways is hypothesized to provide a more favorable therapeutic profile, potentially reducing the side effects commonly seen with other GLP-1 RAs.

Clinical Research and Efficacy
In clinical trials, ecnoglutide has shown significant effectiveness in managing T2D. In a Phase 2 study, patients receiving weekly subcutaneous injections for 20 weeks saw an average reduction of 2.43% in HbA1c levels, with over 40% of participants experiencing a weight loss of at least 5%. The treatment was generally well-tolerated, with mild gastrointestinal symptoms being the most frequently reported adverse effects. Further studies have also demonstrated high efficacy, with a large percentage of patients achieving HbA1c levels below 5.7%.

Regulatory Status and Potential Applications
Ecnoglutide is currently under regulatory review, with promising clinical results supporting its potential as a long-term treatment option for T2D and obesity. Its long-acting formulation could improve patient compliance by reducing the frequency of injections, which is beneficial for chronic disease management.

In the field of pharmaceutical chemistry, ecnoglutide offers a new direction for developing treatments for metabolic disorders. Its advanced peptide structure and selective receptor activation could lead to more effective therapies. In organic and material chemistry, the development of novel drug delivery systems could enhance the bioavailability and stability of ecnoglutide, further boosting its therapeutic potential.

Conclusion
Ecnoglutide represents a significant advancement in the treatment of type 2 diabetes and obesity, demonstrating both efficacy and safety in clinical trials. Its innovative approach to GLP-1 receptor activation and its potential applications across pharmaceutical, organic, and material chemistry make it a key area of interest for ongoing research.

Reference:

Guo, W., Xu, Z., Zou, H., Li, F., Li, Y., Feng, J., ... & Pan, H. (2023). Discovery of ecnoglutide–A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. Molecular Metabolism, 75, 101762.

WANG, G., HU, W., QIN, H. H., ZHENG, Q., NING, J., MENGYING, G., … & JUNAIDI, M. K. (2023). 756-P: A Phase 1c Evaluation of a Novel GLP-1 Analog Ecnoglutide (XW003) for Weight Loss in Adults with Overweight and Obesity. Diabetes, 72(Supplement_1).