Ecnoglutide

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Cat Number

API0233394

CAS Number

2459531-73-6

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CAS Number

2459531-73-6

Synonyms

Ecnoglutide [INN], UNII-KM6YM7L8LH, KM6YM7L8LH

Molecular Formula

C194H304N48O61

Molecular Weight

4285

Smiles

CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC6=CNC=N6)N

General Description

Ecnoglutide is a novel, long-acting glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes and obesity. It is a synthetic peptide analog composed entirely of natural amino acids, which simplifies its manufacturing process.

Mechanism of Action

Ecnoglutide is a "biased" GLP-1 receptor agonist that selectively and potently activates the cyclic adenosine monophosphate (cAMP) signaling pathway while minimizing β-arrestin recruitment and subsequent receptor internalization. This preferential activation of cAMP over receptor desensitization is thought to enhance insulin secretion, improve glycemic control, and promote weight loss.

Application

Ecnoglutide is indicated to improve glycemic control in adults with type 2 diabetes and for chronic weight management in individuals with obesity or overweight with comorbidities.

Guo W, et al. described the discovery and characterization of ecnoglutide (XW003), a novel GLP-1 analog engineered with specific modifications including an Ala8Val substitution and a fatty acid side chain. In vitro, ecnoglutide potently induced cAMP signaling (EC₅₀ = 0.018 nM) without promoting GLP-1 receptor internalization (EC₅₀ > 10 μM), indicating a favorable signaling bias. In rodent models, ecnoglutide significantly reduced blood glucose, promoted insulin secretion, and produced greater body weight reduction compared to semaglutide. A phase 1 trial in healthy participants demonstrated favorable safety, tolerability, and pharmacokinetics, with a half-life of 124–138 hours supporting once-weekly dosing.

Fig. 1 Gastrointestinal stability of ecnoglutide. (Guo W, et al., 2023)

References

Guo W, et al. Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. Mol Metab. 2023;75:101762.

Zhu D, et al. randomized 211 Chinese adults with type 2 diabetes inadequately controlled with diet and exercise or single oral hypoglycemic agents to receive once-weekly ecnoglutide (0.6 mg or 1.2 mg) or placebo for 24 weeks. At week 24, least squares mean HbA1c reductions were –1.96% with ecnoglutide 0.6 mg and –2.43% with ecnoglutide 1.2 mg versus –0.87% with placebo, with estimated treatment differences of –1.09% and –1.56%, respectively (both P < 0.001).

Fig. 2 Efficacy outcomes of 0.6 mg and 1.2 mg ecnoglutide once weekly versus placebo at weeks 24 and 52. (Zhu D, et al, 2026)

References

Zhu D, et al. Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a multi-centre, randomised, double-blind, placebo-controlled, phase 3 trial. Nat Commun. 2026;17(1):1420.

Does Ecnoglutide require strict cold chain storage as a GLP-1 analog?

Yes, as a peptide, it is thermally labile. It must be stored and shipped at 2-8°C. We use validated cold chain packaging with continuous temperature monitoring for every shipment.

Is Ecnoglutide prone to aggregation during freeze-thaw cycles?

Absolutely. Freeze-thaw cycling can cause aggregation and loss of biological activity. Consistent refrigerated storage without fluctuation is essential for stability.

What is the stability of Ecnoglutide after reconstitution for injection?

Once formulated, it has limited stability. We provide detailed stability data for in-use conditions, including recommended storage durations after first puncture.

How is the purity of Ecnoglutide confirmed given its peptide nature?

We use a combination of reverse-phase HPLC for chemical purity, SEC-HPLC for aggregate content, and mass spectrometry for identity confirmation.