Survodutide TFA

• CAT Number: I040978
• Molecular Formula: C192H289N47O61.xC2HF3OC2
• Molecular Weight: 4231.62 (free base)
• Purity: ≥95%
• Target: Glucagon-Like Peptide 1 (GLP-1) Receptor

Survodutide (BI 456906) TFA is a potent, selective glucagon receptor/GLP-1 receptor (GCGR/GLP-1R) dual agonist with EC50s of 0.52 nM and 0.33 nM in CHO-K1 cells, respectively. Survodutide TFA, a 29-amino-acid peptide, is a potent acylated peptide containing a C18 fatty acid. Survodutide TFA has robust anti-obesity efficacy achieved by increasing energy expenditure and decreasing food intake[1].
The EC50 is 0.36 nM for Survodutide (BI 456906) TFA in the endogenous mouse GLP-1R in the insulinoma cell line MIN6, and the EC50 is 60 pM for GLP-1. In 0.5% human and mouse plasma, Survodutide TFA shows a similar potency to that of endogenous GLP-1. For the GCGR, in 0.5% human and mouse plasma, Survodutide TFA is 6-fold less potent (0.29 and 0.17 nM, respectively) in relation to endogenous glucagon (47 and 30 pM, respectively)[1].
Proteolytic stability of Survodutide TFA is helped by C-terminal amidation and the introduction of a non-coded amino acid 1-aminocyclobutane-1-carboxylic acid (Ac4c) in position 2, well established as the site of proteolytic activity for dipeptidyl peptidase-4. The desired extended terminal half-life of Survodutide TFA is achieved by the introduction of a glycine–serine linker in position 24, carrying a C18 di-acid[1].
Survodutide (BI 456906; 3, 10, 20, 30 nmol/kg; SC; daily; 30 days) TFA achieves a greater bodyweight-lowering efficacy in diet-induced obese mice compared with maximally effective doses of Semaglutide (HY-114118; 20, 100 nmol/kg). Survodutide TFA dose-dependently reduces plasma glucagon[1].
Survodutide (1, 3, 10, 30, 100 nmol/kg; SC; single dose) TFA dose-dependently reducesacute food intake in WT but not in GLP-1R KO mice (Three-week-old, male, lean NMRI outbred mice)[1].
Survodutide (1, 3, 10, 30, 100 nmol/kg; SC; single dose) TFA engages the glucagon receptor in vivo upon single dosing, increases liver nicotinamide N-methyltransferase mRNA, and reduces plasma serine and glutamine[1].
Survodutide (SC injection) TFA causes mean residence times of 44 and 140 h and Tmax values of 7 and 51 h obtained in mice and dogs, respectively[1].
Pharmacokinetic Parameters of Survodutide (BI 456906) in mice and dogs[1].

Mice (20 nmol/kg; SC)
Dogs (10 nmol/kg; SC)

Tmax (h)
7
50.7

Cmax (nM)
84.9
62.0

AUC0-∞ (nM∗h)
4640
9540

Reference

[1]. Tina Zimmermann, et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab. 2022 Dec:66:101633.
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