Survodutide TFA  (Synonyms: BI 456906 TFA)

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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 T_max values of 7 and 51 h obtained in mice and dogs, respectively^[1].
Pharmacokinetic Parameters of Survodutide (BI 456906) in mice and dogs^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

4231.62 (free base)

C₁₉₂H₂₈₉N₄₇O₆₁.xC₂HF₃OC₂

Solid

White to off-white

H-{1-amino-1-cyclobutanecarboxylic acid}-QGTFTSDYSKYLDERAAKDFIK-{GGSGSG-γE-C18 di-acid)}-WLESA-NH2

Room temperature in continental US; may vary elsewhere.

Sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

• [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.  [Content Brief]