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SAR441255

Molecular wt
4866.56
Compound class
Synthetic unimolecular GLP-1/GIP/GCG receptor triagonist peptide
SAR441255, a triple GLP-1/GIP/glucagon receptor agonist peptide, research use only
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SAR441255

SAR441255 is a 39-residue synthetic peptide on the exendin-4 scaffold with balanced agonism at the GLP-1, GIP and glucagon receptors. One of very few triagonists with published human target-engagement data.

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Description

SAR441255 is a 39-residue synthetic peptide with a C-terminal amide, built on the exendin-4 scaffold rather than on native GLP-1 or glucagon. It is a balanced triple agonist at the GLP-1, GIP and glucagon receptors, which distinguishes it from the dual GLP-1/glucagon agonists that dominate the class.

The exendin-4 chassis carries a C-terminal extension that folds back to cage Trp25, giving the peptide greater helicity and metabolic stability than the native hormones it mimics. Fifteen positions were edited onto that scaffold to tune receptor balance.

Sanofi discontinued the programme in the third quarter of 2019, roughly four months after its Phase 1 trial began, then published the full clinical and translational dataset in Cell Metabolism in January 2022: in vitro pharmacology, a 42-day non-human primate study, PET receptor occupancy imaging and first-in-human results. That makes SAR441255 one of very few triagonists with published human target-engagement data, and it has continued to appear in academic imaging work since.

Supplied as a reference standard for laboratory research use only. Composition and identity are stated on the batch-specific COA for the lot supplied.

Compound Class Synthetic unimolecular GLP-1/GIP/GCG receptor triagonist peptide
IUPAC Name (2S)-5-[[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[[1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2R)-1-[[2-[(2S)-2-[(2S)-2-[[(2S)-1-[[1-[[(2S)-6-amino-1-[(2S)-2-[(2S)-2-[(2S)-2-[[(2S)-1,6-diamino-1-oxohexan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-5-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-2-methylpropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-6-oxohexyl]amino]-2-[[(4S)-4-carboxy-4-(hexadecanoylamino)butanoyl]amino]-5-oxopentanoic acid
Molecular Formula C₂₂₅H₃₅₅N₅₇O₆₃
Molecular Weight 4866.56
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