LY3437943 sequence and receptor profile as described in the literature

Identity

LY3437943 is the development code assigned by the sponsor, Eli Lilly and Company, and it is the identifier used throughout this site. The compound is investigational and is not an approved medicine in the United States or anywhere else.

The full residue sequence, the positions of the non-natural residues and the attachment point of the side chain are given in the primary characterisation paper, Coskun et al., Cell Metabolism, 2022. They are deliberately not reproduced here. For material supplied by this company, the lot certificate of analysis is the document that identifies what is in the vial, by mass spectrometry against the expected mass; a sequence printed on a web page is not a substitute for it.

Molecular design as reported

The primary paper describes the molecule as a single peptide chain of 39 residues derived from the GIP sequence, carrying a C20 fatty diacid moiety attached through a linker, with aminoisobutyric acid substitutions at positions that would otherwise be susceptible to dipeptidyl peptidase-4. Those are the structural features that distinguish it from the native hormones; the exact positions are in the paper.

Receptor profile as reported

In cell-based assays reported in the primary paper, LY3437943 is described as an agonist at three receptors concurrently: the GIP receptor, the GLP-1 receptor and the glucagon receptor. GIP and GLP-1 are the incretin hormones; glucagon is not an incretin. The relative potency at each receptor is reported in that paper as EC50 values in receptor-expressing cell lines and is described there as the compound's balance across the three. The figures are not reproduced here, because the correct values are the ones in the primary source, read with its methods.

That three-receptor profile is what places the compound in the triple-hormone receptor agonist class, and what separates it from single-receptor GLP-1 analogues and from the dual GIP and GLP-1 receptor agonists.

Names in the literature

The compound is also referred to in the published literature as retatrutide, the name under which the later clinical papers are indexed. It appears on this page only so that a reader can locate those papers. The identifier used on this site is the development code.

Primary literature

Listed so a reader can go to the source. These papers describe the compounds as studied by others; they are not claims about any material sold here.

1. Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept Cell Metabolism, 2022
2. Urva S, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial The Lancet, 2022

Related

• LY3437943 research peptide, lyophilized
• Multi-Receptor Agonists in Laboratory Research: Dual and Triple Hormone Receptor Designs (GIP, GLP-1, and Glucagon)
• Differences between dual and triple hormone receptor agonist designs in published studies