ORFORGLIPRON
Orforglipron (development codes LY3502970 and OWL-833) is a synthetic, orally bioavailable, small-molecule non-peptide agonist of the glucagon-like peptide-1 receptor (GLP-1R). Unlike the injectable peptide GLP-1 receptor agonists, it is a fully synthetic small molecule rationally designed to overcome the poor oral bioavailability and rapid enzymatic degradation of peptide-based agonists. It is catalogued under CAS number 2212020-52-3 (free base), with a molecular formula of C₄₈H₄₈F₂N₁₀O₅ and a molecular weight of approximately 882.97 g/mol (PubChem CID 137319706).–
Orforglipron has been characterized extensively in cell-culture, animal, and clinical research. It is supplied here strictly as a research-use chemical for in vitro and laboratory investigation, and the research-grade material is distinct from any approved pharmaceutical product. Researchers should be aware that Orforglipron has advanced through late-stage clinical development and that its regulatory status is actively evolving; in some jurisdictions it may be treated as a controlled or restricted substance, and local regulations should be checked before acquisition or use.
Important note on the evidence base: Orforglipron is unusual among the compounds in this catalog in having a substantial clinical-trial record, including Phase 1 through Phase 3 studies in type 2 diabetes and obesity research populations. That clinical literature pertains to the compound as an investigational or approved pharmaceutical under controlled medical conditions; it does not transfer to, or constitute claims about, the research-use chemical supplied here. Researchers should treat the clinical record as scientific background and consult the primary literature in the References section.
Available Products
Mechanism of Action
The research literature on Orforglipron centers on its activity as a non-peptide GLP-1 receptor agonist and on the biased-signalling profile that distinguishes it from peptide agonists. The pathways below are drawn from structural, preclinical, and clinical pharmacology.
Non-peptide GLP-1 receptor agonism
Orforglipron binds and activates the GLP-1 receptor, a class B G-protein-coupled receptor expressed on pancreatic islet cells, in the gastrointestinal tract, and in the central nervous system. In cell assays it induces cAMP accumulation in cells expressing the human GLP-1 receptor with low-nanomolar potency, and it is selective for GLP-1R over the related class B receptors (the glucagon, GIP, and GLP-2 receptors). Activation of the receptor is associated, in the broader GLP-1 literature, with glucose-dependent insulin secretion, suppression of glucagon release, slowing of gastric emptying, and reduced appetite [1].
Biased signalling and partial agonism
A defining mechanistic feature reported for Orforglipron is that it is a partial agonist biased toward G-protein (cAMP) signalling over β-arrestin recruitment at the GLP-1 receptor. Structural work has shown that the small molecule engages a binding mode distinct from that of the endogenous peptide, stabilizing a receptor conformation that favours this biased output. Reduced β-arrestin recruitment is hypothesized in the literature to limit receptor desensitization, though the functional consequences of this bias remain an active research question [1].
Oral bioavailability by design
The principal rationale for Orforglipron’s development was to capture GLP-1-receptor pharmacology in an orally administered small molecule. Its structure supports once-daily oral exposure, and pharmacokinetic work reported that absorption was not meaningfully restricted by food or water intake — a contrast with the stringent fasting and dosing requirements of oral peptide GLP-1 formulations, and a property that makes it a notable tool compound for studying oral GLP-1-receptor engagement [2].
None of the mechanisms summarized here are presented as therapeutic claims for the research-use material supplied here.
Forms and Use in the Research Literature
The information below reflects how Orforglipron appears in the published literature. It is reported strictly for research-reference purposes and does not constitute administration recommendations of any kind.
Receptor and structural pharmacology. In vitro work characterized cAMP signalling, receptor selectivity, and the biased-agonism profile in GLP-1R-expressing cell systems, and structural studies resolved the binding mode of the small molecule at the receptor [1].
Preclinical models. Animal work, including studies in rodents expressing the human GLP-1 receptor and in non-human primates, examined glucose-lowering and food-intake endpoints, with receptor-knockout controls confirming that the glucose effects were GLP-1R-dependent [1].
Clinical research record. A Phase 1a single- and multiple-ascending-dose study in healthy participants characterized safety, tolerability, and pharmacokinetics supporting once-daily oral dosing [2], and subsequent Phase 2 and Phase 3 programs evaluated glycaemic and body-weight endpoints in type 2 diabetes and obesity research populations [3]. As noted above, this clinical record pertains to the compound under medical-trial conditions, not to research-use material.
Capsule format. This product is supplied by Captide Labs in capsule form, consistent with the brand’s capsule-first catalog. As an orally bioavailable small molecule, Orforglipron is inherently suited to a capsule format in research contexts, in contrast to the peptide compounds elsewhere in this catalog whose published work used parenteral routes.
Stability and storage. Orforglipron is supplied as a solid and is typically stored frozen, protected from light and moisture, with stock solutions prepared in an organic solvent such as DMSO, aliquoted, and frozen to avoid repeated freeze-thaw cycles. Each lot supplied by Captide Labs is accompanied by a batch-specific Certificate of Analysis documenting identity and purity by HPLC.
Adverse-event profile. In clinical research, Orforglipron’s adverse-event profile has been reported as broadly consistent with the GLP-1 receptor agonist class (predominantly gastrointestinal effects). This clinical safety information describes the compound under controlled medical-trial conditions and does not establish a safety profile for the research-use chemical or for any use outside those trials. The evolving regulatory status of the compound is relevant context for any research use.
References
- Kawai T, Sun B, Yoshino H, et al. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl Acad Sci U S A. 2020;117(47):29959–29967. doi:10.1073/pnas.2014879117 · PubMed: 33177239
- Pratt E, Ma X, Liu R, et al. Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1a, blinded, placebo-controlled, randomized, single- and multiple-ascending-dose study in healthy participants. Diabetes Obes Metab. 2023;25(9):2634–2641. doi:10.1111/dom.15184 · PubMed: 37272314
- Frias JP, Davies MJ, Rosenstock J, et al. Efficacy and safety of orforglipron in type 2 diabetes and obesity research populations (Phase 2 and Phase 3 program). Representative report: N Engl J Med. 2025. doi:10.1056/NEJMoa2505669 · PubMed: 40544435