orforglipron   Click here for help

GtoPdb Ligand ID: 12175

Synonyms: LY-3502970 | LY3502970 | OWL833
PDB Ligand
Compound class: Synthetic organic
Comment: Oforglipron (LY3502970) is an oral, nonpeptide glucagon-like peptide-1 receptor (GLP-1R) agonist that was developed as a potential antidiabetic medication [1-3]. It is a partial agonist (relative to native GLP-1), that biases GLP-1R signalling towards G protein activation and is devoid of β-arrestin recruitment activity.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

orforglipron is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 154.37
Molecular weight 882.38
XLogP 7.77
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=c1onc([nH]1)[C@@]1(C[C@@H]1C)n1c(cc2c1ccc(c2)[C@H]1CCOC(C1)(C)C)C(=O)N1CCc2c([C@@H]1C)c(n(n2)c1cc(C)c(c(c1)C)F)n1ccn(c1=O)c1ccc2c(c1F)cnn2C
Isomeric SMILES C[C@H]1C[C@]1(c1noc(=O)[nH]1)n1c2c(cc(cc2)[C@H]2CCOC(C2)(C)C)cc1C(=O)N1CCc2nn(c(c2[C@@H]1C)n1ccn(c1=O)c1c(c2c(cc1)n(nc2)C)F)c1cc(c(c(c1)C)F)C
InChI InChI=1S/C48H48F2N10O5/c1-25-18-32(19-26(2)40(25)49)60-42(58-16-15-57(46(58)63)37-11-10-36-33(41(37)50)24-51-55(36)7)39-28(4)56(14-12-34(39)53-60)43(61)38-21-31-20-29(30-13-17-64-47(5,6)23-30)8-9-35(31)59(38)48(22-27(48)3)44-52-45(62)65-54-44/h8-11,15-16,18-21,24,27-28,30H,12-14,17,22-23H2,1-7H3,(H,52,54,62)/t27-,28-,30-,48-/m0/s1
InChI Key USUWIEBBBWHKNI-KHIFEHGGSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Choe HJ, Cho YM. (2021)
Peptidyl and Non-Peptidyl Oral Glucagon-Like Peptide-1 Receptor Agonists.
Endocrinol Metab (Seoul), 36 (1): 22-29. [PMID:33677922]
2. Jeon E, Lee KY, Kim KK. (2023)
Approved Anti-Obesity Medications in 2022 KSSO Guidelines and the Promise of Phase 3 Clinical Trials: Anti-Obesity Drugs in the Sky and on the Horizon.
J Obes Metab Syndr, 32 (2): 106-120. [PMID:37349257]
3. Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA et al.. (2020)
Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.
Proc Natl Acad Sci U S A, 117 (47): 29959-29967. [PMID:33177239]
4. Pratt E, Ma X, Liu R, Robins D, Coskun T, Sloop KW, Haupt A, Benson C. (2023)
Orforglipron (LY3502970), a novel, oral non-peptide glucagon-like peptide-1 receptor agonist: A Phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes.
Diabetes Obes Metab, 25 (9): 2642-2649. [PMID:37264711]
5. Pratt E, Ma X, Liu R, Robins D, Haupt A, Coskun T, Sloop KW, Benson C. (2023)
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, 25 (9): 2634-2641. [PMID:37344954]
6. Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, Ma X, Mather KJ, Haupt A, Robins D et al.. (2023)
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity.
N Engl J Med, 389 (10): 877-888. [PMID:37351564]