GLP1R
Glucagon-like peptide-1 receptor
Design a GLP1R agonist
GLP1R is the receptor for the gut hormone GLP-1, and a target of drugs such as semaglutide and tirzepatide, used to treat type 2 diabetes and obesity. It is a membrane receptor with seven transmembrane helices, and its extracellular side is a small domain of about 120 residues plus three loops. Where the first two challenges used soluble targets, this one uses the receptor itself, supplied in detergent. It adds no species or pH conditions, but it has two requirements: the design has to bind human GLP1R, and it has to activate it. A design must be an agonist, confirmed in a functional assay, to count.
Human GLP1R bound to GLP-1 · PDB 6X18
Target information
Design against the human receptor as supplied in detergent. We recommend targeting a functional epitope such as the peptide-binding groove of the extracellular domain.
Human GLP1R
Receptor in detergent- UniProt reference
- P43220-1 ↗
- Target residues · UniProt
- 24–432 / 409 aa
- Recommended epitope
- Peptide-binding groove of the extracellular domain
- Structure reference
- 6X18 · Chain R ↗
Amino acid sequence
RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSThe receptor is supplied in DDM and CHS detergent. Residues 24–432 cover the extracellular domain, the seven transmembrane helices and the first part of the intracellular tail.
The assay construct carries an N-terminal FLAG tag and a C-terminal polyhistidine tag, and the supplier states that it includes proprietary thermostabilising mutations without listing them. The sequence shown is the wild-type UniProt segment, so the construct may differ from it at some positions.
Activation is measured in a cell-based reporter assay on the confirmed binders. Human cells express GLP1R at their surface and carry a secreted alkaline phosphatase reporter under a cAMP response element. When a design activates the receptor, Gαs signalling raises cAMP and switches the reporter on, and the enzyme secreted into the culture medium is read as luminescence. Each design is compared with untreated cells and with a reference agonist, and a design that does not activate the receptor does not meet the second objective.
Two objectives
This challenge consists of 2 main objectives, and each will be accounted for when selecting the best designs.
01
Binding affinity
Design a binder against human GLP1R. We recommend targeting a functional epitope such as the peptide-binding groove of the extracellular domain, which is also where the hormone GLP-1 and the peptide agonists exendin-4 and semaglutide dock.
We'll measure its binding affinity using the human receptor, supplied in detergent.
02
Receptor activation
The binder has to be an agonist: it has to activate human GLP1R, not only bind it. A design that binds the receptor but does not activate it does not meet this objective.
Confirmed binders will be tested in a functional cell-based assay for activation of the receptor. Activation has to be confirmed there.
How designs are ranked
Every tested design is measured for binding to human GLP1R at pH 7.4, with the design immobilised and the receptor in solution. A design counts as binding when its sensorgram gives a fittable curve and a KD, or, where the curve cannot be fitted, when the association shift clears 300% over the negative control. Confirmed binders then go into the cell-based activation assay.
- 1
Affinity
Lowest KD against human GLP1R among all binders, agonist or not. Binding at the peptide groove counts in its favour. The recommended site is a hint, not a rule: a design that binds elsewhere is measured all the same.
- 2
Activation
Confirmed activation of human GLP1R in the reporter assay, ranked by activation relative to the reference agonist. A binder that does not activate the receptor does not count.
The winner has to meet both objectives: it binds human GLP1R and it activates the receptor. Among the confirmed agonists, the stronger activation wins, then the higher affinity, and each step also awards an honourable mention to the best design that did not win.
Which designs are tested is a separate step from who wins. Track 1 teams get their ranked designs tested; for Tracks 2 and 3, Claude selects from all submissions with a prompt we publish in full. Read the selection prompt
Timeline
Oct 12 – 25, 2026
- 1nowSubmit designs
Submissions open
Design, review, and submit. Submissions close Sunday, October 25 at 23:59 Anywhere on Earth (AoE).
- 2
Submissions closed
The window is closed. No further designs are accepted for this challenge.
- 3
Selection in progress
Anthropic and Adaptyv select designs for synthesis using a Claude-based workflow, published after the competition.
- 4
Wet-lab validation in progress
Selected designs go to Adaptyv's automated lab for experimental validation.
Submission requirements
- Length
- 10–250 amino acids
- Format
- Single chain protein, nanobody, scFv, or Fab
- Designs per participant
- Up to 40 for Track 1, up to 20 for Tracks 2 and 3
- Design
- De novo designs only