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Context, anatomy, and key evidence

← Peptide library

oral GLP-1 small molecule

Danuglipron

Published evidence · coverage incomplete
Anatomical contextAnatomy connections are not mapped yet.

No body region is highlighted until this profile has a supported anatomical connection. This does not mean the peptide has no biological effects.

Read published mechanism findings ↓

At a glance

What is it—and why does it matter?

Danuglipron (PF-06882961) is an orally active, non-peptide small-molecule agonist of the GLP-1 receptor in humans (and monkeys). CHEMBL4518483 bound to FAP-tagged human GLP-1R in a CHO-cell radioligand binding assay with Ki = 80.0 nM (displacing [3H]PF-06883365). In CHO-K1 cells expressing human GLP-1R, danuglipron functioned as a receptor agonist measured via cAMP accumulation; the reported potency was EC50 = 0.71 nM under BETP-sensitized conditions. This organism-based PK result reports oral bioavailability (F) in ICR mice after 5 mg/kg oral dosing of danuglipron, indicating the proportion of exposure relative to an IV reference as defined by the assay.

Sources for this introduction: [1] [2] [3] [4]

This published profile is a reference in progress. Findings retain their source context; missing topics are marked below.

What is it?

A molecule, not a product name.

Identity

Danuglipron is described as an oral small-molecule agonist of the GLP-1 receptor (a non-peptide GLP-1RA).

Sources[3]pubmedNovel GLP-1-based Medications for Type 2 Diabetes and Obesity.the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron”

    Novel GLP-1-based Medications for Type 2 Diabetes and Obesity. · Abstract

    pubmed:41054801:93c84d0dbf77:93c84d0dbf77

Identity

Danuglipron (PF-06882961) is an orally active, non-peptide small-molecule agonist of the GLP-1 receptor in humans (and monkeys).

Sources[2]iuphar-commentsIUPHAR ligand commentaryDanuglipron (PF-06882961) is a small molecule, non-peptide, orally active agonist of the human (and monkey) glucagon-like peptide-1 receptor (GLP-1R) [Reference 41855] [Reference 43828].
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Danuglipron (PF-06882961) is a small molecule, non-peptide, orally active agonist of the human (and monkey) glucagon-like peptide-1 receptor (GLP-1R) [Reference 41855] [Reference 43828].”

    IUPHAR ligand commentary · General comments

    iuphar-comments:12064:c087bf40bde6:c087bf40bde6

How does it work?

Target, response, and disposition.

Mechanism

In a CHO-K1 cell assay, CHEMBL4518483 activated human GLP-1R (cAMP accumulation) with EC50 = 1.1 nM (30 mins, without BETP).

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Agonist activity at human GLP-1R expressed in CHO-K1 cells assessed as cAMP accumulation incubated for 30 mins in absence of BETP by plate reader method Assay format: cell-based format Standard result: EC50 = 1.1 nM
Reported result
EC50 = 1.1 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Agonist activity at human GLP-1R expressed in CHO-K1 cells assessed as cAMP accumulation incubated for 30 mins in absence of BETP by plate reader method Assay format: cell-based format Standard result: EC50 = 1.1 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929055

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Mechanism

CHEMBL4518483 bound to FAP-tagged human GLP-1R in a CHO-cell radioligand binding assay with Ki = 80.0 nM (displacing [3H]PF-06883365).

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Displacement of [3H]PF-06883365 from FAP-tagged human GLP-1R expressed in CHO cells assessed as inhibition constant by radioligand binding assay Assay format: cell-based format Standard result: Ki = 80.0 nM
Reported result
Ki = 80.0 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Displacement of [3H]PF-06883365 from FAP-tagged human GLP-1R expressed in CHO cells assessed as inhibition constant by radioligand binding assay Assay format: cell-based format Standard result: Ki = 80.0 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929140

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Pharmacokinetics

This organism-based PK measurement reports systemic exposure after oral dosing in Wistar Han rats; the peak concentration (Cmax) for danuglipron at 100 mg/kg was 5075.5 nM over a sampling window up to 24 hrs.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Cmax in Wistar Han rat at 100 mg/kg, po measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: Cmax = 5075.5 nM[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Cmax in Wistar Han rat at 100 mg/kg, po measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: Cmax = 5075.5 nM
Reported result
Cmax = 5075.5 nM
Source records
2
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Cmax in Wistar Han rat at 100 mg/kg, po measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: Cmax = 5075.5 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929045

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6
  2. supports · Source-backed record
    “Assay: Cmax in Wistar Han rat at 100 mg/kg, po measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: Cmax = 5075.5 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929045

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Pharmacokinetics

Bioavailability (F) is an animal estimate under the stated conditions; it may vary with formulation and study design details not given here.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Oral bioavailability in cynomologus monkey at 5 mg/kg measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: F = 5.0 %
Reported result
F = 5.0 %
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Oral bioavailability in cynomologus monkey at 5 mg/kg measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: F = 5.0 %”

    ChEMBL activities for CHEMBL4518483 · Activity 24929175

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Pharmacokinetics

In human Caco-2 cells at 10 uM, CHEMBL4518483 had apical-to-basolateral permeability of 3.93 10^-6 cm/s after 120 mins.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Permeability across apical to basolateral in human Caco-2 cells at 10 uM incubated for 120 mins by LC-MS/MS analysis Assay format: cell-based format Standard result: permeability = 3.93 10^-6 cm/s
Reported result
permeability = 3.93 10^-6 cm/s
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Permeability across apical to basolateral in human Caco-2 cells at 10 uM incubated for 120 mins by LC-MS/MS analysis Assay format: cell-based format Standard result: permeability = 3.93 10^-6 cm/s”

    ChEMBL activities for CHEMBL4518483 · Activity 26030363

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Pharmacokinetics

AUC(0 to infinity) summarizes overall systemic exposure; in Sprague-Dawley rats given danuglipron orally at 5 mg/kg, AUC (0 to infinity) was 654.59 ng.hr.mL-1 over sampling up to 24 hrs.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: AUC (0 to infinity) in Sprague-Dawley rat at 5 mg/kg, po measured up to 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: AUC = 654.59 ng.hr.mL-1
Reported result
AUC = 654.59 ng.hr.mL-1
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: AUC (0 to infinity) in Sprague-Dawley rat at 5 mg/kg, po measured up to 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: AUC = 654.59 ng.hr.mL-1”

    ChEMBL activities for CHEMBL4518483 · Activity 29183865

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Pharmacokinetics

In Sprague-Dawley rats given 5 mg/kg orally, CHEMBL4518483 had T1/2 = 3.61 hr (measured up to 24 hrs).

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Half life in Sprague-Dawley rat at 5 mg/kg, po measured up to 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: T1/2 = 3.61 hr
Reported result
T1/2 = 3.61 hr
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Half life in Sprague-Dawley rat at 5 mg/kg, po measured up to 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: T1/2 = 3.61 hr”

    ChEMBL activities for CHEMBL4518483 · Activity 29183833

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Pharmacokinetics

Tmax summarizes time-to-peak plasma concentration after dosing; for danuglipron in Wistar Han rats at 5 mg/kg by mouth, Tmax was 0.5 hr in sampling up to 24 hrs.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Standard result: Tmax = 0.5 hr[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Tmax in Wistar Han rat at 5 mg/kg, po measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: Tmax = 0.5 hr
Reported result
Tmax = 0.5 hr
Source records
2
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Standard result: Tmax = 0.5 hr”

    ChEMBL activities for CHEMBL4518483 · Activity 24929155

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6
  2. supports · Source-backed record
    “Assay: Tmax in Wistar Han rat at 5 mg/kg, po measured upto 24 hrs by LC-MS/MS analysis Assay format: organism-based format Standard result: Tmax = 0.5 hr”

    ChEMBL activities for CHEMBL4518483 · Activity 24929155

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Pharmacokinetics

This organism-based PK result reports oral bioavailability (F) in ICR mice after 5 mg/kg oral dosing of danuglipron, indicating the proportion of exposure relative to an IV reference as defined by the assay.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Oral bioavailability in ICR mouse at 5 mg/kg by LC-MS/MS analysis Assay format: organism-based format Standard result: F = 54.17 %[1]chembl-activitiesChEMBL activities for CHEMBL4518483Standard result: F = 54.17 %
Reported result
F = 54.17 %
Source records
2
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Oral bioavailability in ICR mouse at 5 mg/kg by LC-MS/MS analysis Assay format: organism-based format Standard result: F = 54.17 %”

    ChEMBL activities for CHEMBL4518483 · Activity 26030415

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6
  2. supports · Source-backed record
    “Standard result: F = 54.17 %”

    ChEMBL activities for CHEMBL4518483 · Activity 26030415

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

What has been studied?

What the evidence says.

Study findings

In CHO cells, CHEMBL4518483 activated cynomolgus monkey GLP-1R (cAMP accumulation) with EC50 = 4.4 nM.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Assay: Activation of cynomolgus monkey GLP-1R expressed in CHO cells assessed as increase in cAMP accumulation Assay format: cell-based format Standard result: EC50 = 4.4 nM
Reported result
EC50 = 4.4 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Assay: Activation of cynomolgus monkey GLP-1R expressed in CHO cells assessed as increase in cAMP accumulation Assay format: cell-based format Standard result: EC50 = 4.4 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929144

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Study findings

In CHO-K1 cells expressing human GLP-1R, danuglipron functioned as a receptor agonist measured via cAMP accumulation; the reported potency was EC50 = 0.71 nM under BETP-sensitized conditions.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Standard result: EC50 = 1.1 nM[1]chembl-activitiesChEMBL activities for CHEMBL4518483Standard result: EC50 = 0.71 nM
Reported result
EC50 = 1.1 nM
Source records
2
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Standard result: EC50 = 1.1 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929055

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6
  2. supports · Source-backed record
    “Standard result: EC50 = 0.71 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929050

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Study findings

In a radioligand binding assay using CHO cells expressing FAP-tagged human GLP-1R, danuglipron competed with [3H]PF-06883365, yielding an inhibition constant Ki = 80.0 nM as a measure of binding affinity under the assay conditions.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Standard result: Ki = 80.0 nM
Reported result
Ki = 80.0 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Standard result: Ki = 80.0 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929140

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Study findings

In CHO-K1 cells expressing human GLP-1R, danuglipron’s maximal functional response in a cAMP assay was reported as Emax = 79.0% at 20 uM (relative to control) without BETP.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Standard result: Emax = 79.0 %
Reported result
Emax = 79.0 %
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Standard result: Emax = 79.0 %”

    ChEMBL activities for CHEMBL4518483 · Activity 24929083

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Study findings

Using HEK293 cells expressing FAP-tagged human GLP-1R, danuglipron triggered receptor internalization with a reported EC50 = 230.0 nM, indicating lower potency for this endpoint than for cAMP signaling in other assays.

Sources[1]chembl-activitiesChEMBL activities for CHEMBL4518483Standard result: EC50 = 230.0 nM
Reported result
EC50 = 230.0 nM
Source records
1
Independent studies
1

Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.

Exact passages, locators, and provenance
  1. supports · Source-backed record
    “Standard result: EC50 = 230.0 nM”

    ChEMBL activities for CHEMBL4518483 · Activity 24929064

    chembl-activities:chembl4518483:b22cc4f1a8c6:b22cc4f1a8c6

Risks and interactions

Risks, organized for scanning.

This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.

Products and regulatory status

Same ingredient. Different records.

This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.

Administration context

The practical clinical context.

This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.

Research status + gaps

What still needs better answers?

  • No publishable claim yet for: administration, contraindication, interaction, regulatory, safety
  • 101 compiled claim(s) withheld by automated assurance: assurance_score_below_0.58 (51), assurance_score_below_0.72 (48), current_regulatory_source_required (24), extraction_ambiguity (69), high_risk_requires_regulatory_or_two_independent_sources (47), no_direct_support (95), proposal_not_staged (5)

These are the limits of this profile, not an exhaustive list of scientific uncertainties.

References + discovery

Open the records yourself.

  1. ChEMBL activities for CHEMBL4518483 ↗

    chembl-activities · published 2026-08-26 · retrieved 2026-08-26T08:42:26Z

  2. IUPHAR ligand commentary ↗

    iuphar-comments · published 2026-08-26 · retrieved 2026-08-26T08:42:26Z

  3. Novel GLP-1-based Medications for Type 2 Diabetes and Obesity. ↗

    pubmed · published 2026-03-11 · retrieved 2026-08-25T22:43:25Z

Publication history and provenance

Version 9 · Automated assessment · 2026-08-27T11:42:45Z

9facd58c82d7f1066d006c5f826a4f21cff8322d35d25de005619bf75367255e