| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
GLP-1 receptor (GLP-1R). Lotiglipron is a potent and selective small-molecule agonist of the GLP-1 receptor, a class B GPCR. By activating this receptor, it enhances insulin secretion, suppresses glucagon release, and delays gastric emptying, leading to improved glycemic control and weight loss.
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| ln Vitro |
Lotiglipron is a potent agonist of the human GLP-1 receptor. In cell-based functional assays, it stimulates cAMP production with an EC50 in the low nanomolar range. Its oral bioavailability and once-daily dosing profile are key properties that differentiate it from injectable peptide agonists. In vitro, it has a favorable selectivity profile with minimal off-target activity.
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| ln Vivo |
In clinical trials, once-daily oral administration of Lotiglipron demonstrated significant and clinically meaningful reductions in HbA1c (glycated hemoglobin) and body weight in patients with type 2 diabetes. The magnitude of weight loss was similar to that achieved with injectable GLP-1 agonists, confirming its potent in vivo efficacy.
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| Enzyme Assay |
A cell-free assay for GLP-1 agonists is performed using membranes from cells overexpressing the human GLP-1 receptor. Membranes are incubated with a radiolabeled high-affinity GLP-1 agonist (e.g., [125I]GLP-1) and varying concentrations of Lotiglipron. After filtration to separate bound and free ligand, the radioactivity is counted to calculate the Ki for receptor binding.
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| Cell Assay |
A cellular functional assay is performed using HEK293 cells stably expressing the human GLP-1 receptor. Cells are seeded in 96-well plates and treated with varying concentrations of Lotiglipron. After incubation, intracellular cAMP accumulation is measured using a homogeneous time-resolved fluorescence (HTRF) or luminescence-based detection kit to calculate the EC50 for receptor activation.
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| Animal Protocol |
The primary in vivo efficacy data for Lotiglipron comes from Phase I and II clinical trials. The drug is administered orally once daily to patients with type 2 diabetes. Endpoints include the change from baseline in HbA1c (after ~12-16 weeks), fasting plasma glucose, and body weight. Safety and tolerability are also assessed.
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| ADME/Pharmacokinetics |
Lotiglipron is designed as an oral, once-daily GLP-1 agonist. Pharmacokinetic studies in humans confirmed its oral bioavailability, and it was formulated for once-daily dosing. However, Pfizer discontinued its development in 2023 due to safety concerns related to elevated liver enzymes observed in clinical trials.
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| Toxicity/Toxicokinetics |
The development of Lotiglipron was discontinued in 2023 due to safety findings. In Phase I and II trials, dose-dependent elevations in liver enzymes (transaminases) were observed in some patients. While no cases of Hyatt's law (a marker of severe drug-induced liver injury) were reported, the signal was considered sufficient to halt further development for safety reasons.
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| References | |
| Additional Infomation |
Lotiglipron is a small molecule drug. Its International Nonproprietary Name (INN) prefix "-glipron" indicates that lotiglipron is a glucagon-like peptide-1 receptor (GLP-1R) agonist. Lotiglipron is currently being investigated in the clinical trial NCT05579977 (this trial aims to understand the efficacy of the investigational drug (PF-07081532) and Rebexasil in patients with type 2 diabetes, and to investigate the efficacy of PF-07081532 alone in obese individuals). The monoisotopic molecular weight of lotiglipron is 574.2 Da.
Lotiglipron was a highly anticipated candidate in the race to develop the first oral small-molecule GLP-1 agonist. It was part of Pfizer's partnership with Sosei Group to leverage their oral GPCR agonist platform. While ultimately discontinued due to liver safety signals, its development provided valuable insights into the challenges of developing safe, non-peptide agonists for class B GPCRs. Pfizer is continuing to develop a backup molecule, danuglipron. |
| Molecular Formula |
C31H31CLN4O5
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|---|---|
| Molecular Weight |
575.054646730423
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| Exact Mass |
574.198
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| CAS # |
2401892-75-7
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| PubChem CID |
146609022
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
41
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| Complexity |
938
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1=CN=C(C=C1)[C@@]1(C)OC2=CC=CC(=C2O1)C1CCN(CC2=NC3C=CC(C(=O)O)=CC=3N2C[C@@H]2CCO2)CC1
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| InChi Key |
SVPYZAJTWFQTSM-UGDMGKLASA-N
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| InChi Code |
InChI=1S/C31H31ClN4O5/c1-31(27-8-6-21(32)16-33-27)40-26-4-2-3-23(29(26)41-31)19-9-12-35(13-10-19)18-28-34-24-7-5-20(30(37)38)15-25(24)36(28)17-22-11-14-39-22/h2-8,15-16,19,22H,9-14,17-18H2,1H3,(H,37,38)/t22-,31-/m0/s1
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| Chemical Name |
2-[[4-[(2S)-2-(5-chloropyridin-2-yl)-2-methyl-1,3-benzodioxol-4-yl]piperidin-1-yl]methyl]-3-[[(2S)-oxetan-2-yl]methyl]benzimidazole-5-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 125 mg/mL (217.37 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7390 mL | 8.6949 mL | 17.3898 mL | |
| 5 mM | 0.3478 mL | 1.7390 mL | 3.4780 mL | |
| 10 mM | 0.1739 mL | 0.8695 mL | 1.7390 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT05671653
Conditions:ObesityLink: https://clinicaltrials.gov/ct2/show/NCT05788328
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT05510245
Conditions:Type 2 Diabetes|Renal Impairment
Title:A Study to Understand How the Study Medicine (PF-07081532) is Processed and Eliminated in Healthy Men
Status:Completed
updateDate:2024-09-24
Ctid:NCT05652647
Link: https://clinicaltrials.gov/ct2/show/NCT05652647
Conditions:Healthy ParticipantsLink: https://clinicaltrials.gov/ct2/show/NCT05745701
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT05478603
Conditions:Hepatic Impairment|Healthy VolunteersLink: https://clinicaltrials.gov/ct2/show/NCT05158244
Conditions:Type 2 Diabetes MellitusLink: https://clinicaltrials.gov/ct2/show/NCT05677867
Conditions:Overweight|ObesityLink: https://clinicaltrials.gov/ct2/show/NCT05579977
Conditions:Diabetes Mellitus|ObesityLink: https://clinicaltrials.gov/ct2/show/NCT04305587
Conditions:Diabetes Mellitus Type 2Link: https://clinicaltrials.gov/ct2/show/NCT04148209
Conditions:HealthyProducts are for research use only; We do not sell to patients
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