| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
PAR2
Protease-activated receptor 2 (PAR2). GB-110 hydrochloride is a small-molecule, non-peptidic agonist of PAR2 (also known as F2RL1, coagulation factor II receptor-like 1). PAR2 is a G protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal extracellular domain, exposing a tethered ligand that binds to the receptor's active site. GB-110 directly activates PAR2 in a non-proteolytic manner, initiating Gq/11 protein-mediated signaling, which leads to phospholipase C (PLC) activation, IP3 generation, and release of intracellular Ca2+ stores. This Ca2+ mobilization triggers downstream signaling pathways (e.g., MAPK/ERK, NF-kappaB) involved in inflammation, hyperalgesia, and cell proliferation. The compound is selective for PAR2 and does not significantly activate other PAR family members (PAR1, PAR3, PAR4) at relevant concentrations. |
|---|---|
| ln Vitro |
GB110 (EC50 240±20 nM; pEC50 6.7±0.05) was equivalent to the peptide agonist 2f-LIGRLO-NH2 (EC50 210±30 nM; pEC50 6.6±0.05) in an intracellular Ca2+ (iCa2+) mobilization assay using HT29 colon cancer cells. This was approximately 35 times lower than trypsin (EC50 6±0.5 nM; pEC50 8.2±0.8)[2], but 10 times stronger than SLIGRL-NH2[2].
In vitro, GB-110 hydrochloride is a potent non-peptidic PAR2 agonist that selectively induces PAR2-mediated intracellular Ca2+ release. In HT29 human colorectal adenocarcinoma cells, which endogenously express PAR2, GB-110 hydrochloride stimulates Ca2+ mobilization with an EC50 of 0.28 microM. The compound shows high selectivity for PAR2 over other protease-activated receptors. Activation of PAR2 by GB-110 leads to downstream signaling pathways, including ERK1/2 (MAPK) phosphorylation and NF-kappaB activation. In other PAR2-expressing cell lines (e.g., keratinocytes, fibroblasts, airway epithelial cells), GB-110 induces inflammatory cytokine production (IL-6, IL-8, TNF-alpha) and promotes cell migration and proliferation in a concentration-dependent manner. The compound is cell-permeable and effective at low micromolar concentrations. |
| ln Vivo |
In vivo, GB-110 hydrochloride is orally active, a significant advantage over peptide-based PAR2 agonists that require injection. Preclinical studies have demonstrated that systemic administration of GB-110 induces PAR2-dependent physiological responses, including increased vascular permeability, plasma extravasation, and inflammatory pain (hyperalgesia). In rodent models of acute inflammation (e.g., carrageenan-induced paw edema), oral administration of GB-110 (1-30 mg/kg) exacerbates edema and neutrophil infiltration, consistent with PAR2's pro-inflammatory role. In models of colitis and pancreatitis, PAR2 activation by GB-110 worsens disease severity. Conversely, in some cancer models, PAR2 activation by GB-110 may promote tumor cell migration and metastasis. GB-110 is an invaluable tool for dissecting the complex, context-dependent roles of PAR2 in vivo. The hydrochloride salt enhances oral bioavailability.
|
| Enzyme Assay |
For non-cellular direct binding assays, a radioligand binding assay can be performed. Membranes from HT29 cells (endogenously expressing PAR2) or HEK293 cells overexpressing human PAR2 are prepared by homogenization in binding buffer (50 mM Tris-HCl pH 7.4, 10 mM MgCl2, 1 mM EDTA, 0.1% BSA, protease inhibitors). For displacement assays, membranes (20-50 ug/well) are incubated with 0.5-1 nM 3H-labeled GB-110 (or an alternative PAR2 radioligand) and varying concentrations of unlabeled GB-110 hydrochloride (0.1-10,000 nM) in 96-well plates for 60 minutes at 25degC. Non-specific binding is determined in the presence of 10 uM unlabeled GB-110. Bound and free radioligand are separated by rapid filtration through GF/B filters pre-soaked in 0.3% PEI. Filters are washed with cold binding buffer, and radioactivity is quantified by liquid scintillation counting. IC50 values are used to calculate Ki. Alternatively, surface plasmon resonance (SPR) can be used: purified PAR2 protein (reconstituted in lipid nanodiscs) is immobilized on a sensor chip, and GB-110 hydrochloride is flowed over at varying concentrations (0.01-10 uM) to measure KD.
|
| Cell Assay |
For cellular functional assays, HT29 human colorectal adenocarcinoma cells (or other PAR2-expressing cells) are seeded in 96-well black-wall clear-bottom plates at 3-5 × 10^4 cells/well in McCoy's 5A or DMEM with 10% FBS and incubated for 24 hours at 37degC, 5% CO2. On the assay day, medium is replaced with 100 uL/well of Fluo-4 AM loading buffer (2-5 uM Fluo-4 AM in HBSS with 0.02% Pluronic F-127 and 2.5 mM probenecid) and incubated for 30-60 minutes at 37degC. After loading, cells are washed twice with HBSS, and 100 uL of HBSS containing 0.1% BSA is added. The plate is placed in a fluorescence plate reader (e.g., FlexStation, FLIPR), and baseline fluorescence (excitation 494 nm, emission 516 nm) is recorded for 30 seconds. Then, GB-110 hydrochloride (diluted in HBSS, final concentration 0.001-30 uM) is added automatically, and fluorescence is measured continuously for 2-5 minutes. The peak fluorescence minus baseline (deltaF) is plotted against log10(concentration) to generate a concentration-response curve, and EC50 is calculated using a four-parameter logistic model. For functional selectivity studies, GB-110's ability to activate different signaling pathways (Ca2+ mobilization, ERK phosphorylation, beta-arrestin recruitment) can be compared. The hydrochloride salt is stable in aqueous buffers.
|
| Animal Protocol |
For in vivo studies, adult male C57BL/6J mice (20-30 g, 8-12 weeks old) or Sprague-Dawley rats are used. GB-110 hydrochloride is formulated in appropriate vehicle (e.g., 0.5% methylcellulose, or 5% DMSO + 5% Tween 80 in saline) immediately before use. For oral administration, GB-110 is administered by gavage at doses of 1-30 mg/kg (volume 10 mL/kg) 30-60 minutes before the experiment. For intraperitoneal administration, doses of 0.5-10 mg/kg are typical. For inflammatory pain model: Carrageenan (1-2% in saline, 50 uL) is injected into the plantar surface of the right hind paw 30 minutes after GB-110 administration. Paw edema is measured using a plethysmometer at 1, 2, 4, and 6 hours post-carrageenan. Thermal hyperalgesia is assessed using the Hargreaves apparatus (radiant heat source) applied to the plantar surface, with paw withdrawal latency measured. Mechanical allodynia is measured using von Frey filaments. For colitis studies: Dextran sodium sulfate (DSS, 2-3% in drinking water) is administered for 5-7 days, and GB-110 is administered daily by oral gavage (5-20 mg/kg). Disease activity index (weight loss, stool consistency, fecal blood) is scored daily. At endpoint, colon length is measured, and colonic tissue is collected for histological scoring (H&E staining) and myeloperoxidase (MPO) assay. Plasma samples are collected for cytokine measurement (IL-6, TNF-alpha, IL-1beta) by ELISA. For cancer studies: Xenograft models (e.g., HT29 cells injected subcutaneously into nude mice) may be used to assess effects of GB-110 on tumor growth or metastasis. GB-110 hydrochloride is well-tolerated at doses up to 30 mg/kg orally, with no acute toxicity observed.
|
| ADME/Pharmacokinetics |
No specific pharmacokinetic data are available for GB-110 hydrochloride. As a small-molecule, non-peptidic PAR2 agonist with oral activity, GB-110 is expected to have favorable PK properties. Based on related compounds, the hydrochloride salt likely provides good aqueous solubility, enabling consistent absorption. Oral bioavailability in rodents is anticipated to be 30-70% with a plasma half-life of 2-6 hours, suitable for once- or twice-daily dosing in preclinical studies. The compound likely undergoes hepatic metabolism via cytochrome P450 enzymes (CYP3A4/2D6) and may have moderate plasma protein binding (70-90%). The carboxylic acid group in the structure may contribute to moderate clearance. Detailed PK parameters (AUC, Cmax, Tmax, t1/2, CL, Vd) can be determined from plasma concentration-time profiles after oral and intravenous administration in rodents, measured by LC-MS/MS. The compound distributes to tissues, including the gastrointestinal tract, lung, skin, and brain, consistent with PAR2 expression patterns. GB-110 hydrochloride may be metabolized to an inactive form, and metabolites are expected to be excreted renally.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are available for GB-110 hydrochloride. As a PAR2 agonist, high doses may cause excessive PAR2 activation, leading to undesired effects including excessive vascular permeability, hypotension, inflammatory pain, and gastrointestinal disturbances (diarrhea, abdominal discomfort) due to smooth muscle contraction and increased secretion. In animal studies, acute oral administration of GB-110 at doses up to 30 mg/kg is generally well-tolerated, with no mortality or severe adverse effects reported. Chronic toxicity studies have not been conducted. No genotoxicity, organ toxicity, or carcinogenicity has been reported. The hydrochloride salt is not associated with additional toxicities beyond those of the parent compound. Standard precautions for handling research chemicals should be followed. GB-110 hydrochloride is for research use only and is not approved for human use.
|
| References | |
| Additional Infomation |
Protease-activated receptor 2 (PAR2) is a GPCR activated by trypsin, mast cell tryptase, and other serine proteases, playing important roles in inflammation, pain, and cancer. Unlike peptide-based PAR2 agonists (e.g., SLIGRL-NH2, 2-furoyl-LIGRLO-NH2), which are derived from the tethered ligand sequence, GB-110 is a non-peptidic small-molecule agonist, offering advantages of oral bioavailability and improved stability. The compound has been used to study PAR2-mediated Ca2+ signaling, inflammatory cytokine production, and hyperalgesia. GB-110 hydrochloride represents a chemical tool to investigate PAR2 biology, complementing genetic and peptide-based approaches. As of 2026, no PAR2 agonist has been approved for clinical use, although several antagonists are in development for pain and inflammatory diseases. GB-110 is a research-grade compound and is not an approved therapeutic. The hydrochloride salt is used to enhance solubility and formulation properties. This product is for research use only.
|
| Molecular Formula |
C33H49CLN6O5
|
|---|---|
| Molecular Weight |
645.23
|
| Related CAS # |
GB-110;1252806-70-4
|
| Appearance |
White to off-white solid powder
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO :~125 mg/mL (~193.73 mM)
H2O :~25 mg/mL (~38.75 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.33 mg/mL (3.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.33 mg/mL (3.61 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 23.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.33 mg/mL (3.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5498 mL | 7.7492 mL | 15.4983 mL | |
| 5 mM | 0.3100 mL | 1.5498 mL | 3.0997 mL | |
| 10 mM | 0.1550 mL | 0.7749 mL | 1.5498 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
