| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
GPR81 agonist 1 targets GPR81 (HCAR1), a G protein-coupled receptor that is activated by lactate. The compound acts as a potent agonist with EC50 values of 58 nM for human GPR81 and 50 nM for mouse GPR81. It also functions as an agonist-positive allosteric modulator (Ago-PAM) for HCAR1. Activation of GPR81 inhibits lipolysis in adipocytes.
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| ln Vitro |
GPR81 Agonist 1 (Compound 2) in cell buffer (1–1000 nM) in 3T3-L1 adipocytes downstream of adipocytes [1].
In vitro, GPR81 agonist 1 is a potent and highly selective GPR81 agonist with EC50s of 58 nM and 50 nM for human and mouse GPR81, respectively. It inhibits lipolysis in differentiated 3T3-L1 adipocytes. The compound displays remarkable selectivity for GPR81 over GPR109a, making it a valuable tool for studying GPR81-mediated signaling without off-target effects. |
| ln Vivo |
GPR81 agonist 1 (100 mg/kg; i.p.) inhibits cellular adipose subparts without skin flushing [1]. GPR81 Agonist 1 (10 mg/kg; i.p.) demonstrates high absorption (71%)
In vivo, GPR81 agonist 1 suppresses lipolysis in mice without causing cutaneous flushing. It improves insulin resistance and glycemic control in mouse models of diabetes and obesity. The compound mimics lactate's effects, providing a valuable pharmacological tool for studying metabolic diseases. Its selective activation of GPR81 enables exploration of therapeutic strategies targeting metabolic and inflammatory disorders. |
| Enzyme Assay |
The in vitro receptor binding/activation assay for GPR81 agonist 1 involves measuring GPR81-mediated signaling in cells expressing the receptor. Calcium mobilization assays using fluorescent calcium indicators (e.g., Fluo-4) or cAMP accumulation assays are performed to assess receptor activation. The EC50 values (58 nM for human, 50 nM for mouse) are determined from dose-response curves.
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| Cell Assay |
Cellular assays are performed using differentiated 3T3-L1 adipocytes treated with GPR81 agonist 1 at varying concentrations. Lipolysis is assessed by measuring glycerol or free fatty acid release into the culture medium. The compound's ability to inhibit lipolysis is quantified and compared to vehicle controls.
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| Animal Protocol |
Animal/Disease Models: Male C57/BL6 black mouse[1]
Doses: 10 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Ip (pharmacokinetic/PK/PK analysis) Experimental Results: demonstrated good bioavailability (71%) and Cmax (6.3 μM). In vivo animal studies for GPR81 agonist 1 are conducted in mouse models of diabetes and obesity. The compound is administered orally or by injection. Blood glucose levels, insulin sensitivity, and lipolysis are measured. Cutaneous flushing is assessed as a measure of off-target effects (the compound does not cause flushing). |
| ADME/Pharmacokinetics |
GPR81 agonist 1 has favorable properties for an orally active research compound. It is soluble in DMSO at 10 mM. The compound is available as a solid powder that should be stored at -20°C (12 months) or 4°C (6 months), while solutions should be stored at -80°C (6 months) or -20°C (6 months). Specific PK parameters are not detailed in the available sources.
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| Toxicity/Toxicokinetics |
Toxicity data for GPR81 agonist 1 are not extensively detailed in the available sources. The compound does not cause cutaneous flushing in mice, indicating a favorable side-effect profile compared to other hydroxycarboxylic acid receptor agonists. As a research compound, it is not intended for therapeutic use. Specific toxicological profiles are not available.
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| References | |
| Additional Infomation |
GPR81 agonist 1 is a research compound for studying GPR81 function in metabolic diseases. It is a potent and selective agonist that mimics lactate's effects. The compound is available from commercial suppliers for research use only. References describing its discovery and characterization include Sakurai T, et al. Eur J Pharmacol. 2014;727:1-7 and Lind S, et al. Br J Pharmacol. 2025.
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| Molecular Formula |
C22H30N4O2S2
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|---|---|
| Molecular Weight |
446.629202365875
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| Exact Mass |
446.181
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| CAS # |
1620992-67-7
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| PubChem CID |
86279608
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
606
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(=C(C2=CC=CS2)N=C1NC(C1CCC(C)CC1)=O)CC(N1CCN(C)CC1)=O
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| InChi Key |
ZLQAEANISSHOLB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H30N4O2S2/c1-15-5-7-16(8-6-15)21(28)24-22-23-20(17-4-3-13-29-17)18(30-22)14-19(27)26-11-9-25(2)10-12-26/h3-4,13,15-16H,5-12,14H2,1-2H3,(H,23,24,28)
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| Chemical Name |
4-methyl-N-[5-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-thiophen-2-yl-1,3-thiazol-2-yl]cyclohexane-1-carboxamide
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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 : ~50 mg/mL (~111.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.60 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 25.0 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: ≥ 2.5 mg/mL (5.60 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2390 mL | 11.1949 mL | 22.3899 mL | |
| 5 mM | 0.4478 mL | 2.2390 mL | 4.4780 mL | |
| 10 mM | 0.2239 mL | 1.1195 mL | 2.2390 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.
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