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| 1mg |
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| Targets |
SR146131 targets the cholecystokinin subtype 1 (CCK1) receptor, a G protein-coupled receptor primarily involved in the regulation of gastrointestinal motility, pancreatic enzyme secretion, and satiety signaling. It acts as a potent and selective non-peptide agonist, exhibiting high affinity and selectivity for the CCK1 receptor over other receptor subtypes.
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| ln Vitro |
At an IC50 value of 0.56 ± 0.10 nM, SR 146131 inhibits the binding of [125I]-BH-CCK-8S to the CCK1 site on the 3T3-hCCK1 cell membrane. At elevated concentrations, SR 146131 also prevented radiolabeled CCK from binding to the CCK2 site in CHO-hCCK2 membranes, with an IC50 of 162 ± 27 nM. Strong CCK1 agonist SR 146131 affects several intracellular processes linked to CCK1 receptor activation in several cell types, including: While SR 146131 in 3T3-hCCK1 cells behaved as a full CCK1 receptor agonist in terms of [Ca2+]i release and IP1 generation, the CCK1 receptor agonist had no effect on MAPK activation and early gene expression in this cell line. Additionally, in two neuroblastoma cell lines, SR 146131 functions as a partial agonist [1].
SR146131 is a potent CCK1 receptor agonist. It inhibits the binding of [125I]-BH-CCK-8S to CCK1 sites on 3T3-hCCK1 cell membranes with an IC50 value of 0.56 ± 0.10 nM. On [Ca2+]i release and IP1 formation, SR146131 appears as a full CCK1 receptor agonist, but acts as a partial agonist on MAPK activation and early gene expression in 3T3-hCCK1 cells. |
| ln Vivo |
SR 146131 entirely prevents mice from emptying their gallbladder or stomach (oral ED50 of 2.7 and 66 μg/kg, respectively). When neuropeptide Y (1-36) is administered to non-fasting rats (from 0.3 mg/kg PO), fasted gerbils (from 0.1 mg/kg PO), and diet-restricted marmosets (from 3 mg/kg PO), SR 146131 dose-dependently lowers food intake in fasted rats (from 0.1 mg/kg p.o.). Rats' paraventricular nucleus of the hypothalamus had more Fos-positive cells when exposed to SR 146131 (10 mg/kg po). Mice's locomotor activity is decreased when SR 146131 (0.3 mg/kg po) is administered orally [1].
As an orally bioavailable compound, SR146131 is expected to exhibit in vivo activity through CCK1 receptor activation. Its effects would include modulation of gastrointestinal function and satiety, consistent with the known physiology of CCK1 receptor signaling. Specific in vivo efficacy data and dosing regimens are not extensively detailed in standard reference sources. |
| Enzyme Assay |
The receptor binding affinity of SR146131 can be assessed using radioligand binding assays with membrane preparations from cells expressing the human CCK1 receptor (e.g., 3T3-hCCK1 cells). Competition binding experiments are performed with increasing concentrations of SR146131 against a fixed concentration of a radiolabeled CCK ligand, such as [125I]-BH-CCK-8S. Non-specific binding is determined in the presence of an excess of a reference compound.
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| Cell Assay |
The functional activity of SR146131 at the CCK1 receptor is evaluated in vitro using cell lines expressing the receptor, such as 3T3-hCCK1 or IMR-32 human neuroblastoma cells. Intracellular calcium release ([Ca2+]i) is measured using calcium-sensitive fluorescent dyes. Inositol monophosphate (IP1) accumulation and MAPK activation can also be assessed to characterize the compound's signaling profile.
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| Animal Protocol |
Specific in vivo animal experimental protocols for SR146131 are not extensively detailed in standard reference sources. For evaluating its effects on gastrointestinal function or satiety, SR146131 would be administered orally to rodent models. Parameters such as gastric emptying, intestinal transit, and food intake would be measured to assess CCK1 receptor-mediated effects.
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| ADME/Pharmacokinetics |
SR146131 is described as orally bioavailable, indicating good absorption following oral administration. It has a molecular formula of C34H40ClN3O5S and a molecular weight of 638.22. Specific pharmacokinetic parameters such as half-life, volume of distribution, and clearance are not extensively detailed in standard reference sources.
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| Toxicity/Toxicokinetics |
The toxicity profile of SR146131 is not extensively documented in standard reference sources. As a potent CCK1 receptor agonist, potential adverse effects may include those related to CCK1 receptor activation, such as gastrointestinal disturbances, gallbladder contraction, and pancreatic enzyme secretion. Specific LD50 values and organ-specific toxicity data are not readily available.
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| References |
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| Additional Infomation |
SR146131 (CAS# 221671-61-0) is also known by its IUPAC name 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-5,7-dimethylindol-1-yl]acetic acid. It is a research tool for studying CCK1 receptor signaling and physiology.
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| Molecular Formula |
C32H36CLN3O5S
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| Molecular Weight |
610.17
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| Exact Mass |
609.206
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| CAS # |
221671-61-0
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| PubChem CID |
9852833
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| Appearance |
White to off-white solid powder
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| LogP |
8.286
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
42
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| Complexity |
925
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NFDFTMICKVDYLQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H36ClN3O5S/c1-18-12-19(2)30-21(13-18)14-24(36(30)17-28(37)38)31(39)35-32-34-29(22-15-26(41-4)23(33)16-25(22)40-3)27(42-32)11-10-20-8-6-5-7-9-20/h12-16,20H,5-11,17H2,1-4H3,(H,37,38)(H,34,35,39)
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| Chemical Name |
2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-5,7-dimethylindol-1-yl]acetic acid
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| Synonyms |
SR-146131; SR 146131; SR146131
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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 : ~250 mg/mL (~409.73 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (3.41 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: 2.08 mg/mL (3.41 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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: ≥ 2.08 mg/mL (3.41 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 | 1.6389 mL | 8.1944 mL | 16.3889 mL | |
| 5 mM | 0.3278 mL | 1.6389 mL | 3.2778 mL | |
| 10 mM | 0.1639 mL | 0.8194 mL | 1.6389 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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