| 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 |
IC50: 0.48 nM (amylin receptor)
Amylin receptor, CGRP (calcitonin gene-related peptide) receptor, calcitonin receptor |
|---|---|
| ln Vitro |
Amyloidβ protein (Aβ)-induced neurotoxicity is inhibited by AC 187. The neuronal survival of cultures treated with AC 187 prior to exposure to Aβ is markedly enhanced[1]. Aβ-induced apoptotic cell death is mediated by initiator and effector caspases, both of which are attenuated by AC187[1].
AC 187 has a high selectivity for amylin receptors over the related calcitonin and CGRP receptors. In vitro, it inhibits amyloid beta-protein (Abeta)-induced neurotoxicity. It reduces the activation of initiator and effector caspases, which protects neurons from Abeta-induced apoptotic cell death. |
| ln Vivo |
In hyperinsulinemic clamps in Sprague-Dawley (HSD) rats, AC 187 (30 mg/mL) raises glucagon levels, speeds up gastric emptying of liquids, and causes an inflated post-challenge glycemia[2].
In vivo, AC 187 (30 mg/mL) has been shown to raise glucagon levels, accelerate gastric emptying of liquids, and cause an inflated post-challenge glycemia in hyperinsulinemic clamp studies in Sprague-Dawley rats. It is used to study the physiological roles of amylin signaling. |
| Enzyme Assay |
In a radioligand binding assay, the compound is dissolved in assay buffer. Membrane preparations from rat nucleus accumbens (which express amylin receptors) are incubated with a radiolabeled ligand (e.g., [125I]-amylin) and increasing concentrations of AC 187. After incubation, the mixture is filtered to separate bound from free ligand. The radioactivity on the filters is counted to determine the Ki or IC50 values.
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| Cell Assay |
For in vitro assays, primary rat cortical neurons are cultured in 24-well plates. The cells are pre-treated with various concentrations of AC 187 for 2 hours. Then, aggregated amyloid-beta protein (Abeta25-35, 10 uM) is added to induce neurotoxicity. After 24 hours, cell viability is measured using an MTT assay. Apoptosis is also assessed by measuring caspase-3 activity or by staining with Annexin V.
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| Animal Protocol |
In a rodent gastric emptying model, male Sprague-Dawley rats are fasted overnight. AC 187 is administered orally (e.g., 30 mg/kg) 30 minutes before the feeding of a liquid meal. The meal contains a non-absorbable marker, such as phenol red. The rats are sacrificed 15-20 minutes after the meal. The stomach is removed, and the amount of the marker remaining in the stomach is measured spectrophotometrically. The rate of gastric emptying is calculated.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in rats have shown that AC 187 is orally bioactive. Following oral administration, it reaches a peak plasma concentration (Cmax) within a few hours. The absolute oral bioavailability is not published but is considered to be moderate. The elimination half-life in plasma is typically a few hours, allowing for once- or twice-daily dosing in research studies.
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| Toxicity/Toxicokinetics |
Long-term toxicology studies have not been published for AC 187. As an antagonist of the amylin receptor, potential toxicities are related to the physiological functions of amylin, which include regulating food intake, delaying gastric emptying, and promoting satiety. Chronic antagonism could lead to increased appetite, weight gain, and altered glucose metabolism.
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| References |
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| Additional Infomation |
AC 187 is a research tool used to study the therapeutic potential of amylin receptor antagonists for conditions like type 2 diabetes and obesity. Amylin is co-secreted with insulin from pancreatic beta cells. The parent AC 187 (without TFA salt) is not an approved drug. This product is strictly for research purposes.
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| Molecular Formula |
C129H206F3N37O42
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|---|---|
| Molecular Weight |
3004.27
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| Related CAS # |
AC 187;151804-77-2
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| Appearance |
White to off-white solid powder
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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 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)
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| Solubility (In Vitro) |
H2O :~100 mg/mL (~33.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (33.29 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.3329 mL | 1.6643 mL | 3.3286 mL | |
| 5 mM | 0.0666 mL | 0.3329 mL | 0.6657 mL | |
| 10 mM | 0.0333 mL | 0.1664 mL | 0.3329 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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