| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
Calcium-sensing receptor (CaSR) (pKa = 6.36 ± 0.07, Logαβ = 2.01 ± 0.12, LogτB = -0.10 ± 0.04) [1]
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|---|---|
| ln Vivo |
In rodents, AC265347 suppressed PTH release at concentrations that were 300-fold lower than those that suppressed blood Ca2+ concentrations, suggesting a lower propensity to induce hypocalcaemia compared to cinacalcet. [1]
AC265347 potently suppressed parathyroid hormone (PTH) release in rats with a lower propensity to cause hypocalcaemia compared to cinacalcet. [1] |
| Cell Assay |
The AC265347 compound was tested in Ca2+ mobilisation assays using FlpIn TREX HEK293 cells stably expressing the wild-type CaSR. Cells were seeded at 80,000 cells/well in poly-D-lysine-coated 96-well plates and incubated overnight at 37°C with 5% CO2 in the presence of 100 ng/mL tetracycline. Cells were washed in assay buffer (150 mM NaCl, 2.6 mM KCl, 1.18 mM MgCl2, 10 mM D-glucose, 10 mM HEPES, 0.1 mM CaCl2, 0.5% BSA, 4 mM probenecid, pH 7.4) and loaded with 1 μM Fluo-8-AM in assay buffer for 1 hour. Agonist (Ca2+) and PAMs (including AC265347) at concentrations of 0, 0.03, 0.1, 0.3, 1, 3, or 10 μM were co-added, and measurements of Ca2+ mobilisation were performed in duplicate at 37°C using a Flexstation with 490 nm excitation and 520 nm emission. Data were normalised to the percentage of the ionomycin response (1 μM ionomycin was used as an internal assay control). Concentration-response curves to Ca2+ were generated in the absence and presence of multiple concentrations of test compounds. The data were fitted to an operational model of allosterism to quantify PAM affinity (pKa), cooperativity (αβ), and efficacy (τB). For AC265347 (compound 2), the following parameters were obtained from n=4 independent experiments: pKa = 6.36 ± 0.07, Logαβ = 2.01 ± 0.12, LogτB = -0.10 ± 0.04. [1]
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| Toxicity/Toxicokinetics |
AC265347 has a lower propensity to cause hypocalcaemia compared to cinacalcet in rodent models. [1]
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| References | |
| Additional Infomation |
AC265347 is an ago-positive allosteric modulator (ago-PAM) of the calcium-sensing receptor (CaSR). It acts by potentiating CaSR-mediated suppression of PTH release. The compound was originally identified by ACADIA Pharmaceuticals. In this study, AC265347 was used as the parent compound for structure-activity relationship studies, and its racemate was characterised. The (S)-enantiomer of AC265347 demonstrated the highest potency, but it was only 2.5-fold more potent than the racemate mixture. AC265347 is chemically distinct from clinically approved CaSR PAMs such as cinacalcet, evocalcet, and etelcalcetide. It may offer benefits over current CaSR PAMs due to its reduced adverse effect potential. [1]
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| Molecular Formula |
C17H17NOS
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|---|---|
| Molecular Weight |
283.387983083725
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| Exact Mass |
283.103
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| CAS # |
1253901-26-6
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| PubChem CID |
52943938
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.168
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
350
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IGSZVEPQZANNAB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H17NOS/c1-11-8-9-13(12(2)10-11)17(3,19)16-18-14-6-4-5-7-15(14)20-16/h4-10,19H,1-3H3
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| Chemical Name |
1-(1,3-benzothiazol-2-yl)-1-(2,4-dimethylphenyl)ethanol
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.5287 mL | 17.6435 mL | 35.2871 mL | |
| 5 mM | 0.7057 mL | 3.5287 mL | 7.0574 mL | |
| 10 mM | 0.3529 mL | 1.7644 mL | 3.5287 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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