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| Targets |
Calcium-sensing receptor (CaSR). SB-423562 is a potent, selective, and short-acting antagonist of the calcium-sensing receptor. It inhibits CaSR-mediated signaling with an IC50 value of 73.0 nM. By blocking this receptor, the compound mimics a state of hypocalcemia, leading to a transient increase in PTH secretion, which is a key mechanism for stimulating bone formation.
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| ln Vitro |
SB-423562 shows potent inhibitory activity against the calcium-sensing receptor (CaSR) with an IC50 value of 73.0 nM in vitro. This inhibition blocks CaSR-mediated signaling in cells expressing the human receptor. The compound's activity is characterized by its ability to transiently increase PTH levels, a direct consequence of CaSR antagonism, which is the basis for its potential application in osteoporosis research.
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| ln Vivo |
As a short-acting CaSR antagonist, SB-423562 is designed to provide a transient increase in plasma PTH concentrations in vivo. This PTH spike is intended to stimulate bone formation, making the compound a potential therapeutic for osteoporosis. The short-acting nature of the compound is a key feature, as it allows for pulsatile PTH stimulation, which is known to be anabolic for bone, while minimizing prolonged exposure that could lead to bone resorption.
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| Enzyme Assay |
In vitro receptor binding and functional assays are employed to characterize SB-423562's interaction with the CaSR. Typically, radioligand binding assays or surface plasmon resonance can be used to measure the compound's affinity for the receptor. To assess its antagonistic activity, HEK-293 cells transfected with the human CaSR are used in functional assays where the inhibition of CaSR-mediated signaling by the compound is measured, allowing for the determination of its IC50 (73.0 nM).
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| Cell Assay |
The in vitro cellular activity of SB-423562 is evaluated using HEK-293 cells that have been stably transfected with the human calcium-sensing receptor. These cells are treated with increasing concentrations of the compound in the presence of a CaSR agonist. The inhibition of downstream signaling, such as intracellular calcium mobilization or MAPK pathway activation, is then measured to determine the compound's potency and to confirm its antagonistic effect, yielding an IC50 of 73.0 nM.
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| Animal Protocol |
While specific animal study details are limited, SB-423562's in vivo effects are typically assessed in rat models. The compound demonstrates a clearance rate of 89.0 mL/min/kg in rats, indicating its pharmacokinetic profile. In efficacy models for osteoporosis, the compound would be administered orally, and its ability to transiently increase PTH and subsequently stimulate bone formation would be measured by assessing bone mineral density and markers of bone turnover.
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| ADME/Pharmacokinetics |
SB-423562 is an orally active small molecule. Its pharmacokinetic profile has been characterized in rats, showing a clearance rate of 89.0 mL/min/kg. The compound's molecular weight is 436.54, and its molecular formula is C26H32N2O4. As a short-acting agent, its duration of action is a critical parameter for its intended use in osteoporosis, allowing for controlled, pulsatile stimulation of bone formation without sustained receptor blockade.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for SB-423562. As a research compound for osteoporosis, its safety profile would be a key area of investigation. Given its mechanism of action as a CaSR antagonist, potential toxicities could be related to alterations in calcium homeostasis, such as hypocalcemia or hypercalcemia, depending on the duration and extent of receptor blockade. Standard preclinical toxicology studies would be required to assess its safety.
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| References | |
| Additional Infomation |
Calcium-sensitive receptor antagonists; structure can be found in the first article.
SB-423562 (CAS#: 351490-27-2) is a short-acting calcium-sensing receptor (CaSR) antagonist. It is an orally active compound that transiently increases plasma PTH concentrations, stimulating bone formation, and is therefore of interest for osteoporosis research. It is available as a high-purity research compound. While it shows promise as a bone anabolic agent, it has not been approved for clinical use and remains an investigational tool for studying calcium metabolism and bone diseases. |
| Molecular Formula |
C26H32N2O4
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|---|---|
| Molecular Weight |
436.54
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| Exact Mass |
436.236
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| CAS # |
351490-27-2
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| PubChem CID |
9910902
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| Appearance |
White to off-white solid powder
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| LogP |
3.879
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
32
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| Complexity |
644
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)(CC1CC2=CC=CC=C2C1)NC[C@H](COC3=C(C=CC(=C3)CCC(=O)O)C#N)O
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| InChi Key |
NJBFJCJKWWIKRD-HSZRJFAPSA-N
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| InChi Code |
InChI=1S/C26H32N2O4/c1-26(2,14-19-11-20-5-3-4-6-21(20)12-19)28-16-23(29)17-32-24-13-18(8-10-25(30)31)7-9-22(24)15-27/h3-7,9,13,19,23,28-29H,8,10-12,14,16-17H2,1-2H3,(H,30,31)/t23-/m1/s1
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| Chemical Name |
3-[4-cyano-3-[(2R)-3-[[1-(2,3-dihydro-1H-inden-2-yl)-2-methylpropan-2-yl]amino]-2-hydroxypropoxy]phenyl]propanoic acid
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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: 5 mg/mL (11.45 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.29 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 10.0 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. Solubility in Formulation 2: ≥ 1 mg/mL (2.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2907 mL | 11.4537 mL | 22.9074 mL | |
| 5 mM | 0.4581 mL | 2.2907 mL | 4.5815 mL | |
| 10 mM | 0.2291 mL | 1.1454 mL | 2.2907 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.
Link: https://clinicaltrials.gov/ct2/show/NCT02204579
Conditions:Autosomal Dominant Hypocalcemia (ADH)Products are for research use only; We do not sell to patients
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