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| Targets |
mGluR5 (metabotropic glutamate receptor 5). (S,S)-BMS-984923 is the less active (S,S)-enantiomer of BMS-984923. It exhibits an EC50 >1 microM for the mGluR5 receptor, representing a >1,600-fold reduction in functional potency relative to its active (R,R)-enantiomer BMS-984923, which displays a binding affinity Ki = 0.6 nM. This dramatic enantioselectivity demonstrates that the mGluR5 binding site is stereospecific.
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| ln Vitro |
In vitro, (S,S)-BMS-984923 shows weak activity at mGluR5 with EC50 >1 microM, in contrast to the active (R,R)-enantiomer which is a potent silent allosteric modulator (Ki = 0.6 nM). The compound does not significantly modulate glutamate-induced calcium responses at concentrations up to 1 microM. It is used as an inactive enantiomer control to confirm that observed effects of the racemic mixture or active enantiomer are due to specific mGluR5 modulation rather than off-target activities.
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| ln Vivo |
In vivo, (S,S)-BMS-984923 is not expected to produce significant pharmacological effects due to its low potency at mGluR5. It is used as a negative control in behavioral and physiological studies to validate the specificity of the active (R,R)-enantiomer's effects. No significant CNS activity has been reported for this inactive enantiomer at the doses where the active isomer shows efficacy.
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| Enzyme Assay |
Standard cell-free binding assays for (S,S)-BMS-984923 use membrane preparations from HEK-293 cells stably expressing human mGluR5. Membranes (15-20 microg protein) are incubated with 1-2 nM [3H]MPEP (a selective mGluR5 radioligand) or other mGluR5 allosteric radioligands and varying concentrations of the compound (0.01-10000 nM) in 50 mM Tris-HCl buffer pH 7.4 containing 2.5 mM CaCl2 and 5 mM MgCl2 for 60 minutes at room temperature. Non-specific binding is determined in the presence of 10 microM MPEP or 100 microM glutamate. Bound radioligand is separated by rapid filtration through GF/B filters presoaked in 0.5% polyethyleneimine, followed by three washes with ice-cold buffer. Filter-bound radioactivity is measured by liquid scintillation counting. IC50 values are calculated, and Ki values are derived. (S,S)-BMS-984923 shows significantly lower binding affinity (Ki > 1 microM) compared to the active (R,R)-enantiomer (Ki = 0.6 nM). For functional allosteric binding characterization, radiolabeled positive allosteric modulators of mGluR5 may be used to assess binding to the allosteric site.
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| Cell Assay |
For functional in vitro assays, HEK-293 or CHO cells stably expressing human mGluR5 are seeded in 96-well plates (40,000 cells/well) in DMEM/F-12 supplemented with 10% FBS for 48 hours. For calcium mobilization assays, cells are loaded with Fluo-4 AM (2.5 microM) in HBSS buffer containing 20 mM HEPES and 2.5 mM probenecid for 60 minutes at 37degC. Cells are pre-incubated with varying concentrations of (S,S)-BMS-984923 (0.01-10000 nM) for 5-15 minutes, then stimulated with an EC80 concentration of glutamate (10-50 microM) or an mGluR5 positive allosteric modulator. Fluorescence is measured using a fluorescence plate reader (excitation 485 nm, emission 525 nm). The percentage modulation (potentiation or inhibition) of the agonist response is calculated relative to vehicle control. For (S,S)-BMS-984923, EC50 > 1 microM for functional modulation, indicating >1,600-fold lower potency than the active (R,R)-enantiomer. For IP accumulation assays, cells are labeled with [3H]myo-inositol, and inositol phosphates are quantified after agonist stimulation in the presence of the compound. The inactive (S,S)-enantiomer shows no significant effect at concentrations up to 10 microM. Selectivity is confirmed by testing on other mGlu receptor subtypes.
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| Animal Protocol |
In vivo animal studies with (S,S)-BMS-984923 are typically conducted alongside the active (R,R)-enantiomer to serve as a negative control. Protocols use male C57BL/6 mice (20-30 g) or Sprague-Dawley rats (250-350 g). The compound is formulated in 10% DMSO/40% PEG300/5% Tween-80/45% saline or 0.5% methylcellulose and administered by intraperitoneal injection (0.1-10 mg/kg) or oral gavage (1-30 mg/kg) 30-60 minutes before testing. Behavioral assays may include locomotor activity (open field test), anxiety-related behaviors (elevated plus maze, light-dark box), cognitive function (novel object recognition, Morris water maze), or nociception (tail-flick, hot-plate). Blood and brain samples are collected at termination to confirm compound exposure by LC-MS/MS. (S,S)-BMS-984923 is expected to produce no significant behavioral effects at doses where the active (R,R)-enantiomer shows efficacy, confirming that the effects of the active isomer are mediated by specific mGluR5 modulation rather than off-target mechanisms. Doses of (S,S)-BMS-984923 up to 10 mg/kg typically show no difference from vehicle control in behavioral assays.
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| ADME/Pharmacokinetics |
(S,S)-BMS-984923 (molecular weight 374.82 Da, formula C22H15ClN2O2) is a small molecule with physicochemical properties similar to the active (R,R)-enantiomer. The compound is lipophilic with moderate solubility in DMSO and organic solvents. It is expected to be brain-penetrant. The active (R,R)-enantiomer BMS-984923 has good oral bioavailability (estimated 40-60% in rodents) and plasma half-life of 2-4 hours. As an inactive enantiomer, (S,S)-BMS-984923 may have similar absorption and distribution properties but may be metabolized differently due to stereospecific metabolism. Detailed pharmacokinetic parameters for the (S,S)-enantiomer have not been published.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data for (S,S)-BMS-984923 are limited. As an inactive enantiomer, it is not expected to produce significant on-target toxicity. In short-term studies at doses up to 10 mg/kg IP in mice, no adverse effects or mortality have been reported. Higher doses may be required to observe any toxicity. The compound has not been formally evaluated in genotoxicity, carcinogenicity, or reproductive toxicity studies. Standard laboratory safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
(S,S)-BMS-984923 is the less active (S,S)-enantiomer of BMS-984923, a potent mGluR5 silent allosteric modulator. This compound is used as a negative control in mGluR5 pharmacology studies to demonstrate enantioselectivity of the active (R,R)-enantiomer. BMS-984923 itself is a potent mGluR5 silent allosteric modulator (Ki = 0.6 nM) developed for potential therapeutic applications in schizophrenia and fragile X syndrome. CAS number: 1375752-77-4. For research use only, not for therapeutic use.
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| Molecular Formula |
C22H15CLN2O2
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| Molecular Weight |
374.819704294205
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| Exact Mass |
374.082
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| CAS # |
1375752-77-4
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| Related CAS # |
BMS-984923;1375752-78-5
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| PubChem CID |
69083885
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| Appearance |
White to off-white solid powder
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| LogP |
4.4
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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 |
4
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| Heavy Atom Count |
27
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| Complexity |
592
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1C=CC=CC=1[C@H]1[C@H](C2C=NC=C(C#CC3C=CC=CC=3)C=2)NC(=O)O1
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| InChi Key |
IAYVUQJOKDFLAL-SFTDATJTSA-N
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| InChi Code |
InChI=1S/C22H15ClN2O2/c23-19-9-5-4-8-18(19)21-20(25-22(26)27-21)17-12-16(13-24-14-17)11-10-15-6-2-1-3-7-15/h1-9,12-14,20-21H,(H,25,26)/t20-,21-/m0/s1
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| Chemical Name |
(4S,5S)-5-(2-chlorophenyl)-4-[5-(2-phenylethynyl)pyridin-3-yl]-1,3-oxazolidin-2-one
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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 | 2.6679 mL | 13.3397 mL | 26.6795 mL | |
| 5 mM | 0.5336 mL | 2.6679 mL | 5.3359 mL | |
| 10 mM | 0.2668 mL | 1.3340 mL | 2.6679 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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