| 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 |
mGluR5 (metabotropic glutamate receptor 5).
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| ln Vitro |
BMS-984923 binds to mGluR5 with exceptionally high affinity, exhibiting a Ki of 0.6 nM. This potent binding allows it to potently inhibit the PrPC-mGluR5 interaction and block pathological Aβo signaling, without affecting normal physiological glutamate signaling. This unique mechanism of action distinguishes it from traditional agonists or antagonists.
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| ln Vivo |
BMS-984923 has high oral bioavailability and BBB penetration (7.5 mg/kg or 15 mg/kg, oral gavage, once)[1].
In animal models of Alzheimer's disease, BMS-984923 has been shown to reverse aging-dependent loss of functional connectivity. Its ability to rescue synaptic density and functional connectivity deficits in aged AD mice highlights its therapeutic potential. The compound's ability to selectively block pathological signaling while preserving normal function is a key feature of its in vivo activity. |
| Enzyme Assay |
In vitro receptor binding assays are performed to determine the affinity of BMS-984923 for mGluR5. Radioligand binding studies using membrane preparations from cells expressing the receptor are conducted. The compound's ability to displace a specific radiolabeled ligand from the receptor is measured to calculate its Ki value (0.6 nM).
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| Cell Assay |
Cells expressing mGluR5 are used to evaluate the functional effects of BMS-984923. The compound's ability to inhibit pathological Aβo-induced signaling, such as PrPC-mGluR5 interaction, is assessed without affecting physiological glutamate responses. This is typically measured by monitoring downstream signaling pathways or receptor conformational changes.
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| Animal Protocol |
Animal/Disease Models: C57Bl6J male mice[1].
Doses: 7.5 mg/kg or 15 mg/ kg (pharmacokinetic/PK Analysis) Route of Administration: Oral gavage, once. Experimental Results: The plasma concentration exceeded 2 μM at 10 hr. Brain concentrations were nearly as high as plasma concentrations when measured 3 hr after a 7.5 mg/kg oral dose In vivo studies are conducted in mouse models of Alzheimer's disease to evaluate the therapeutic potential of BMS-984923. The compound is typically administered orally, taking advantage of its good oral bioavailability and BBB penetration. Its effects on synaptic density, functional connectivity, and cognitive function are assessed to determine its efficacy in reversing disease-related deficits. |
| ADME/Pharmacokinetics |
BMS-984923 demonstrates good oral bioavailability and excellent blood-brain barrier (BBB) penetration. These favorable pharmacokinetic properties are critical for its potential as a therapeutic agent for CNS disorders. Detailed PK parameters (e.g., t1/2, Cmax, AUC) would be available from preclinical studies but are not publicly detailed.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available. However, its mechanism of action as a silent allosteric modulator suggests a potentially favorable safety profile, as it does not directly activate or block the receptor but rather modulates pathological signaling. Standard toxicology studies would be required for clinical development.
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| References |
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| Additional Infomation |
BMS-984923 is a first-in-class mGluR5 silent allosteric modulator that has entered clinical trials for Alzheimer's disease. It has been investigated in a Phase I clinical trial (NCT05804383). Its ability to selectively block pathogenic Aβo signaling while preserving normal glutamate function makes it a promising therapeutic candidate. It is also known as ALX001.
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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 # |
1375752-78-5
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| Related CAS # |
(S,S)-BMS-984923;1375752-77-4
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| PubChem CID |
69084898
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| Appearance |
Off-white to light yellow 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-NHCUHLMSSA-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-/m1/s1
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| Chemical Name |
(4R,5R)-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) |
DMSO: 50 mg/mL (133.40 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.67 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 25.0 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: 2.5 mg/mL (6.67 mM) in 10% DMSO + 90% Corn Oil (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 25.0 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 | 2.6679 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05804383
Conditions:Alzheimer's DiseaseLink: https://clinicaltrials.gov/ct2/show/NCT06632990
Conditions:Drug Drug Interaction (DDI)Link: https://clinicaltrials.gov/ct2/show/NCT04805983
Conditions:Alzheimer Disease
Title:Food Effect Study of BMS-984923 in Healthy Older Adult Volunteers
Status:Unknown status
updateDate:2024-07-30
Ctid:NCT05817643
Link: https://clinicaltrials.gov/ct2/show/NCT05817643
Conditions:Alzheimer Disease|DementiaProducts are for research use only; We do not sell to patients
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