BMS-984923 is a potent mGluR5 silent isomeric modulator with good affinity (Ki = 0.6 nM), good oral bioavailability (F) and BBB (blood-brain barrier) permeability. BMS-984923 can effectively inhibit the PrPC-mGluR5 interaction and inhibit pathological Aβo signaling without affecting physiological glutamate signaling.

Physicochemical Properties

Molecular Formula	C22H15CLN2O2
Molecular Weight	374.819704294205
Exact Mass	374.082
CAS #	1375752-78-5
Related CAS #	(S,S)-BMS-984923;1375752-77-4
PubChem CID	69084898
Appearance	Off-white to light yellow solid powder
LogP	4.4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	592
Defined Atom Stereocenter Count	2
SMILES	ClC1C=CC=CC=1[C@@H]1[C@@H](C2C=NC=C(C#CC3C=CC=CC=3)C=2)NC(=O)O1
InChi Key	IAYVUQJOKDFLAL-NHCUHLMSSA-N
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
Chemical Name	(4R,5R)-5-(2-chlorophenyl)-4-[5-(2-phenylethynyl)pyridin-3-yl]-1,3-oxazolidin-2-one
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vivo	BMS-984923 has high oral bioavailability and BBB penetration (7.5 mg/kg or 15 mg/kg, oral gavage, once)[1].
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
References	[1]. Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer's Mouse Phenotypes. Cell Rep. 2017 Jul 5;20(1):76-88. [2]. Oxazolidinone-based allosteric modulators of mGluR5: Defining molecular switches to create a pharmacological tool box. Bioorg Med Chem Lett. 2016 Sep 1;26(17):4165-9.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (133.40 mM)

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.