GLPG0974 is a free fatty acid receptor-2 (FFA2/GPR43) antagonist (inhibitor) with IC50 of 9 nM.

Physicochemical Properties

Molecular Formula	C25H25N2O4SCL
Molecular Weight	484.995
Exact Mass	484.122
Elemental Analysis	C, 61.91; H, 5.20; Cl, 7.31; N, 5.78; O, 13.20; S, 6.61
CAS #	1391076-61-1
Related CAS #	(S)-GLPG0974;2326220-69-1
PubChem CID	57520598
Appearance	Off-white to light yellow solid powder
LogP	4.3
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	8
Heavy Atom Count	33
Complexity	752
Defined Atom Stereocenter Count	1
SMILES	C[C@@]1(CCN1C(=O)C2=CSC3=CC=CC=C32)C(=O)N(CCCC(=O)O)CC4=CC(=CC=C4)Cl
InChi Key	MPMKMQHJHDHPBE-RUZDIDTESA-N
InChi Code	InChI=1S/C25H25ClN2O4S/c1-25(11-13-28(25)23(31)20-16-33-21-9-3-2-8-19(20)21)24(32)27(12-5-10-22(29)30)15-17-6-4-7-18(26)14-17/h2-4,6-9,14,16H,5,10-13,15H2,1H3,(H,29,30)/t25-/m1/s1
Chemical Name	4-[[(2R)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid
Synonyms	GLPG-0974; GLPG 0974; GLPG0974
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 Vitro	In vitro, GLPG0974 significantly suppresses buffer salt-induced neutrophil migration. In a human whole blood assay, it also shows suppression of the neutrophil pharmacodynamic (PD) marker CD11b activating buffer epitope [AE][1].
ln Vivo	GLPG0974 demonstrated exceptional pharmacokinetic characteristics concerning toxicity, with a 47% bioavailability and a dosage rise that was linear following 5 and 30 mg/kg of the powdered medication. The program's objective of achieving lengthy target coverage in people is congruent with the reported rise in half-life following higher doses of Manhattan [1].
References	[1]. Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA2) antagonist: from hit to clinic. J Med Chem. 2014 Dec 11;57(23):10044-57.
Additional Infomation	GLPG-0974 is under investigation in clinical trial NCT01721980 (Multiple Ascending Dose Study of GLPG0974 in Healthy Subjects).

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~412.37 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 5 mg/mL (10.31 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: 5 mg/mL (10.31 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 50.0 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 3: ≥ 5 mg/mL (10.31 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 50.0 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	2.0619 mL	10.3093 mL	20.6186 mL
	5 mM	0.4124 mL	2.0619 mL	4.1237 mL
	10 mM	0.2062 mL	1.0309 mL	2.0619 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.