GLPG2451 is an enhancer of cystic fibrosis transmembrane conductance regulator (CFTR) that potently enhances hypothermia-rescued F508del CFTR with EC50 of 11.1 nM.

Physicochemical Properties

Molecular Formula	C16H16F3N3O5S
Molecular Weight	419.3756
Exact Mass	419.076
CAS #	2055015-61-5
PubChem CID	124106089
Appearance	Light yellow to yellow solid powder
LogP	2.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	6
Heavy Atom Count	28
Complexity	632
Defined Atom Stereocenter Count	1
SMILES	S(C1C([H])=C([H])C(=C([H])C=1[H])OC(F)(F)F)(C1C([H])=NC(C(N([H])C([H])([H])[C@]([H])(C([H])([H])[H])O[H])=O)=C(C=1[H])N([H])[H])(=O)=O
InChi Key	UMOGNCVNHXWFIX-VIFPVBQESA-N
InChi Code	InChI=1S/C16H16F3N3O5S/c1-9(23)7-22-15(24)14-13(20)6-12(8-21-14)28(25,26)11-4-2-10(3-5-11)27-16(17,18)19/h2-6,8-9,23H,7,20H2,1H3,(H,22,24)/t9-/m0/s1
Chemical Name	3-amino-N-[(2S)-2-hydroxypropyl]-5-[4-(trifluoromethoxy)phenyl]sulfonylpyridine-2-carboxamide
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 G551D/F508del cells, GLPG2451's EC50 value is 675 nM, and its effectiveness is 147% that of VX770[1].
References	[1]. Identification and Characterization of Novel CFTR Potentiators. Front Pharmacol. 2018 Oct 26;9:1221.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~596.12 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.96 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 20.8 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: ≥ 2.08 mg/mL (4.96 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 20.8 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: ≥ 2.08 mg/mL (4.96 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 20.8 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	2.3845 mL	11.9224 mL	23.8447 mL
	5 mM	0.4769 mL	2.3845 mL	4.7689 mL
	10 mM	0.2384 mL	1.1922 mL	2.3845 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.