Aldumastat (GLPG1972;S201086) is a specific, orally bioactive ADAMTS-5 (IC50=19 nM) inhibitor that is 8 times more selective than ADAMTS-4 (IC50=156 nM). Aldumastat has antimetabolic activity and may be used in osteoarthritis research.

Physicochemical Properties

Molecular Formula	C20H24F2N4O3
Molecular Weight	406.426371574402
Exact Mass	406.181
CAS #	1957278-93-1
PubChem CID	121448788
Appearance	White to off-white solid powder
LogP	1.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	29
Complexity	679
Defined Atom Stereocenter Count	2
SMILES	FC1C=C(C=C(C=1)N1CCN(C[C@@H]1C)C(CC[C@@]1(C(NC(N1)=O)=O)C1CC1)=O)F
InChi Key	CMLVKUWQFZQPPS-YUNKPMOVSA-N
InChi Code	InChI=1S/C20H24F2N4O3/c1-12-11-25(6-7-26(12)16-9-14(21)8-15(22)10-16)17(27)4-5-20(13-2-3-13)18(28)23-19(29)24-20/h8-10,12-13H,2-7,11H2,1H3,(H2,23,24,28,29)/t12-,20-/m0/s1
Chemical Name	(5S)-5-cyclopropyl-5-[3-[(3S)-4-(3,5-difluorophenyl)-3-methylpiperazin-1-yl]-3-oxopropyl]imidazolidine-2,4-dione
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

Targets	ADAMTS-5 19 nM (IC50) ADAMTS-4 156 nM (IC50) MMP-2 1158 nM (IC50) MMP-14 >3198 nM (IC50)
ln Vivo	In mice, rats, and dogs, GLPG1972 (oral gavage; 5 mg/kg; single dosage) showed positive pharmacokinetic characteristics. In mice, rats, and dogs, the oral availability (F%) is 25, 58%, and 97%, respectively [1].
References	[1]. Discovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis. J Med Chem. 2021 Mar 25;64(6):2937-2952.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (246.04 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (12.30 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 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 (12.30 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 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 (12.30 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	2.4604 mL	12.3022 mL	24.6045 mL
	5 mM	0.4921 mL	2.4604 mL	4.9209 mL
	10 mM	0.2460 mL	1.2302 mL	2.4604 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.