Darexaban (YM150) is a potent, selective and orally bioactive factor Xa (FXa) inhibitor (antagonist) with IC50 of 54.6 nM. Darexaban displays high selectivity against other related serine proteases like trypsin, thrombin, and kallikrein. Darexaban has anticoagulant and antithrombotic effects.

Physicochemical Properties

Molecular Formula	C27H30N4O4
Molecular Weight	474.5515
Exact Mass	474.227
CAS #	365462-23-3
PubChem CID	9912771
Appearance	Off-white to light yellow solid powder
LogP	4.196
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	35
Complexity	691
Defined Atom Stereocenter Count	0
InChi Key	IJNIQYINMSGIPS-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H30N4O4/c1-30-15-4-16-31(18-17-30)21-11-7-19(8-12-21)27(34)29-25-23(5-3-6-24(25)32)28-26(33)20-9-13-22(35-2)14-10-20/h3,5-14,32H,4,15-18H2,1-2H3,(H,28,33)(H,29,34)
Chemical Name	N-[2-hydroxy-6-[(4-methoxybenzoyl)amino]phenyl]-4-(4-methyl-1,4-diazepan-1-yl)benzamide
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	When taken orally, darexaban, an inhibitor of factor Xa (FXa), is quickly and thoroughly metabolized to produce its glucuronide conjugate, YM-222714. In addition to inhibiting prothrombin activation caused by the prothrombinase complex or entire blood clots with potency comparable to that of free FXa, darexaban also specifically and competitively inhibits human FXa [2].
ln Vivo	In mice, Darexaban decreased FXa activity in plasma with an ED50 value of 24.8 mg/kg. Darexaban 3 mg/kg can extend prothrombin time (PT) [2]. In a mouse model of pulmonary thromboembolism (PE), darexaban dosage-dependently reduced mortality, with a substantial impact at a dose of 10 mg/kg [2]. In a mouse model of FeCl3-induced venous thrombosis (VT), Darexaban (0.3-10 mg/kg) dose-dependently reduced thromboprotein content, with significant effects at doses of 3 mg/kg or higher [2].
References	[1]. Discovery of N-[2-hydroxy-6-(4-methoxybenzamido)phenyl]-4- (4-methyl-1,4-diazepan-1-yl)benzamide (darexaban, YM150) as a potent and orally available factor Xa inhibitor. J Med Chem. 2011 Dec 8;54(23):8051-65. [2]. Darexaban: anticoagulant effects in mice and human plasma in vitro, antithrombotic effects in thrombosis and bleeding models in mice and effects of anti-inhibitor coagulant complex and recombinant factor VIIa. Thromb Res. 2013 May;131(5. [3]. Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors. Molecules. 2016 Feb 4;21(2):185.
Additional Infomation	Darexaban has been used in trials studying the prevention and basic science of Japanese, Caucasian, Thromboembolism, Pharmacodynamics, and Pharmacokinetics, among others. Tanexaban is an orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Tanexaban is extensively metabolized in the liver to its active metabolite and is excreted by the kidneys and in the feces.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~526.81 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.38 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 (4.38 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 (4.38 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	2.1073 mL	10.5363 mL	21.0726 mL
	5 mM	0.4215 mL	2.1073 mL	4.2145 mL
	10 mM	0.2107 mL	1.0536 mL	2.1073 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.