DS-1040 Tosylate is an orally bioactive, selective thrombin-activatable fibrinolysis inhibitor (TAFIa) inhibitor (antagonist) with IC50s of 5.92 nM and 8.01 nM for human and rat TAFIa, respectively. DS-1040 Tosylate is a fibrinolysis enhancer for use in thromboembolic diseases.

Physicochemical Properties

Molecular Formula	C23H35N3O5S
Molecular Weight	465.606105089188
Exact Mass	465.229
CAS #	1335138-89-0
PubChem CID	53464385
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	8
Heavy Atom Count	32
Complexity	536
Defined Atom Stereocenter Count	1
SMILES	S(C1C=CC(C)=CC=1)(O)(=O)=O.C(C1N=CN([C@@H]2CC[C@@H](C)CC2)C=1)[C@@H](C(=O)O)CCCN
InChi Key	BEUWOXSXOMMLGF-JYGFLIHTSA-N
InChi Code	InChI=1S/C16H27N3O2.C7H8O3S/c1-12-4-6-15(7-5-12)19-10-14(18-11-19)9-13(16(20)21)3-2-8-17;1-6-2-4-7(5-3-6)11(8,9)10/h10-13,15H,2-9,17H2,1H3,(H,20,21);2-5H,1H3,(H,8,9,10)/t12?,13-,15?;/m0./s1
Chemical Name	(2S)-5-amino-2-[[1-(4-methylcyclohexyl)imidazol-4-yl]methyl]pentanoic acid;4-methylbenzenesulfonic acid
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	Human carboxypeptidase N (CPN) is inhibited in vitro by DS-1040 Tosylate, with an IC50 of 3.02 mM[1].
ln Vivo	At doses of 0.005 mg/kg and above, DS-1040 Tosylate (0.0005-0.5 mg/kg; IV) considerably lowers the microthrombotic index [1]. In a microthrombosis model, DS1040 (0.016, 0.031, 0.063, 0.13, 0.25, 0.50 mg/kg; iv) raises plasma D-dimer levels in a dose-dependent manner. The relative ED50 and EDmax are 122 and 221 nmol/L[1]. Moreover, oral DS-1040 (0.25, 0.5, 1, 2, 4, 8, 16 mg/kg) raises plasma D-dimer concentrations. The values for EC50 and ECmax are, respectively, 114 and 231 nmol/L[1].
Animal Protocol	Animal/Disease Models: Male Slc: Wistar rat [1] Doses: 0.0005, 0.005, 0.05, 0.5 mg/kg Route of Administration: IV Experimental Results: The microthrombotic index was Dramatically diminished at doses of 0.005 mg/kg and greater.
References	[1]. Fibrinolytic potential of DS-1040, a novel orally available inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa). Thromb Res. 2018 Aug;168:96-101.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~214.77 mM) H2O : ≥ 50 mg/mL (~107.39 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (10.74 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 (10.74 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 (10.74 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. Solubility in Formulation 4: 100 mg/mL (214.77 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1477 mL	10.7386 mL	21.4772 mL
	5 mM	0.4295 mL	2.1477 mL	4.2954 mL
	10 mM	0.2148 mL	1.0739 mL	2.1477 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.