ASP-4058 is a selective, orally bioactive second-generation agonist of sphingosine phosphate receptors 1 and 5 (S1P1 and S1P5), which can improve experimental autoimmune encephalomyelitis in mice and has a good safety profile .

Physicochemical Properties

Molecular Formula	C19H12F6N4O2
Molecular Weight	442.314604759216
Exact Mass	442.086
CAS #	952565-91-2
Related CAS #	952510-14-4 (HCl);
PubChem CID	16755143
Appearance	White to off-white solid powder
LogP	5.4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	4
Heavy Atom Count	31
Complexity	621
Defined Atom Stereocenter Count	1
SMILES	FC([C@H](C)OC1C=CC(C2=NC(C3C=CC4=C(C=3)NC=N4)=NO2)=CC=1C(F)(F)F)(F)F
InChi Key	NJNXCJPSMWKXHO-VIFPVBQESA-N
InChi Code	InChI=1S/C19H12F6N4O2/c1-9(18(20,21)22)30-15-5-3-11(6-12(15)19(23,24)25)17-28-16(29-31-17)10-2-4-13-14(7-10)27-8-26-13/h2-9H,1H3,(H,26,27)/t9-/m0/s1
Chemical Name	3-(3H-benzimidazol-5-yl)-5-[3-(trifluoromethyl)-4-[(2S)-1,1,1-trifluoropropan-2-yl]oxyphenyl]-1,2,4-oxadiazole
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: This product requires protection from light (avoid light exposure) during transportation and storage.
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 Vivo	ASP4058 (oral, once daily for 21 days) lowered clinical ratings in a dose-dependent manner, with cumulative clinical scores of 15.5±1.48, 9.50±2.17 and 0.3 mg/kg from day 0 to 21 dpi, respectively. 1.17±0.619 in rats, respectively, and 15.5±0.619 in the vehicle-treated group. ASP4058 reduces weight loss in EAE rats [1]. ASP4058 (oral, daily from days 12 to 45) maintained clinical ratings at relatively low levels, with cumulative clinical scores (18-45 dpi) of 6.90 ± 2.85 and 5.60 for the 0.1 and 0.3 mg/kg dosage treatment groups, respectively. ±2.21, respectively, in mice. The ED50 value of ASP4058 is 0.063 mg/kg[1].
Animal Protocol	Animal/Disease Models: Male Lewis rats with induced EAE [1]. Doses: 0.03, 0.1 or 0.3 mg/kg. Route of Administration: po (po (oral gavage)) one time/day for 21 days. Experimental Results: Clinical scores and cumulative clinical scores were diminished in a dose-dependent manner. Animal/Disease Models: SJL mice immunized with PLP139-151 and boosted with pertussis toxin developed relapsing-remitting EAE[1]. Doses: 0.1 and 0.3 mg/kg Route of Administration: Orally one time/day from days 12 to 45. Experimental Results: Clinical scores and cumulative clinical scores (18-45 dpi) were maintained at relatively low levels.
References	[1]. ASP4058, a Novel Agonist for Sphingosine 1-Phosphate Receptors 1 and 5, Ameliorates Rodent Experimental Autoimmune Encephalomyelitis with a Favorable Safety Profile. PLoS One. 2014 Oct 27;9(10):e110819.
Additional Infomation	ASP4058 has been used in trials studying Food Effect of ASP4058 and Pharmacokinetics of ASP4058.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 50 mg/mL (~113.04 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.83 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 12.5 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: 1.25 mg/mL (2.83 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 12.5 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: ≥ 1.25 mg/mL (2.83 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 12.5 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	2.2609 mL	11.3043 mL	22.6086 mL
	5 mM	0.4522 mL	2.2609 mL	4.5217 mL
	10 mM	0.2261 mL	1.1304 mL	2.2609 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.