SMS2-IN-2 is a potent, selective, orally bioavailable inhibitor of sphingomyelin synthase 2 (SMS2) with IC50s of 100 nM for SMS2 and 56 μM for SMS1. Can reduce chronic inflammatory response.

Physicochemical Properties

Molecular Formula	C19H13CLFN3O2
Molecular Weight	369.776826620102
Exact Mass	369.068
CAS #	2241838-28-6
PubChem CID	134813905
Appearance	White to off-white solid powder
LogP	4.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	26
Complexity	461
Defined Atom Stereocenter Count	0
SMILES	ClC1C=CC(=CC=1COC1=CC=CC2=C1C(=NO2)NC1C=NC=CC=1)F
InChi Key	VZWFUUUUCXTDJT-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H13ClFN3O2/c20-15-7-6-13(21)9-12(15)11-25-16-4-1-5-17-18(16)19(24-26-17)23-14-3-2-8-22-10-14/h1-10H,11H2,(H,23,24)
Chemical Name	4-[(2-chloro-5-fluorophenyl)methoxy]-N-pyridin-3-yl-1,2-benzoxazol-3-amine
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 Vivo	In mice with db/db backgrounds, SMS2-IN-2 (compound 15w; 20, 50 mg/kg/day, orally for 6 weeks) decreases chronic inflammation [1].
Animal Protocol	Animal/Disease Models: Type 2 Diabetes Mellitus (T2DM) db/db mouse model (4 to 5 weeks) [1] Doses: 20, 50 mg/kg/day Route of Administration: Oral daily for 6 weeks Experimental Results: IL-6 Dramatically lower and insulin levels.
References	[1]. Discovery of 4-Benzyloxybenzo[ d]isoxazole-3-amine Derivatives as Highly Selective and Orally Efficacious Human Sphingomyelin Synthase 2 Inhibitors that Reduce Chronic Inflammation in db/ db Mice. J Med Chem. 2018 Sep 27;61(18):8241-8254.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~338.04 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.62 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 (5.62 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	2.7043 mL	13.5216 mL	27.0431 mL
	5 mM	0.5409 mL	2.7043 mL	5.4086 mL
	10 mM	0.2704 mL	1.3522 mL	2.7043 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.