HSK0935 (HSK-0935) is a novel and potent SGLT2 inhibitor (IC50 of 1.3 nM) with potential antihyperglycemic activities. As an inhibitor of Sodium-Dependent Glucose Cotransporter 2 (SGLT2), it has the potential to be used for the Treatment of Type 2 Diabetes.

Physicochemical Properties

Molecular Formula	C22H25CLO7
Molecular Weight	436.882706403732
Exact Mass	436.128
CAS #	1638851-44-1
PubChem CID	86282875
Appearance	White to off-white solid powder
LogP	1.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	30
Complexity	586
Defined Atom Stereocenter Count	5
SMILES	ClC1C=CC(=CC=1CC1C=CC(=CC=1)OCC)[C@]12[C@@H]([C@H]([C@@H]([C@@](CO1)(OC)O2)O)O)O
InChi Key	UFWQAQJFRMQRFR-CUUWFGFTSA-N
InChi Code	InChI=1S/C22H25ClO7/c1-3-28-16-7-4-13(5-8-16)10-14-11-15(6-9-17(14)23)22-20(26)18(24)19(25)21(27-2,30-22)12-29-22/h4-9,11,18-20,24-26H,3,10,12H2,1-2H3/t18-,19-,20+,21-,22-/m0/s1
Chemical Name	(1S,2S,3R,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-methoxy-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol
Synonyms	HSK 0935 HSK-0935 HSK0935
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	IC50: 1.3 nM (SGLT2)[1]
ln Vitro	HSK0935 (Compound 31) has a strong hSGLT1/hSGLT2 selectivity of 843-fold and good hSGLT2 inhibition at 1.3 nM[1].
ln Vivo	In Sprague-Dawley (SD) rats, HSK0935 administration (1, 3, and 10 mg/kg) exhibits strong urine glucose excretion, but in Rhesus monkeys, it has a greater impact[1]. HSK0935 is well tolerated up to 300 mg/kg in beagle dogs, with no fatalities or serious side effects observed in a 28-day repeat-dose toxicology study[1].
References	[1]. Discovery of a Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor (HSK0935) for the Treatment of Type 2 Diabetes. J Med Chem. 2017 May 25;60(10):4173-4184.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~228.90 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.72 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 25.0 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: ≥ 2.5 mg/mL (5.72 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 25.0 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	2.2890 mL	11.4448 mL	22.8896 mL
	5 mM	0.4578 mL	2.2890 mL	4.5779 mL
	10 mM	0.2289 mL	1.1445 mL	2.2890 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.