| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 25mg | |||
| Other Sizes |
| Targets |
IC50: 1.3 nM (SGLT2)[1]
HSK0935 targets SGLT2, a protein primarily expressed in the proximal tubules of the kidney that is responsible for the reabsorption of the majority of filtered glucose. By inhibiting SGLT2, it reduces glucose reabsorption, leading to increased urinary glucose excretion and lower blood glucose levels. It exhibits an impressive 843-fold selectivity over SGLT1, minimizing gastrointestinal side effects. |
|---|---|
| ln Vitro |
HSK0935 (Compound 31) has a strong hSGLT1/hSGLT2 selectivity of 843-fold and good hSGLT2 inhibition at 1.3 nM[1].
In vitro, HSK0935 potently inhibits human SGLT2 with an IC50 of 1.3 nM. Its high selectivity for SGLT2 over SGLT1 (843-fold) ensures that its glucose-lowering effects are achieved without significant inhibition of intestinal glucose absorption, which can cause gastrointestinal distress. |
| 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].
In vivo, HSK0935 is expected to exhibit potent antihyperglycemic activity. As an orally available SGLT2 inhibitor, it would reduce blood glucose levels in animal models of diabetes by promoting urinary glucose excretion. Its high selectivity suggests a favorable side-effect profile, with reduced risk of gastrointestinal issues associated with SGLT1 inhibition. |
| Enzyme Assay |
SGLT2 inhibitory activity is assessed using an in vitro assay with cells (e.g., CHO cells) stably expressing human SGLT2. The uptake of a radiolabeled glucose analog, such as [¹⁴C]-α-methyl-glucopyranoside (AMG), is measured in the presence of varying concentrations of HSK0935. The IC50 is calculated from the inhibition curve.
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| Cell Assay |
The functional activity of HSK0935 is evaluated in renal proximal tubule epithelial cells expressing SGLT2. Cells are treated with the compound, and glucose uptake is measured using a fluorescent glucose analog or radiolabeled glucose. The compound's ability to inhibit glucose uptake is determined, confirming its cellular activity.
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| Animal Protocol |
The in vivo efficacy of HSK0935 is evaluated in animal models of type 2 diabetes, such as db/db mice or streptozotocin-induced diabetic rats. HSK0935 is administered orally, and blood glucose levels are measured over time. Urinary glucose excretion is also quantified to confirm the mechanism of action.
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| ADME/Pharmacokinetics |
As an orally available small molecule, HSK0935 is expected to have good oral bioavailability. Its pharmacokinetic properties are typical of SGLT2 inhibitors, with rapid absorption and a half-life suitable for once-daily dosing. It is primarily excreted unchanged in the urine.
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| Toxicity/Toxicokinetics |
SGLT2 inhibitors are generally well-tolerated. Common adverse effects include increased risk of urinary tract and genital infections due to glycosuria. Dehydration and hypotension may occur in some patients, particularly those on diuretics.
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| References | |
| Additional Infomation |
HSK0935 is a research compound being developed as an antidiabetic agent. It is a potent and highly selective SGLT2 inhibitor with significant potential for the treatment of type 2 diabetes. It is not approved for clinical use and is intended for research purposes only.
|
| Molecular Formula |
C22H25CLO7
|
|---|---|
| Molecular Weight |
436.882706403732
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| Exact Mass |
436.128
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| CAS # |
1638851-44-1
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| PubChem CID |
86282875
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| Appearance |
White to off-white solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
586
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| Defined Atom Stereocenter Count |
5
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| 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
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| 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
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| 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
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| Synonyms |
HSK 0935 HSK-0935 HSK0935
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~228.90 mM)
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|---|---|
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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