| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 500mg | |||
| Other Sizes |
| Targets |
The primary target of KGA-2727 is sodium glucose cotransporter 1 (SGLT1), a transporter protein responsible for glucose absorption in the intestine and glucose reabsorption in the kidney. KGA-2727 is a potent, selective, high-affinity inhibitor of SGLT1 with Ki values of 97.4 nM and 43.5 nM for human SGLT1 and rat SGLT1, respectively. The compound shows excellent selectivity for SGLT1 over SGLT2, with selectivity ratios of 140 (human) and 390 (rat). By inhibiting SGLT1, KGA-2727 reduces glucose absorption from the intestine and glucose reabsorption in the kidney, thereby lowering blood glucose levels.
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| ln Vitro |
Good linearity for human SGLT1 and SGLT2 is demonstrated by the Dixon plot study of KGA-2727. Dixon plot results show that KGA-2727 inhibits these SGLTs in a way that is competitive. KGA2727 inhibits SGLT1 and SGLT2's absorption of methyl-D-glucopyranoside (AMG) in a dose-dependent manner [1].
KGA-2727 inhibits SGLT1 with Ki values of 97.4 nM and 43.5 nM for human SGLT1 and rat SGLT1, respectively. The compound shows excellent selectivity for SGLT1 over SGLT2, with selectivity ratios of 140 (human) and 390 (rat). This selectivity is important for avoiding the side effects associated with SGLT2 inhibition, such as increased risk of urinary tract infections and ketoacidosis. The compound's pyrazole-O-glucoside structure contributes to its high affinity and selectivity for SGLT1. |
| ln Vivo |
KGA-2727 decreased the rise in plasma glucose following a glucose load in the oral glucose tolerance test conducted in streptozotocin-induced diabetic rats, suggesting that KGA-2727 ameliorated postprandial hyperglycemia [1]. In Zucker diabetic fat (ZDF) rats, long-term administration of KGA-2727 decreased plasma glucose and glycated hemoglobin levels. KGA-2727 can also improve the morphological alterations of the pancreatic islets and renal distal tubules in ZDF rats, maintaining glucose-stimulated insulin production and lowering urine glucose excretion [1].
KGA-2727 has antidiabetic efficacy and is used for the treatment of diabetes. By inhibiting SGLT1, the compound reduces glucose absorption from the intestine and glucose reabsorption in the kidney, leading to lower blood glucose levels. The compound's selectivity for SGLT1 over SGLT2 allows it to exert antidiabetic effects without the side effects associated with SGLT2 inhibition. In vivo efficacy would be evaluated in diabetic animal models such as db/db mice or STZ-induced diabetic rats. |
| Enzyme Assay |
No specific non-cell assay protocol is available for KGA-2727. For SGLT1 inhibitors, standard cell-free assays include radioligand binding or transport assays using membrane preparations from cells expressing recombinant SGLT1. The compound's inhibition of [¹⁴C]-glucose uptake or binding of radiolabeled inhibitors can be measured to determine Ki values. These assays provide quantitative data on the compound's affinity for SGLT1 and selectivity over SGLT2.
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| Cell Assay |
No specific cell-based assay protocol is available for KGA-2727. For SGLT1 inhibitors, standard cellular assays use cells expressing recombinant human or rat SGLT1. Cells are treated with KGA-2727 in the presence of [¹⁴C]-glucose or a fluorescent glucose analog, and glucose uptake is measured. The compound's inhibition of glucose uptake is measured to determine IC50 or Ki values. Selectivity over SGLT2 can be assessed using cells expressing SGLT2.
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| Animal Protocol |
No specific animal protocol is available for KGA-2727. For antidiabetic studies, standard in vivo models include diabetic rodents such as db/db mice, ob/ob mice, or STZ-induced diabetic rats. KGA-2727 is administered orally for 2-4 weeks. Blood glucose levels, oral glucose tolerance, and HbA1c are measured throughout the study. Body weight, food intake, and metabolic parameters are also monitored. At the end of the study, tissues are collected for histology and biochemical analysis.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is publicly available for KGA-2727. The compound has a molecular weight of 536.62 and formula C26H40N4O8. As a pyrazole-O-glucoside, it would be expected to have reasonable oral bioavailability for antidiabetic applications. The compound's glucoside moiety may be metabolized by intestinal or hepatic glucosidases. Comprehensive pharmacokinetic studies would be required to determine absorption, distribution, metabolism, and excretion parameters.
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| Toxicity/Toxicokinetics |
No detailed toxicology data is publicly available for KGA-2727. As a research compound with antidiabetic potential, standard preclinical toxicology would be required for therapeutic development. The compound's selectivity for SGLT1 over SGLT2 may contribute to a favorable safety profile by avoiding the side effects associated with SGLT2 inhibition. However, comprehensive safety evaluation would be necessary before any clinical application. The compound is for research use only.
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| References | |
| Additional Infomation |
KGA-2727 has the molecular formula C26H40N4O8 and molecular weight 536.62. The chemical name is 3-{[3-(3-methyl-4-{[5-(propan-2-yl)-3-{[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-1H-pyrazol-4-yl]methyl}phenoxy)propyl]amino}propanamide. The compound has a pyrazole-O-glucoside structure and is the first selective SGLT1 inhibitor. It has antidiabetic efficacy and is used for the treatment of diabetes. No clinical trial status has been identified; it remains a research tool for studying SGLT1 biology and diabetes.
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| Molecular Formula |
C26H40N4O8
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| Molecular Weight |
536.6178
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| Exact Mass |
536.284
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| CAS # |
666842-36-0
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| Related CAS # |
666842-36-0
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| PubChem CID |
10052896
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| Appearance |
White to yellow solid powder
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| LogP |
0.6
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| Hydrogen Bond Donor Count |
7
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
38
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| Complexity |
719
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1[C@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])O[H])OC1C(C([H])([H])C2C([H])=C([H])C(=C([H])C=2C([H])([H])[H])OC([H])([H])C([H])([H])C([H])([H])N([H])C([H])([H])C([H])([H])C(N([H])[H])=O)=C(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])N=1
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| InChi Key |
MDBARDSTXONTFS-MNDUUMEHSA-N
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| InChi Code |
InChI=1S/C26H40N4O8/c1-14(2)21-18(25(30-29-21)38-26-24(35)23(34)22(33)19(13-31)37-26)12-16-5-6-17(11-15(16)3)36-10-4-8-28-9-7-20(27)32/h5-6,11,14,19,22-24,26,28,31,33-35H,4,7-10,12-13H2,1-3H3,(H2,27,32)(H,29,30)/t19-,22-,23+,24-,26+/m1/s1
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| Chemical Name |
3-(3-{4-[3-(beta-D-glucopyranosyloxy)-5-isopropyl-1Hpyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)propionamide
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| Synonyms |
KGA-2727 KGA 2727 KGA2727.
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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 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)
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| Solubility (In Vitro) |
DMSO : ~200 mg/mL (~372.70 mM)
Ethanol : ~100 mg/mL (~186.35 mM) H2O : ~20 mg/mL (~37.27 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.32 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 (9.32 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (9.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8635 mL | 9.3176 mL | 18.6352 mL | |
| 5 mM | 0.3727 mL | 1.8635 mL | 3.7270 mL | |
| 10 mM | 0.1864 mL | 0.9318 mL | 1.8635 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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