| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Glucokinase (GK / GCK). RO 28-1675 is a potent allosteric activator of glucokinase with an EC50 of 54 nM. Glucokinase is a key enzyme in glucose metabolism that catalyzes the phosphorylation of glucose to glucose-6-phosphate, the first step in glycolysis. It acts as a glucose sensor in pancreatic β-cells and hepatocytes, regulating insulin secretion and hepatic glucose uptake.
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| ln Vitro |
The inhibitory impact of human glucokinase regulating protein (GKRP) can be counteracted by RO-28-1675 [2].
In vitro, RO 28-1675 demonstrates potent glucokinase activation with an EC50 of 54 nM. The compound increases Vmax and decreases the [S]1/2 of the GK-catalyzed reaction, and frees GK from the inhibitory action of GKRP. It augments hepatic glucose metabolism and glucose-induced insulin secretion from isolated rodent pancreatic islets. |
| ln Vivo |
In wild-type C57BL/6J mice, RO-28-1675 (50 mg/kg; oral) lowers blood glucose levels [2]. Following oral treatment (10 mg/kg), RO-28-1675 has a high oral bioavailability (92.8% in mice) and Cmax (1140 μg/mL).
In vivo, RO 28-1675 lowers blood glucose levels and increases hepatic glucose uptake in rodent models of type 2 diabetes mellitus. At a dose of 50 mg/kg orally in male C57Bl/6J mice, the compound caused a statistically significant reduction in fasting glucose levels and improvement in glucose tolerance relative to vehicle-treated animals. These effects support the potential of glucokinase activators for the treatment of type 2 diabetes. |
| Enzyme Assay |
Cell-free enzyme assays for RO 28-1675 use recombinant human glucokinase (GK) and its substrate glucose in the presence of ATP. The compound is incubated with the enzyme at varying concentrations (0.001-10000 nM) for 30-60 minutes at 37°C. GK activity is measured by detecting the production of glucose-6-phosphate using a coupled enzyme assay with glucose-6-phosphate dehydrogenase, monitoring NADPH production spectrophotometrically at 340 nm. EC50 values are calculated from dose-response curves.
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| Cell Assay |
In vitro cellular assays for RO 28-1675 are performed using isolated rodent pancreatic islets or hepatocytes. Islets are isolated from rat or mouse pancreas and cultured in 96-well plates. The islets are treated with RO 28-1675 at concentrations ranging from 0.01-1000 nM in the presence of varying glucose concentrations (2-20 mM) for 1-2 hours. Insulin secretion is measured by ELISA or radioimmunoassay. Glucose uptake in hepatocytes is measured using radiolabeled 2-deoxyglucose. EC50 values for glucose-dependent insulin secretion are determined from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: 10weeks old male C57BL/6J mice [2]
Doses: 50 mg/kg Route of Administration: Oral Experimental Results:Lower blood sugar levels. Animal/Disease Models: C57BL/6J mice[1] Doses: 10 mg/kg (pharmacokinetic/PK/PK analysis Route of Administration: Oral Experimental Results:Oral bioavailability (92.8%), Cmax (1140 μg/mL), T max ( 3.3h). In vivo efficacy studies are conducted in rodent models of type 2 diabetes, such as db/db mice, ob/ob mice, or high-fat diet-induced diabetic mice. RO 28-1675 is administered orally at doses typically ranging from 10-100 mg/kg. Blood glucose levels are measured at various time points after dosing using a glucometer. Glucose tolerance tests are performed by oral glucose challenge (2 g/kg) and measuring blood glucose at multiple time points. Insulin levels are measured by ELISA. Hepatic glucose uptake is assessed using radiolabeled glucose analogs. Body weight, food intake, and HbA1c levels are monitored in chronic studies. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of RO 28-1675 demonstrate that the compound is orally active. PK parameters such as Cmax, Tmax, AUC, half-life, and oral bioavailability are determined in preclinical species. The compound's favorable PK properties support oral dosing for type 2 diabetes research. Metabolic stability is assessed using liver microsome or hepatocyte incubation studies.
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| Toxicity/Toxicokinetics |
Toxicological data for RO 28-1675 are limited to preclinical research studies. As a glucokinase activator, potential toxicities may include hypoglycemia and effects on hepatic lipid metabolism. Standard toxicology studies would be required for clinical development. At research-grade doses used in animal models, the compound is generally well-tolerated.
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| References |
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| Additional Infomation |
(2R)-3-cyclopentyl-2-(4-methylsulfonylphenyl)-N-(2-thiazolyl)propionamide is a member of the acetamide class of compounds.
RO 28-1675 is a research compound for studying glucokinase biology and validating glucokinase activation as a therapeutic strategy for type 2 diabetes. It is not an approved drug and has not entered clinical trials. The compound is available from chemical suppliers for research purposes only. Its potent allosteric activation of glucokinase and ability to lower blood glucose in diabetic models make it a valuable tool for studying glucose metabolism and developing anti-diabetic therapies. The compound should be stored at -20°C and handled according to standard laboratory safety protocols. |
| Molecular Formula |
C18H22N2O3S2
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|---|---|
| Molecular Weight |
378.50888
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| Exact Mass |
378.107
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| CAS # |
300353-13-3
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| PubChem CID |
9886086
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| Appearance |
White to off-white solid powder
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| LogP |
5.003
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
547
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CS(=O)(=O)C1=CC=C(C=C1)[C@@H](CC2CCCC2)C(=O)NC3=NC=CS3
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| InChi Key |
NEQSWPCDHDQINX-MRXNPFEDSA-N
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| InChi Code |
InChI=1S/C18H22N2O3S2/c1-25(22,23)15-8-6-14(7-9-15)16(12-13-4-2-3-5-13)17(21)20-18-19-10-11-24-18/h6-11,13,16H,2-5,12H2,1H3,(H,19,20,21)/t16-/m1/s1
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| Chemical Name |
(2R)-3-Cyclopentyl-2-[4-(methanesulfonyl)phenyl]-N-(thiazol-2-yl)propionamide
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| Synonyms |
RO28-1675 RO-28-1675 RO 28-1675 RO028-1675 RO-028-1675 RO 028-1675
RO281675 RO 281675 RO-281675 Ro 0281675 Ro-0281675 Ro0281675.
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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 : ~50 mg/mL (~132.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.60 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 (6.60 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 25.0 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: ≥ 2.5 mg/mL (6.60 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 | 2.6419 mL | 13.2097 mL | 26.4194 mL | |
| 5 mM | 0.5284 mL | 2.6419 mL | 5.2839 mL | |
| 10 mM | 0.2642 mL | 1.3210 mL | 2.6419 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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