5.09665

Glucokinase Activator III, Ro-28-1675

• Synonym(s): Glucokinase Activator III, Ro-28-1675, GK Activator III, Hexokinase D Activator III, Hexokinase IV Activator III, Ro-28-0450 ( R)-enantiomer, RO0281675, GK Activator III, Hexokinase D Activator III, Hexokinase IV Activator III, Ro-28-0450 (R)-enantiomer, RO0281675
• Empirical Formula (Hill Notation): C₁₈H₂₂N₂O₃S₂
• CAS Number: 300353-13-3
• Molecular Weight: 378.51
• UNSPSC Code: 12352200

Properties

• Assay: ≥98% (HPLC)
• Quality Level: 100
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: white
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C
• 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
• InChI key: NEQSWPCDHDQINX-MRXNPFEDSA-N

Description

General description

A cell-permeable thiazolyl-propanamide compound that acts as a glucokinase (GK) activator by increasing V_max and decreasing [S]_1/2 of GK-catalyzed reaction as well as freeing GK from the inhibitory action of GK regulatory protein (GKRP), resulting in increased. Induces GK nuclear-to-cytosol translocation in primary rat hepatocytes and reduces glucose concentration for insulin secretion stimulation from isolated rat pancreatic islets (threshold [glucose] = 3 mM vs 6 mM with or without 3 µM Ro-28-1675). Exhibits in vivo glucose-lowering and insulin-releasing activity in non-diabetic C57BL/6 mice and Wistar rats and is efficacious in several murine and rodent type II diabetes mellitus (T2DM) models (10 to 50 mg/kg via p.o.). Does not affect hexokinase I or II activity.

A cell-permeable thiazolyl-propanamide compound that acts as an allosteric glucokinase-(GK) selective activator, increasing V_max and decreasing [S]_1/2 (by 1.5- and 4.3-fold, respectively, at 3 µM; [Glucose] = 5 mM) in human GK enzymatic assays, as well as freeing GK from the inhibitory action of GK regulatory protein (GKRP), resulting in increased GK nuclear-to-cytosol translocation in primary rat hepatocytes (EC₅₀/[Glucose] = 0.16 µM/16.8 mM, 0.27 µM/8.4 mM, 2.2 µM/2.8 mM) and reduced glucose concentration for stimulating insulin secretion from isolated rat pancreatic islets (threshold [glucose] = 3 mM vs 6 mM with or without 3 µM Ro-28-1675). Exhibits in vivo glucose-lowering and insulin-releasing activity in non-diabetic C57BL/6 mice and Wistar rats and is efficacious in several murine (KK/Upj-Ay/J, ob/ob, and diet-induced obese C57BL/6) and rodent (Goto-Kakizaki) type II diabetes mellitus (T2DM) models (10 to 50 mg/kg via p.o.), while efficacy is no longer observed in older hypoinsulinemic db/db mice with blood glucose levels reaching 300 mg/dl. Reported not to affect the activity of hexokinase I or II and display no activity toward GK-independent insulin release from β cells upon 2-Ketoisocaproic acid (α-KIC) stimulation.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Glucokinase

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Wolff, M., et al. 2008. J. Biomol. Screen13, 837.

Grimsby, J., et al. 2003. Science301, 370.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable