Ro 28-1675 (Ro-0281675) is a novel, potent and allosteric GK activator with a SC1.5 value of 0.24± 0.0019 uM. Ro 28-1675 reduced fasting and postprandial glucose levels following an OGTT, was well tolerated, and displayed no adverse effects related to drug administration other than hypoglycemia at the maximum dose (400 mg).

Physicochemical Properties

Molecular Formula	C18H22N2O3S2
Molecular Weight	378.50888
Exact Mass	378.107
CAS #	300353-13-3
PubChem CID	9886086
Appearance	White to off-white solid powder
LogP	5.003
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	25
Complexity	547
Defined Atom Stereocenter Count	1
SMILES	CS(=O)(=O)C1=CC=C(C=C1)[C@@H](CC2CCCC2)C(=O)NC3=NC=CS3
InChi Key	NEQSWPCDHDQINX-MRXNPFEDSA-N
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
Chemical Name	(2R)-3-Cyclopentyl-2-[4-(methanesulfonyl)phenyl]-N-(thiazol-2-yl)propionamide
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.
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

ln Vitro	The inhibitory impact of human glucokinase regulating protein (GKRP) can be counteracted by RO-28-1675 [2].
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).
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).
References	[1]. Discovery, structure-activity relationships, pharmacokinetics, and efficacy of glucokinase activator (2R)-3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide (RO0281675). J Med Chem. 2010 May 13;53(9):3618-25. [2]. Allosteric activators of glucokinase: potential role in diabetes therapy. Science. 2003 Jul 18;301(5631):370-3.
Additional Infomation	(2R)-3-cyclopentyl-2-(4-methylsulfonylphenyl)-N-(2-thiazolyl)propanamide is a member of acetamides.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~132.10 mM)

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. 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. 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	2.6419 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.