Dorzagliatin (RO-5305552; HMS-5552; sinogliatin) is an investigational antidiabetic agent acting as a dual-acting glucokinase activator (GKA) that is able to improves glycaemic control and pancreatic β-cell function in type 2 diabete. As of 2022 Oct 8, Dorzagliatin gained approval from the Chinese FDA (NMPA) for treating types II diabetes. Glucokinase (GK) plays a critical role in the control of whole-body glucose homeostasis. The novel GKA, HMS5552, exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients.
Physicochemical Properties
| Molecular Formula | C22H27CLN4O5 |
| Molecular Weight | 462.931 |
| Exact Mass | 462.166 |
| CAS # | 1191995-00-2 |
| Related CAS # | 1191995-14-8 (HCl);1191995-00-2; |
| PubChem CID | 57920094 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 761.7±60.0 °C at 760 mmHg |
| Flash Point | 414.5±32.9 °C |
| Vapour Pressure | 0.0±2.7 mmHg at 25°C |
| Index of Refraction | 1.631 |
| LogP | 2.78 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 32 |
| Complexity | 691 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC(C)C[C@@H](C(=O)NC1=NN(C=C1)C[C@H](CO)O)N2CC(=CC2=O)OC3=CC=CC=C3Cl |
| InChi Key | HMUMWSORCUWQJO-QAPCUYQASA-N |
| InChi Code | InChI=1S/C22H27ClN4O5/c1-14(2)9-18(22(31)24-20-7-8-26(25-20)11-15(29)13-28)27-12-16(10-21(27)30)32-19-6-4-3-5-17(19)23/h3-8,10,14-15,18,28-29H,9,11-13H2,1-2H3,(H,24,25,31)/t15-,18+/m1/s1 |
| Chemical Name | (2S)-2-[4-(2-chlorophenoxy)-2-oxo-2,5-dihydro-1H-pyrrol-1-yl]-N-{1-[(2R)-2,3-dihydroxypropyl]-1H-pyrazol-3-yl}-4-methylpentanamide |
| Synonyms | Dorzagliatinsinogliatin, HMS 5552RO-5305552 HMS-5552 RO5305552 HMS5552RO 5305552 |
| 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 Vivo | Dorzagliatin has a hypoglycemic impact on blood glucose levels of diabetes cholesterol (low dose: 10 mg/kg, high dose: 30 mg/kg; intragastric formulation; daily at 8:00 a.m. for one month) [2]. |
| Animal Protocol |
Animal/Disease Models: Male Sprague -Dawley (SD) rat (age approximately 6-8 weeks, body weight 200-230 g) [2 doses: low dose (10 mg/kg) and high dose (30 mg/kg) Route of Administration: intragastric (po) (po)administration (ig)); daily (8:00 a.m.) for one month Experimental Results: Produces a hypoglycemic effect on blood sugar levels. |
| References |
[1]. Dorzagliatin (HMS5552), a novel dual-acting glucokinase activator, improves glycaemic control and pancreatic β-cell function in patients with type 2 diabetes: A 28-day treatment study using biomarker-guided patient selection. Diabetes Obes Metab. 2018 Sep;20(9):2113-2120. [2]. Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus. J Diabetes Res. 2017;2017:5812607. |
| Additional Infomation | Dorzagliatin is under investigation in clinical trial NCT03173391 (Long-term Efficacy and Safety of HMS5552 in T2DM). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~125 mg/mL (~270.02 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.49 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 20.8 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: ≥ 2.08 mg/mL (4.49 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 20.8 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: ≥ 2.08 mg/mL (4.49 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 20.8 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 | 2.1602 mL | 10.8008 mL | 21.6015 mL | |
| 5 mM | 0.4320 mL | 2.1602 mL | 4.3203 mL | |
| 10 mM | 0.2160 mL | 1.0801 mL | 2.1602 mL |