Dorzagliatin
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 329496

CAS#: 1191995-00-2 (free base)

Description: Dorzagliatin, also known as HMS 5552, RO5305552 and sinogliatin, is a novel Dual-Acting Glucokinase Activator, which Improves Glycaemic Control and Pancreatic β-Cell Function in Patients With Type 2 Diabetes. By addressing the defect of the glucose sensor function of glucokinase, dorzagliatin has the potential to restore the impaired glucose homeostasis state of people with type 2 diabetes and serve as a first-line standard-of-care therapy for the treatment of the disease, or as a cornerstone therapy when taken in combination with currently approved anti-diabetes drugs.

Chemical Structure

img
Dorzagliatin
CAS# 1191995-00-2 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 329496
Name: Dorzagliatin
CAS#: 1191995-00-2 (free base)
Chemical Formula: C22H27ClN4O5
Exact Mass: 462.17
Molecular Weight: 462.931
Elemental Analysis: C, 57.08; H, 5.88; Cl, 7.66; N, 12.10; O, 17.28

Price and Availability

Size Price Availability Quantity
50mg USD 550 2 Weeks
100mg USD 950 2 Weeks
200mg USD 1450 2 Weeks
500mg USD 2850 2 Weeks
1g USD 3950 2 Weeks
2g USD 6450 2 Weeks
Bulk inquiry

Related CAS #: 1191995-14-8 (HCl)   1191995-00-2 (free base)    

Synonym: Dorzagliatin; HMS 5552; HMS-5552; HMS5552; RO5305552; RO-5305552; RO 5305552; Sinogliatin-isomer

IUPAC/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

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

SMILES Code: CC(C)C[C@H](N1C(C=C(OC2=CC=CC=C2Cl)C1)=O)C(NC3=NN(C[C@@H](O)CO)C=C3)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: Dorzagliatin (HMS5552), a dual-acting glucokinase (GK) activator, improves glycaemic control and pancreatic β-cell function in type 2 diabetes.
In vitro activity: TBD
In vivo activity: Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats. HMS5552 treatment significantly lowered the blood glucose levels and improved GK activity and insulin resistance. These data suggest that 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. Reference: J Diabetes Res. 2017;2017:5812607. https://pubmed.ncbi.nlm.nih.gov/28191470/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 108.5 234.38
Ethanol 92.0 198.73

Preparing Stock Solutions

The following data is based on the product molecular weight 462.93 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Wang P, Liu H, Chen L, Duan Y, Chen Q, Xi S. 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. doi: 10.1155/2017/5812607. Epub 2017 Jan 16. PMID: 28191470; PMCID: PMC5278194.
In vitro protocol: TBD
In vivo protocol: 1. Wang P, Liu H, Chen L, Duan Y, Chen Q, Xi S. 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. doi: 10.1155/2017/5812607. Epub 2017 Jan 16. PMID: 28191470; PMCID: PMC5278194.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

1: Yang W, Zhu D, Gan S, Dong X, Su J, Li W, Jiang H, Zhao W, Yao M, Song W, Lu Y, Zhang X, Li H, Wang G, Qiu W, Yuan G, Ma J, Li W, Li Z, Wang X, Zeng J, Yang Z, Liu J, Liang Y, Lu S, Zhang H, Liu H, Liu P, Fan K, Jiang X, Li Y, Su Q, Ning T, Tan H, An Z, Jiang Z, Liu L, Zhou Z, Zhang Q, Li X, Shan Z, Xue Y, Mao H, Shi L, Ye S, Zhang X, Sun J, Li P, Yang T, Li F, Lin J, Zhang Z, Zhao Y, Li R, Guo X, Yao Q, Lu W, Qu S, Li H, Tan L, Wang W, Yao Y, Chen D, Li Y, Gao J, Hu W, Fei X, Wu T, Dong S, Jin W, Li C, Zhao D, Feng B, Zhao Y, Zhang Y, Li X, Chen L. Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2022 May;28(5):974-981. doi: 10.1038/s41591-022-01803-5. Epub 2022 May 12. PMID: 35551292; PMCID: PMC9117147.


2: Syed YY. Dorzagliatin: First Approval. Drugs. 2022 Dec;82(18):1745-1750. doi: 10.1007/s40265-022-01813-0. PMID: 36449148.


3: Zhu D, Li X, Ma J, Zeng J, Gan S, Dong X, Yang J, Lin X, Cai H, Song W, Li X, Zhang K, Zhang Q, Lu Y, Bu R, Shao H, Wang G, Yuan G, Ran X, Liao L, Zhao W, Li P, Sun L, Shi L, Jiang Z, Xue Y, Jiang H, Li Q, Li Z, Fu M, Liang Z, Guo L, Liu M, Xu C, Li W, Yu X, Qin G, Yang Z, Su B, Zeng L, Geng H, Shi Y, Zhao Y, Zhang Y, Yang W, Chen L. Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med. 2022 May;28(5):965-973. doi: 10.1038/s41591-022-01802-6. Epub 2022 May 12. PMID: 35551294.


4: Chow E, Wang K, Lim CKP, Tsoi STF, Fan B, Poon E, Luk AOY, Ma RCW, Ferrannini E, Mari A, Chen L, Chan JCN. Dorzagliatin, a Dual-Acting Glucokinase Activator, Increases Insulin Secretion and Glucose Sensitivity in Glucokinase Maturity- Onset Diabetes of the Young and Recent-Onset Type 2 Diabetes. Diabetes. 2023 Feb 1;72(2):299-308. doi: 10.2337/db22-0708. PMID: 36342518; PMCID: PMC9871194.


5: Zhu D, Gan S, Liu Y, Ma J, Dong X, Song W, Zeng J, Wang G, Zhao W, Zhang Q, Li Y, Fang H, Lv X, Shi Y, Tian H, Ji L, Gao X, Zhang L, Bao Y, Lei M, Li L, Zeng L, Li X, Hou X, Zhao Y, Hu T, Ge X, Zhao G, Li Y, Zhang Y, Chen L. Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose- ranging, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Diabetes Endocrinol. 2018 Aug;6(8):627-636. doi: 10.1016/S2213-8587(18)30105-0. Epub 2018 May 4. Erratum in: Lancet Diabetes Endocrinol. 2018 May 10;: PMID: 29735394.


6: Toulis KA, Nirantharakumar K, Pourzitaki C, Barnett AH, Tahrani AA. Glucokinase Activators for Type 2 Diabetes: Challenges and Future Developments. Drugs. 2020 Apr;80(5):467-475. doi: 10.1007/s40265-020-01278-z. PMID: 32162273.


7: Ren Y, Li L, Wan L, Huang Y, Cao S. Glucokinase as an emerging anti-diabetes target and recent progress in the development of its agonists. J Enzyme Inhib Med Chem. 2022 Dec;37(1):606-615. doi: 10.1080/14756366.2021.2025362. PMID: 35067153; PMCID: PMC8788356.


8: Lin F, He R, Ling B, Wang L, Jiang T, Yu B. Dorzagliatin for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials. Clin Ther. 2023 Sep 28:S0149-2918(23)00356-9. doi: 10.1016/j.clinthera.2023.09.011. Epub ahead of print. PMID: 37777375.


9: Yu Y, Yang X, Tong K, Yin S, Hu G, Zhang F, Jiang P, Zhou M, Jian W. Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis. Front Cardiovasc Med. 2022 Nov 23;9:1041044. doi: 10.3389/fcvm.2022.1041044. PMID: 36505359; PMCID: PMC9727304.


10: Yang R, Ren S, Jin X, Sun Y, Dong Y, Zhang J, Liang W, Chen L. Determination of unbound fraction of dorzagliatin in human plasma by equilibrium dialysis and LC-MS/MS and its application to a clinical pharmacokinetic study. J Pharm Biomed Anal. 2021 Feb 20;195:113854. doi: 10.1016/j.jpba.2020.113854. Epub 2020 Dec 31. PMID: 33388639.


11: Zhu XX, Zhu DL, Li XY, Li YL, Jin XW, Hu TX, Zhao Y, Li YG, Zhao GY, Ren S, Zhang Y, Ding YH, Chen L. 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. doi: 10.1111/dom.13338. Epub 2018 May 30. PMID: 29707866.


12: Miao J, Fu P, Ren S, Hu C, Wang Y, Jiao C, Li P, Zhao Y, Tang C, Qian Y, Yang R, Dong Y, Rong J, Wang Y, Jin X, Sun Y, Chen L. Effect of renal impairment on the pharmacokinetics and safety of dorzagliatin, a novel dual-acting glucokinase activator. Clin Transl Sci. 2022 Feb;15(2):548-557. doi: 10.1111/cts.13174. Epub 2021 Nov 11. PMID: 34706161; PMCID: PMC8841463.


13: Wang K, Feng L, Zhang J, Zou Q, Xu F, Sun Z, Tang F, Chen L. Population Pharmacokinetic Analysis of Dorzagliatin in Healthy Subjects and Patients with Type 2 Diabetes Mellitus. Clin Pharmacokinet. 2023 Oct;62(10):1413-1425. doi: 10.1007/s40262-023-01286-8. Epub 2023 Aug 3. PMID: 37537410; PMCID: PMC10520121.


14: Dutta D, Khandelwal D, Kumar M, Sharma M. Efficacy and safety of novel dual glucokinase activator dorzagliatin in type-2 diabetes A meta-analysis. Diabetes Metab Syndr. 2023 Jan;17(1):102695. doi: 10.1016/j.dsx.2022.102695. Epub 2022 Dec 20. PMID: 36566614.


15: Zeng J, Gan S, Mi N, Liu Y, Su X, Zhang W, Zhang J, Yu F, Dong X, Han M, Luo J, Zhang Y, Chen L, Ma J. Diabetes remission in drug-naïve patients with type 2 diabetes after dorzagliatin treatment: A prospective cohort study. Diabetes Obes Metab. 2023 Oct;25(10):2878-2887. doi: 10.1111/dom.15179. Epub 2023 Jun 29. PMID: 37385967.


16: Chen L, Zhang J, Sun Y, Zhao Y, Liu X, Fang Z, Feng L, He B, Zou Q, Tracey GJ. A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity. Nat Commun. 2023 Mar 14;14(1):1405. doi: 10.1038/s41467-023-36946-7. PMID: 36918550; PMCID: PMC10014962.


17: Sharma P, Singh S, Sharma N, Singla D, Guarve K, Grewal AS. Targeting human Glucokinase for the treatment of type 2 diabetes: an overview of allosteric Glucokinase activators. J Diabetes Metab Disord. 2022 Mar 11;21(1):1129-1137. doi: 10.1007/s40200-022-01019-x. PMID: 35673438; PMCID: PMC9167346.


18: Li W, Zhang X, Sun Y, Liu Z. Recent clinical advances of glucokinase activators in the treatment of diabetes mellitus type 2. Pharmazie. 2020 Jun 1;75(6):230-235. doi: 10.1691/ph.2020.0409. PMID: 32539915.


19: Bloomgarden Z. Glucokinase and the potential of glucokinase activation in type 2 diabetes. J Diabetes. 2019 Aug;11(8):626-627. doi: 10.1111/1753-0407.12937. Epub 2019 May 17. PMID: 31013387.


20: Thilagavathi R, Hosseini-Zare MS, Malini M, Selvam C. A comprehensive review on glucokinase activators: Promising agents for the treatment of Type 2 diabetes. Chem Biol Drug Des. 2022 Feb;99(2):247-263. doi: 10.1111/cbdd.13979. Epub 2021 Nov 10. PMID: 34714587.