Dorzagliatin

Summary

Dorzagliatin (CHEMBL4297508) is a phase-3 clinical-stage small-molecule hypoglycemic agent (ATC A10BX18) targeting GCK; indicated across 3 conditions including type 2 diabetes mellitus and diabetes mellitus.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: A10BX18
• Targets: 1 (GCK)
• Indications: 3 conditions
• Clinical trials: 23
• Chemistry: 462.9 Da · C22H27ClN4O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4297508
Name	Dorzagliatin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	57920094
ChEBI	CHEBI:234514
ATC	A10BX18
Molecular formula	C22H27ClN4O5
Molecular weight	462.9
InChIKey	HMUMWSORCUWQJO-QAPCUYQASA-N

SMILES: CC(C)C[C@@H](C(=O)NC1=NN(C=C1)C[C@H](CO)O)N2CC(=CC2=O)OC3=CC=CC=C3Cl

IUPAC name: (2S)-2-[3-(2-chlorophenoxy)-5-oxo-2H-pyrrol-1-yl]-N-[1-[(2R)-2,3-dihydroxypropyl]pyrazol-3-yl]-4-methylpentanamide

ChEBI definition: A secondary carboxamide resulting from the formal condensation of the carboxy group of (2S)-2-[4-(2-chlorophenoxy)-2-oxo-2,5-dihydro-1H-pyrrol-1-yl]-4-methylpentanoic acid with the amino group of (2R)-3-(3-amino-1H-pyrrol-1-yl)propane-1,2-diol. It is an allosteric glucokinase activator developed by Hua Medicine for the treatment of type 1 and 2 diabetes mellitus , and diabetic kidney disease.

Pharmacological roles (ChEBI): hypoglycemic agent, enzyme activator.

Also known as: Dorzagliatin, Dorzagliatina, Dorzagliatine, HMS-5552, Hms5552, HMS5552, RO-5305552, RO5305552, Sinogliatin, DORZAGLIATIN

Patent coverage: 57 distinct patent families (221 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 185 (84%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
GCK	Glucokinase	Activation			P35557

Bioactivity

No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).

Target pathways

Aggregated over 1 target gene(s): GCK.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	GCK
Regulation of gene expression in beta cells	1	GCK
Defective GCK causes maturity-onset diabetes of the young 2 (MODY2)	1	GCK
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	GCK
Glycolysis	1	GCK
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	GCK

Dominant GO biological processes

GO term	Targets
intracellular glucose homeostasis	1
glucose metabolic process	1
glucose catabolic process	1
glycolytic process	1
regulation of glycolytic process	1
NADP+ metabolic process	1
response to glucose	1
positive regulation of insulin secretion	1
cellular response to insulin stimulus	1
glucose homeostasis	1
regulation of potassium ion transport	1
cellular response to leptin stimulus	1
negative regulation of gluconeogenesis	1
positive regulation of glycogen biosynthetic process	1
regulation of insulin secretion	1

Indications & clinical

Indications

3 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148
diabetes mellitus	3	MONDO:0005015	EFO:0000400
glucose intolerance	1	MONDO:0001076	HP:0001952

Clinical trials

Total trials: 23.

Phase distribution

Phase	Trials
PHASE1	12
PHASE3	3
PHASE2	3
Not specified	3
PHASE4	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06263348	PHASE4	UNKNOWN	A Post-Marketing Safety Study of Dorzagliatin in Patients With Type 2 Diabetes
NCT05098470	PHASE3	ACTIVE_NOT_RECRUITING	Effects of Modulators of Gluconeogenesis, Glycogenolysis and Glucokinase Activity
NCT03141073	PHASE3	COMPLETED	Long-term Efficacy and Safety of HMS5552 add-on to Metformin in T2DM Subjects
NCT03173391	PHASE3	COMPLETED	Long-term Efficacy and Safety of HMS5552 in T2DM Subjects
NCT06976658	PHASE2	RECRUITING	Glucokinase Activator in Monogenic Diabetes
NCT02561338	PHASE2	COMPLETED	A Multi-center 12-week Study of HMS5552 in T2DM
NCT04531631	PHASE2	COMPLETED	Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in T2D and Monogenic Diabetes
NCT05468229	PHASE1/PHASE2	UNKNOWN	Dorzagliatin and 1st Phase Insulin and Beta-cell Glucose Sensitivity in IGT and NGT
NCT06995651	PHASE1	RECRUITING	Dorzagliatin in Pancreatic Insufficient Cystic Fibrosis
NCT01952535	PHASE1	COMPLETED	A Clinical Study to Evaluate Safety, Tolerability and Pharmacokinetics of Oral HMS5552 in Healthy Volunteers
NCT02077452	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HMS5552 in Patients With Type 2 Diabetes
NCT02386982	PHASE1	COMPLETED	Beta Cell Function and Related Pharmacodynamics of HMS5552 in T2DM Patients
NCT02597400	PHASE1	COMPLETED	Drug-Drug Interaction Study of Glucokinase Activator HMS5552 and Metformin in T2DM
NCT03158506	PHASE1	COMPLETED	Human Mass Balance Study of HMS5552 in Healthy Subjects
NCT03790787	PHASE1	COMPLETED	Drug Interaction Study Between Dorzagliatin and Empagliflozin
NCT03790839	PHASE1	COMPLETED	Drug Interaction Study Between Dorzagliatin and Sitagliptin
NCT04080596	PHASE1	COMPLETED	DDI Study to Investigate the Impact of Itraconazole on the Pharmacokinetics of Dorzagliatin
NCT04080609	PHASE1	COMPLETED	DDI Study Between Dorzagliatin and Rifampicin
NCT04324424	PHASE1	COMPLETED	A Clinical Study to Access the Pharmacokinetics of HMS5552 in Renal Impaired Subjects and Healthy Volunteers
NCT04426708	PHASE1	COMPLETED	A Clinical Study to Access the Pharmacokinetics of HMS5552 in Hepatic Impaired Subjects and Healthy Volunteers
NCT06222476	Not specified	NOT_YET_RECRUITING	Effect of Dorzagliatin on Renal Function Outcomes in People With Type 2 Diabetes: a Multicentric, Prospective, Randomized Study.
NCT06671340	Not specified	NOT_YET_RECRUITING	Chronic Dorzagliatin on Insulin and Incretin Function in Intermediate Hyperglycemia and Type 2 Diabetes
NCT04091854	Not specified	UNKNOWN	The Progress of Diabetes Mellitus After HMS5552 Treatment in Type 2 Diabetes Mellitus

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

6 molecules share ≥1 primary target. Top 6 by shared-target count:

Molecule	Source	Status	Shared targets
AZD-1656	ChEMBL	Phase 2	GCK
MK-0941 FREE BASE	ChEMBL	Phase 2	GCK
NERIGLIATIN	ChEMBL	Phase 2	GCK
PF-04991532	ChEMBL	Phase 2	GCK
PIRAGLIATIN	ChEMBL	Phase 2	GCK
Crizotinib	PubChem	Approved	GCK