GCK

Summary

GCK (glucokinase, HGNC:4195) is a protein-coding gene on chromosome 7p13, encoding Hexokinase-4 (P35557). Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia.

Source: NCBI Gene 2645 — RefSeq curated summary.

At a glance

• Gene–disease (curated): monogenic diabetes (Definitive, ClinGen) — +8 more curated relationships
• GWAS associations: 47
• Clinical variants (ClinVar): 1,349 total — 334 pathogenic, 284 likely-pathogenic
• Phenotypes (HPO): 80
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000162

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4195
Approved symbol	GCK
Name	glucokinase
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	HK4, HKIV
Ensembl gene	ENSG00000106633
Ensembl biotype	protein_coding
OMIM	138079
Entrez	2645

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000336642, ENST00000345378, ENST00000395796, ENST00000403799, ENST00000437084, ENST00000459642, ENST00000473353, ENST00000476008, ENST00000616242, ENST00000671824, ENST00000672743, ENST00000673284, ENST00000682635, ENST00000683378

RefSeq mRNA: 6 — MANE Select: NM_000162 NM_000162, NM_001354800, NM_001354801, NM_001354803, NM_033507, NM_033508

CCDS: CCDS5479, CCDS5480, CCDS94091, CCDS94092

Canonical transcript exons

ENST00000403799 — 10 exons

Exon	Start	End
ENSE00000680807	44149969	44150064
ENSE00000680809	44150956	44151075
ENSE00000680812	44153301	44153463
ENSE00000832574	44145497	44145730
ENSE00000832576	44147650	44147833
ENSE00000832577	44149760	44149859
ENSE00000832580	44152271	44152425
ENSE00001362239	44188909	44189439
ENSE00001689304	44144275	44145280
ENSE00003605854	44146463	44146618

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 88.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4009 / max 439.2052, expressed in 31 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83856	0.3742	22
83854	0.0177	7
204425	0.0090	3

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	88.54	gold quality
adenohypophysis	UBERON:0002196	88.35	gold quality
islet of Langerhans	UBERON:0000006	82.30	gold quality
right atrium auricular region	UBERON:0006631	80.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.36	gold quality
cerebellar hemisphere	UBERON:0002245	78.25	gold quality
cardiac atrium	UBERON:0002081	78.12	gold quality
cerebellar cortex	UBERON:0002129	77.95	gold quality
hypothalamus	UBERON:0001898	77.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.47	silver quality
cerebellum	UBERON:0002037	76.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.10	gold quality
right frontal lobe	UBERON:0002810	74.20	gold quality
cingulate cortex	UBERON:0003027	73.98	gold quality
anterior cingulate cortex	UBERON:0009835	73.81	gold quality
amygdala	UBERON:0001876	73.63	gold quality
prefrontal cortex	UBERON:0000451	73.31	gold quality
nucleus accumbens	UBERON:0001882	72.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.58	gold quality
cortical plate	UBERON:0005343	71.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.27	gold quality
right lobe of liver	UBERON:0001114	70.38	gold quality
ascending aorta	UBERON:0001496	70.32	gold quality
apex of heart	UBERON:0002098	70.27	gold quality
thoracic aorta	UBERON:0001515	70.25	gold quality
brain	UBERON:0000955	70.23	gold quality
central nervous system	UBERON:0001017	70.21	gold quality
forebrain	UBERON:0001890	70.16	gold quality
popliteal artery	UBERON:0002250	70.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	6.50
E-ANND-3	no	2.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting GCK, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-6838-3P	98.40	65.88	559
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• G-to-A polymorphism in the hepatic GCK promoter is associated with hepatic insulin resistance in normotensive Asian Indians with normal glucose tolerance. (PMID:11112984)
• These results are consistent with GKRP having one single binding site for phosphate esters. They also show that a missense mutation of GKRP can lead to a gain of function (PMID:11756407)
• Mutations are not a common cause of permanent neonatal diabetes in France. (PMID:11914755)
• mutations in maturity-onset diabetes of the young (MODY) candidate genes in 22 Spanish families. (PMID:12050210)
• insulin regulates both the association of GK with secretory granules and the activity of the enzyme within the pancreatic beta-cell. (PMID:12101177)
• Four novel GCK mutations, namely IVS2-7G>A, G72R, T206R and S263P, were identified in Canadian MODY patients. (PMID:12442280)
• Twenty different mutations in the HNF-4alpha, GCK and HNF-1alpha in 29 families. Three of 3, 10 of 11 and 1 of 6 of the mutations identified in HNF-4alpha, GCK and HNF-1alpha respectively, were new. (PMID:12627330)
• two novel spontaneous GCK-activating mutations whose clinical phenotype clearly differs from mutations in ATP-sensitive K(+) channel genes (PMID:12941786)
• summary of glucokinase mutations in glucose metabolism disorders. (PMID:14517946)
• Autosomal recessive inheritance and GLK deficiency are features typical for an inborn error of metabolism, which occurred in the glucose-insulin signaling pathway in these subjects. (PMID:14578306)
• fructose-2,6-diphosphate can stimulate hepatic glucokinase gene expression in an insulin-independent manner (PMID:14617577)
• high-fat feeding impairs both insulin- and exercise-stimulated muscle glucose uptake, but only exercise-stimulated MGU was corrected by HK II overexpression (PMID:14747279)
• We have found GLUT-2 and glucokinase mRNAs in several brain regions, including the ventromedial and arcuate nuclei of the hypothalamus (PMID:15009676)
• A G(-30)A polymorphism in the beta-cell-specific promoter of glucokinase (GK-30PM)increases the risk of CAD in individuals with and without type 2 diabetes mellitus. (PMID:15173029)
• Range of the clinical phenotype caused by GCK mutations varies from complete insulin deficiency to extreme hyperinsulinemia. (PMID:15277402)
• a mutation of the GCK gene was found in families and patients with maturity-onset diabetes of the young (PMID:15305805)
• Data describe the glucokinase V62M mutation identified in two families and co-segregating with hyperglycemia to understand how this mutation resulted in reduced function. (PMID:15677479)
• COmmon genetic variation, in addition to rare mutations and environmental factors, can affect both fastinsg blood glucose and birth weight. (PMID:15677518)
• 5 novel mutations within the GCK gene, associated with Maturity-onset diabetes of the young, are discussed. (PMID:15841481)
• relative prevalence of 3% of MODY1 (two different mutations in two families), 10% of MODY2 (seven in eight), and 36% of MODY3 (21 in 28) among Danish kindred clinically diagnosed as MODY (PMID:15928245)
• Two new activating mutations of human glucokinase increase the affinity of the enzyme for glucose. (PMID:15987895)
• identification and functional characterization of missense mutations in the GCK gene in diabetic families that result in protein mutations Leu165–>Phe, Glu265–>Lys and Thr206–>Met. (PMID:16173921)
• glucokinase -30G>A polymorphism associates with elevated fasting and post-oral glucose tolerance test glycemia in the middle-aged whites as well as with impaired glucose regulation and WHO-defined metabolic syndrome (PMID:16186409)
• The prevalence of structural mutations in glucokinase gene responsible for early-onset diabetes appears to be rare among Chinese patients. (PMID:16331569)
• Families of young children with fasting hyperglycemia with family histories of diabetes showed mutations in glucokinase. (PMID:16444761)
• The -30G–>A polymorphism of the beta-cell-specific promoter of GCK and the I27L polymorphism of HNF1A seem to increase the risk of GDM in Scandinavian women. (PMID:16752173)
• The prevalence of mutations in the GSK gene was studied in Polish women with gestational diabetes. (PMID:16963153)
• The alteration in glucokinase (GK) activity caused by polymorphic activating mutations may have a more profound biological impact than the alleviation of inhibition caused by interaction with GKRP. (PMID:17082186)
• Different type 2 doabetes mutations impair glucokinase function through different mechanisms such as enzymatic activity, protein stability and increased interaction with the flucokinase receptor (PMID:17186219)
• GCK is associated with fetal growth and birth weight (PMID:17186458)
• Lack of genetic predisposition in offspring to progressive beta cell dysfunction in glucokinase mutation of mmothrs. (PMID:17216282)
• data support control of GK activity and Km through the ratio of distinct conformers (super-open, open, and closed) through either substrate or other ligand binding and/or dissociation (PMID:17260972)
• A study evaluating the extent to which common variation in the six known maturity-onset diabetes of the young (MODY) genes, which cause a monogenic form of type 2 diabetes, is associated with type 2 diabetes is presented. (PMID:17327436)
• results suggest that cellular loss of GK catalytic activity rather than impaired translation or enhanced protein degradation may account for the hyperglycemia in subjects with V62M and G72R mutations (PMID:17389332)
• human glucokinase is allosterically activated by free polyubiquitin chains and its ubiquitin-dependent cotranslational proteasomal degradation (PMID:17561510)
• Almost 90% of the MODY cases in the group studied are explained by mutations in the major genes GCK (MODY2) and HNF-1alpha(MODY3), although differences in the relative prevalence of each form could be partly due to patient referral bias. (PMID:17573900)
• GCK is required for JNK and, unexpectedly, p38 activation by three bacterial PAMPs, lipopolysaccharide, peptidoglycan, and flagellin (PMID:17584736)
• Four missense mutations were found in the GCK gene. All mutations in the GCK gene co-segregated with diabetes mellitus. (PMID:17937063)
• study of a pedigree with 8 affected persistent hyperinsulinaemic hypoglycaemia of infancy individuals; the novel GCK mutation G68V is associated with variable phenotypic severity (PMID:17976205)
• adipocyte-derived Wnt signalling molecules regulate insulin secretion, glucokinase gene transcription and beta cell proliferation (PMID:17994217)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gck	ENSDARG00000068006
mus_musculus	Gck	ENSMUSG00000041798
rattus_norvegicus	Gck	ENSRNOG00000061527

Paralogs (4): HKDC1 (ENSG00000156510), HK1 (ENSG00000156515), HK2 (ENSG00000159399), HK3 (ENSG00000160883)

Protein

Protein identifiers

Hexokinase-4 — P35557 (reviewed: P35557)

Alternative names: Glucokinase, Hexokinase type IV, Hexokinase-D

All UniProt accessions (8): P35557, A0A5F9ZGW4, A0A5F9ZHE0, A0A8C8KJG0, A0A8C8PZE6, C9JQD1, H7BXV0, Q53Y25

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively). Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant. Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues. Since insulin secretion parallels glucose metabolism and the low glucose affinity of GCK ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GCK acts as a glucose sensor in the pancreatic beta cell. In pancreas, plays an important role in modulating insulin secretion. In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage. Required to provide D-glucose 6-phosphate for the synthesis of glycogen. Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate.

Subunit / interactions. Monomer. Interacts with MIDN; the interaction occurs preferentially at low glucose levels and results in inhibition of hexokinase activity. Interacts with GCKR; leading to sequestration in the nucleus.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion.

Disease relevance. Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851] A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. The disease is caused by variants affecting the gene represented in this entry. Hyperinsulinemic hypoglycemia, familial, 3 (HHF3) [MIM:602485] A form of hyperinsulinemic hypoglycemia, a clinically and genetically heterogeneous disorder characterized by inappropriate insulin secretion from the pancreatic beta-cells in the presence of low blood glucose levels. HHF3 clinical features include loss of consciousness due to hypoglycemia, hypoglycemic coma, mental retardation due to repeated episodes of hypoglycemia, and seizures. HHF3 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Type 2 diabetes mellitus (T2D) [MIM:125853] A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility is associated with variants affecting the gene represented in this entry. Diabetes mellitus, permanent neonatal, 1 (PNDM1) [MIM:606176] An autosomal recessive form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Subject to allosteric regulation. Low glucose and high fructose-6-phosphate triggers association with the inhibitor GCKR followed by sequestration in the nucleus.

Pathway. Carbohydrate metabolism; hexose metabolism. Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4.

Similarity. Belongs to the hexokinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P35557-1	1	yes
P35557-2	2
P35557-3	3

RefSeq proteins (5): NP_000153, NP_001341729, NP_001341732, NP_277042, NP_277043 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001312	Hexokinase	Family
IPR019807	Hexokinase_BS	Binding_site
IPR022672	Hexokinase_N	Domain
IPR022673	Hexokinase_C	Domain
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00349, PF03727

Enzyme classification (BRENDA):

• EC 2.7.1.1 — hexokinase (BRENDA: 77 organisms, 225 substrates, 336 inhibitors, 483 Km, 134 kcat entries)

Substrate kinetics (BRENDA)

21 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	184
D-GLUCOSE	0.003–45	112
D-FRUCTOSE	0.025–1510	46
D-MANNOSE	0.014–25.41	36
2-DEOXY-D-GLUCOSE	0.033–19.2	24
D-GLUCOSAMINE	0.06–2	12
UTP	0.288–30	7
ITP	1.9–16.6	6
CTP	0.52–5	5
GTP	0.231–0.788	4
N-ACETYL-D-GLUCOSAMINE	0.32–41.6	2
1,5-ANHYDRO-D-GLUCITOL	20	1
1-THIO-D-GLUCOSE	5	1
2-DEOXY-2-FLUORO-D-GLUCOSE	0.2	1
2-DEOXYGLUCOSE	18	1

Catalyzed reactions (Rhea), 4 shown:

• D-mannose + ATP = D-mannose 6-phosphate + ADP + H(+) (RHEA:11028)
• D-fructose + ATP = D-fructose 6-phosphate + ADP + H(+) (RHEA:16125)
• D-glucose + ATP = D-glucose 6-phosphate + ADP + H(+) (RHEA:17825)
• a D-hexose + ATP = a D-hexose 6-phosphate + ADP + H(+) (RHEA:22740)

UniProt features (188 total): sequence variant 118, helix 20, strand 19, binding site 11, mutagenesis site 9, turn 5, splice variant 2, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

35 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3F9M	X-RAY DIFFRACTION	1.5
4NO7	X-RAY DIFFRACTION	1.7
4ISE	X-RAY DIFFRACTION	1.78
4DCH	X-RAY DIFFRACTION	1.79
3VEV	X-RAY DIFFRACTION	1.8
3VF6	X-RAY DIFFRACTION	1.86
6E0I	X-RAY DIFFRACTION	1.9
3IMX	X-RAY DIFFRACTION	2
4IXC	X-RAY DIFFRACTION	2
5V4X	X-RAY DIFFRACTION	2.08
4ISF	X-RAY DIFFRACTION	2.09
4IWV	X-RAY DIFFRACTION	2.1
3H1V	X-RAY DIFFRACTION	2.11
3IDH	X-RAY DIFFRACTION	2.14
3FGU	X-RAY DIFFRACTION	2.15
3S41	X-RAY DIFFRACTION	2.18
3A0I	X-RAY DIFFRACTION	2.2
3QIC	X-RAY DIFFRACTION	2.2
3VEY	X-RAY DIFFRACTION	2.25
1V4S	X-RAY DIFFRACTION	2.3
4RCH	X-RAY DIFFRACTION	2.3
4DHY	X-RAY DIFFRACTION	2.38
5V4W	X-RAY DIFFRACTION	2.39
3ID8	X-RAY DIFFRACTION	2.4
7T78	X-RAY DIFFRACTION	2.4
7T79	X-RAY DIFFRACTION	2.4
3GOI	X-RAY DIFFRACTION	2.52
4MLE	X-RAY DIFFRACTION	2.6
4ISG	X-RAY DIFFRACTION	2.65
3FR0	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35557-F1	93.87	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 256; 290; 295–296; 332–336; 411–415; 78–83; 151–152; 168–169; 204–205; 228; 231

Mutagenesis-validated functional residues (9):

Position	Phenotype
64	increased glucokinase activity based on measure of catalytic efficiency. increased affinity for glucose.
177	small change in glucokinase activity.
197	increased glucokinase activity based on measure of catalytic efficiency. increased affinity for glucose.
211	increased glucokinase activity based on measure of catalytic efficiency. increased affinity for glucose.
214	increased glucokinase activity based on measure of catalytic efficiency. increased affinity for glucose. no effect on af
215	increased glucokinase activity based on measure of catalytic efficiency. increased affinity for glucose. loss of inhibit
256	inactive enzyme with no glucokinase activity.
414	small change in glucokinase activity.
453	increased glucokinase activity based on measure of catalytic efficiency. increased affinity for glucose.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-210745	Regulation of gene expression in beta cells
R-HSA-5619073	Defective GCK causes maturity-onset diabetes of the young 2 (MODY2)
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)
R-HSA-70171	Glycolysis
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes

MSigDB gene sets: 379 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, PID_HNF3B_PATHWAY, GOBP_NADPPLUS_METABOLIC_PROCESS, GOBP_INSULIN_SECRETION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOBP_HORMONE_TRANSPORT, GOBP_CARBOHYDRATE_PHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, KEGG_GLYCOLYSIS_GLUCONEOGENESIS

GO Biological Process (25): intracellular glucose homeostasis (GO:0001678), glucose metabolic process (GO:0006006), glucose catabolic process (GO:0006007), glycolytic process (GO:0006096), regulation of glycolytic process (GO:0006110), NADP+ metabolic process (GO:0006739), response to glucose (GO:0009749), positive regulation of insulin secretion (GO:0032024), cellular response to insulin stimulus (GO:0032869), glucose homeostasis (GO:0042593), regulation of potassium ion transport (GO:0043266), cellular response to leptin stimulus (GO:0044320), negative regulation of gluconeogenesis (GO:0045721), positive regulation of glycogen biosynthetic process (GO:0045725), regulation of insulin secretion (GO:0050796), glucose 6-phosphate metabolic process (GO:0051156), canonical glycolysis (GO:0061621), calcium ion import (GO:0070509), carbohydrate metabolic process (GO:0005975), purine nucleotide metabolic process (GO:0006163), hexose metabolic process (GO:0019318), organophosphate metabolic process (GO:0019637), nicotinamide nucleotide metabolic process (GO:0046496), carbohydrate phosphorylation (GO:0046835), carbohydrate derivative metabolic process (GO:1901135)

GO Molecular Function (13): glucokinase activity (GO:0004340), ATP binding (GO:0005524), D-glucose binding (GO:0005536), fructokinase activity (GO:0008865), mannokinase activity (GO:0019158), glucose sensor activity (GO:0141089), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), hexokinase activity (GO:0004396), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, alcohol group as acceptor (GO:0016773)

GO Cellular Component (5): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC transporter disorders	2
Glycolysis	1
Regulation of beta-cell development	1
Glucose metabolism	1
FOXO-mediated transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hexokinase activity	3
cellular anatomical structure	3
nicotinamide nucleotide metabolic process	2
insulin secretion	2
transferase activity, transferring phosphorus-containing groups	2
cytoplasm	2
intracellular membrane-bounded organelle	2
glucose homeostasis	1
intracellular chemical homeostasis	1
hexose metabolic process	1
glucose metabolic process	1
hexose catabolic process	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
glycolytic process	1
regulation of purine nucleotide catabolic process	1
regulation of generation of precursor metabolites and energy	1
regulation of carbohydrate catabolic process	1
regulation of ATP metabolic process	1
purine nucleotide metabolic process	1
response to hexose	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
response to insulin	1
cellular response to peptide hormone stimulus	1
carbohydrate homeostasis	1
potassium ion transport	1
regulation of metal ion transport	1
cellular response to hormone stimulus	1

Protein interactions and networks

STRING

2197 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCK	GCKR	Q14397	998
GCK	SLC2A2	P11168	960
GCK	INS	P01308	945
GCK	ABCC8	Q09428	944
GCK	KCNJ11	Q14654	899
GCK	HNF1A	P20823	898
GCK	G6PC2	Q9NQR9	894
GCK	PDX1	P52945	868
GCK	MTNR1B	P49286	864
GCK	G6PC1	P35575	862
GCK	PFKFB3	Q16875	858
GCK	H6PD	O95479	845
GCK	KHK	P50053	843
GCK	G6PC3	Q9BUM1	837
GCK	ADPGK	Q9BRR6	836

IntAct

25 interactions, top by confidence:

A	B	Type	Score
GCK	GCKR	psi-mi:“MI:0915”(physical association)	0.720
GCKR	GCK	psi-mi:“MI:0407”(direct interaction)	0.720
SPDYE4	GCK	psi-mi:“MI:0915”(physical association)	0.560
GCK	PFKFB1	psi-mi:“MI:0407”(direct interaction)	0.560
PFKFB1	GCK	psi-mi:“MI:0407”(direct interaction)	0.560
GCK	Gckr	psi-mi:“MI:0915”(physical association)	0.370
Pfkfb1	GCK	psi-mi:“MI:0915”(physical association)	0.370
GCK	Pfkfb3	psi-mi:“MI:0915”(physical association)	0.370
AKT1	GCK	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	GCK	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	GCK	psi-mi:“MI:2364”(proximity)	0.270
SPOP	GCK	psi-mi:“MI:2364”(proximity)	0.270
GCK	SPOP	psi-mi:“MI:2364”(proximity)	0.270
GCK	EGFR	psi-mi:“MI:2364”(proximity)	0.270
GCK	PTEN	psi-mi:“MI:2364”(proximity)	0.270
GCK	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
GCK	BRAF	psi-mi:“MI:2364”(proximity)	0.270
GCK	SPDYE4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): Midn (Two-hybrid), GCK (Two-hybrid), AGL (Co-fractionation), GMIP (Co-fractionation), SMEK2 (Co-fractionation), UGP2 (Co-fractionation), GCK (Affinity Capture-Western), GCKR (Affinity Capture-Western), GCKR (Reconstituted Complex), GCK (FRET), PFKFB3 (PCA), ITGB7 (Negative Genetic), GCK (Negative Genetic), PNMT (Positive Genetic), GCK (Two-hybrid)

ESM2 similar proteins: A0A0K0JFP3, B2RR83, B3M383, O64390, P04806, P04807, P17709, P17710, P17712, P32783, P33284, P35557, P50506, P50521, P52792, P80581, P83776, P91309, P93834, Q02155, Q04409, Q09440, Q09756, Q26609, Q2KNB5, Q2KNB7, Q2KNB9, Q42525, Q5W676, Q6CUZ3, Q6Q8A5, Q6Z398, Q7M753, Q8LQ68, Q92407, Q95ZS2, Q969A8, Q9FLF7, Q9FZG4, Q9I7X6

Diamond homologs: A0A0K0JFP3, A2PYL6, A2PYL7, A2PYL8, O08528, O64390, P04806, P04807, P05708, P17709, P17710, P17712, P19367, P27595, P27881, P27926, P33284, P35557, P50506, P52789, P52790, P52792, P80581, P83776, P93834, Q04409, Q09756, Q1W674, Q1WM15, Q1WM16, Q26609, Q2KNB4, Q2KNB5, Q2KNB7, Q2KNB9, Q2TB90, Q3TRM8, Q42525, Q56XE8, Q5RC71

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PDX1	“up-regulates quantity by expression”	GCK	“transcriptional regulation”
USF1	“up-regulates quantity by expression”	GCK	“transcriptional regulation”
GCK	“up-regulates quantity”	“alpha-D-glucose 6-phosphate(2-)”	“chemical modification”
GCK	“down-regulates quantity”	α-D-glucose	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1349 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	334
Likely pathogenic	284
Uncertain significance	328
Likely benign	96
Benign	41

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098819	NM_000162.5(GCK):c.1139A>C (p.His380Pro)	Pathogenic
1172896	NM_000162.5(GCK):c.660C>A (p.Cys220Ter)	Pathogenic
1195505	NM_000162.5(GCK):c.564_567dup (p.Lys190fs)	Pathogenic
1200795	NM_000162.5(GCK):c.679+1G>A	Pathogenic
1254640	NM_000162.5(GCK):c.148del (p.His50fs)	Pathogenic
1256304	NM_000162.5(GCK):c.1145G>A (p.Cys382Tyr)	Pathogenic
129140	NM_000162.5(GCK):c.1112G>T (p.Cys371Phe)	Pathogenic
129142	NM_000162.5(GCK):c.449T>A (p.Phe150Tyr)	Pathogenic
129143	NM_000162.5(GCK):c.523G>A (p.Gly175Arg)	Pathogenic
129144	NM_000162.5(GCK):c.544G>A (p.Val182Met)	Pathogenic
129146	NM_000162.5(GCK):c.706G>A (p.Glu236Lys)	Pathogenic
1320655	NM_000162.5(GCK):c.1322C>G (p.Ser441Trp)	Pathogenic
1322992	NM_000162.5(GCK):c.18del (p.Arg7fs)	Pathogenic
1338497	NM_000162.5(GCK):c.606_607insACACCGT (p.Val203fs)	Pathogenic
1338522	NM_000162.5(GCK):c.1324G>T (p.Glu442Ter)	Pathogenic
1338573	NM_000162.5(GCK):c.926T>C (p.Leu309Pro)	Pathogenic
1338620	NM_000162.5(GCK):c.1245del (p.His416fs)	Pathogenic
1343440	NM_000162.5(GCK):c.179C>T (p.Thr60Ile)	Pathogenic
1365679	NM_000162.5(GCK):c.1340_1368del (p.Arg447fs)	Pathogenic
1387176	NM_000162.5(GCK):c.86del (p.Asp29fs)	Pathogenic
1405403	NM_000162.5(GCK):c.1019G>A (p.Ser340Asn)	Pathogenic
1427283	NM_000162.5(GCK):c.307del (p.Thr103fs)	Pathogenic
1437236	NM_000162.5(GCK):c.501G>A (p.Trp167Ter)	Pathogenic
1452320	NM_000162.5(GCK):c.140dup (p.Glu48fs)	Pathogenic
1452802	NM_000162.5(GCK):c.1162_1364del203 (p.Val389fs)	Pathogenic
1453011	NM_000162.5(GCK):c.320dup (p.Met107fs)	Pathogenic
1453774	NM_000162.5(GCK):c.867T>A (p.Tyr289Ter)	Pathogenic
1456947	NM_000162.5(GCK):c.728T>C (p.Leu243Pro)	Pathogenic
1464253	NM_000162.5(GCK):c.671T>C (p.Met224Thr)	Pathogenic
1472875	NM_000162.5(GCK):c.1228G>C (p.Gly410Arg)	Pathogenic

SpliceAI

1965 predictions. Top by Δscore:

Variant	Effect	Δscore
7:44145492:CTCA:C	donor_loss	1.0000
7:44145494:CA:C	donor_loss	1.0000
7:44145495:ACC:A	donor_loss	1.0000
7:44145496:C:CT	donor_loss	1.0000
7:44145726:TGTCG:T	acceptor_gain	1.0000
7:44145727:GTCG:G	acceptor_gain	1.0000
7:44145728:TCG:T	acceptor_gain	1.0000
7:44145729:CG:C	acceptor_gain	1.0000
7:44145729:CGC:C	acceptor_gain	1.0000
7:44145731:C:CC	acceptor_gain	1.0000
7:44145739:C:CT	acceptor_gain	1.0000
7:44145740:G:T	acceptor_gain	1.0000
7:44146618:CCTGG:C	acceptor_loss	1.0000
7:44146619:C:CA	acceptor_loss	1.0000
7:44147339:A:AC	donor_gain	1.0000
7:44147340:C:CC	donor_gain	1.0000
7:44147643:T:TA	donor_gain	1.0000
7:44147648:A:AC	donor_gain	1.0000
7:44147649:C:CC	donor_gain	1.0000
7:44147649:CAG:C	donor_gain	1.0000
7:44147829:CGTGC:C	acceptor_gain	1.0000
7:44147834:C:CC	acceptor_gain	1.0000
7:44147839:G:GC	acceptor_gain	1.0000
7:44149758:AC:A	donor_gain	1.0000
7:44149759:CC:C	donor_gain	1.0000
7:44149759:CCCA:C	donor_gain	1.0000
7:44149967:ACC:A	donor_gain	1.0000
7:44149968:CCC:C	donor_gain	1.0000
7:44149968:CCCCT:C	donor_gain	1.0000
7:44150953:CA:C	donor_loss	1.0000

AlphaMissense

3085 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:44149825:T:A	D205V	1.000
7:44149825:T:C	D205G	1.000
7:44149825:T:G	D205A	1.000
7:44150049:A:G	W167R	1.000
7:44150049:A:T	W167R	1.000
7:44150983:A:C	F152L	1.000
7:44150983:A:T	F152L	1.000
7:44150985:A:G	F152L	1.000
7:44145521:C:A	G410V	0.999
7:44145521:C:T	G410D	0.999
7:44147744:A:G	W257R	0.999
7:44147744:A:T	W257R	0.999
7:44147814:G:C	C233W	0.999
7:44147820:A:C	N231K	0.999
7:44147820:A:T	N231K	0.999
7:44149824:G:C	D205E	0.999
7:44149824:G:T	D205E	0.999
7:44149826:C:G	D205H	0.999
7:44149827:A:C	N204K	0.999
7:44149827:A:T	N204K	0.999
7:44150035:G:C	F171L	0.999
7:44150035:G:T	F171L	0.999
7:44150037:A:G	F171L	0.999
7:44150041:C:A	K169N	0.999
7:44150041:C:G	K169N	0.999
7:44150047:C:A	W167C	0.999
7:44150047:C:G	W167C	0.999
7:44145192:C:G	G448R	0.998
7:44145522:C:A	G410C	0.998
7:44145522:C:G	G410R	0.998

dbSNP variants (sampled 300 via entrez): RS1000049414 (7:44156860 C>T), RS1000076673 (7:44183329 G>A), RS1000126456 (7:44151908 A>C), RS1000145377 (7:44173032 G>A), RS1000236360 (7:44145726 T>A,G), RS1000246131 (7:44186577 A>T), RS1000322966 (7:44163305 C>T), RS1000480319 (7:44169870 G>A), RS1000542449 (7:44175691 A>G), RS1000562927 (7:44181501 A>G), RS1000605359 (7:44147514 T>TACGA), RS1000659930 (7:44187347 C>A,T), RS1000733231 (7:44187063 A>G), RS1000772120 (7:44182530 T>C), RS1000784708 (7:44152685 G>T)

Disease associations

OMIM: gene MIM:138079 | disease phenotypes: MIM:125853, MIM:125851, MIM:602485, MIM:125850, MIM:606391, MIM:606176, MIM:600496, MIM:251260, MIM:300672, MIM:615715

GenCC curated gene-disease

Disease	Classification	Inheritance
maturity-onset diabetes of the young type 2	Definitive	Autosomal dominant
hyperinsulinemic hypoglycemia, familial, 3	Definitive	Autosomal dominant
permanent neonatal diabetes mellitus 1	Strong	Autosomal recessive
transient neonatal diabetes mellitus	Strong	Autosomal recessive
diabetes mellitus, noninsulin-dependent	Strong	Autosomal dominant
type 2 diabetes mellitus	Strong	Autosomal dominant
maturity-onset diabetes of the young	Supportive	Autosomal dominant
permanent neonatal diabetes mellitus	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
monogenic diabetes	Definitive	SD

Mondo (18): type 2 diabetes mellitus (MONDO:0005148), maturity-onset diabetes of the young type 2 (MONDO:0007453), hyperinsulinemic hypoglycemia, familial, 3 (MONDO:0011236), maturity-onset diabetes of the young (MONDO:0018911), permanent neonatal diabetes mellitus 1 (MONDO:0100165), monogenic diabetes (MONDO:0015967), gestational diabetes (MONDO:0005406), permanent neonatal diabetes mellitus (MONDO:0100164), maturity-onset diabetes of the young type 3 (MONDO:0010894), familial hyperinsulinism (MONDO:0017182), neonatal diabetes mellitus (MONDO:0016391), diabetes mellitus (MONDO:0005015), Nijmegen breakage syndrome (MONDO:0009623), developmental and epileptic encephalopathy, 2 (MONDO:0010396), maturity-onset diabetes of the young type 1 (MONDO:0007452)

Orphanet (11): MODY (Orphanet:552), Congenital glucokinase-related hyperinsulinism (Orphanet:79299), Rare genetic diabetes mellitus (Orphanet:183625), Isolated permanent neonatal diabetes mellitus (Orphanet:99885), Familial hyperinsulinism (Orphanet:276525), Neonatal diabetes mellitus (Orphanet:224), Nijmegen breakage syndrome (Orphanet:647), Early infantile developmental and epileptic encephalopathy (Orphanet:1934), West syndrome (Orphanet:3451), CDKL5-deficiency disorder (Orphanet:505652), Pancytopenia-developmental delay syndrome (Orphanet:401764)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000124	Renal tubular dysfunction
HP:0000365	Hearing impairment
HP:0000488	Retinopathy
HP:0000819	Diabetes mellitus
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000855	Insulin resistance
HP:0000857	Neonatal insulin-dependent diabetes mellitus
HP:0000956	Acanthosis nigricans
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001324	Muscle weakness
HP:0001325	Hypoglycemic coma
HP:0001488	Bilateral ptosis
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity
HP:0001518	Small for gestational age
HP:0001520	Large for gestational age

GWAS associations

47 associations (top):

Study	Trait	p-value
GCST000276_3	Fasting plasma glucose	1.000000e-25
GCST000303_4	Glycated hemoglobin levels	6.000000e-12
GCST000568_5	Fasting blood glucose	7.000000e-92
GCST000803_3	Glycated hemoglobin levels	1.000000e-20
GCST001233_9	Metabolite levels	2.000000e-19
GCST001436_14	Metabolic syndrome	4.000000e-13
GCST001527_16	Fasting blood glucose (BMI interaction)	8.000000e-56
GCST001965_2	Glycemic traits	3.000000e-10
GCST001965_5	Glycemic traits	5.000000e-18
GCST001965_9	Glycemic traits	3.000000e-09
GCST002270_2	Glycated hemoglobin levels	6.000000e-08
GCST002390_11	Glycated hemoglobin levels	2.000000e-22
GCST002586_9	Fasting plasma glucose	8.000000e-27
GCST005047_3	Type 2 diabetes	6.000000e-06
GCST005146_6	Birth weight	1.000000e-26
GCST005180_9	Homeostasis model assessment of beta-cell function	2.000000e-16
GCST005186_17	Fasting blood glucose	6.000000e-52
GCST005314_2	Offspring birth weight	7.000000e-09
GCST006001_11	Hemoglobin A1c levels	4.000000e-11
GCST006002_10	Blood sugar levels	7.000000e-16
GCST006613_113	Triglycerides	3.000000e-10
GCST007096_125	Pulse pressure	3.000000e-08
GCST007269_212	Pulse pressure	5.000000e-14
GCST007545_3	Coronary artery disease and triglyceride levels (multivariate analysis)	2.000000e-08
GCST007847_48	Type 2 diabetes	5.000000e-12
GCST007899_7	Fasting blood glucose	1.000000e-50
GCST007953_14	Glycated hemoglobin levels	9.000000e-15
GCST007954_30	Glycated hemoglobin levels	9.000000e-38
GCST007954_31	Glycated hemoglobin levels	4.000000e-35
GCST008362_168	Birth weight	4.000000e-61

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004541	HbA1c measurement
EFO:0000195	metabolic syndrome
EFO:0004340	body mass index
EFO:0004344	birth weight
EFO:0004469	HOMA-B
EFO:0005939	parental genotype effect measurement
EFO:0004468	glucose measurement
EFO:0004530	triglyceride measurement
EFO:0005763	pulse pressure measurement
EFO:0009303	fructosamine measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D016640	Diabetes, Gestational	C12.050.703.170; C18.452.394.750.448; C19.246.200
D049932	Nijmegen Breakage Syndrome	C18.452.284.600
C564064	CDKL5 deficiency disorder (supp.)
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)
C538374	Hyperinsulinemic hypoglycemia, familial, 3 (supp.)
C562772	Mason-Type Diabetes (supp.)
C565101	Maturity-Onset Diabetes of the Young, Type 1 (supp.)
C563933	Maturity-Onset Diabetes of the Young, Type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3820 (SINGLE PROTEIN), CHEMBL3885579 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 674 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1783734	PIRAGLIATIN	2	178
CHEMBL2165615	NERIGLIATIN	2	51
CHEMBL2165620	PF-04991532	2	49
CHEMBL3219124	AZD-1656	2	369
CHEMBL3580737	MK-0941 FREE BASE	2	27

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Hexokinases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
AZD1656	Activation	7.24	pEC50

Binding affinities (BindingDB)

125 measured of 133 human assays (165 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl 3-[6-[5-(4-ethylsulfonylphenoxy)-6-(1-methyl-5-oxopyrrolidin-2-yl)-1H-indol-2-yl]-3-pyridinyl]propanoate	EC50	1.9 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
methyl 3-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-pyrazin-2-yl-1H-indol-5-yl]oxy]phenyl]propanoate	EC50	2.1 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
methyl 3-[6-[6-(1-methyl-5-oxopyrrolidin-2-yl)-5-(4-methylsulfonylphenoxy)-1H-indol-2-yl]-3-pyridinyl]propanoate	EC50	3.8 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
methyl 3-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-pyridin-2-yl-1H-indol-5-yl]oxy]phenyl]propanoate	EC50	4.3 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
ethyl 2-[[2-[[3-(3,4-dichlorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetate	EC50	6.2 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
ethyl 2-[[2-[[3-(4-methoxyphenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetate	EC50	7.5 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
ethyl 2-[5-chloro-2-[[3-(3,4-dichlorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetate	EC50	7.6 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
ethyl 2-[5-chloro-2-[[3-(4-fluorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetate	EC50	8 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
methyl 3-[2-[6-(1-methyl-5-oxopyrrolidin-2-yl)-5-(4-methylsulfonylphenoxy)-1H-indol-2-yl]-1,3-thiazol-5-yl]propanoate	EC50	8.9 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
2-[5-chloro-2-[[3-(4-methoxyphenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid	EC50	9 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
3-(4-methoxyphenyl)sulfanyl-N-[5-[2-(methylamino)-2-oxoethyl]sulfanyl-1,3-thiazol-2-yl]-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carboxamide	EC50	10.8 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
2-[[2-[[3-(4-methoxyphenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetic acid	EC50	10.9 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
ethyl 2-[[2-[[3-(4-fluorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetate	EC50	13.4 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
methyl 3-[6-[6-(1-acetylpyrrolidin-2-yl)-5-[[6-(azetidine-1-carbonyl)-3-pyridinyl]oxy]-1H-indol-2-yl]-3-pyridinyl]propanoate	EC50	13.9 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
CHEMBL3113988	IC50	14 nM
ethyl 3-[[2-[[3-(4-methoxyphenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]-2,2-dimethylpropanoate	EC50	14.3 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
3-[[2-[[3-(4-methoxyphenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]-2,2-dimethylpropanoic acid	EC50	16 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
CHEMBL3113989	IC50	16 nM
2-[5-chloro-2-[[3-(4-fluorophenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid	EC50	16.1 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
2-[2-[[3,6-bis[(4-fluorophenyl)sulfanyl]pyridine-2-carbonyl]amino]-5-chloro-1,3-thiazol-4-yl]acetic acid	EC50	16.3 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
2-[[2-[[3-(3,4-dichlorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetic acid	EC50	16.6 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
ethyl 3-[[2-[[3-(4-fluorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]-2,2-dimethylpropanoate	EC50	16.9 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
3-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-pyridin-2-yl-1H-indol-5-yl]oxy]phenyl]propanoic acid	EC50	17.1 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
3-[[2-[[3-(4-fluorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]-2,2-dimethylpropanoic acid	EC50	17.2 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
2-[5-chloro-2-[[3-(4-fluorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid	EC50	18.6 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
ethyl 2-[5-chloro-2-[[6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]-3-[4-(trifluoromethyl)phenyl]sulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetate	EC50	18.9 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
methyl 2-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-pyridin-2-yl-1H-indol-5-yl]oxy]phenyl]acetate	EC50	21 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
methyl 3-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-[5-(trifluoromethyl)-2-pyridinyl]-1H-indol-5-yl]oxy]phenyl]propanoate	EC50	21.8 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
2-[[2-[[3-(4-fluorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetic acid	EC50	23.1 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
2-[5-chloro-2-[[3-(3,4-dichlorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid	EC50	23.3 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
methyl 3-[2-[[3-(4-methoxyphenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]propanoate	EC50	23.4 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
5-[2-[5-(diethoxyphosphorylmethyl)-1,3-thiazol-2-yl]-5-[(6-methylsulfonyl-3-pyridinyl)oxy]-1H-indol-6-yl]-1-methylpyrrolidin-2-one	EC50	23.5 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
2-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-pyridin-2-yl-1H-indol-5-yl]oxy]phenyl]acetic acid	EC50	23.8 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
CHEMBL3113990	IC50	25 nM
ethyl 2-[[2-[[6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]-3-[4-(trifluoromethyl)phenyl]sulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetate	EC50	28.3 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
3-[[2-[[3-(4-fluorophenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]-2,2-dimethylpropanoic acid	EC50	32 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
2-[[2-[[6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]-3-[4-(trifluoromethyl)phenyl]sulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetic acid	EC50	33.7 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
2-[[2-[[3-(4-fluorophenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetic acid	EC50	34 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
ethyl 2-[[2-[[3-(4-methoxyphenyl)sulfanyl-6-(pyridin-2-ylamino)pyridine-2-carbonyl]amino]-1,3-thiazol-5-yl]sulfanyl]acetate	EC50	35.2 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
3-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-[5-(trifluoromethyl)-2-pyridinyl]-1H-indol-5-yl]oxy]phenyl]propanoic acid	EC50	36.4 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
3-[4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-pyrazin-2-yl-1H-indol-5-yl]oxy]phenyl]propanoic acid	EC50	39.1 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
2-[5-chloro-2-[[6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]-3-[4-(trifluoromethyl)phenyl]sulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid	EC50	44 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
US9453038, 33	EC50	47.4 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
ethyl 2-[5-chloro-2-[[3-(4-methoxyphenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetate	EC50	47.6 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
US9453038, 30	EC50	49.1 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
ethyl 2-[2-[[3-(4-fluorophenyl)sulfanyl-6-[(4-methyl-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetate	EC50	49.3 nM	US-9527838: 2-pyridinecarboxamide derivatives, compositions containing such compounds, and methods of treatment
3-[6-[6-(1-methyl-5-oxopyrrolidin-2-yl)-5-(4-methylsulfonylphenoxy)-1H-indol-2-yl]-3-pyridinyl]propanoic acid	EC50	51.5 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
3-[6-[5-(4-ethylsulfonylphenoxy)-6-(1-methyl-5-oxopyrrolidin-2-yl)-1H-indol-2-yl]-3-pyridinyl]propanoic acid	EC50	53.4 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
[6-[5-(4-ethylsulfonylphenoxy)-6-(1-methyl-5-oxopyrrolidin-2-yl)-1H-indol-2-yl]-3-pyridinyl]-methylphosphinic acid	EC50	53.6 nM	US-9453038: Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
CHEMBL3113991	IC50	56 nM

ChEMBL bioactivities

1393 potent at pChembl≥5 of 1426 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.31	IC50	0.488	nM	STAUROSPORINE
9.10	EC50	0.8	nM	CHEMBL4067028
9.09	IC50	0.81	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL3319533
9.00	EC50	1	nM	CHEMBL4086771
8.85	EC50	1.4	nM	CHEMBL4086782
8.72	EC50	1.9	nM	CHEMBL3918883
8.70	IC50	2	nM	CHEMBL3113985
8.70	EC50	2	nM	CHEMBL4086782
8.68	EC50	2.1	nM	CHEMBL3893442
8.68	EC50	2.1	nM	CHEMBL4068048
8.67	Kd	2.16	nM	CHEMBL3217925
8.62	Kd	2.42	nM	CHEMBL3580738
8.62	EC50	2.4	nM	CHEMBL4067028
8.62	EC50	2.4	nM	CHEMBL4083339
8.53	Kd	2.93	nM	MK-0941 FREE BASE
8.47	EC50	3.4	nM	CHEMBL4104680
8.43	EC50	3.7	nM	CHEMBL4067028
8.42	EC50	3.8	nM	CHEMBL3901777
8.42	EC50	3.8	nM	CHEMBL4086771
8.40	IC50	4	nM	CHEMBL3114185
8.38	EC50	4.2	nM	CHEMBL4078915
8.38	EC50	4.2	nM	CHEMBL4067028
8.37	EC50	4.3	nM	CHEMBL3969091
8.35	EC50	4.5	nM	CHEMBL4078915
8.35	EC50	4.5	nM	CHEMBL4086771
8.32	EC50	4.8	nM	CHEMBL4067037
8.32	EC50	4.8	nM	CHEMBL4068048
8.30	EC50	5	nM	CHEMBL3235148
8.30	IC50	5	nM	CHEMBL3319529
8.30	IC50	5	nM	CHEMBL3319549
8.30	IC50	5	nM	CHEMBL3319540
8.30	IC50	5	nM	CHEMBL3319534
8.26	EC50	5.5	nM	CHEMBL4086771
8.24	EC50	5.7	nM	CHEMBL4092800
8.22	IC50	6	nM	CHEMBL3114186
8.22	IC50	6	nM	CHEMBL3114183
8.22	IC50	6	nM	CHEMBL3319544
8.22	IC50	6	nM	CHEMBL3578107
8.22	EC50	6	nM	CHEMBL3577715
8.22	EC50	6	nM	CHEMBL3577727
8.22	EC50	6	nM	CHEMBL3577728
8.22	EC50	6	nM	CHEMBL3577729
8.22	EC50	6	nM	CHEMBL3577735
8.15	IC50	7	nM	CHEMBL3113980
8.15	IC50	7	nM	CHEMBL3319542
8.15	IC50	7	nM	CHEMBL3319541
8.15	IC50	7	nM	CHEMBL3578087
8.15	EC50	7	nM	CHEMBL3577736
8.10	EC50	8	nM	CHEMBL3235155

PubChem BioAssay actives

1145 with measured affinity, of 2890 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715336: Inhibition of human GCK using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0005	uM
1-methyl-5-[5-[(6-methylsulfonyl-3-pyridinyl)oxy]-2-[5-(trifluoromethyl)-2-pyridinyl]-1H-indol-6-yl]pyrrolidin-2-one	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0008	uM
1-methyl-5-[5-[(6-methylsulfonyl-3-pyridinyl)oxy]-2-pyridin-2-yl-1H-indol-6-yl]pyrrolidin-2-one	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0008	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(1-methylpyrazol-4-yl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0010	uM
1-methyl-5-[5-[(6-methylsulfonyl-3-pyridinyl)oxy]-2-(5-methyl-1,3-thiazol-2-yl)-1H-indol-6-yl]pyrrolidin-2-one	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0010	uM
5-[5-(4-ethylsulfonylphenoxy)-2-[5-(trifluoromethyl)-2-pyridinyl]-1H-indol-6-yl]-1-methylpyrrolidin-2-one	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0014	uM
1,1,1-trifluoro-2-[4-[(2S)-2-(3-oxa-8-azabicyclo[3.2.1]octan-8-ylmethyl)-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol	1068881: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by Alpha Screen assay	ic50	0.0020	uM
5-[2-[5-(2-hydroxypropan-2-yl)-2-pyridinyl]-5-[(6-methylsulfonyl-3-pyridinyl)oxy]-1H-indol-6-yl]-1-methylpyrrolidin-2-one	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0021	uM
methyl 6-[6-(1-methyl-5-oxopyrrolidin-2-yl)-5-[(6-methylsulfonyl-3-pyridinyl)oxy]-1H-indol-2-yl]pyridine-3-carboxylate	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0034	uM
2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1068881: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by Alpha Screen assay	ic50	0.0040	uM
1-methyl-5-[5-[(6-methylsulfonyl-3-pyridinyl)oxy]-2-pyrazin-2-yl-1H-indol-6-yl]pyrrolidin-2-one	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0042	uM
ethyl 4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-[5-(trifluoromethyl)-2-pyridinyl]-1H-indol-5-yl]oxy]benzoate	1446942: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 2.5 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0048	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(3-methoxyprop-1-ynyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0050	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(1-ethylpyrazol-4-yl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0050	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(4-methylthiophen-2-yl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0050	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-pyridin-3-yl-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0050	uM
N-[4-[2-(ethylamino)-2-oxoethyl]-1,3-thiazol-2-yl]-3-(3-methyl-2-pyridinyl)-5-(4-methylsulfonylphenoxy)benzamide	1129057: Activation of recombinant human pancreatic glucokinase using 10 mM glucose by spectrophotometry	ec50	0.0050	uM
2-[5-chloro-2-[[3-(4-methoxyphenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid	1446979: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0057	uM
2-[2-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-3-pyridinyl]phenol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0060	uM
3-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)-5-[2-[3-(2-pyrrolidin-1-ylethylamino)phenyl]ethynyl]benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0060	uM
3-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)-5-[2-[3-(2-piperidin-1-ylethylamino)phenyl]ethynyl]benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0060	uM
3-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)-5-[2-[3-(2-pyrrolidin-1-ylethoxy)phenyl]ethynyl]benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0060	uM
(2R)-2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]propane-1,2-diol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0060	uM
(2S)-2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1-trifluoropropan-2-ol	1068881: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by Alpha Screen assay	ic50	0.0060	uM
2-[4-[4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1068881: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by Alpha Screen assay	ic50	0.0060	uM
3-[2-[3-[2-(dimethylamino)ethylamino]phenyl]ethynyl]-5-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0060	uM
3-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)-5-[3-(oxan-2-yloxy)prop-1-ynyl]benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0060	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-phenyl-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0070	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(2-fluorophenyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0070	uM
3-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)-5-[2-[3-(2-piperidin-1-ylethoxy)phenyl]ethynyl]benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0070	uM
2-[6-[6-[(6-amino-3-pyridinyl)sulfonyl]-2-anilino-3-pyridinyl]-3-pyridinyl]-1,1,1-trifluoropropan-2-ol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0070	uM
1,1,1-trifluoro-2-[4-[(2S)-2-[[(3S)-3-methylmorpholin-4-yl]methyl]-4-thiophen-2-ylsulfonylpiperazin-1-yl]phenyl]propan-2-ol	1068881: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by Alpha Screen assay	ic50	0.0070	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(3-fluorophenyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0080	uM
N-[4-[(1-methoxypropan-2-ylamino)methyl]-1,3-thiazol-2-yl]-3-(3-methyl-2-pyridinyl)-5-(4-methylsulfonylphenoxy)benzamide	1129057: Activation of recombinant human pancreatic glucokinase using 10 mM glucose by spectrophotometry	ec50	0.0080	uM
3-[(2S)-1-methoxypropan-2-yl]oxy-5-[2-[3-[2-(2-methylimidazol-1-yl)ethylamino]phenyl]ethynyl]-N-(1-methylpyrazol-3-yl)benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0090	uM
(2R)-2-[4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-prop-1-ynylpiperazin-1-yl]phenyl]-1,1,1-trifluoropropan-2-ol	1068881: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by Alpha Screen assay	ic50	0.0090	uM
1-[4-[5-[(5-pyridin-2-ylsulfanyl-3-quinolin-5-yloxy-2-pyridinyl)amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone	1653850: Activation of glucokinase (unknown origin)	ec50	0.0093	uM
4-[[6-(1-methyl-5-oxopyrrolidin-2-yl)-2-[5-(trifluoromethyl)-2-pyridinyl]-1H-indol-5-yl]oxy]benzoic acid	1446944: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0096	uM
2-[5-chloro-2-[[3-(4-fluorophenyl)sulfanyl-6-pyridin-2-ylsulfanylpyridine-2-carbonyl]amino]-1,3-thiazol-4-yl]acetic acid	1446979: Activation of recombinant human glucokinase assessed as conversion of D-glucose to D-glucose-6-phosphate in presence of 10 mM glucose by G6PDH coupled spectrophotometric assay	ec50	0.0096	uM
2-[4-[5-[(6-amino-3-pyridinyl)sulfonyl]-1,3-thiazol-2-yl]-3-chlorophenyl]propane-1,2-diol	1226494: Inhibition of human biotin-labeled GKRP and fluorescein-labeled human GK interaction preincubated for 20 mins prior to fluorescein-labeled human GK addition measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0100	uM
3-methyl-2-[4-[(1-methylpyrazol-3-yl)amino]quinazolin-6-yl]oxybenzonitrile	437790: Activation of N-terminal His-tagged human recombinant liver glucokinase expressed in Escherichia coli BL21 (DE3) by glucose-6-phosphate dehydrogenase coupled continuous spectrophotometric assay in presence of 10 mM glucose	ec50	0.0100	uM
5-[2-(1-ethylpiperidin-4-yl)-1,3-thiazol-5-yl]-3-(pyridin-4-ylmethoxy)pyridin-2-amine	1679420: Inhibition of human GCK using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0102	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(4-fluorophenyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0110	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(5-fluoro-3-pyridinyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0110	uM
3-[2-(1H-indol-5-yl)ethynyl]-5-[(2S)-1-methoxypropan-2-yl]oxy-N-(1-methylpyrazol-3-yl)benzamide	1226037: Activation of recombinant human pancreatic glucokinase using 10 mM glucose as substrate by G6PDH coupled assay	ec50	0.0120	uM
2-[(Z)-1-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentylethenyl]-1H-pyrrolo[2,3-b]pyridine	1276628: Activation of recombinant human glucokinase assessed as NADPH formation using glucose as substrate incubated for 30 mins in presence of NADP+ and glucose 6-phosphate dehydrogenase	ec50	0.0124	uM
2-[6-[4-[(6-amino-3-pyridinyl)sulfonyl]piperazin-1-yl]-5-(3-hydroxyprop-1-ynyl)-3-pyridinyl]-1,1,1,3,3,3-hexafluoropropan-2-ol	1182398: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP compound incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by AlphaScreen assay	ic50	0.0140	uM
1-[5-(cyclohexylmethyl)-3-[(2-ethyl-3-pyridinyl)oxy]-2-pyridinyl]-3-methylurea	1176538: Activation of human recombinant Glucokinase measured over 5 mins by G6-PD coupled assay in presence of 5 mM glucose	ec50	0.0140	uM
1-[4-(2,6-difluorophenoxy)-5-(6-ethoxy-3-pyridinyl)-2-pyridinyl]-3-methylurea	1627607: Activation of human recombinant glucokinase using 5 mM glucose monitored over 5 mins in presence of NAD+ by glucose 6-phosphate dehydrogenase coupled assay	ec50	0.0140	uM
(1R,5R,6R)-8-[[(2S)-4-thiophen-2-ylsulfonyl-1-[4-[(2R)-1,1,1-trifluoro-2-hydroxypropan-2-yl]phenyl]piperazin-2-yl]methyl]-3-oxa-8-azabicyclo[3.2.1]octan-6-ol	1068881: Inhibition of fluorescein-labeled human GK interaction with biotin-labeled human GKRP incubated for 20 mins prior to addition of fluorescein-labeled GK measured after 2 to 4 hrs by Alpha Screen assay	ic50	0.0140	uM

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases methylation, decreases expression, affects cotreatment	2
mono-(2-ethylhexyl)phthalate	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, affects cotreatment, affects expression	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	2
benzo(b)fluoranthene	affects cotreatment, affects expression	1
bisphenol A	decreases expression	1
fluoranthene	affects cotreatment, affects expression	1
1,2,5,6-dibenzanthracene	affects cotreatment, affects expression	1
4-aminophenylarsenoxide	decreases reaction, affects binding	1
benazol P	affects expression	1
benzamide	increases activity	1
1-methylphenanthrene	affects cotreatment, affects expression	1
dibenzo(a,l)pyrene	affects cotreatment, affects expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
fenugreek seed meal	affects expression	1
tetraarsenic tetrasulfide	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide	decreases reaction, increases expression, increases reaction	1
Imatinib Mesylate	affects cotreatment, decreases expression	1
Atorvastatin	decreases expression, increases reaction	1
Resveratrol	increases reaction, decreases reaction, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	increases methylation	1
Estradiol	increases expression	1
Folic Acid	decreases expression	1
Metformin	decreases expression, decreases activity, decreases reaction	1
Rifampin	decreases expression, increases reaction	1

ChEMBL screening assays

228 unique, capped per target: 226 binding, 1 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032034	Binding	Activation of flag-tagged human recombinant liver glucokinase expressed in Escherichia coli by glucose-6-phosphate dehydrogenase coupled continuous spectrophotometric assay in presence of 2.5 mM glucose	Structure-activity relationships of 3,5-disubstituted benzamides as glucokinase activators with potent in vivo efficacy. — Bioorg Med Chem
CHEMBL4813785	ADMET	Inhibition of human hexokinase-4 at 20 uM relative to control	Synthesis, biochemical, and biological evaluation of C2 linkage derivatives of amino sugars, inhibitors of glucokinase from Trypanosoma cruzi. — Bioorg Med Chem Lett
CHEMBL865109	Functional	Activation of glucokinase	Design of a potent, soluble glucokinase activator with excellent in vivo efficacy. — Bioorg Med Chem Lett

Cellosaurus cell lines

9 cell lines: 5 induced pluripotent stem cell, 2 spontaneously immortalized cell line, 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4NV	QBRIi010-A	Induced pluripotent stem cell	Male
CVCL_A4NW	QBRIi011-A	Induced pluripotent stem cell	Male
CVCL_A4NX	QBRIi010-B	Induced pluripotent stem cell	Male
CVCL_A4NY	QBRIi010-C	Induced pluripotent stem cell	Male
CVCL_AJ80	GM13532	Transformed cell line	Female
CVCL_C9JN	SDQLCHi063-A	Induced pluripotent stem cell	Male
CVCL_HA58	BHK-PPI-C16-GCK	Spontaneously immortalized cell line	Male
CVCL_HA59	BHK-PPI-C16-GCK-GLUT	Spontaneously immortalized cell line	Male
CVCL_HA63	Melligen	Cancer cell line	Male

Clinical trials (associated diseases)

321 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02624817	PHASE4	COMPLETED	Long-Term Sulfonylurea Response in KCNJ11 Neonatal Diabetes
NCT02624830	PHASE4	UNKNOWN	Long-Term Sulfonylurea Response in ABCC8 Neonatal Diabetes (SuResponsSUR)
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes