ENPP1

Summary

ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1, HGNC:3356) is a protein-coding gene on chromosome 6q23.2, encoding Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (P22413). Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels.

This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5’ triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with ‘idiopathic’ infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance.

Source: NCBI Gene 5167 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arterial calcification, generalized, of infancy, 1 (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 935 total — 55 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 168
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_006208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3356
Approved symbol	ENPP1
Name	ectonucleotide pyrophosphatase/phosphodiesterase 1
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Aliases	PC-1, PCA1
Ensembl gene	ENSG00000197594
Ensembl biotype	protein_coding
OMIM	173335
Entrez	5167

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 5 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000459624, ENST00000486853, ENST00000513998, ENST00000647893, ENST00000647981, ENST00000650147, ENST00000650437, ENST00000650507, ENST00000683687, ENST00000684147, ENST00000684536, ENST00000684674, ENST00000922186

RefSeq mRNA: 1 — MANE Select: NM_006208 NM_006208

CCDS: CCDS5150

Canonical transcript exons

ENST00000647893 — 25 exons

Exon	Start	End
ENSE00000763731	131864866	131864938
ENSE00000763735	131861595	131861704
ENSE00000763737	131860387	131860506
ENSE00000763739	131858668	131858747
ENSE00001147074	131854926	131855023
ENSE00001147082	131852175	131852235
ENSE00001147089	131851142	131851267
ENSE00001388381	131890341	131895155
ENSE00003459242	131872923	131873050
ENSE00003477160	131864506	131864571
ENSE00003478626	131883694	131883774
ENSE00003480135	131879880	131880034
ENSE00003497377	131882345	131882474
ENSE00003551547	131849990	131850106
ENSE00003565246	131886562	131886724
ENSE00003586924	131847776	131847848
ENSE00003587062	131874268	131874337
ENSE00003589126	131878542	131878593
ENSE00003601053	131884931	131885063
ENSE00003607573	131876992	131877161
ENSE00003620099	131869358	131869489
ENSE00003628761	131875776	131875863
ENSE00003641164	131868018	131868126
ENSE00003642026	131872070	131872101
ENSE00003834150	131808020	131808275

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 98.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2821 / max 801.1181, expressed in 1012 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69800	7.2821	1012

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	98.09	gold quality
decidua	UBERON:0002450	95.52	gold quality
cartilage tissue	UBERON:0002418	95.28	gold quality
cauda epididymis	UBERON:0004360	93.64	gold quality
calcaneal tendon	UBERON:0003701	93.60	gold quality
tendon of biceps brachii	UBERON:0008188	93.04	gold quality
liver	UBERON:0002107	92.16	gold quality
tendon	UBERON:0000043	91.73	gold quality
right lobe of liver	UBERON:0001114	90.65	gold quality
synovial joint	UBERON:0002217	89.94	gold quality
placenta	UBERON:0001987	89.31	gold quality
corpus epididymis	UBERON:0004359	88.99	gold quality
body of uterus	UBERON:0009853	87.39	gold quality
myometrium	UBERON:0001296	87.25	gold quality
layer of synovial tissue	UBERON:0007616	87.01	gold quality
buccal mucosa cell	CL:0002336	85.78	gold quality
periodontal ligament	UBERON:0008266	85.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.13	gold quality
caput epididymis	UBERON:0004358	84.93	gold quality
body of pancreas	UBERON:0001150	84.24	gold quality
descending thoracic aorta	UBERON:0002345	84.12	gold quality
stromal cell of endometrium	CL:0002255	83.97	gold quality
thyroid gland	UBERON:0002046	83.60	gold quality
trachea	UBERON:0003126	83.39	gold quality
mammary duct	UBERON:0001765	83.21	gold quality
amniotic fluid	UBERON:0000173	82.96	gold quality
epithelium of mammary gland	UBERON:0003244	82.86	gold quality
smooth muscle tissue	UBERON:0001135	82.53	gold quality
pancreas	UBERON:0001264	82.49	gold quality
uterus	UBERON:0000995	82.37	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	412.30
E-MTAB-10290	yes	211.53
E-MTAB-6701	yes	67.66
E-ANND-3	yes	17.49
E-MTAB-6678	yes	7.07
E-CURD-112	yes	5.81
E-GEOD-70580	no	629.47
E-MTAB-8271	no	522.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FGF2, IL1B, JUN, MSX2, RUNX2, TGFB1

miRNA regulators (miRDB)

191 targeting ENPP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5698	99.97	68.49	2029

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The IVS15-14T –> C substitution in the human NPPS gene is associated not only with susceptibility to, but also with severity of OPLL. (PMID:11771660)
• polymorphic in normoalbuminuric type 1 diabetic patients (PMID:12126783)
• in type 1 diabetic patients, the ACE and the PC-1 genes interact in increasing the individual risk of having a faster diabetic nephropathy progression (PMID:12147786)
• Amino acid variant (K121Q) has no impact on progression of diabetic nephropathy in type 1 diabetic patients (PMID:12147787)
• Insulin modulates PC-1 processing and recruitment in cultured human cells.autophosphorylation. Insulin stimulates PC-1 posttranslational processing and translocation to the plasma membrane, which in turn impairs insulin receptor signaling. (PMID:12441313)
• PC1 has a role in predisposition to early myocardial infarction (PMID:12483464)
• In healthy normoglycemic Finnish subjects, the K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with impaired insulin secretion or dyslipidemia. (PMID:12547881)
• study suggests that both examined polymorphisms: the -308 G/A in the promoter region of TNF-alpha and K121Q amino acid variant of the PC-1 influence the development of insulin resistance as a prediabetic quantitative trait in a Polish population (PMID:12715715)
• Mutations in ENPP1 are associated with ‘idiopathic’ infantile arterial calcification. (PMID:12881724)
• PC-1 K121Q polymorphism associates with primary insulin resistance in migrant Asian Indians. High frequency of this polymorphism may be one factor contributing to insulin resistance susceptibility in Asian Indians. (PMID:14671192)
• PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic, contributing to both insulin resistance and type 2 diabetes. (PMID:15001634)
• Interaction between the K121Q polymorphism of the PC-1 gene and birth length affects insulin sensitivity and increases susceptibility to type 2 diabetes and hypertension in adulthood (PMID:15126519)
• The K121Q polymorphism of the plasma cell membrane glycoprotein 1 gene is significantly associated with polycystic ovary syndrome (PCOS) susceptibility. (PMID:15374726)
• Plays a role in insulin resistance and suggests that animals with overexpression of human PC-1 in liver may be interesting models to investigate insulin resistance and glucose intolerance. (PMID:15677494)
• Our study supports the hypothesis that ENPP1 121Q predicts genetic susceptibility to type 2 diabetes in both South Asians and Caucasians. (PMID:15793263)
• Increased lymphocyte PC-1 activity was associated with end-stage renal failure patients on haemodialysis (PMID:15802034)
• The IVS20-11delT variant of the NPPS gene and the A861G variant of the leptin receptor gene are associated with more extensive OPLL, but not with the frequency with which it occurs. (PMID:15834329)
• ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1/PC-1) 121Q variant is associated with a progressive deterioration of the insulin resistance-atherogenic phenotype and earlier onset of type 2 diabetes and myocardial infarction (PMID:16186408)
• The K121Q polymorphism of the plasma cell membrane glycoprotein-1 (PC-1) gene is unlikely to be a major genetic factor predisposing to preeclampsia in Finnish women. (PMID:16272817)
• Overexpression of ENPP1 induces insulin resistance and hyperglycemia. (PMID:16278247)
• Analysis of the DNA variations of ENPP1 provides a first molecular basis for the physiopathologic association between severe insulin resistance and obesity, and further type 2 diabetes. (PMID:16527214)
• the K121Q variant of the ENPP1 gene has very little, if any, impact on type 2 diabetes (T2D) susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D (PMID:16607460)
• the ENPP1 K121Q polymorphism does not seem to influence the risk of insulin resistance or type 2 diabetes in Danish white subjects; however, a meta-analysis of the present and published studies demonstrates evidence of association with type 2 diabetes (PMID:16865358)
• we found a new SNP, rs997509, in intron 1 that is strongly associated with risk of type 2 diabetes in obese individuals. (PMID:16936213)
• role of the K121Q polymorphism or derived ENPP1 haplotypes in increased susceptibility to obesity and early impairment of glucose and insulin metabolism in children. (PMID:16968801)
• a significant association of PC-1 K121Q with obesity (PMID:17026496)
• No evidence that previously associated variants of ENPP1 are associated with type 2 diabetes or obesity in the U.K. population. (PMID:17065358)
• No association with three variants and body mass index or type 2 diabetes. (PMID:17065359)
• PC-1 (ENPP1) 121Q allele is associated with the genetic susceptibility for metabolic syndrome in patients with coronary heart disease (PMID:17129580)
• Ectonucleotide pyrophosphatase phosphodiesterase 1 as a ‘gatekeeper’ of insulin receptors. (PMID:17143316)
• There is a lack of correlation between genetic expression of ENPP1 and body mass index. This may suggest that glucose metabolism is more complex than lipid metabolism. (PMID:17287921)
• THE 121Q allele frequency may contribute to increased susceptibility to type 2 diabetes observed in US minority groups. (PMID:17493546)
• Overexpression of ENPP1 in insulin target tissues is an early, intrinsic defect observed in human insulin resistance (PMID:17563456)
• functional interactions between alkaline phosphatase and ENPP1(PC-1) may link insulin resistance to vascular calcification. (PMID:17606264)
• Nominal evidence of association between the K121Q polymorphism and both severe adult obesity at baseline and risk of hyperglycaemia or type 2 diabetes . (PMID:17704904)
• Our results suggest that the ENPP1121Q allele might contribute to the genetic susceptibility to abdominal obesity among subjects with MS. (PMID:17986276)
• The ENPP1 Q121 variant increases risk of type 2 diabetes under a recessive model of inheritance in whites, an effect that appears to be modulated by body mass index. (PMID:18071025)
• K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample. (PMID:18176722)
• Variants in the distal region of the ENPP1 gene may contribute to diabetes or diabetic nephropathy susceptibility in African Americans. (PMID:18184924)
• Results describe the activities of ectonucleotide pyrophosphatase/phosphodiesterase and adenosine deaminase in patients with uterine cervix neoplasia. (PMID:18222177)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	enpp1	ENSDARG00000005789
mus_musculus	Enpp1	ENSMUSG00000037370
rattus_norvegicus	Enpp1	ENSRNOG00000013994
caenorhabditis_elegans		WBGENE00007753
caenorhabditis_elegans		WBGENE00007755
caenorhabditis_elegans		WBGENE00015283

Paralogs (6): ENPP4 (ENSG00000001561), ENPP5 (ENSG00000112796), ENPP2 (ENSG00000136960), ENPP3 (ENSG00000154269), ENPP6 (ENSG00000164303), ENPP7 (ENSG00000182156)

Protein

Protein identifiers

Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 — P22413 (reviewed: P22413)

Alternative names: Alkaline phosphodiesterase I, Membrane component chromosome 6 surface marker 1, Nucleotide diphosphatase, Nucleotide pyrophosphatase, Phosphodiesterase I/nucleotide pyrophosphatase 1, Plasma-cell membrane glycoprotein PC-1

All UniProt accessions (5): A0A3B3ISN7, A0A3B3IST7, A0A3B3IU14, E9PE72, P22413

UniProt curated annotations — full annotation on UniProt →

Function. Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels. PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals. Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5’ triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3’,5’-cAMP to AMP. May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling. Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect. Appears to modulate insulin sensitivity and function. Also involved in melanogenesis. Also able to hydrolyze 2’,3’-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production. 2’,3’-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2’,3’-cGAMP hydrolysis is therefore unclear. Not able to hydrolyze the 2’,3’-cGAMP linkage isomer 3’-3’-cGAMP.

Subunit / interactions. Homodimer. Interacts with INSR; leading to inhibit INSR autophosphorylation and subsequent activation of INSR kinase activity. Monomeric.

Subcellular location. Cell membrane. Basolateral cell membrane Secreted.

Tissue specificity. Expressed in plasma cells and also in a number of non-lymphoid tissues, including the distal convoluted tubule of the kidney, chondrocytes and epididymis. Expressed in melanocytes but not in keratinocytes.

Post-translational modifications. Autophosphorylated as part of the catalytic cycle of phosphodiesterase/pyrophosphatase activity. N-glycosylated. The secreted form is produced through cleavage at Lys-103 by intracellular processing.

Disease relevance. Ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475] A calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. Patients with OPLL frequently present with a severe myelopathy that can lead to tetraparesis. The disease is caused by variants affecting the gene represented in this entry. Arterial calcification of infancy, generalized, 1 (GACI1) [MIM:208000] A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure. 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. Hypophosphatemic rickets, autosomal recessive, 2 (ARHR2) [MIM:613312] A hereditary form of hypophosphatemic rickets, a disorder of proximal renal tubule function that causes phosphate loss, hypophosphatemia and skeletal deformities, including rickets and osteomalacia unresponsive to vitamin D. Symptoms are bone pain, fractures and growth abnormalities. The disease is caused by variants affecting the gene represented in this entry. Cole disease (COLED) [MIM:615522] A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.

Cofactor. Binds 2 Zn(2+) ions per subunit.

Domain organisation. The di-leucine motif is required for basolateral targeting in epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells. The nuclease-like domain is most probably catalytically inactive as residues that are essential for catalysis in the DNA/RNA non-specific endonucleases are not conserved. However, it is required for the stability of the protein and the catalytic activity born by the phosphodiesterase domain.

Similarity. Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.

RefSeq proteins (1): NP_006199* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001212	Somatomedin_B_dom	Domain
IPR001604	Endo_G_ENPP1-like_dom	Domain
IPR002591	Phosphodiest/P_Trfase	Family
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR020436	SMB_chordata	Domain
IPR020821	ENPP1-3/EXOG-like_nuc-like	Domain
IPR036024	Somatomedin_B-like_dom_sf	Homologous_superfamily
IPR044925	His-Me_finger_sf	Homologous_superfamily
IPR044929	DNA/RNA_non-sp_Endonuclease_sf	Homologous_superfamily

Pfam: PF01033, PF01223, PF01663

Enzyme classification (BRENDA):

• EC 3.6.1.9 — nucleotide diphosphatase (BRENDA: 33 organisms, 282 substrates, 447 inhibitors, 181 Km, 58 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.0062–78	14
NAD+	0.004–31.2	12
FAD	0.005–1.8	10
UDP-GLUCOSE	0.62–50	8
NADH	0.042–20	7
THYMIDINE 5’-MONOPHOSPHATE P-NITROPHENYL ESTER	0.066–20	7
UTP	0.0566–33	7
4-NITROPHENYL-5’-THYMIDINE MONOPHOSPHATE	0.0618–0.222	5
4-NITROPHENYL-5’-TMP	0.027–0.1185	4
AP3A	0.0051–0.0495	4
ADENOSINE 5’-PHOSPHOSULFATE	0.5–3	3
ADP	0.18–4.3	3
ADP-GLUCOSE	0.7–0.8	3
ADP-RIBOSE	0.5–18.9	3
BIS(4-NITROPHENYL)PHOSPHATE	2.1–3	3

Catalyzed reactions (Rhea), 8 shown:

• ATP + H2O = AMP + diphosphate + H(+) (RHEA:14245)
• a ribonucleoside 5’-triphosphate + H2O = a ribonucleoside 5’-phosphate + diphosphate + H(+) (RHEA:23996)
• 3’,5’-cyclic AMP + H2O = AMP + H(+) (RHEA:25277)
• CTP + H2O = CMP + diphosphate + H(+) (RHEA:27762)
• GTP + H2O = GMP + diphosphate + H(+) (RHEA:29391)
• UTP + H2O = UMP + diphosphate + H(+) (RHEA:29395)
• P(1),P(4)-bis(5’-adenosyl) tetraphosphate + H2O = AMP + ATP + 2 H(+) (RHEA:32039)
• 2’,3’-cGAMP + 2 H2O = GMP + AMP + 2 H(+) (RHEA:58808)

UniProt features (205 total): sequence variant 51, binding site 43, helix 31, strand 29, disulfide bond 16, turn 9, glycosylation site 9, region of interest 4, chain 2, topological domain 2, domain 2, site 2, short sequence motif 1, compositionally biased region 1, active site 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6WFJ	X-RAY DIFFRACTION	2.5
6WET	X-RAY DIFFRACTION	2.6
6WEU	X-RAY DIFFRACTION	2.65
6WEW	X-RAY DIFFRACTION	2.73
6WEV	X-RAY DIFFRACTION	2.9
8GHR	ELECTRON MICROSCOPY	3.2
2YS0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22413-F1	91.35	0.87

Antibody-complex structures (SAbDab): 1 — 8GHR

Functional residue map

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

Catalytic / active sites (3): 256 (amp-threonine intermediate); 102–103 (cleavage); 915 (essential for catalytic activity)

Ligand- & substrate-binding residues (43): 218; 218; 256; 256; 256; 256; 256; 277; 277; 277; 277; 290 …

Post-translational modifications (1): 256

Disulfide bonds (16): 108–122, 112–140, 120–133, 126–132, 149–166, 154–184, 164–177, 170–176, 195–241, 203–415, 431–530, 480–868, 614–672, 626–726, 628–711, 838–848

Glycosylation sites (9): 179, 285, 341, 477, 585, 643, 700, 731, 748

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-196843	Vitamin B2 (riboflavin) metabolism
R-HSA-199220	Vitamin B5 (pantothenate) metabolism

MSigDB gene sets: 702 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOCC_VACUOLAR_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOMF_NUCLEASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_INORGANIC_ANION_TRANSPORT

GO Biological Process (26): generation of precursor metabolites and energy (GO:0006091), phosphate-containing compound metabolic process (GO:0006796), immune response (GO:0006955), nucleoside triphosphate catabolic process (GO:0009143), gene expression (GO:0010467), bone mineralization (GO:0030282), negative regulation of cell growth (GO:0030308), melanocyte differentiation (GO:0030318), regulation of bone mineralization (GO:0030500), negative regulation of bone mineralization (GO:0030502), inorganic diphosphate transport (GO:0030505), intracellular phosphate ion homeostasis (GO:0030643), cellular response to insulin stimulus (GO:0032869), response to ATP (GO:0033198), negative regulation of fat cell differentiation (GO:0045599), negative regulation of glycogen biosynthetic process (GO:0045719), ATP metabolic process (GO:0046034), negative regulation of D-glucose import across plasma membrane (GO:0046325), negative regulation of insulin receptor signaling pathway (GO:0046627), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427), phosphate ion homeostasis (GO:0055062), nucleic acid metabolic process (GO:0090304), obsolete negative regulation of hh target transcription factor activity (GO:1990787), vesicle-mediated transport (GO:0016192), biomineral tissue development (GO:0031214), animal organ development (GO:0048513)

GO Molecular Function (22): nucleic acid binding (GO:0003676), 3’,5’-cyclic-AMP phosphodiesterase activity (GO:0004115), exonuclease activity (GO:0004527), phosphodiesterase I activity (GO:0004528), dinucleotide phosphatase activity (GO:0004551), scavenger receptor activity (GO:0005044), insulin receptor binding (GO:0005158), calcium ion binding (GO:0005509), ATP binding (GO:0005524), zinc ion binding (GO:0008270), phosphatase activity (GO:0016791), polysaccharide binding (GO:0030247), GTP diphosphatase activity (GO:0036219), UTP diphosphatase activity (GO:0036221), protein homodimerization activity (GO:0042803), nucleoside triphosphate diphosphatase activity (GO:0047429), ATP diphosphatase activity (GO:0047693), 3’-phosphoadenosine 5’-phosphosulfate binding (GO:0050656), cyclic-GMP-AMP hydrolase activity (GO:0106177), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside triphosphate diphosphatase activity	3
cellular anatomical structure	3
metabolic process	2
bone mineralization	2
purine ribonucleotide metabolic process	2
binding	2
pyrophosphatase activity	2
adenyl ribonucleotide binding	2
immune system process	1
response to stimulus	1
nucleoside triphosphate metabolic process	1
nucleoside phosphate catabolic process	1
macromolecule biosynthetic process	1
ossification	1
biomineral tissue development	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
pigment cell differentiation	1
regulation of ossification	1
regulation of biomineral tissue development	1
negative regulation of ossification	1
regulation of bone mineralization	1
negative regulation of biomineral tissue development	1
inorganic anion transport	1
phosphate ion homeostasis	1
intracellular chemical homeostasis	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
glycogen biosynthetic process	1
regulation of glycogen biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of glycogen metabolic process	1

Protein interactions and networks

STRING

1728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENPP1	PHEX	P78562	908
ENPP1	NT5E	P21589	880
ENPP1	ALPL	P05186	864
ENPP1	FGF23	Q9GZV9	861
ENPP1	GDPD1	Q8N9F7	828
ENPP1	GDPD3	Q7L5L3	822
ENPP1	PHOSPHO1	Q8TCT1	822
ENPP1	SLC34A3	Q8N130	813
ENPP1	ANKH	Q9HCJ1	796
ENPP1	ABCC6	P78420	732
ENPP1	CAPN10	Q9HC96	680
ENPP1	AHSG	P02765	648
ENPP1	IBSP	P21815	644
ENPP1	CLCN5	P51795	640
ENPP1	KL	Q9UEF7	631

IntAct

85 interactions, top by confidence:

A	B	Type	Score
EIF2B2	SLC27A2	psi-mi:“MI:0914”(association)	0.640
ABCG2	ENPP1	psi-mi:“MI:0407”(direct interaction)	0.600
ENPP1	ABCG2	psi-mi:“MI:0915”(physical association)	0.600
ABCG2	ENPP1	psi-mi:“MI:0915”(physical association)	0.600
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
FNTB	BLTP3B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
GPC3	CLGN	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
FANCE	ENPP1	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
FNTB	CAPN1	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
FLVCR1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
ENPP1	INSR	psi-mi:“MI:2364”(proximity)	0.470
INSR	ENPP1	psi-mi:“MI:0915”(physical association)	0.470
Dlg4	ENPP1	psi-mi:“MI:0407”(direct interaction)	0.440
		psi-mi:“MI:0914”(association)	0.350
ATP6V0D1		psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
FANCE	GNPAT	psi-mi:“MI:0914”(association)	0.350

BioGRID (98): ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), PSMD12 (Affinity Capture-Western), PSMA1 (Affinity Capture-Western), PSMB1 (Affinity Capture-Western), ENPP1 (Biochemical Activity), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), ENPP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A4D0V7, C5H5C4, F6Q1T7, O70309, O75354, P17405, P18084, P18424, P22413, P50747, P52850, P58242, P61642, P80747, Q04519, Q0VBD0, Q0VD19, Q13219, Q52KP5, Q58CQ9, Q5QQ51, Q5STE3, Q64687, Q6DFZ6, Q6KFX9, Q6MZW2, Q6P988, Q6UWX4, Q6YGZ1, Q6ZXD2, Q71RP1, Q812F8, Q8BJQ9, Q8C1F4, Q8C419, Q8N5D6, Q8N6G5, Q8R116

Diamond homologs: A0A2D0TC04, A1A4K5, A2VDP5, J3SBP3, J3SEZ3, O14638, O94323, P06802, P0DQQ4, P15396, P22413, P84039, P97675, Q0VA77, Q13822, Q3TIW9, Q566N0, Q5EZ72, Q5R5M5, Q5RAC0, Q64610, Q6AX80, Q6DYE8, Q6UWV6, Q8BTJ4, Q924C3, Q9EQG7, Q9R1E6, Q9UJA9, Q9Y6X5, W8E7D1, P90754, A1YYW7, B0BND0, F1N5C8, P90755, Q58D68, Q5BKW7, Q5RB45, Q6DDP3

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
ENPP1	“down-regulates activity”	INSR	binding
FGF2	“up-regulates quantity by expression”	ENPP1	“transcriptional regulation”
RUNX2	“up-regulates quantity by expression”	ENPP1	“transcriptional regulation”
ENPP1	up-regulates	Bone_mineralization
HSPA1A	“up-regulates quantity”	ENPP1	“post transcriptional regulation”
HSPA1B	“up-regulates quantity”	ENPP1	“post transcriptional regulation”
IL1B	“down-regulates quantity by repression”	ENPP1	“transcriptional regulation”
TGFB1	“up-regulates quantity by expression”	ENPP1	“transcriptional regulation”
ENPP1	“down-regulates quantity”	“3’,5’-cyclic AMP”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metal ion SLC transporters	5	46.2×	6e-06
R-HSA-425366	6	16.7×	1e-04
SLC-mediated transmembrane transport	8	7.3×	8e-04
Transport of small molecules	11	4.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
zinc ion transmembrane transport	8	59.1×	4e-10
intracellular zinc ion homeostasis	6	30.4×	9e-06
amino acid transport	5	16.4×	2e-03
transport across blood-brain barrier	6	11.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	55
Likely pathogenic	35
Uncertain significance	423
Likely benign	211
Benign	130

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1179191	NM_006208.3(ENPP1):c.2344C>T (p.Arg782Ter)	Pathogenic
13585	NM_006208.3(ENPP1):c.2677G>T (p.Glu893Ter)	Pathogenic
13587	NM_006208.3(ENPP1):c.1072_1082del (p.Gln358fs)	Pathogenic
13592	NM_006208.3(ENPP1):c.1112A>T (p.Tyr371Phe)	Pathogenic
13593	NM_006208.3(ENPP1):c.2444+702_*868del	Pathogenic
13594	NM_006208.3(ENPP1):c.797G>T (p.Gly266Val)	Pathogenic
13595	NM_006208.3(ENPP1):c.2248dup (p.Ser750fs)	Pathogenic
13596	NM_006208.3(ENPP1):c.2702A>C (p.Tyr901Ser)	Pathogenic
13597	NM_006208.3(ENPP1):c.783C>G (p.Tyr261Ter)	Pathogenic
13598	NM_006208.3(ENPP1):c.878_879del (p.Lys293fs)	Pathogenic
1526269	NM_006208.3(ENPP1):c.1028C>A (p.Ser343Ter)	Pathogenic
1699955	NM_006208.3(ENPP1):c.915+1G>A	Pathogenic
1699956	NM_006208.3(ENPP1):c.2741T>A (p.Leu914Ter)	Pathogenic
1699957	NM_006208.3(ENPP1):c.511A>T (p.Lys171Ter)	Pathogenic
1699959	NM_006208.3(ENPP1):c.574del (p.Glu192fs)	Pathogenic
1699961	NM_006208.3:c.(1091+1_1092-1)_(1164+1_1165-1)del	Pathogenic
1699962	NM_006208.3(ENPP1):c.1094del (p.Pro365fs)	Pathogenic
1699963	NM_006208.3(ENPP1):c.1273+1G>A	Pathogenic
1699964	NM_006208.3(ENPP1):c.196_197del (p.Ala66fs)	Pathogenic
1699966	NM_006208.3(ENPP1):c.2230C>T (p.Gln744Ter)	Pathogenic
1699967	NM_006208.3(ENPP1):c.26dup (p.Gly10fs)	Pathogenic
1699971	NM_006208.3(ENPP1):c.1273+2T>C	Pathogenic
1699972	NM_006208.3(ENPP1):c.208A>T (p.Lys70Ter)	Pathogenic
1699973	NM_006208.3(ENPP1):c.2192del (p.Asn731fs)	Pathogenic
1699974	NM_006208.3(ENPP1):c.2300del (p.Gln767fs)	Pathogenic
1699975	NM_006208.3(ENPP1):c.2664del (p.Ile889fs)	Pathogenic
1928268	NM_006208.3(ENPP1):c.2429dup (p.Leu810fs)	Pathogenic
2136472	NM_006208.3(ENPP1):c.1412A>G (p.Tyr471Cys)	Pathogenic
2136474	NM_006208.3(ENPP1):c.2713_2717del (p.Lys905fs)	Pathogenic
2584779	NM_006208.3(ENPP1):c.2230+5G>A	Pathogenic

SpliceAI

3637 predictions. Top by Δscore:

Variant	Effect	Δscore
6:131808272:GCTG:G	donor_gain	1.0000
6:131849988:A:AG	acceptor_gain	1.0000
6:131849988:AGTT:A	acceptor_loss	1.0000
6:131849989:G:GC	acceptor_gain	1.0000
6:131849989:GT:G	acceptor_gain	1.0000
6:131849989:GTT:G	acceptor_gain	1.0000
6:131849989:GTTA:G	acceptor_gain	1.0000
6:131849989:GTTAA:G	acceptor_gain	1.0000
6:131850104:CAG:C	donor_loss	1.0000
6:131850105:AG:A	donor_loss	1.0000
6:131850106:GGTA:G	donor_loss	1.0000
6:131850107:G:GA	donor_loss	1.0000
6:131850108:T:G	donor_loss	1.0000
6:131860383:TTAG:T	acceptor_loss	1.0000
6:131860384:TAG:T	acceptor_loss	1.0000
6:131860385:A:AG	acceptor_gain	1.0000
6:131860385:A:T	acceptor_loss	1.0000
6:131860385:AG:A	acceptor_gain	1.0000
6:131860385:AGG:A	acceptor_gain	1.0000
6:131860386:G:GG	acceptor_gain	1.0000
6:131860386:GG:G	acceptor_gain	1.0000
6:131860386:GGG:G	acceptor_gain	1.0000
6:131860386:GGGA:G	acceptor_gain	1.0000
6:131860502:AACCA:A	donor_gain	1.0000
6:131860503:ACCA:A	donor_gain	1.0000
6:131860504:CCA:C	donor_gain	1.0000
6:131860504:CCAG:C	donor_loss	1.0000
6:131860505:CA:C	donor_gain	1.0000
6:131860505:CAGT:C	donor_loss	1.0000
6:131860506:AGTG:A	donor_loss	1.0000

AlphaMissense

6133 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:131847804:T:A	I90K	0.999
6:131849998:T:A	C108S	0.998
6:131849999:G:A	C108Y	0.998
6:131849999:G:C	C108S	0.998
6:131850040:T:A	C122S	0.998
6:131850041:G:C	C122S	0.998
6:131850073:T:C	C133R	0.998
6:131847788:T:C	C85R	0.997
6:131847804:T:G	I90R	0.997
6:131847810:G:A	G92D	0.997
6:131849998:T:C	C108R	0.997
6:131850000:C:G	C108W	0.997
6:131850040:T:C	C122R	0.997
6:131850073:T:A	C133S	0.997
6:131850074:G:A	C133Y	0.997
6:131850074:G:C	C133S	0.997
6:131850075:T:G	C133W	0.997
6:131854961:A:T	D218V	0.997
6:131861643:T:A	W322R	0.997
6:131861643:T:C	W322R	0.997
6:131847798:C:A	T88K	0.996
6:131847809:G:C	G92R	0.996
6:131847816:T:A	I94K	0.996
6:131849999:G:T	C108F	0.996
6:131850041:G:A	C122Y	0.996
6:131850041:G:T	C122F	0.996
6:131850042:T:G	C122W	0.996
6:131850052:T:C	C126R	0.996
6:131850053:G:A	C126Y	0.996
6:131850054:T:G	C126W	0.996

dbSNP variants (sampled 300 via entrez): RS1000047589 (6:131855976 G>A), RS1000114145 (6:131858239 G>A), RS1000241254 (6:131864003 A>C,G), RS1000256451 (6:131816497 A>G), RS1000301135 (6:131876199 G>T), RS1000336343 (6:131826369 AGCT>A), RS1000420306 (6:131856268 T>C), RS1000424634 (6:131877238 C>T), RS1000455578 (6:131869904 G>A,T), RS1000465208 (6:131823106 G>C), RS1000585748 (6:131830408 C>T), RS1000628848 (6:131874770 T>C), RS1000684584 (6:131821421 T>C), RS1000738038 (6:131821130 A>G), RS1000759032 (6:131868624 T>G)

Disease associations

OMIM: gene MIM:173335 | disease phenotypes: MIM:208000, MIM:125853, MIM:613312, MIM:615522, MIM:601665, MIM:617284

GenCC curated gene-disease

Disease	Classification	Inheritance
arterial calcification, generalized, of infancy, 1	Definitive	Autosomal recessive
hypopigmentation-punctate palmoplantar keratoderma syndrome	Strong	Autosomal dominant
hypophosphatemic rickets, autosomal recessive, 2	Strong	Autosomal recessive
autosomal recessive hypophosphatemic rickets	Supportive	Autosomal recessive
arterial calcification of infancy	Supportive	Autosomal dominant
autosomal recessive inherited pseudoxanthoma elasticum	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
arterial calcification, generalized, of infancy, 1	Definitive	AR
hypopigmentation-punctate palmoplantar keratoderma syndrome	Limited	AD

Mondo (12): arterial calcification, generalized, of infancy, 1 (MONDO:0008817), type 2 diabetes mellitus (MONDO:0005148), obesity disorder (MONDO:0011122), hypophosphatemic rickets, autosomal recessive, 2 (MONDO:0013219), hypopigmentation-punctate palmoplantar keratoderma syndrome (MONDO:0014227), inherited obesity (MONDO:0019182), hypophosphatemic rickets (MONDO:0024300), intellectual disability (MONDO:0001071), dystonia 28, childhood-onset (MONDO:0015004), autosomal recessive hypophosphatemic rickets (MONDO:0017324), arterial calcification of infancy (MONDO:0018870), autosomal recessive inherited pseudoxanthoma elasticum (MONDO:0009925)

Orphanet (8): Generalized arterial calcification of infancy (Orphanet:51608), Autosomal recessive hypophosphatemic rickets (Orphanet:289176), Hypopigmentation-punctate palmoplantar keratoderma syndrome (Orphanet:324561), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Genetic obesity (Orphanet:77828), Dystonia 28 (Orphanet:589618), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

168 total (30 of 168 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000117	Renal phosphate wasting
HP:0000121	Nephrocalcinosis
HP:0000164	Abnormality of the dentition
HP:0000365	Hearing impairment
HP:0000381	Stapes ankylosis
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000474	Thickened nuchal skin fold
HP:0000488	Retinopathy
HP:0000505	Visual impairment
HP:0000573	Retinal hemorrhage
HP:0000592	Blue sclerae
HP:0000630	Abnormal retinal arterial/arteriolar morphology
HP:0000670	Carious teeth
HP:0000684	Delayed eruption of teeth
HP:0000685	Hypoplasia of teeth
HP:0000737	Irritability
HP:0000765	Abnormal thorax morphology
HP:0000822	Hypertension
HP:0000855	Insulin resistance
HP:0000951	Abnormality of the skin
HP:0000961	Cyanosis
HP:0000962	Hyperkeratosis
HP:0000969	Edema
HP:0000974	Hyperextensible skin
HP:0000978	Bruising susceptibility
HP:0000982	Palmoplantar keratoderma

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_810	Obesity-related traits	3.000000e-06
GCST008163_207	Height	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011561	Pseudoxanthoma Elasticum	C14.907.454.530; C15.378.463.515.530; C16.131.831.766; C16.320.850.750; C17.300.766; C17.800.804.766; C17.800.827.750
D063730	Rickets, Hypophosphatemic	C05.116.198.816.875; C18.452.104.816.875; C18.452.174.845.875; C18.452.750.400.750; C18.654.521.500.133.770.734.875
C537440	Arterial calcification of infancy (supp.)
C567647	Hypophosphatemic Rickets, Autosomal Recessive, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5925 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 36,848 (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
CHEMBL265502	SURAMIN	3	36,848

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Cyclic GMP-AMP turnover

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
ISM5939	Inhibition	9.35	pIC50
ENPP1 inhibitor 27	Inhibition	8.92	pIC50
vizenpistat	Inhibition	8.22	pIC50
ENPP1 inhibitor 29f	Inhibition	7.17	pIC50

Binding affinities (BindingDB)

177 measured of 223 human assays (223 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3,5-difluoro-4-[[7-methoxy-2-oxo-3-(2,2,2-trifluoroethyl)imidazo[4,5-c][1,8]naphthyridin-1-yl]methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,5-difluoro-4-[(8-methoxy-2-oxo-4H-[1,3]oxazino[5,4-c][1,8]naphthyridin-1-yl)methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,5-difluoro-4-[(9-fluoro-8-methoxy-2-oxo-3,4-dihydropyrimido[5,4-c]quinolin-1-yl)methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,5-difluoro-4-[(8-methoxy-2-oxopyrido[3,2-c][1,8]naphthyridin-1-yl)methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,5-difluoro-4-[(8-methoxy-2-oxo-4H-[1,3]oxazino[5,4-c]quinolin-1-yl)methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,5-difluoro-4-[(9-fluoro-8-methoxy-2-oxo-3,4-dihydropyrazino[2,3-c][1,8]naphthyridin-1-yl)methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,5-difluoro-4-[[8-methoxy-2-oxo-3-(2,2,2-trifluoroethyl)-4H-pyrimido[5,4-c][1,8]naphthyridin-1-yl]methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
6-[(8-methoxy-2-oxo-4H-[1,3]oxazino[5,4-c][1,8]naphthyridin-1-yl)methyl]pyridine-3-sulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3-fluoro-4-[(8-methoxy-2-oxo-4H-[1,3]oxazino[5,4-c][1,8]naphthyridin-1-yl)methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
4-[(3-cyclopropyl-8-methoxy-2-oxo-4H-pyrimido[5,4-c][1,8]naphthyridin-1-yl)methyl]-3,5-difluorobenzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,5-difluoro-4-[(8-methoxy-2,3-dioxo-4H-pyrazino[2,3-c][1,5]naphthyridin-1-yl)methyl]benzenesulfonamide	IC50	0.15 nM	US-20250115609: AROMATIC HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR AND USES THEREOF
3,4,5-trimethoxy-N-(1-methylbenzimidazol-5-yl)benzamide	EC50	0.316 nM	US-20260001886: ENPP1 INHIBITORS I
3,5-difluoro-4-[[6-methoxy-3-methyl-7-(1-methylpyrazol-3-yl)pyrrolo[3,2-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-methoxy-7-phenylpyrrolo[3,2-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-methoxy-3-methyl-7-phenylpyrrolo[3,2-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(3,6-dimethyl-7-phenylpyrrolo[3,2-c]pyridin-1-yl)methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-methyl-7-phenylpyrrolo[3,2-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(3,6-dimethyl-7-phenylpyrrolo[3,2-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-methoxy-3-methyl-2-oxo-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(3,6-dimethyl-2-oxo-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-methoxy-2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-methoxy-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[(6-methoxy-2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3-fluoro-4-[(6-methoxy-2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(2,6-dimethyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[(6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(4-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(2,6-dimethyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(2,4-dimethyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[[6-(difluoromethoxy)-2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[[6-methyl-7-phenyl-2-(trifluoromethyl)imidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
2-fluoro-4-[(6-methoxy-2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
[4-[(2,6-dimethyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]phenyl] sulfamate	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[[2-(difluoromethyl)-6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl]methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(2-cyclopropyl-6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(4-cyano-2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[[6-methyl-7-phenyl-2-(trideuteriomethyl)imidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[(2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[[7-(2-fluorophenyl)-2,6-dimethylimidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[[7-(3-fluorophenyl)-2,6-dimethylimidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[[7-(4-fluorophenyl)-2,6-dimethylimidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[[2-(fluoromethyl)-6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(6-ethyl-2-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[[2-[(dimethylamino)methyl]-6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl]methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
3,5-difluoro-4-[[6-methyl-7-phenyl-2-(2,2,2-trifluoroethyl)imidazo[4,5-c]pyridin-1-yl]methyl]benzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[[2-(cyclopropylmethyl)-6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl]methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
4-[(7-cyclopropyl-2,6-dimethylimidazo[4,5-c]pyridin-1-yl)methyl]-3,5-difluorobenzenesulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF
6-[(2-cyclopropyl-6-methyl-7-phenylimidazo[4,5-c]pyridin-1-yl)methyl]pyridine-3-sulfonamide	IC50	0.5 nM	US-20250101019: ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP1) INHIBITORS AND USES THEREOF

ChEMBL bioactivities

574 potent at pChembl≥5 of 661 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.05	IC50	0.09	nM	CHEMBL5566114
10.00	IC50	0.1	nM	CHEMBL5566114
9.80	IC50	0.16	nM	CHEMBL5556000
9.70	IC50	0.2	nM	CHEMBL6174154
9.66	IC50	0.22	nM	CHEMBL5826130
9.52	IC50	0.3	nM	CHEMBL5560511
9.32	IC50	0.48	nM	CHEMBL5561670
9.30	IC50	0.5	nM	CHEMBL5915707
9.30	IC50	0.5	nM	CHEMBL5560556
9.28	IC50	0.52	nM	CHEMBL5555976
9.25	IC50	0.56	nM	CHEMBL5566818
9.20	IC50	0.63	nM	CHEMBL6149286
9.18	IC50	0.66	nM	CHEMBL5558246
9.14	IC50	0.72	nM	CHEMBL5558533
9.10	IC50	0.8	nM	CHEMBL5556506
9.06	IC50	0.87	nM	CHEMBL5826130
9.03	IC50	0.94	nM	CHEMBL5567749
9.03	IC50	0.94	nM	CHEMBL5777245
9.01	IC50	0.97	nM	CHEMBL6169586
9.00	IC50	1	nM	CHEMBL6145273
8.97	IC50	1.07	nM	CHEMBL6175795
8.96	IC50	1.1	nM	CHEMBL6172085
8.96	IC50	1.1	nM	CHEMBL6151998
8.92	IC50	1.21	nM	CHEMBL5818525
8.92	IC50	1.2	nM	CHEMBL6164492
8.92	IC50	1.2	nM	CHEMBL6171102
8.91	IC50	1.23	nM	CHEMBL6160451
8.85	IC50	1.41	nM	CHEMBL5527873
8.85	IC50	1.4	nM	CHEMBL6173019
8.82	IC50	1.5	nM	CHEMBL6160796
8.81	IC50	1.53	nM	CHEMBL6163224
8.77	IC50	1.7	nM	CHEMBL5557547
8.75	IC50	1.77	nM	CHEMBL5556761
8.75	IC50	1.79	nM	CHEMBL5816478
8.74	IC50	1.8	nM	CHEMBL6160465
8.74	IC50	1.8	nM	CHEMBL6164747
8.74	IC50	1.8	nM	CHEMBL6171252
8.73	IC50	1.84	nM	CHEMBL6150796
8.72	IC50	1.9	nM	CHEMBL5557547
8.68	IC50	2.1	nM	CHEMBL5555976
8.68	IC50	2.1	nM	CHEMBL6162440
8.67	IC50	2.14	nM	CHEMBL5568520
8.66	IC50	2.2	nM	CHEMBL6147702
8.66	IC50	2.2	nM	CHEMBL6172306
8.66	IC50	2.2	nM	CHEMBL6159611
8.62	IC50	2.4	nM	CHEMBL5563471
8.60	IC50	2.5	nM	CHEMBL6173950
8.57	IC50	2.7	nM	CHEMBL6160626
8.54	IC50	2.88	nM	CHEMBL6146109
8.51	IC50	3.06	nM	CHEMBL5859913

PubChem BioAssay actives

383 with measured affinity, of 963 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
2-[(1S,5R)-3-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)-3-azabicyclo[3.1.0]hexan-6-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0001	uM
2-[4-methyl-1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0002	uM
2-[1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0003	uM
6-[(7,8-dimethoxy-2,4-dimethylimidazo[4,5-c]quinolin-1-yl)methyl]pyridine-3-sulfonamide	2074403: Inhibition of human ENPP1 using TMP-pNP as substrate at pH 9.5 preincubated for 30 mins followed by substrate addition and measured after 60 mins by absorbance based assay	ic50	0.0005	uM
2-[1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0005	uM
[1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)azepan-4-yl]methylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0006	uM
2-[4-fluoro-1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0007	uM
2-[4-hydroxy-1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0007	uM
2-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0008	uM
2-[4-methoxy-1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0009	uM
5-fluoro-6-[[6-methoxy-7-phenyl-2-(trifluoromethyl)imidazo[4,5-c]pyridin-1-yl]methyl]pyridine-3-sulfonamide	2074409: Inhibition of ENNP1 (unknown origin) using 2’,3’-cGAMP as substrate preincubated with compound followed by substrate addition and measured after 60 mins by AMP-Glo reagent based assay	ic50	0.0010	uM
[1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]methylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0014	uM
N-hydroxy-2-[4-[(7-methoxy-1,8-naphthyridin-4-yl)oxy]phenyl]acetamide	2074396: Inhibition of ECD-his tagged human ENPP1 using 2’,3’-cGAMP as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by AMP-Glo assay	ic50	0.0017	uM
4-[(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)amino]butylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0018	uM
2-[1-(8-methoxyquinazolin-4-yl)piperidin-4-yl]ethylphosphonic acid	2074388: Inhibition of ENPP1 (unknown origin) using cGAMP as substrate assessed as inhibition constant at pH 7.4	ki	0.0020	uM
2-[1-(3-cyano-8-methoxyquinolin-4-yl)piperidin-4-yl]ethylphosphonic acid	2074388: Inhibition of ENPP1 (unknown origin) using cGAMP as substrate assessed as inhibition constant at pH 7.4	ki	0.0020	uM
[4-[(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0021	uM
2-[1-(6-chloro-7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0024	uM
3-methyl-5-[4-methyl-4-[(sulfamoylamino)methyl]piperidin-1-yl]-2-oxo-1,4-dihydropyrimido[4,5-d]pyrimidine;hydrochloride	1934341: Inhibition of ENPP1 (unknown origin)	ic50	0.0037	uM
3-[1-(2-oxo-1H-quinolin-5-yl)piperidin-4-yl]propylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0040	uM
2-[1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)-4-(trifluoromethyl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0040	uM
2-(1H-benzimidazol-2-ylmethyl)-N-[(E)-1-(2-chlorophenyl)ethylideneamino]-4-hydroxy-1,1-dioxo-1lambda6,2-benzothiazine-3-carboxamide	2074620: Inhibition of ENPP1 (unknown origin)	ic50	0.0042	uM
2-[(6-amino-7H-purin-8-yl)sulfanyl]-N-(3,4-dimethoxyphenyl)acetamide	1170611: Inhibition of human NPP1 using p-Nph-5’-TMP as substrate	ki	0.0050	uM
8-(2-fluoro-6-methoxyphenyl)-N-[5-fluoro-2-[4-(sulfamoylamino)piperidin-1-yl]phenyl]imidazo[1,2-a]pyrazine-6-carboxamide	2131186: Inhibition of C-terminal flag-tagged recombinant human ENPP1 (110 to 926 residues) extracted from HEK293F cells using p-Nph-5’-TMP as substrate by absorbance based assay	ic50	0.0057	uM
2-[1-(8-methyl-7-oxopyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0062	uM
2-[1-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)azetidin-3-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0062	uM
2-[4-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperazin-1-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0085	uM
[4-[(5-carbamoylimidazo[4,5-b]pyridin-1-yl)methyl]phenyl]boronic acid	2074408: Inhibition of ENPP1 (unknown origin) using TMP-pNP as substrate preincubated for 10 mins followed by substrate addition and measured immediately under pH 8.8 by absorbance based multimode plate reader analysis	ic50	0.0100	uM
[1-[[(2S)-2-amino-3,3-dimethylbutanoyl]amino]-3-[1-(8-methoxyquinazolin-4-yl)piperidin-4-yl]propan-2-yl]phosphonic acid	2074388: Inhibition of ENPP1 (unknown origin) using cGAMP as substrate assessed as inhibition constant at pH 7.4	ki	0.0100	uM
7-methoxy-4-[4-[(sulfamoylamino)methyl]phenyl]quinoline	2021553: Inhibition of recombinant human ENPP1 using cGAMP as substrate assessed as inhibition of cGAMP hydrolysis preincubated for 5 to 10 mins followed by substrate addition and measured after 90 mins by AMP-Glo reagent based luminescence plate reader analysis	ic50	0.0110	uM
6,7-dimethoxy-4-[4-[2-(sulfamoylamino)ethyl]piperidin-1-yl]quinazoline	2074391: Inhibition of ENPP1 (unknown origin) using cGAMP as substrate assessed as inhibition constant at pH 9	ki	0.0110	uM
2-[1-(6-methoxy-7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)piperidin-4-yl]ethylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0126	uM
4-[[4-formyl-5,6-dimethyl-3-(phosphonooxymethyl)-2-pyridinyl]diazenyl]benzene-1,3-disulfonic acid	2074620: Inhibition of ENPP1 (unknown origin)	ic50	0.0150	uM
[7-(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)-7-azaspiro[3.5]nonan-2-yl]methylphosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0189	uM
N-(3,4-dimethoxyphenyl)-2-[(6-oxo-1,7-dihydropurin-8-yl)sulfanyl]acetamide	1170611: Inhibition of human NPP1 using p-Nph-5’-TMP as substrate	ki	0.0200	uM
[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-[[dihydroxyphosphinothioyloxy(hydroxy)phosphoryl]methyl]phosphinic acid	1153903: Mixed type inhibition of human NPP1 using pNP-TMP as substrate after 20 mins by Dixon and Cornish-Bowden method	ki	0.0200	uM
4-[4-methyl-4-[(sulfamoylamino)methyl]piperidin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine	2074395: Inhibition of recombinant human ENPP1 using 2’,3’-cGAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 90 mins by ADP-Glo assay	ic50	0.0250	uM
(2R)-3-(3,4-dihydroxyphenyl)-2-[(E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxypropanoic acid	2074621: Binding affinity to human ENPP1 assessed as inhibition constant	ki	0.0269	uM
[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfanylphosphinothioyl] [[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-sulfanylphosphinothioyl]oxy-hydroxyphosphoryl] hydrogen phosphate	1369990: Inhibition of human NPP1 using pNP-TMP as substrate preincubated for 3 mins followed by substrate addition measured after 15 mins	ki	0.0270	uM
8-(2-fluoro-6-methoxyphenyl)-N-[5-fluoro-2-[4-(sulfamoylamino)piperidin-1-yl]phenyl]-2-methylimidazo[1,2-a]pyrazine-6-carboxamide	2131186: Inhibition of C-terminal flag-tagged recombinant human ENPP1 (110 to 926 residues) extracted from HEK293F cells using p-Nph-5’-TMP as substrate by absorbance based assay	ic50	0.0271	uM
N-(3,4-dimethoxyphenyl)-2-[(5-methoxy-1H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]acetamide	1170611: Inhibition of human NPP1 using p-Nph-5’-TMP as substrate	ki	0.0296	uM
5-[3-fluoro-4-[(sulfamoylamino)methyl]phenyl]-3-methyl-2-oxo-1,4-dihydropyrido[2,3-d]pyrimidine;hydrochloride	1934341: Inhibition of ENPP1 (unknown origin)	ic50	0.0323	uM
[4-[[(7-oxo-8H-pyrido[2,3-d]pyrimidin-4-yl)amino]methyl]phenyl]phosphonic acid	2080851: Inhibition of human recombinant ENPP1 expressed in HEK293T cells using cGAMP as substrate at pH 7.5 measured after 3.5 hrs in presence of ATP by luminescence based AMP-glo assay	ic50	0.0340	uM
N-(3,4-dimethoxyphenyl)-2-[(2,6-dioxo-3,7-dihydropurin-8-yl)sulfanyl]acetamide	1170611: Inhibition of human NPP1 using p-Nph-5’-TMP as substrate	ki	0.0358	uM
8-(2,6-difluorophenyl)-N-[5-fluoro-2-[4-(sulfamoylamino)piperidin-1-yl]phenyl]imidazo[1,2-a]pyrazine-6-carboxamide	2131186: Inhibition of C-terminal flag-tagged recombinant human ENPP1 (110 to 926 residues) extracted from HEK293F cells using p-Nph-5’-TMP as substrate by absorbance based assay	ic50	0.0359	uM
6,7-dimethoxy-1-oxo-4-[4-[(sulfamoylamino)methyl]phenyl]-2H-phthalazine	2021553: Inhibition of recombinant human ENPP1 using cGAMP as substrate assessed as inhibition of cGAMP hydrolysis preincubated for 5 to 10 mins followed by substrate addition and measured after 90 mins by AMP-Glo reagent based luminescence plate reader analysis	ic50	0.0370	uM
2-[(2-amino-7H-purin-6-yl)sulfanyl]-N-(4-hydroxy-3-methoxyphenyl)acetamide	2074415: Inhibition of ENPP1 (unknown origin) assessed as inhibition constant	ki	0.0380	uM
1-oxo-4-[[4-(sulfamoylamino)phenyl]methyl]-2H-phthalazine	2021553: Inhibition of recombinant human ENPP1 using cGAMP as substrate assessed as inhibition of cGAMP hydrolysis preincubated for 5 to 10 mins followed by substrate addition and measured after 90 mins by AMP-Glo reagent based luminescence plate reader analysis	ic50	0.0390	uM
2-[(2-amino-7H-purin-6-yl)sulfanyl]-N-(4-hydroxy-3-methoxyphenyl)butanamide	2074415: Inhibition of ENPP1 (unknown origin) assessed as inhibition constant	ki	0.0410	uM
N-(3,4-dimethoxyphenyl)-2-(3H-imidazo[4,5-c]pyridin-2-ylsulfanyl)acetamide	1170611: Inhibition of human NPP1 using p-Nph-5’-TMP as substrate	ki	0.0442	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
bisphenol A	affects cotreatment, increases expression, affects expression, decreases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects methylation	4
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	2
Manganese	increases expression, affects cotreatment, decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, increases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
nickel sulfate	increases expression	1
beta-glycerophosphoric acid	increases activity, increases expression, decreases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
incobotulinumtoxinA	decreases expression	1

ChEMBL screening assays

167 unique, capped per target: 154 binding, 13 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004221	Binding	Activity of human NPP1 expressed in human 293T cells assessed as drug hydrolysis at 100 uM after 20 mins by reverse-phase HPLC relative to p-nitrophenyl-thymidine-5-monophosphate	Identification of hydrolytically stable and selective P2Y(1) receptor agonists. — Eur J Med Chem
CHEMBL2090463	ADMET	Hydrolytic stability of the compound assessed as human NPP1-mediated hydrolysis measuring UMP formation after 2 hrs by HPLC analysis	UDP made a highly promising stable, potent, and selective P2Y6-receptor agonist upon introduction of a boranophosphate moiety. — Bioorg Med Chem

Cellosaurus cell lines

7 cell lines: 4 transformed cell line, 2 finite cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9EA	Ubigene HEK293 ENPP1 KO	Transformed cell line	Female
CVCL_E1W1	HAP1 ENPP1 (-)	Cancer cell line	Male
CVCL_EG72	GM10439	Finite cell line	Female
CVCL_EG73	GM10440	Transformed cell line	Female
CVCL_EJ63	GM14556	Transformed cell line	Male
CVCL_FA40	GM14553	Finite cell line	Female
CVCL_FA41	GM14554	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus