PTPN1

Summary

PTPN1 (protein tyrosine phosphatase non-receptor type 1, HGNC:9642) is a protein-coding gene on chromosome 20q13.13, encoding Tyrosine-protein phosphatase non-receptor type 1 (P18031). Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response.

The protein encoded by this gene is the founding member of the protein tyrosine phosphatase (PTP) family, which was isolated and identified based on its enzymatic activity and amino acid sequence. PTPs catalyze the hydrolysis of the phosphate monoesters specifically on tyrosine residues. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP has been shown to act as a negative regulator of insulin signaling by dephosphorylating the phosphotryosine residues of insulin receptor kinase. This PTP was also reported to dephosphorylate epidermal growth factor receptor kinase, as well as JAK2 and TYK2 kinases, which implicated the role of this PTP in cell growth control, and cell response to interferon stimulation. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5770 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory syndrome (Limited, GenCC)
• GWAS associations: 16
• Clinical variants (ClinVar): 49 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9642
Approved symbol	PTPN1
Name	protein tyrosine phosphatase non-receptor type 1
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196396
Ensembl biotype	protein_coding
OMIM	176885
Entrez	5770

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000371621, ENST00000541713, ENST00000859844, ENST00000859845, ENST00000859846, ENST00000924651

RefSeq mRNA: 2 — MANE Select: NM_002827 NM_001278618, NM_002827

CCDS: CCDS13430, CCDS63309

Canonical transcript exons

ENST00000371621 — 10 exons

Exon	Start	End
ENSE00000509635	50561363	50561453
ENSE00000662795	50568380	50568478
ENSE00000662796	50574517	50574654
ENSE00000662797	50578420	50578629
ENSE00000662798	50579168	50579329
ENSE00000662799	50579703	50579926
ENSE00001172461	50581265	50581460
ENSE00001455694	50582692	50585241
ENSE00001455721	50510383	50510590
ENSE00003532872	50564969	50565069

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 94.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 92.1665 / max 816.0765, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185253	82.3244	1826
185254	9.8420	1275

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper lobe of left lung	UBERON:0008952	94.68	gold quality
right lung	UBERON:0002167	94.25	gold quality
upper lobe of lung	UBERON:0008948	93.78	gold quality
spleen	UBERON:0002106	91.72	gold quality
vermiform appendix	UBERON:0001154	90.99	gold quality
monocyte	CL:0000576	90.76	gold quality
lymph node	UBERON:0000029	90.72	gold quality
granulocyte	CL:0000094	90.69	gold quality
leukocyte	CL:0000738	90.65	gold quality
tibial artery	UBERON:0007610	90.65	gold quality
popliteal artery	UBERON:0002250	90.64	gold quality
metanephros cortex	UBERON:0010533	90.51	gold quality
ascending aorta	UBERON:0001496	90.48	gold quality
thoracic aorta	UBERON:0001515	90.48	gold quality
mononuclear cell	CL:0000842	90.46	gold quality
aorta	UBERON:0000947	90.40	gold quality
left adrenal gland	UBERON:0001234	90.38	gold quality
descending thoracic aorta	UBERON:0002345	90.11	gold quality
left adrenal gland cortex	UBERON:0035825	90.10	gold quality
right adrenal gland cortex	UBERON:0035827	90.04	gold quality
gastrocnemius	UBERON:0001388	90.01	gold quality
right coronary artery	UBERON:0001625	89.73	gold quality
stromal cell of endometrium	CL:0002255	89.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.67	gold quality
lower esophagus	UBERON:0013473	89.65	gold quality
left uterine tube	UBERON:0001303	89.62	gold quality
right adrenal gland	UBERON:0001233	89.55	gold quality
left ovary	UBERON:0002119	89.46	gold quality
esophagus	UBERON:0001043	89.31	gold quality
left coronary artery	UBERON:0001626	89.28	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.71
E-MTAB-8498	yes	8.67
E-CURD-88	yes	5.68
E-MTAB-7606	no	712.46
E-CURD-112	no	2.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ATF6, EGR1, FLI1, MECP2, NFKB, PARP1, PAX3, TXK, YBX1

miRNA regulators (miRDB)

128 targeting PTPN1, 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-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Literature-anchored findings (GeneRIF, showing 40)

• Moderate overabundance of PTP-1B in liver tissue does not alter insulin action on glucose metabolism, and the site of action of PTP-1B is presumably at insulin-responsive target tissue or tissues other than the liver. (PMID:11703427)
• variation in 3’ UTR of hPTP1B increases specific gene expression and associates with insulin resistance (PMID:11833006)
• PTP1B reduces the level of gene expression of SOCS3 and other leptin-regulated genes, and conversely, the expression of genes down-regulated by leptin was enhanced by PTP1B over-expression (PMID:12354677)
• Data show that an increase in soluble protein-tyrosine phosphatase 1B activity contributes to the anti-migratory, but not anti-mitogenic, actions of human Sprouty 2. (PMID:12414790)
• PTP1B inhibitory agents can be acquired by targeting the area defined by residues Lys-41, Arg-47, and Asp-48, in addition to the previously identified second aryl phosphate-binding pocket. (PMID:12547827)
• Data show that Y box-binding protein-1 (YB-1) is a regulator of protein tyrosine phosphatase 1B (PTP1B) expression, and highlight PTP1B as a critical regulator of insulin- and cytokine-mediated signal transduction. (PMID:12554649)
• PTP1B inhibition by S-nitrosylation is caused by formation of a mixed disulfide (PMID:12573287)
• dynamics of the interaction between the insulin receptor and this protein in living cells (PMID:12634852)
• PTP1B plays an important role in the integrin-mediated dephosphorylation of LAT in human platelets and is involved in the control of irreversible aggregation upon FcgammaRIIa stimulation (PMID:12857726)
• mutation of pro387leu in PTP-1B was not associated with type 2 diabetes in Chinese (PMID:14514610)
• PTP-1B appears not only to interact with and dephosphorylate the insulin-stimulated insulin receptor in a perinuclear endosome compartment but is also involved in maintaining the IR in a dephosphorylated state during its biosynthesis (PMID:14722096)
• PTP1B has a role as a negative regulator of IR activation in hepatocytes (PMID:14976221)
• PTP1B has a role in insulin resistance (PMID:15031294)
• analysis the relative abundance of PTP1B in RBCs of different age indicated that the PTP activity undergoes oxidative inactivation that can be further differentiated into reversible and irreversible components (PMID:15039022)
• Neither of the HSD3B1 or PTP1B variants were associated with hypertension (PMID:15097232)
• PTP1B single nucleotide polymorphisms may interact with environmental factors to induce more severe phenotypes in morbidly obese subjects. (PMID:15235769)
• protein tyrosine phosphatase 1B can be allosterically inhibited (PMID:15258570)
• PTPN1 is a significant contributor to type 2 diabetes susceptibility in the Caucasian population. (PMID:15504984)
• significant association with metabolic traits consistent with the proposed in vivo role for the PTP-1B protein. (PMID:15504985)
• Our results provided evidence that upregulation of insulin signaling by reducing PTP1B liver with RNAi can be a potent diabetes treatment method. (PMID:15737620)
• protein-tyrosine phosphatase 1B has a role in integrin signaling (PMID:15866871)
• PTP1B interacts with TRPV6 in vivo and plays a role in TRPV6-mediated calcium influx in HEK293 cells (PMID:15894168)
• The association of common single nucleotide polymorphisms (SNPs) and haplotypes in PTPN1 with type 2 diabetes, fasting plasma glucose, and insulin sensitivity in a large collection of subjects is reported. (PMID:15919813)
• protein tyrosine phosphatase 1B (PTPN1) IVS6+G82G homozygotes showed higher levels of all measures of adiposity and G82 allele heterozygotes are potentially at higher risk for type 2 diabetes (PMID:15919835)
• PTP1B was inhibited by cytochrome c and microperoxidase; a variety of redox-active metabolites and hemes can oxidatively inactivate PTPs with potentially profound implications for signal transduction (PMID:15998263)
• Data show that protein-tyrosine phosphatase (PTP)-1B is an essential positive regulator of the initiation of outside-in alphaIIbbeta3 integrin signaling in platelets. (PMID:16115959)
• The association between 6 single nucleotide polymorphisms and their effect on leptin, body fat, insulin sensitivity, and metabolic syndrome in female twins is reported. (PMID:16249458)
• Catalytic activity of PTP1B is controlled by cell adhesion. (PMID:16289152)
• PTP-1B/inhibitor complexes show a conformation-assisted inhibition mechanism as the basis for inhibitor selectivity (PMID:16407290)
• PTP1B mediates of RhoA-dependent phosphorylation of p130Cas. (PMID:16644720)
• findings suggest that protein tyrosine phosphatase 1B(PTP1B) plays an important role in neuroendocrine differentiation, and therefore, may possibly be involved in the progression of prostate cancer (PMID:16652382)
• PTPN1 variants may modulate the lipid profile, thereby influencing susceptibility to metabolic disease (PMID:16677372)
• molecular dynamics study of WPD loop movement in PTP1B (PMID:16713994)
• Noonan syndrome affected individuals show heterozygous PTPN11 mutations (PMID:17056636)
• PTPase activities of PTP1B or CD45 were abolished by low concentrations of (1)O(2) (PMID:17081112)
• Direct interaction between ER membrane-bound PTP1B and its plasma membrane-anchored targets was demonstrated. (PMID:17092689)
• C-terminal domain of protein tyrosine phosphatase-1B shows an improvement in affinity but may also provide for specificity over other phosphatases. [protein tyrosine phosphatase-1B] (PMID:17135270)
• The significance of exercise-induced alterations in cytosolic SHP2 and insulin-stimulated Akt pSer(473) on the improvement in insulin sensitivity requires further elucidation. (PMID:17185494)
• Single nucleotide polymorphisms are unlikely to have a major role in the aetiology of type 2 diabetes or obesity in Pima Indians. (PMID:17333110)
• protein-tyrosine phosphatase 1B governs differential recruitment of signaling pathways involved in EGFR regulation of epithelial ion transport. (PMID:17339316)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpn1	ENSDARG00000007923
mus_musculus	Ptpn1	ENSMUSG00000027540
rattus_norvegicus	Ptpn1	ENSRNOG00000010574

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN18 (ENSG00000072135), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), PTPRZ1 (ENSG00000106278), PTPN5 (ENSG00000110786), PTPN6 (ENSG00000111679), PTPRB (ENSG00000127329), PTPN12 (ENSG00000127947), PTPRE (ENSG00000132334), PTPRA (ENSG00000132670), PTPN22 (ENSG00000134242), PTPRF (ENSG00000142949), PTPN7 (ENSG00000143851), PTPRG (ENSG00000144724), PTPRJ (ENSG00000149177), PTPRO (ENSG00000151490), PTPN14 (ENSG00000152104), PTPRK (ENSG00000152894), PTPRR (ENSG00000153233), PTPRD (ENSG00000153707), PTPRN2 (ENSG00000155093), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Tyrosine-protein phosphatase non-receptor type 1 — P18031 (reviewed: P18031)

Alternative names: Protein-tyrosine phosphatase 1B

All UniProt accessions (3): A8K3M3, B4DSN5, P18031

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.

Subunit / interactions. Interacts with EPHA3 (phosphorylated); dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts with MET. Interacts with NCK1.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in keratinocytes (at protein level).

Post-translational modifications. Oxidized on Cys-215; the Cys-SOH formed in response to redox signaling reacts with the alpha-amido of the following residue to form a sulfenamide cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction. Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50. S-nitrosylation of Cys-215 inactivates the enzyme activity. Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.

RefSeq proteins (2): NP_001265547, NP_002818* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR012265	Ptpn1/Ptpn2	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR051985	NR_tyrosine_phosphatase	Family

Pfam: PF00102

Enzyme classification (BRENDA):

• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	0.0008–148	84
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.0039–0.862	27
P-NITROPHENYL PHOSPHATE	0.0024–10	20
DADEPYLIPQQG	0.0003–0.1	12
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
4,6,8-TRIMETHYL-2-OXO-2H-CHROMEN-7-YL DIHYDROGEN	0.02–0.156	3
SASASPYSASA	0.53–2.3	3
1-NAPHTHYL PHOSPHATE	1.19–1.88	2
3,6-FLUORESCEIN DIPHOSPHATE	15–19	2
4-METHYLUMBELLIFERYL PHOSPHATE	0.953–2.41	2
BOVINE SERUM ALBUMIN	0.0001–0.0003	2

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (70 total): strand 17, modified residue 16, helix 13, turn 9, mutagenesis site 3, binding site 3, region of interest 2, sequence variant 2, chain 1, domain 1, cross-link 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

439 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7MN9	X-RAY DIFFRACTION	1.24
7MKZ	X-RAY DIFFRACTION	1.4
9C66	X-RAY DIFFRACTION	1.4
8U1E	X-RAY DIFFRACTION	1.43
8G65	X-RAY DIFFRACTION	1.45
7MNA	X-RAY DIFFRACTION	1.47
7MOU	X-RAY DIFFRACTION	1.48
2CM2	X-RAY DIFFRACTION	1.5
7GTW	X-RAY DIFFRACTION	1.51
7GTX	X-RAY DIFFRACTION	1.51
5QGF	X-RAY DIFFRACTION	1.51
7GU5	X-RAY DIFFRACTION	1.52
7GU9	X-RAY DIFFRACTION	1.53
8G67	X-RAY DIFFRACTION	1.53
8G69	X-RAY DIFFRACTION	1.53
7GTY	X-RAY DIFFRACTION	1.54
6XEA	X-RAY DIFFRACTION	1.55
2F71	X-RAY DIFFRACTION	1.55
8SKL	X-RAY DIFFRACTION	1.55
8XOY	X-RAY DIFFRACTION	1.55
5QGB	X-RAY DIFFRACTION	1.55
5QDK	X-RAY DIFFRACTION	1.55
7GU6	X-RAY DIFFRACTION	1.56
5QF3	X-RAY DIFFRACTION	1.56
5QFE	X-RAY DIFFRACTION	1.56
5QDQ	X-RAY DIFFRACTION	1.57
5QGC	X-RAY DIFFRACTION	1.59
7GT3	X-RAY DIFFRACTION	1.59
7GU1	X-RAY DIFFRACTION	1.59
7GU4	X-RAY DIFFRACTION	1.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18031-F1	81.70	0.67

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 (1): 215 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 181; 215–221; 262

Post-translational modifications (17): 20, 50, 66, 215, 215, 215, 215, 242, 243, 352, 363, 365, 368, 378, 386, 215–216, 1

Mutagenesis-validated functional residues (3):

Position	Phenotype
50	no phosphorylation.
181	substrate-trapping mutant.
215	catalytically inactive mutant; abolishes sulfhydration.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-354192	Integrin signaling
R-HSA-6807004	Negative regulation of MET activity
R-HSA-77387	Insulin receptor recycling
R-HSA-877312	Regulation of IFNG signaling
R-HSA-8849472	PTK6 Down-Regulation
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-912694	Regulation of IFNA/IFNB signaling
R-HSA-982772	Growth hormone receptor signaling
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

MSigDB gene sets: 562 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_SYNAPSE_ASSEMBLY

GO Biological Process (49): positive regulation of systemic arterial blood pressure (GO:0003084), negative regulation of cell population proliferation (GO:0008285), insulin receptor signaling pathway (GO:0008286), regulation of signal transduction (GO:0009966), negative regulation of signal transduction (GO:0009968), positive regulation of heart rate (GO:0010460), positive regulation of cardiac muscle cell apoptotic process (GO:0010666), negative regulation of cell-substrate adhesion (GO:0010812), negative regulation of neuron projection development (GO:0010977), actin cytoskeleton organization (GO:0030036), regulation of endocytosis (GO:0030100), regulation of proteolysis (GO:0030162), negative regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030948), endoplasmic reticulum unfolded protein response (GO:0030968), response to nutrient levels (GO:0031667), regulation of intracellular protein transport (GO:0033157), cellular response to unfolded protein (GO:0034620), peptidyl-tyrosine dephosphorylation (GO:0035335), platelet-derived growth factor receptor-beta signaling pathway (GO:0035791), cellular response to platelet-derived growth factor stimulus (GO:0036120), IRE1-mediated unfolded protein response (GO:0036498), insulin receptor recycling (GO:0038020), negative regulation of MAP kinase activity (GO:0043407), cellular response to fibroblast growth factor stimulus (GO:0044344), positive regulation of JNK cascade (GO:0046330), negative regulation of insulin receptor signaling pathway (GO:0046627), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), regulation of type I interferon-mediated signaling pathway (GO:0060338), growth hormone receptor signaling pathway via JAK-STAT (GO:0060397), negative regulation of ERK1 and ERK2 cascade (GO:0070373), cellular response to hypoxia (GO:0071456), cellular response to nitric oxide (GO:0071732), vascular endothelial cell response to oscillatory fluid shear stress (GO:0097706), regulation of postsynapse assembly (GO:0150052), regulation of hepatocyte growth factor receptor signaling pathway (GO:1902202), negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902236), positive regulation of IRE1-mediated unfolded protein response (GO:1903896), negative regulation of PERK-mediated unfolded protein response (GO:1903898), cellular response to angiotensin (GO:1904385), negative regulation of vascular associated smooth muscle cell migration (GO:1904753)

GO Molecular Function (15): RNA binding (GO:0003723), phosphoprotein phosphatase activity (GO:0004721), protein tyrosine phosphatase activity (GO:0004725), non-membrane spanning protein tyrosine phosphatase activity (GO:0004726), insulin receptor binding (GO:0005158), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), protein kinase binding (GO:0019901), receptor tyrosine kinase binding (GO:0030971), cadherin binding (GO:0045296), ephrin receptor binding (GO:0046875), protein phosphatase 2A binding (GO:0051721), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (16): cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), mitochondrial crista (GO:0030061), endosome lumen (GO:0031904), protein-containing complex (GO:0032991), sorting endosome (GO:0097443), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Signaling by MET	1
Signaling by Insulin receptor	1
Interferon gamma signaling	1
Signaling by PTK6	1
Transcriptional Regulation by MECP2	1
Interferon alpha/beta signaling	1
Cytokine Signaling in Immune system	1
Response of endothelial cells to shear stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
signaling receptor binding	3
endosome	3
signal transduction	2
intracellular organelle lumen	2
cytoplasm	2
synapse	2
regulation of systemic arterial blood pressure	1
positive regulation of blood pressure	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
regulation of heart rate	1
positive regulation of heart contraction	1
cardiac muscle cell apoptotic process	1
positive regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
negative regulation of cell adhesion	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
cytoskeleton organization	1
actin filament-based process	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
proteolysis	1
regulation of protein metabolic process	1
negative regulation of signal transduction	1

Protein interactions and networks

STRING

2936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN1	EGFR	P00533	978
PTPN1	KDR	P35968	938
PTPN1	RMDN3	Q96TC7	908
PTPN1	IRS1	P35568	903
PTPN1	PTS	Q03393	896
PTPN1	CDH17	Q12864	868
PTPN1	JAK2	O60674	849
PTPN1	INS	P01308	835
PTPN1	TXN	P10599	794
PTPN1	TXN2	Q99757	788
PTPN1	IGF1R	P08069	786
PTPN1	SRC	P12931	784
PTPN1	MET	P08581	771
PTPN1	INSR	P06213	760
PTPN1	GRB2	P29354	746

IntAct

447 interactions, top by confidence:

A	B	Type	Score
PTPN1	INSR	psi-mi:“MI:0203”(dephosphorylation reaction)	0.980
EGFR	PTPN1	psi-mi:“MI:0403”(colocalization)	0.900
EGFR	PTPN1	psi-mi:“MI:0915”(physical association)	0.900
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PTPN1	GHR	psi-mi:“MI:0407”(direct interaction)	0.650
PTPN1	GHR	psi-mi:“MI:0203”(dephosphorylation reaction)	0.650
PTPN1	GHR	psi-mi:“MI:0915”(physical association)	0.650
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
	PTPN1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.620
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
PTPN1	PIGP	psi-mi:“MI:0915”(physical association)	0.560
	PTPN1	psi-mi:“MI:0915”(physical association)	0.560
PTPN1	TMEM86B	psi-mi:“MI:0915”(physical association)	0.560
PTPN1	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
PTPN1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
PTPN1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (837): PTPN1 (Two-hybrid), PTPN1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN1 (Affinity Capture-MS), PTPN1 (Synthetic Lethality), AGR3 (Two-hybrid), BCAS3 (Two-hybrid), CASC3 (Two-hybrid), CASZ1 (Two-hybrid), CCL5 (Two-hybrid)

ESM2 similar proteins: A0A2R8QFQ6, A4IFE4, A9X1D0, B0VX69, B5FW36, C1FXW2, D1LYT2, D3Z7P3, G3MWR8, G3V6U9, O13016, O46411, O88508, O94925, O95544, P13264, P18031, P18507, P20417, P21548, P22723, P35790, P35821, P41227, P47870, P58058, Q01134, Q0VAM2, Q14722, Q1LZ53, Q2KI14, Q3ULA2, Q3UX61, Q4V8K3, Q4W5Z4, Q5RC04, Q5SRY7, Q5ZML9, Q6ZPR4, Q7RTP6

Diamond homologs: A0A6I8TCE0, A1L1L3, A2ALK8, A4IFW2, B0V2N1, B0X4T2, B1AUH1, B2GV87, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, G5EC24, G5EGJ9, H2KZM6, O02695, O08617, O13016, O35239, O55082, P06800, P16620, P17706, P18031, P18052, P18433, P20417, P23467, P23468, P23469, P23470, P23471, P26045, P28191, P29074, P29350, P29351, P29352

SIGNOR signaling

116 interactions.

A	Effect	B	Mechanism
PTPN1	down-regulates	LAT	dephosphorylation
PTPN1	up-regulates	SRC	dephosphorylation
PTPN1	down-regulates	PRKCD	dephosphorylation
PTPN1	“down-regulates activity”	IGF1R	dephosphorylation
PTPN1	down-regulates	AKT	dephosphorylation
PTPN1	down-regulates	JAK2	dephosphorylation
PTPN1	“down-regulates activity”	TYK2	dephosphorylation
PTPN1	down-regulates	STAT3	dephosphorylation
PTPN1	up-regulates	ACTN1	dephosphorylation
PTPN1	down-regulates	PTK2	dephosphorylation
PTPN1	down-regulates	MAPK15	dephosphorylation
PTPN1	down-regulates	MET	dephosphorylation
PTPN1	down-regulates	TRPV6	dephosphorylation
PTPN1	down-regulates	ROS1	dephosphorylation
PTPN1	down-regulates	PDGFRB	dephosphorylation
(E)-3-tosylacrylonitrile	down-regulates	PTPN1	“chemical inhibition”
PTPN1	“up-regulates activity”	SRC	dephosphorylation
PTPN1	“down-regulates activity”	LAT	dephosphorylation
PTPN1	“down-regulates activity”	JAK2	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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
GRB2 events in EGFR signaling	5	29.5×	6e-05
SHC1 events in EGFR signaling	5	27.7×	6e-05
Constitutive Signaling by EGFRvIII	5	27.7×	6e-05
Insulin receptor signalling cascade	5	26.0×	6e-05
Signaling by ERBB2 ECD mutants	5	26.0×	6e-05
GRB2 events in ERBB2 signaling	5	24.6×	7e-05
Tie2 Signaling	5	23.3×	8e-05
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	22.1×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	5	13.2×	7e-03
insulin receptor signaling pathway	8	11.2×	2e-04
cell surface receptor protein tyrosine kinase signaling pathway	9	9.8×	1e-04
protein autophosphorylation	10	9.1×	9e-05
positive regulation of MAPK cascade	13	6.6×	9e-05
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	11	5.4×	2e-03
positive regulation of cell migration	11	4.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	26
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4532808	NM_002827.4(PTPN1):c.625G>A (p.Gly209Arg)	Pathogenic
4812120	NM_002827.4(PTPN1):c.456_460del (p.Tyr153fs)	Pathogenic
4818965	NM_002827.4(PTPN1):c.409_422del (p.Asp137fs)	Likely pathogenic

SpliceAI

1895 predictions. Top by Δscore:

Variant	Effect	Δscore
20:50510589:AGGTG:A	donor_loss	1.0000
20:50510591:GTGC:G	donor_loss	1.0000
20:50561357:TTGTA:T	acceptor_loss	1.0000
20:50561358:TGTA:T	acceptor_loss	1.0000
20:50561359:GTAGG:G	acceptor_loss	1.0000
20:50561360:TAGGA:T	acceptor_loss	1.0000
20:50561361:AG:A	acceptor_gain	1.0000
20:50561362:GG:G	acceptor_gain	1.0000
20:50561449:TCCCT:T	donor_gain	1.0000
20:50561453:TG:T	donor_loss	1.0000
20:50561454:G:GC	donor_loss	1.0000
20:50561454:G:GG	donor_gain	1.0000
20:50561455:TA:T	donor_loss	1.0000
20:50561456:AAG:A	donor_loss	1.0000
20:50564965:TCA:T	acceptor_loss	1.0000
20:50564966:CAGT:C	acceptor_loss	1.0000
20:50564967:A:AG	acceptor_gain	1.0000
20:50564967:AGT:A	acceptor_loss	1.0000
20:50564967:AGTT:A	acceptor_gain	1.0000
20:50564968:G:GC	acceptor_gain	1.0000
20:50564968:GT:G	acceptor_gain	1.0000
20:50564968:GTT:G	acceptor_gain	1.0000
20:50564968:GTTG:G	acceptor_gain	1.0000
20:50564968:GTTGA:G	acceptor_gain	1.0000
20:50565066:CCAG:C	donor_gain	1.0000
20:50565067:CAG:C	donor_gain	1.0000
20:50565068:AG:A	donor_gain	1.0000
20:50565069:GG:G	donor_gain	1.0000
20:50565069:GGT:G	donor_loss	1.0000
20:50565070:G:GG	donor_gain	1.0000

AlphaMissense

2896 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:50510573:T:A	W16R	1.000
20:50510573:T:C	W16R	1.000
20:50561403:C:A	A35D	1.000
20:50561431:T:A	N44K	1.000
20:50561431:T:G	N44K	1.000
20:50561432:A:G	R45G	1.000
20:50561433:G:C	R45T	1.000
20:50561433:G:T	R45M	1.000
20:50561434:G:C	R45S	1.000
20:50561434:G:T	R45S	1.000
20:50561435:T:C	Y46H	1.000
20:50561435:T:G	Y46D	1.000
20:50561436:A:G	Y46C	1.000
20:50561441:G:C	D48H	1.000
20:50561442:A:C	D48A	1.000
20:50561445:T:A	V49D	1.000
20:50561451:C:A	P51H	1.000
20:50564981:G:C	R56P	1.000
20:50565010:T:C	Y66H	1.000
20:50565018:C:A	N68K	1.000
20:50565018:C:G	N68K	1.000
20:50565019:G:C	A69P	1.000
20:50565020:C:A	A69D	1.000
20:50565022:A:C	S70R	1.000
20:50565024:T:A	S70R	1.000
20:50565024:T:G	S70R	1.000
20:50565062:T:A	L83H	1.000
20:50565062:T:C	L83P	1.000
20:50565069:G:C	Q85H	1.000
20:50565069:G:T	Q85H	1.000

dbSNP variants (sampled 300 via entrez): RS1000062132 (20:50528341 A>G), RS1000108722 (20:50535111 G>T), RS1000145246 (20:50519178 A>G), RS1000153249 (20:50578531 G>C), RS1000180234 (20:50522882 T>C,G), RS1000292236 (20:50553049 C>G), RS1000307576 (20:50509386 G>GGGATTA), RS1000341494 (20:50542156 C>G), RS1000365406 (20:50559541 A>G), RS1000433379 (20:50528644 G>A,T), RS1000517465 (20:50524110 C>T), RS1000544439 (20:50579618 C>T), RS1000582349 (20:50554282 G>C), RS1000613854 (20:50510871 A>G), RS1000637535 (20:50561790 G>A,T)

Disease associations

OMIM: gene MIM:176885 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory syndrome	Limited	Autosomal dominant

Mondo (2): type 1 interferonopathy of childhood (MONDO:0957408), autoinflammatory syndrome (MONDO:0019751)

Orphanet (1): Type 1 interferonopathy of childhood (Orphanet:481671)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000855	Insulin resistance
HP:0003584	Late onset
HP:0005978	Type II diabetes mellitus
HP:0031819	Increased waist to hip ratio

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST004785_6	Vitiligo	9.000000e-09
GCST005580_178	Intraocular pressure	2.000000e-08
GCST006394_59	Intraocular pressure	8.000000e-09
GCST006412_129	Intraocular pressure	5.000000e-10
GCST007552_30	Colorectal cancer	1.000000e-06
GCST007681_1	Thyroid stimulating hormone levels	2.000000e-08
GCST007856_33	Colorectal cancer or advanced adenoma	8.000000e-13
GCST007856_4	Colorectal cancer or advanced adenoma	4.000000e-11
GCST007856_5	Colorectal cancer or advanced adenoma	2.000000e-07
GCST009725_66	Intraocular pressure	1.000000e-08
GCST009869_68	Colorectal cancer	2.000000e-06
GCST90000025_689	Appendicular lean mass	2.000000e-19
GCST90002379_164	Basophil count	8.000000e-10
GCST90002381_253	Eosinophil count	2.000000e-18
GCST90002382_532	Eosinophil percentage of white cells	1.000000e-20
GCST90002389_425	Lymphocyte percentage of white cells	2.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004980	appendicular lean mass
EFO:0005090	basophil count
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL335 (SINGLE PROTEIN), CHEMBL5465230 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066021 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 574,229 (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
CHEMBL1169	AMINOSALICYLIC ACID	4	51,677
CHEMBL1200712	EVANS BLUE	4	24,260
CHEMBL1640	TRYPAN BLUE	4	122,262
CHEMBL1756	ESTRAMUSTINE PHOSPHATE	4	56
CHEMBL295124	BERBERINE	4	26,682
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL408	TROGLITAZONE	4	38,856
CHEMBL48449	CANTHARIDIN	4	4,679
CHEMBL499915	CARBENOXOLONE	4	3,947
CHEMBL595	PIOGLITAZONE	4	57,130
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL265502	SURAMIN	3	36,848
CHEMBL50	QUERCETIN	3	74,559
CHEMBL169	URSOLIC ACID	2	20,825
CHEMBL184041	ERTIPROTAFIB	2	174
CHEMBL230006	ENOXOLONE	2	24,361
CHEMBL284616	CHLOROGENIC ACID	2	41,945
CHEMBL404519	BEVIRIMAT	2	791
CHEMBL508583	TRODUSQUEMINE	2	605
CHEMBL5095164	OSUNPROTAFIB	2	22
CHEMBL5314543	TEGEPROTAFIB	2
CHEMBL8659	OLEIC ACID	2
CHEMBL269277	BETULINIC ACID	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein tyrosine phosphatases non-receptor type (PTPN)

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
compound 182 [PMID: 37500611]	Inhibition	9.2	pIC50
tegeprotafib	Inhibition	9.0	pIC50
(+)-4 enantiomer [PMID: 39046805]	Inhibition	8.57	pKi
HPN	Inhibition	6.2	pIC50
trodusquemine	Inhibition	6.0	pIC50
compound 7b [Haftchenary et al., 2013]	Inhibition	5.31	pIC50
NC1	Inhibition	5.1	pKi
chlorogenic acid	Inhibition	4.96	pIC50
I-C11	Inhibition	4.93	pIC50

Binding affinities (BindingDB)

327 measured of 507 human assays (511 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2R)-2-{[(1S)-1-carbamoyl-2-{4-[difluoro(phosphono)methyl]phenyl}ethyl]carbamoyl}-2-(1-{4-[difluoro(phosphono)methyl]phenyl}acetamido)acetic acid	IC50	0.4 nM
({4-[(2S)-2-carbamoyl-2-[(2S)-2-(1-{4-[difluoro(phosphono)methyl]phenyl}acetamido)-3-phenylpropanamido]ethyl]phenyl}difluoromethyl)phosphonic acid	IC50	1.7 nM
({7-[2-(1H-1,2,3-benzotriazol-1-yl)-2-({6-bromo-7-[difluoro(phosphono)methyl]quinolin-2-yl}methyl)-3-oxo-3-phenylpropyl]-3-bromonaphthalen-2-yl}difluoromethyl)phosphonic acid (10i)	IC50	3 nM
3-{4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}benzene-1-phosphonic acid	IC50	3 nM
({7-[2-({7-[(aminosulfinyl)difluoromethyl]-6-bromonaphthalen-2-yl}methyl)-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxo-3-phenylpropyl]-3-bromonaphthalen-2-yl}difluoromethyl)phosphonic acid (10j)	IC50	4 nM
({2-[2-({7-[(aminosulfinyl)difluoromethyl]-6-bromoquinolin-2-yl}methyl)-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxo-3-phenylpropyl]-6-bromoquinolin-7-yl}difluoromethyl)phosphonic acid (10o)	IC50	4 nM
({2-[2-(1H-1,2,3-benzotriazol-1-yl)-2-({6-bromo-7-[difluoro(phosphono)methyl]quinolin-2-yl}methyl)-3-oxo-3-phenylpropyl]-6-bromoquinolin-7-yl}difluoromethyl)phosphonic acid (10n)	IC50	5 nM
6-{4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}-2-(1-methoxy-3-methylbutyl)quinoline-8-phosphonic acid	IC50	5 nM
({7-[2-(1H-1,2,3-benzotriazol-1-yl)-2-({6-bromo-7-[difluoro(phosphono)methyl]naphthalen-2-yl}methyl)-3-oxo-3-phenylpropyl]-3-bromonaphthalen-2-yl}difluoromethyl)phosphonic acid (10h)	IC50	5 nM
({7-[2-({7-[(aminosulfinyl)difluoromethyl]-6-bromoquinolin-2-yl}methyl)-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxo-3-phenylpropyl]-3-bromonaphthalen-2-yl}difluoromethyl)phosphonic acid (10k)	IC50	6 nM
5-{4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}-2-(3-methylbutoxy)benzene-1-phosphonic acid	IC50	6 nM
6-{4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}-2-(1-hydroxy-3-methylbutyl)quinoline-8-phosphonic acid	IC50	6 nM
5-{4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}-2-methoxybenzene-1-phosphonic acid	IC50	10 nM
6-{4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}-2-[1-(methoxymethoxy)-3-methylbutyl]quinoline-8-phosphonic acid	IC50	11 nM
6-{4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}-2-methylquinoline-8-phosphonic acid	IC50	12 nM
({4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-(3,4-difluorophenyl)propyl]phenyl}difluoromethyl)phosphonic acid	IC50	13 nM
({4-[2-(1H-1,2,3-benzotriazol-1-yl)-3-{4-[difluoro(phosphono)methyl]phenyl}-2-phenylpropyl]phenyl}difluoromethyl)phosphonic acid	IC50	16 nM
({7-[2-({4-[(aminosulfinyl)difluoromethyl]-3-bromophenyl}methyl)-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxo-3-phenylpropyl]-3-bromonaphthalen-2-yl}difluoromethyl)phosphonic acid (10d)	IC50	19 nM
({7-[2-(1H-1,2,3-benzotriazol-1-yl)-2-({3-bromo-4-[difluoro(phosphono)methyl]phenyl}methyl)-3-oxo-3-phenylpropyl]-3-bromonaphthalen-2-yl}difluoromethyl)phosphonic acid (10b)	IC50	20 nM
({2-[2-(1H-1,2,3-benzotriazol-1-yl)-2-({3-bromo-4-[difluoro(phosphono)methyl]phenyl}methyl)-3-oxo-3-phenylpropyl]-6-bromoquinolin-7-yl}difluoromethyl)phosphonic acid (10l)	IC50	21 nM
({2-[2-({4-[(aminosulfinyl)difluoromethyl]-3-bromophenyl}methyl)-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxo-3-phenylpropyl]-6-bromoquinolin-7-yl}difluoromethyl)phosphonic acid (10m)	IC50	22 nM
3-({5-[(N-Acetyl-3-{4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl}-L-alanyl)amino]pentyl}oxy)-2-naphthoic Acid	KI	22 nM
({4-[(4E)-2-(1,3-benzothiazol-2-yl)-2-(1H-1,2,3-benzotriazol-1-yl)-5-phenylpent-4-en-1-yl]phenyl}difluoromethyl)phosphonic acid	IC50	23 nM
5,5’,5’’-[1,3,6-naphthalenetriyltris(sulfonylimino)]tris[1,3-benzenesulfonate analogue	KI	25 nM
Sodium orthovanadate (SOV)	IC50	25.4 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[3-cyano-4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]benzenesulfonamide	IC50	31 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[3-fluoro-4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]benzenesulfonamide	IC50	34 nM
(2S)-N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-{4-[(5S)-1,1,3-trioxo-1,2-thiazolidin-5-yl]phenyl}ethyl]-2-acetamido-3-phenylpropanamide	IC50	35 nM
(S)-isothiazolidinone	IC50	35 nM
({4-[2-(1H-1,2,3-benzotriazol-1-yl)-2-phenyl-3-(4-phenylphenyl)propyl]phenyl}difluoromethyl)phosphonic acid	IC50	38 nM
({4-[(4E)-2-(1H-1,2,3-benzotriazol-1-yl)-2-[4-(methoxycarbonyl)phenyl]-5-phenylpent-4-en-1-yl]phenyl}difluoromethyl)phosphonic acid	IC50	39 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]-4-bromo-3-(trifluoromethyl)benzene-1-sulfonamide	IC50	40 nM
({4-[(2S)-2-carbamoyl-2-[2-(1-{4-[difluoro(phosphono)methyl]phenyl}acetamido)acetamido]ethyl]phenyl}difluoromethyl)phosphonic acid	IC50	42 nM
({7-[2-(1H-1,2,3-benzotriazol-1-yl)-2-({4-[difluoro(phosphono)methyl]phenyl}methyl)-3-oxo-3-phenylpropyl]-3-bromonaphthalen-2-yl}difluoromethyl)phosphonic acid (10a)	IC50	46 nM
[(4-{2-[(2S)-2-(1-{4-[difluoro(phosphono)methyl]phenyl}acetamido)-3-phenylpropanamido]ethyl}phenyl)difluoromethyl]phosphonic acid	IC50	46 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]-3,5-dichlorobenzene-1-sulfonamide	IC50	51 nM
N-[(1S)-1-(1H-benzoimidazol-2-yl)-2-[4-[(5S)-1,1,3-trioxo-1,2-thiazolidin-5-yl]phenyl]ethyl]-7-methyl-10-oxa-7-azabicyclo[4.4.0]deca-2,4,11-triene-3-sulfonamide	IC50	59 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[3-methyl-4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]benzenesulfonamide	IC50	59 nM
(2S)-N-[(1S)-1-carbamoyl-2-[4-(1,1,3-trioxo-2,3-dihydro-1,2-thiazol-5-yl)phenyl]ethyl]-3-phenyl-2-{1-[4-(1,1,3-trioxo-2,3-dihydro-1,2-thiazol-5-yl)phenyl]acetamido}propanamide	IC50	65 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]-3-fluorobenzene-1-sulfonamide	IC50	66 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[3-chloro-4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]benzenesulfonamide	IC50	75 nM
1:1 mixture of diastereomers	KI	76 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]-4-methylbenzene-1-sulfonamide	IC50	80 nM
[[4-[2-[(2-acetamido-3-phenylpropanoyl)amino]-3-[[1-amino-6-[(4-ethylbenzoyl)amino]-1-oxohexan-2-yl]amino]-3-oxopropyl]phenyl]-difluoromethyl]phosphonic acid	IC50	87 nM	US-9217012: Inhibitors of protein tyrosine phosphatases
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]-3-methyl-4-phenylbenzene-1-sulfonamide	IC50	90 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]-4-(propan-2-yl)benzene-1-sulfonamide	IC50	100 nM
({4-[(4E)-2-(1H-1,2,3-benzotriazol-1-yl)-2,5-diphenylpent-4-en-1-yl]phenyl}difluoromethyl)phosphonic acid	IC50	109 nM
N-{(1S)-2-[4-(1,1-dioxido-3-oxoisothiazolidin-5-yl)phenyl]-1-[5-(trifluoromethyl)-1H-benzimidazol-2-yl]ethyl}-2,2,2-trifluoroacetamide	IC50	110 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]-3-phenoxybenzene-1-sulfonamide	IC50	110 nM
N-[(1S)-1-(1H-1,3-benzodiazol-2-yl)-2-[4-(1,1,3-trioxo-1,2-thiazolidin-5-yl)phenyl]ethyl]benzenesulfonamide	IC50	120 nM

ChEMBL bioactivities

3187 potent at pChembl≥5 of 4712 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	MICROCYSTIN-LR
9.52	IC50	0.3	nM	CALYCULIN A
9.38	IC50	0.42	nM	CHEMBL4524071
9.30	IC50	0.5	nM	CALYCULIN A
9.22	IC50	0.6	nM	CHEMBL5619806
9.20	IC50	0.63	nM	CHEMBL5619806
9.20	IC50	0.63	nM	CHEMBL6177218
9.17	IC50	0.67	nM	TAUTOMYCIN
9.17	Ki	0.68	nM	CHEMBL244563
9.16	IC50	0.69	nM	OSUNPROTAFIB
9.04	Ki	0.92	nM	CHEMBL184444
9.00	Ki	1	nM	CHEMBL395722
9.00	IC50	1	nM	CHEMBL5070507
9.00	IC50	1	nM	CHEMBL5085615
9.00	IC50	1	nM	CHEMBL5076419
9.00	IC50	1	nM	TEGEPROTAFIB
8.93	IC50	1.17	nM	MICROCYSTIN-LR
8.92	IC50	1.2	nM	CALYCULIN A
8.91	IC50	1.24	nM	OKADAIC ACID
8.85	Ki	1.4	nM	CHEMBL1235987
8.83	IC50	1.49	nM	CALYCULIN
8.77	Ki	1.7	nM	CHEMBL1232186
8.70	Ki	2	nM	CHEMBL230862
8.70	Ki	2	nM	CHEMBL230860
8.62	Ki	2.4	nM	PHOSPHONODIFLUOROMETHYL PHENYLALANINE
8.62	Ki	2.4	nM	CHEMBL326115
8.62	IC50	2.4	nM	CHEMBL326115
8.62	Ki	2.4	nM	CHEMBL5279725
8.60	IC50	2.5	nM	OSUNPROTAFIB
8.55	IC50	2.8	nM	CHEMBL5619195
8.52	IC50	3	nM	CHEMBL269166
8.52	Ki	3	nM	CHEMBL243268
8.52	Ki	3	nM	CHEMBL397415
8.52	Ki	3	nM	CHEMBL243267
8.52	IC50	3	nM	CHEMBL4524071
8.51	IC50	3.09	nM	CHEMBL5559660
8.47	IC50	3.4	nM	OKADAIC ACID
8.43	IC50	3.7	nM	CHEMBL3103433
8.40	Ki	4	nM	CHEMBL541214
8.40	Ki	4	nM	CHEMBL387614
8.40	Ki	4	nM	CHEMBL390245
8.35	IC50	4.5	nM	CHEMBL426373
8.33	IC50	4.7	nM	CHEMBL5423615
8.33	IC50	4.7	nM	CHEMBL259628
8.31	Ki	4.9	nM	CHEMBL3818452
8.30	IC50	5	nM	CHEMBL267488
8.30	IC50	5	nM	CHEMBL266753
8.30	IC50	5	nM	CHEMBL590235
8.30	Ki	5	nM	CHEMBL230645
8.30	IC50	5	nM	CHEMBL4542052

PubChem BioAssay actives

2096 with measured affinity, of 6100 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
(2E,5R,6S,9S,12S,13S,16R)-9-[3-(diaminomethylideneamino)propyl]-2-ethylidene-12-[(1E,3E,5S,6S)-6-methoxy-3,5-dimethyl-7-phenylhepta-1,3-dienyl]-1,6,13-trimethyl-3,7,10,14,19-pentaoxo-1,4,8,11,15-pentazacyclononadecane-5,16-dicarboxylic acid	164504: Observed inhibition activity against protein phosphatase 1 (PP1)	ic50	0.0004	uM
(2R)-3-[[(2S)-1-amino-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-2-[[2-[4-[difluoro(phosphono)methyl]phenyl]acetyl]amino]-3-oxopropanoic acid	1797035: Phosphatase Inhibition Assay from Article 10.1074/jbc.M607913200: “Structural insights into the design of nonpeptidic isothiazolidinone-containing inhibitors of protein-tyrosine phosphatase 1B.”	ic50	0.0004	uM
5-[1-fluoro-3-hydroxy-7-(3-hydroxy-3-methylbutoxy)naphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129505: Inhibition of PTP1B (unknown origin)	ic50	0.0006	uM
5-[(7R)-1-fluoro-3-hydroxy-7-(3-methylbutylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084059: Inhibition of human PTP1B	ic50	0.0007	uM
5-[3-[(1-benzylsulfonylpiperidin-4-yl)amino]phenyl]-3-(carboxymethoxy)-4-chlorothiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0007	uM
[(3R,4R,5R,8S,9S,12R)-12-[(2S,3S,6R,8S,9R)-3,9-dimethyl-8-[(3S)-3-methyl-4-oxopentyl]-1,7-dioxaspiro[5.5]undecan-2-yl]-5,9-dihydroxy-4-methoxy-2,8-dimethyl-7-oxotridecan-3-yl] (3R)-3-hydroxy-3-(4-methyl-2,5-dioxofuran-3-yl)propanoate	164505: Observed inhibition activity of the compounds against protein phosphatases 1 (PP1)	ic50	0.0007	uM
5-[7-(1-cyclopropylsulfonylpyrrolidin-3-yl)-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[7-[1-(cyclopropylmethyl)pyrazol-4-yl]-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
4-[8-fluoro-6-hydroxy-7-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)naphthalen-2-yl]oxy-2,2-dimethylbutanenitrile	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[7-(2-cyclopropylethylamino)-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[1-fluoro-3-hydroxy-7-[(3S)-3-hydroxybutoxy]naphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[7-[2-(2,2-difluorocyclopropyl)ethoxy]-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[7-(1-ethylsulfonyl-2,5-dihydropyrrol-3-yl)-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[1-fluoro-3-hydroxy-7-[1-(3-methylbutylsulfonyl)-2,5-dihydropyrrol-3-yl]naphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
4-[8-fluoro-3,6-dihydroxy-7-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)naphthalen-2-yl]oxy-2,2-dimethylbutanenitrile	1808175: Inhibition of PTPN1 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[[2-(methanesulfonamido)phenyl]methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0010	uM
(5R,8S,11R,12S,15S,18S,19S,22R)-15-[3-(diaminomethylideneamino)propyl]-18-[(1E,3E,5S,6S)-6-methoxy-3,5-dimethyl-7-phenylhepta-1,3-dienyl]-1,5,12,19-tetramethyl-2-methylidene-8-(2-methylpropyl)-3,6,9,13,16,20,25-heptaoxo-1,4,7,10,14,17,21-heptazacyclopentacosane-11,22-dicarboxylic acid	164505: Observed inhibition activity of the compounds against protein phosphatases 1 (PP1)	ic50	0.0012	uM
(2R)-3-[(2S,6R,8S,11R)-2-[(E,2R)-4-[(2S,2’R,4R,4aS,6R,8aR)-4-hydroxy-2-[(1S,3S)-1-hydroxy-3-[(2S,3R,6S)-3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl]butyl]-3-methylidenespiro[4a,7,8,8a-tetrahydro-4H-pyrano[3,2-b]pyran-6,5’-oxolane]-2’-yl]but-3-en-2-yl]-11-hydroxy-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-hydroxy-2-methylpropanoic acid	164504: Observed inhibition activity against protein phosphatase 1 (PP1)	ic50	0.0012	uM
5-[3-[[1-[(2-aminophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]-4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0020	uM
5-[3-[[1-[(2-acetamidophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]-4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0020	uM
4-amino-5-[3-[(E)-3-(3-hydroxy-2-methoxycarbonylphenoxy)prop-1-enyl]phenyl]-1,2-oxazole-3-carboxylic acid	1942826: Inhibition of PTP1B (unknown origin) assessed as inhibition constant	ki	0.0021	uM
(3S)-4-[[(2S)-1-amino-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-3-[[2-[4-[difluoro(phosphono)methyl]phenyl]acetyl]amino]-4-oxobutanoic acid	1328333: Inhibition of PTP1B (unknown origin)	ic50	0.0024	uM
(3S)-4-[[(2R)-1-amino-3-[4-[difluoro(phosphono)methyl]phenyl]-1-oxopropan-2-yl]amino]-3-[[2-[4-[difluoro(phosphono)methyl]phenyl]acetyl]amino]-4-oxobutanoic acid	1942826: Inhibition of PTP1B (unknown origin) assessed as inhibition constant	ki	0.0024	uM
5-[7-(cyclopropylmethylamino)-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129505: Inhibition of PTP1B (unknown origin)	ic50	0.0028	uM
[3-[4-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]phenyl]phosphonic acid	1309447: Inhibition of flag-tagged PTP1B (1 to 321 residues) (unknown origin) expressed in bacterial expression system by UV/Vis spectrophotometry	ic50	0.0030	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-methylphenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0030	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2,6-dimethylphenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0030	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-methoxyphenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0030	uM
5-(3-ethyl-6-fluoro-8-hydroxy-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084059: Inhibition of human PTP1B	ic50	0.0031	uM
5-[3-[(1-benzylsulfonylpiperidin-4-yl)amino]phenyl]-4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid	1266405: Inhibition of PTP1B (unknown origin)	ki	0.0040	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-chlorophenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0040	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-methylphenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0040	uM
[[4-[(2S)-3-[[(2S)-1-amino-6-[(3-bromo-4-methylbenzoyl)amino]-1-oxohexan-2-yl]amino]-2-[[(2S)-2-[[2-(4-hydroxy-3-methoxyphenyl)acetyl]amino]-3-phenylpropanoyl]amino]-3-oxopropyl]phenyl]-difluoromethyl]phosphonic acid	2038375: Inhibition of PTP1B (unknown origin) using pNPP as substrate by spectrophotometric analysis	ic50	0.0047	uM
[(3-bromo-7-cyanonaphthalen-2-yl)-difluoromethyl]phosphonic acid	2129505: Inhibition of PTP1B (unknown origin)	ic50	0.0047	uM
[[4-[(2S)-3-amino-2-[[(2S)-2-[[2-[4-[difluoro(phosphono)methyl]phenyl]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-oxopropyl]phenyl]-difluoromethyl]phosphonic acid	1309467: Inhibition of PTP1B catalytic domain (1 to 321 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using p-Nitrophenyl phosphate as substrate	ki	0.0049	uM
[[4-[2-(benzotriazol-1-yl)-3-[3-bromo-4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]-difluoromethyl]phosphonic acid	165319: Inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) was determined in fluorescein diphosphate (FDP) assay	ic50	0.0050	uM
[6-[4-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]-2-(1-methoxy-3-methylbutyl)quinolin-8-yl]phosphonic acid	1309447: Inhibition of flag-tagged PTP1B (1 to 321 residues) (unknown origin) expressed in bacterial expression system by UV/Vis spectrophotometry	ic50	0.0050	uM
[7-[4-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]-2-(1-methoxy-3-methylbutyl)quinolin-8-yl]phosphonic acid	1634003: Inhibition of human FLAG-tagged PTP1B catalytic domain (1 to 298) expressed in Escherichia coli using fluorescein diphosphate as substrate by fluorescence based method	ic50	0.0050	uM
[[6-[2-(benzotriazol-1-yl)-3-[6-bromo-7-[difluoro(phosphono)methyl]naphthalen-2-yl]-1-oxo-1-phenylpropan-2-yl]-3-bromonaphthalen-2-yl]-difluoromethyl]phosphonic acid	1942843: Inhibition of PTP1B (unknown origin) using pNPP as substrate	ic50	0.0050	uM
[7-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]-2-(1-methoxy-3-methylbutyl)quinolin-8-yl]phosphonic acid	1942839: Inhibition of human PTP1B (1 to 298 residues) expressed in Escherichia coli using FDP as substrate by microplate reader	ic50	0.0050	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-chlorophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0050	uM
[5-[4-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]-2-(3-methylbutoxy)phenyl]phosphonic acid	1797069: PTP1B and TCPTP Inhibition Assay from Article 10.1021/bi035098j: “The structural basis for the selectivity of benzotriazole inhibitors of PTP1B.”	ic50	0.0060	uM
[6-[4-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]-2-(1-hydroxy-3-methylbutyl)quinolin-8-yl]phosphonic acid	1797069: PTP1B and TCPTP Inhibition Assay from Article 10.1021/bi035098j: “The structural basis for the selectivity of benzotriazole inhibitors of PTP1B.”	ic50	0.0060	uM
[[4-[2-[[4-[difluoro(phosphono)methyl]phenyl]methyl]-3-oxo-2,3-diphenylpropyl]-2-propan-2-yloxycarbonylphenyl]-difluoromethyl]phosphonic acid	1942785: Inhibition of human PTP1B (1 to 321 residues) expressed in Escherichia coli using FDP as substrate	ic50	0.0060	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[[2-(trifluoromethyl)phenyl]methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0060	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2,6-dimethylphenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297806: Inhibition of human recombinant PTP1B	ki	0.0060	uM
[[4-[2-[[4-[difluoro(phosphono)methyl]phenyl]methyl]-3-oxo-2,3-diphenylpropyl]phenyl]-difluoromethyl]phosphonic acid	1942785: Inhibition of human PTP1B (1 to 321 residues) expressed in Escherichia coli using FDP as substrate	ic50	0.0060	uM
[[2-chloro-4-(3-oxo-2,3-diphenylpropyl)phenyl]-difluoromethyl]phosphonic acid	1942785: Inhibition of human PTP1B (1 to 321 residues) expressed in Escherichia coli using FDP as substrate	ic50	0.0060	uM
[[2-bromo-4-[[4-(4-bromo-3-sulfamoylphenyl)phenyl]methylsulfanylmethyl]phenyl]-difluoromethyl]phosphonic acid	343956: Inhibition of human PTP1B expressed in Escherichia coli BL21(DE3) cells	ic50	0.0060	uM
5-[2-fluoro-5-[(E)-3-(3-hydroxy-2-methoxycarbonylphenoxy)prop-1-enyl]phenyl]-1,2-oxazole-3-carboxylic acid	1942826: Inhibition of PTP1B (unknown origin) assessed as inhibition constant	ki	0.0069	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ursolic Acid	decreases activity	4
3-N-1(spermine)-7, 24-dihydroxy-5-cholestane 24-sulfate	affects binding, decreases activity	3
Rotenone	affects reaction, increases phosphorylation, decreases expression	3
1,2-naphthoquinone	decreases activity, increases metabolic processing, increases reaction	2
Arsenic Trioxide	decreases activity, decreases expression, decreases reaction, increases reaction	2
Acetylcysteine	decreases activity, decreases expression, decreases reaction, increases reaction, increases expression	2
Tunicamycin	affects reaction, increases phosphorylation, decreases expression	2
Vanadates	decreases activity, decreases reaction	2
aristolochic acid I	increases expression	1
fumosorinone	decreases expression	1
FR900359	affects phosphorylation	1
kuwanon-L	decreases activity	1
bisphenol F	increases expression	1
ursonic acid	decreases activity	1
quinone	decreases activity	1
methylmercuric chloride	decreases activity	1
9,10-phenanthrenequinone	affects cotreatment, decreases activity, increases oxidation, decreases reaction	1
deoxynivalenol	increases expression	1
morin	decreases activity	1
nitrophenylphosphate	decreases reaction, increases hydrolysis	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
fucosterol	decreases activity	1
sodium arsenite	increases expression	1
ricinine	decreases expression	1
tetrathiomolybdate	increases oxidation, decreases reaction	1
sodium molybdate(VI)	decreases activity, increases abundance	1
sodium tungstate(VI)	decreases activity, increases abundance	1
4-hydroxy-2-nonenal	decreases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1

ChEMBL screening assays

1225 unique, capped per target: 1210 binding, 10 functional, 4 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009263	Binding	Inhibition of of PTP1B assessed as residual enzyme activity at 100 uM	Novel 2-aryl-naphtho[1,2-d]oxazole derivatives as potential PTP-1B inhibitors showing antihyperglycemic activities. — Eur J Med Chem
CHEMBL4625403	ADMET	Inhibition of human PTP1B	A chalcone derivative binds a putative allosteric site of YopH: Inhibition of a virulence factor of Yersinia. — Bioorg Med Chem Lett
CHEMBL5622564	Toxicity	Inhibition of recombinant human PTP1B using pNPP as substrate preincubated for 5 mins followed by substrate addition and measured for 10 mins	Design, synthesis and biological evaluation of 3-substituted-2-thioxothiazolidin-4-one (rhodanine) derivatives as antitubercular agents against Mycobacterium tuberculosis protein tyrosine phosphatase B. — Eur J Med Chem

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2220	U-HO1	Cancer cell line	Male
CVCL_B2CR	Abcam HeLa PTPN1 KO	Cancer cell line	Female
CVCL_B8NF	Abcam HCT 116 PTPN1 KO	Cancer cell line	Male
CVCL_B9QQ	Abcam A-549 PTPN1 KO	Cancer cell line	Male
CVCL_D2H4	Abcam MCF-7 PTPN1 KO	Cancer cell line	Female
CVCL_D9Q3	Ubigene HEK293 PTPN1 KO	Transformed cell line	Female
CVCL_TH57	HAP1 PTPN1 (-) 1	Cancer cell line	Male
CVCL_TH58	HAP1 PTPN1 (-) 2	Cancer cell line	Male
CVCL_UI40	U-HO1-PTPN1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION