PTPN2

Summary

PTPN2 (protein tyrosine phosphatase non-receptor type 2, HGNC:9650) is a protein-coding gene on chromosome 18p11.21, encoding Tyrosine-protein phosphatase non-receptor type 2 (P17706). Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR.

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. 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. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported.

Source: NCBI Gene 5771 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory syndrome of childhood (Strong, GenCC)
• GWAS associations: 51
• Clinical variants (ClinVar): 68 total
• Phenotypes (HPO): 45
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002828

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9650
Approved symbol	PTPN2
Name	protein tyrosine phosphatase non-receptor type 2
Location	18p11.21
Locus type	gene with protein product
Status	Approved
Aliases	TCELLPTP, TC-PTP, TCPTP, TC45, TC48
Ensembl gene	ENSG00000175354
Ensembl biotype	protein_coding
OMIM	176887
Entrez	5771

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000309660, ENST00000327283, ENST00000353319, ENST00000585666, ENST00000587497, ENST00000587703, ENST00000589086, ENST00000589216, ENST00000589444, ENST00000591115, ENST00000591305, ENST00000591497, ENST00000591901, ENST00000592059, ENST00000592776, ENST00000643397, ENST00000643900, ENST00000644814, ENST00000645191, ENST00000645816, ENST00000646492, ENST00000907073, ENST00000907074, ENST00000932005, ENST00000932006

RefSeq mRNA: 5 — MANE Select: NM_002828 NM_001207013, NM_001308287, NM_002828, NM_080422, NM_080423

CCDS: CCDS11863, CCDS11864, CCDS11865, CCDS59306, CCDS77155

Canonical transcript exons

ENST00000309660 — 9 exons

Exon	Start	End
ENSE00001183625	12801970	12802151
ENSE00001861628	12792152	12794485
ENSE00003492890	12817156	12817365
ENSE00003521982	12836791	12836891
ENSE00003589082	12825810	12825944
ENSE00003627414	12859164	12859254
ENSE00003679261	12830943	12831041
ENSE00003686320	12814203	12814355
ENSE00003848808	12884073	12884237

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.6433 / max 191.4961, expressed in 1823 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171258	31.6325	1821
171257	1.3497	868
171259	0.2902	138
171260	0.2204	90
171255	0.1187	69
171256	0.0318	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.64	gold quality
granulocyte	CL:0000094	96.60	gold quality
monocyte	CL:0000576	96.60	gold quality
mononuclear cell	CL:0000842	96.56	gold quality
leukocyte	CL:0000738	96.45	gold quality
tonsil	UBERON:0002372	95.71	gold quality
parotid gland	UBERON:0001831	95.67	gold quality
cartilage tissue	UBERON:0002418	95.67	gold quality
oocyte	CL:0000023	95.42	gold quality
lymph node	UBERON:0000029	95.20	gold quality
body of pancreas	UBERON:0001150	95.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.75	gold quality
thymus	UBERON:0002370	94.63	gold quality
epithelium of nasopharynx	UBERON:0001951	94.27	gold quality
cerebellar hemisphere	UBERON:0002245	94.27	gold quality
tongue squamous epithelium	UBERON:0006919	94.21	gold quality
minor salivary gland	UBERON:0001830	94.20	gold quality
bone marrow cell	CL:0002092	94.19	gold quality
cerebellar cortex	UBERON:0002129	94.18	gold quality
spleen	UBERON:0002106	94.10	gold quality
vermiform appendix	UBERON:0001154	94.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.98	gold quality
saliva-secreting gland	UBERON:0001044	93.91	gold quality
tendon	UBERON:0000043	93.83	gold quality
cortical plate	UBERON:0005343	93.83	gold quality
bone marrow	UBERON:0002371	93.76	gold quality
mouth mucosa	UBERON:0003729	93.74	gold quality
calcaneal tendon	UBERON:0003701	93.62	gold quality
pancreas	UBERON:0001264	93.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	6.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3, STAT5A

miRNA regulators (miRDB)

152 targeting PTPN2, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504

Literature-anchored findings (GeneRIF, showing 40)

• Results identify TC45 as a protein tyrosine phosphatase responsible for the dephosphorylation of Stat1 in the nucleus. (PMID:12138178)
• TcPTP phosphorylation is regulated by STAT1 (PMID:12171910)
• regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation (PMID:12359225)
• TCPTP activates p53 and induces caspase-1-dependent apoptosis in a human tumor cell line. (PMID:12459463)
• Insulin makes the TC48-D182A & TC45-D182A “substrate-trapping” mutants form stable complexes with the tyrosine-phosphorylated IR beta-subunit. Differentially localized TCPTP variants dephosphorylate the IR & downregulate insulin signaling in vivo. (PMID:12612081)
• An important function of TC-PTP is the induction of the nitric oxide pathway that mediates inhibition of T cell proliferation. (PMID:12847239)
• Tc-PTP has a novel role in the regulation of type 1 interferon-stimulated gene expression (PMID:14600148)
• in a STI571-resistant CML sublines, TC-PTP was markedly downregulated. TC-PTP-transduced cells showed dramatic decrease of STAT5 phosphorylation and restored sensitivity to imatinib mesylate as monitored by reduced proliferation and increased apoptosis (PMID:15539083)
• Data suggest that TC48 translocates to the Golgi complex along the secretory pathway, whereas its endoplasmic reticulum localization is maintained by selective retrieval enabled by interactions with p25 and p23. (PMID:16595549)
• Single nucleotide polymorphism in PTPN2 gene is associated with ulcerative colitis (PMID:18438405)
• PTP1B and TCPTP play distinct and non-redundant roles in the regulation of the Met receptor-tyrosine kinase (PMID:18819921)
• matrix-controlled TCPTP phosphatase activity can inhibit VEGFR2 signalling, and the growth, migration and differentiation of human endothelial cells (PMID:18840653)
• TCPTP is a negative regulator of SFK, JAK1 and STAT3 signalling during the cell cycle. (PMID:18948751)
• PTPN2 regulates cytokine-induced apoptosis and may thereby contribute to the pathogenesis of type 1 diabetes. (PMID:19336676)
• TC-PTP as an important effector of the MYC-driven proliferation program in B-cell lymphomas (PMID:19755676)
• Suggest a functional role for PTPN2 in maintaining the intestinal epithelial barrier and in the pathophysiology of Crohn’s disease. (PMID:19818778)
• Data reveal PTPN2, PTPRJ and PTEN as potent regulators of Akt signalling which contribute to ameliorating the consequences of oncogenic K-Ras activity. (PMID:19922411)
• PTP1B and TC-PTP are positively implicated in IGF-2-induced migration of MCF-7 cells, suggesting that they could play a role in metastasis development. (PMID:20059965)
• the polymorphic marker C1858T of the PTPN22 gene is associated with T1DM in Russian patients. (PMID:20088380)
• confirmed an association between Crohn disease (CD) and PTPN2, and phenotypic analysis showed an association of this SNP with late age at first diagnosis, inflammatory and penetrating CD behaviour, need for bowel resection and being a smoker at diagnosis (PMID:20403149)
• Our study provides genetic and functional evidence for a tumor suppressor role of PTPN2 and suggests that expression of PTPN2 may modulate response to treatment. (PMID:20473312)
• Silencing of PTPN2 directs epidermal growth factor receptor signaling toward increased phosphatidylinositol 3-kinase activation and increased suppression of epithelial chloride secretory responses. (PMID:20689057)
• pCav-1 is a new substrate of TCPTP and that integrin alpha1beta1 acts as a negative regulator of Cav-1 phosphorylation by activating TCPTP. (PMID:20940300)
• data indicate that PTPN2 activity could play a crucial role in the establishment of chronic inflammatory conditions in the intestine, such as Crohn disease. (PMID:21115548)
• Data suggest that decreased expression of PTPN2 may indirectly modulate IL-2 responsiveness. (PMID:21179116)
• IRF-8-induced repression of Toll-like receptor (TLR)3 is specifically mediated by ligand-activated association with Src homology 2 domain-containing protein tyrosine phosphatase. (PMID:21220691)
• We replicated the association of PTPN2 polymorphism with earlier onset of type 1 diabetes and propose that the rs2542151*G allele confers risk to an earlier onset of type 1 diabetes. (PMID:21246196)
• Data suggest association of PTPN2 deletion in T-ALL with activating JAK1 mutations. Data confirm strong association of PTPN2 deletion with TLX1 and NUP214-ABL1 expression. PTPN2 down-regulation reduces lymphoid cell sensitivity to JAK inhibition. (PMID:21551237)
• PTPN2 is a tumor suppressor gene in T-cell malignancies. (PMID:21791476)
• The possibility of cellular phospho-C3G (pC3G) being a substrate of the intracellular T-cell protein tyrosine phosphatase TC-PTP (PTPN2) using the human neuroblastoma cell line, was studied. (PMID:21876762)
• Findings suggest that local IFN production may interact with a genetic factor (PTPN2) to induce aberrant proapoptotic activity of the BH3-only protein Bim, resulting in increased beta-cell apoptosis via JNK activation and the intrinsic apoptotic pathway. (PMID:21984578)
• Loss of PTPN2 is associated with the onset and perpetuation of chronic intestinal inflammation. (PMID:21987459)
• single nucleotide polymorphism in PTPN2 gene is associated with Crohn’s disease. (PMID:22021207)
• c-Src is capable of phosphorylating tyr residues of c-Fos whereas the phosphatase TC45 T-cell protein-tyr phosphatase (TC-PTP) dephosphorylates them (PMID:22105363)
• phospho-Ser727 determines the duration of STAT3 activity largely through TC45. (PMID:22233524)
• An association of the PTPN2 and IL2RA genes with juvenile idiopathic arthritis was found. (PMID:22294642)
• A positive correlation was observed between mRNA expression of PTPN2 and NKX2-3 in B cells and in intestinal tissues from both Crohn’s disease and ulcerative colitis patients. (PMID:22377701)
• Studies indicate that PTP1B and TCPTP act together in vitro and in vivo to regulate insulin receptor (IR) signaling and glucose homeostasis. (PMID:22404968)
• The study indicates that IL23R-rs11805303 and PTPN2-rs2542151 might contribute to the development of ulcerative colitis and NOD2-P268S might be involved in the etiology of Crohn’s disease in the Chinese Han population. (PMID:22426692)
• data confirm the association of PTPN2 variants with susceptibility to both Crohn’s disease and ulcerative colitis, suggesting a common disease pathomechanism for these diseases (PMID:22457781)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpn2a	ENSDARG00000016481
danio_rerio	ptpn2b	ENSDARG00000035986
mus_musculus	Ptpn2	ENSMUSG00000024539
rattus_norvegicus	Ptpn2	ENSRNOG00000017453
drosophila_melanogaster	Ptp61F	FBGN0267487

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), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Tyrosine-protein phosphatase non-receptor type 2 — P17706 (reviewed: P17706)

Alternative names: T-cell protein-tyrosine phosphatase

All UniProt accessions (11): A0A2R8YD79, A8K3N4, P17706, D3DUJ3, K7EIE9, K7EIY0, K7ELS9, K7ENP9, K7EQG9, K7ER87, K7ERU1

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Also plays an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA.

Subunit / interactions. Interacts with RMDN3. Isoform 1 interacts with TMED9. Isoform 1 interacts with STX17; dephosphorylates STX17. Interacts with ITGA1 (via cytoplasmic domain); activates the phosphatase activity towards EGFR. Interacts with TRAF2; probably involved in tumor necrosis factor-mediated signaling. Interacts with MET. Interacts with FAM220A and STAT3; interaction with FAM220A promotes interaction of PTPN2 with transcriptional activator STAT3, leading to dephosphorylation of STAT3 by PTPN2 and negative regulation of STAT3 transcriptional activator activity.

Subcellular location. Endoplasmic reticulum. Endoplasmic reticulum-Golgi intermediate compartment Nucleus. Cytoplasm. Cell membrane.

Tissue specificity. Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta.

Post-translational modifications. Specifically phosphorylated in a cell cycle-dependent manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated through phosphorylation by PKR.

Induction. Up-regulated by IL4/interleukin-4 (at protein level).

Miscellaneous. Minor isoform. Major isoform. Contains a nuclear location signal at positions 377-381 and an autoinhibitory region acting through intramolecular interactions is found at positions 353-387.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P17706-1	1, PTPB, p48TC, TC48, TC-PTPb	yes
P17706-2	2, PTPA, p45TC, TC45, TC-PTPa
P17706-3	3
P17706-4	4

RefSeq proteins (5): NP_001193942, NP_001295216, NP_002819, NP_536347, NP_536348 (=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 (57 total): strand 14, helix 12, modified residue 8, turn 6, mutagenesis site 5, splice variant 3, binding site 3, region of interest 2, chain 1, domain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
7F5O	X-RAY DIFFRACTION	1.7
7F5N	X-RAY DIFFRACTION	1.93
8U0H	X-RAY DIFFRACTION	1.93
9VRR	X-RAY DIFFRACTION	1.95
9VRS	X-RAY DIFFRACTION	2
9UYS	X-RAY DIFFRACTION	2.04
7UAD	X-RAY DIFFRACTION	2.04
9C54	X-RAY DIFFRACTION	2.05
9UZT	X-RAY DIFFRACTION	2.17
9C55	X-RAY DIFFRACTION	2.36
6ZZ4	X-RAY DIFFRACTION	2.43
9C56	X-RAY DIFFRACTION	2.43
1L8K	X-RAY DIFFRACTION	2.56
8UH6	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17706-F1	86.20	0.65

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): 216 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 182; 216–222; 260

Post-translational modifications (8): 68, 216, 293, 298, 304, 304, 22, 52

Mutagenesis-validated functional residues (5):

Position	Phenotype
182	substrate-trapping mutant; catalytically inactive it forms a stable complex with physiological substrates including insr
222	impairs phosphatase activity.
304	alters phosphorylation by cyclin-dependent kinases of isoform 2 but has no effect on its phosphatase activity.
350–352	alters location to the endoplasmic reticulum; isoform 1.
380	prevents location to the nucleus; isoform 2.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6807004	Negative regulation of MET activity
R-HSA-9008059	Interleukin-37 signaling
R-HSA-9833482	PKR-mediated signaling
R-HSA-877312	Regulation of IFNG signaling

MSigDB gene sets: 629 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LIPID_STORAGE, AAGCAAT_MIR137, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION

GO Biological Process (36): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of cell population proliferation (GO:0008285), insulin receptor signaling pathway (GO:0008286), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), negative regulation of lipid storage (GO:0010888), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), erythrocyte differentiation (GO:0030218), peptidyl-tyrosine dephosphorylation (GO:0035335), insulin receptor recycling (GO:0038020), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), negative regulation of tyrosine phosphorylation of STAT protein (GO:0042532), glucose homeostasis (GO:0042593), negative regulation of macrophage differentiation (GO:0045650), positive regulation of gluconeogenesis (GO:0045722), negative regulation of receptor signaling pathway via JAK-STAT (GO:0046426), negative regulation of insulin receptor signaling pathway (GO:0046627), negative regulation of inflammatory response (GO:0050728), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of chemotaxis (GO:0050922), regulation of type II interferon-mediated signaling pathway (GO:0060334), negative regulation of type II interferon-mediated signaling pathway (GO:0060336), negative regulation of type I interferon-mediated signaling pathway (GO:0060339), negative regulation of interleukin-6-mediated signaling pathway (GO:0070104), negative regulation of ERK1 and ERK2 cascade (GO:0070373), regulation of hepatocyte growth factor receptor signaling pathway (GO:1902202), negative regulation of interleukin-2-mediated signaling pathway (GO:1902206), negative regulation of interleukin-4-mediated signaling pathway (GO:1902215), negative regulation of macrophage colony-stimulating factor signaling pathway (GO:1902227), negative regulation of positive thymic T cell selection (GO:1902233), positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902237), positive regulation of PERK-mediated unfolded protein response (GO:1903899), negative regulation of platelet-derived growth factor receptor-beta signaling pathway (GO:2000587), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311), regulation of type I interferon-mediated signaling pathway (GO:0060338)

GO Molecular Function (11): protein tyrosine phosphatase activity (GO:0004725), non-membrane spanning protein tyrosine phosphatase activity (GO:0004726), integrin binding (GO:0005178), protein kinase binding (GO:0019901), syntaxin binding (GO:0019905), receptor tyrosine kinase binding (GO:0030971), STAT family protein binding (GO:0097677), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome lumen (GO:0031904), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by MET	1
Interleukin-1 family signaling	1
Antimicrobial mechanism of IFN-stimulated genes	1
Interferon gamma signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membrane-bounded organelle	3
cytoplasm	3
negative regulation of cellular process	2
lymphocyte differentiation	2
negative regulation of response to external stimulus	2
signaling receptor binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
regulation of lipid storage	1
lipid storage	1
negative regulation of lipid localization	1
B cell activation	1
T cell activation	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
protein dephosphorylation	1
receptor recycling	1
positive regulation of insulin receptor signaling pathway	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
tyrosine phosphorylation of STAT protein	1
regulation of tyrosine phosphorylation of STAT protein	1
negative regulation of receptor signaling pathway via JAK-STAT	1
negative regulation of peptidyl-tyrosine phosphorylation	1
carbohydrate homeostasis	1
negative regulation of myeloid leukocyte differentiation	1
macrophage differentiation	1
regulation of macrophage differentiation	1
gluconeogenesis	1
regulation of gluconeogenesis	1

Protein interactions and networks

STRING

2336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN2	PTS	Q03393	823
PTPN2	RMDN3	Q96TC7	763
PTPN2	NKX2-3	Q8TAU0	746
PTPN2	CLEC16A	Q2KHT3	692
PTPN2	JAK3	P52333	690
PTPN2	IFIH1	Q9BYX4	683
PTPN2	IL2RA	P01589	678
PTPN2	TAGAP	Q8N103	667
PTPN2	SH2B3	Q9UQQ2	663
PTPN2	TLX1	P31314	659
PTPN2	STAT4	Q14765	654
PTPN2	BACH2	Q9BYV9	653
PTPN2	KDR	P35968	651
PTPN2	NUP214	P35658	644
PTPN2	IRGM	A1A4Y4	630

IntAct

83 interactions, top by confidence:

A	B	Type	Score
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
CDC42	WASL	psi-mi:“MI:0217”(phosphorylation reaction)	0.750
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
PTPN2	GHR	psi-mi:“MI:0407”(direct interaction)	0.650
PTPN2	GHR	psi-mi:“MI:0203”(dephosphorylation reaction)	0.650
PTPN2	GHR	psi-mi:“MI:0915”(physical association)	0.650
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
KLRG2	GLRX3	psi-mi:“MI:0914”(association)	0.640
SDF2L1	OLFM2	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
PTPN2	COL5A1	psi-mi:“MI:0915”(physical association)	0.590
	PTPN2	psi-mi:“MI:0915”(physical association)	0.560
PTPN2		psi-mi:“MI:0915”(physical association)	0.560
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ASGR1	PTPN2	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530

BioGRID (286): PTPN2 (Affinity Capture-MS), COL5A1 (Affinity Capture-MS), PTPN2 (Co-fractionation), PTPN2 (Co-fractionation), VARS (Co-fractionation), PTPN2 (Proximity Label-MS), PTPN2 (Proximity Label-MS), PTPN2 (Proximity Label-MS), PTPN2 (Affinity Capture-MS), PTPN2 (Affinity Capture-MS), APLP2 (Affinity Capture-MS), APP (Affinity Capture-MS), CALU (Affinity Capture-MS), CASC4 (Affinity Capture-MS), CSPG5 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PPP7, F1NV61, O01382, O08738, O35397, O75601, O88600, O95757, P00860, P11926, P14019, P17706, P27117, P27119, P27120, P29452, P29466, P34932, P35233, P42574, P43527, P48722, P55210, P55212, P55213, P55214, P55866, P70677, P89116, P97864, Q06180, Q08DY9, Q14790, Q2PFV2, Q2TFN9, Q3T0P5, Q5E9C1, Q5IS54, Q5IS99, Q5RDM4

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

55 interactions.

A	Effect	B	Mechanism
PTPN2	down-regulates	EGFR	dephosphorylation
CDK1	unknown	PTPN2	phosphorylation
CDK2	unknown	PTPN2	phosphorylation
PTPN2	“down-regulates activity”	JAK3	dephosphorylation
PTPN2	“down-regulates activity”	STAT1	dephosphorylation
PTPN2	“down-regulates activity”	STAT5A	dephosphorylation
PTPN2	“down-regulates activity”	JAK1	dephosphorylation
PTPN2	down-regulates	WASL	dephosphorylation
PTPN2	down-regulates	FYN	dephosphorylation
PTPN2	down-regulates	SRC	dephosphorylation
PTPN2	down-regulates	INSR	dephosphorylation
PTPN2	down-regulates	MET	dephosphorylation
PTPN2	down-regulates	KDR	dephosphorylation
PTPN2	up-regulates	GJA1	dephosphorylation
PTPN2	“down-regulates activity”	STAT6	dephosphorylation
PTPN2	“down-regulates activity”	INSR	dephosphorylation
PTPN2	“down-regulates activity”	MET	dephosphorylation
PTPN2	“down-regulates activity”	SHC1	dephosphorylation
PTPN2	unknown	KDR	dephosphorylation
PTPN2	“down-regulates activity”	KDR	dephosphorylation
PTPN2	down-regulates	AKT1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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
Regulation of activated PAK-2p34 by proteasome mediated degradation	5	21.8×	1e-04
Regulation of ornithine decarboxylase (ODC)	5	21.2×	1e-04
Vpu mediated degradation of CD4	5	20.8×	1e-04
Autodegradation of the E3 ubiquitin ligase COP1	5	20.8×	1e-04
Ubiquitin-dependent degradation of Cyclin D	5	20.8×	1e-04
Cross-presentation of soluble exogenous antigens (endosomes)	5	19.8×	1e-04
Vif-mediated degradation of APOBEC3G	5	19.8×	1e-04
AUF1 (hnRNP D0) binds and destabilizes mRNA	5	19.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2535 predictions. Top by Δscore:

Variant	Effect	Δscore
18:12801964:GCTTA:G	donor_loss	1.0000
18:12801965:CTTA:C	donor_loss	1.0000
18:12801966:TTAC:T	donor_loss	1.0000
18:12801967:TA:T	donor_loss	1.0000
18:12801968:A:AC	donor_gain	1.0000
18:12801968:ACCTC:A	donor_loss	1.0000
18:12801969:C:CA	donor_loss	1.0000
18:12801969:C:CC	donor_gain	1.0000
18:12801969:CCT:C	donor_gain	1.0000
18:12801969:CCTCT:C	donor_gain	1.0000
18:12802147:CGTTT:C	acceptor_gain	1.0000
18:12802148:GTTT:G	acceptor_gain	1.0000
18:12802149:TTT:T	acceptor_gain	1.0000
18:12802149:TTTCT:T	acceptor_loss	1.0000
18:12802150:TT:T	acceptor_gain	1.0000
18:12802150:TTC:T	acceptor_loss	1.0000
18:12802151:TCT:T	acceptor_loss	1.0000
18:12802152:C:CC	acceptor_gain	1.0000
18:12802152:C:CG	acceptor_loss	1.0000
18:12802156:G:C	acceptor_gain	1.0000
18:12802156:G:GC	acceptor_gain	1.0000
18:12802169:A:AC	acceptor_gain	1.0000
18:12802169:A:C	acceptor_gain	1.0000
18:12814219:C:CA	donor_gain	1.0000
18:12814355:TC:T	acceptor_loss	1.0000
18:12814356:C:A	acceptor_loss	1.0000
18:12814356:C:CC	acceptor_gain	1.0000
18:12814357:T:A	acceptor_loss	1.0000
18:12825808:A:AC	donor_gain	1.0000
18:12825809:C:CC	donor_gain	1.0000

AlphaMissense

2751 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:12814267:A:G	L265P	1.000
18:12814281:C:A	Q260H	1.000
18:12814281:C:G	Q260H	1.000
18:12814288:A:G	L258P	1.000
18:12814297:C:A	R255L	1.000
18:12814297:C:G	R255P	1.000
18:12814298:G:C	R255G	1.000
18:12814305:T:A	R252S	1.000
18:12814305:T:G	R252S	1.000
18:12814306:C:A	R252I	1.000
18:12814306:C:G	R252T	1.000
18:12817178:A:G	L228P	1.000
18:12817190:C:A	G224V	1.000
18:12817190:C:T	G224D	1.000
18:12817191:C:G	G224R	1.000
18:12817193:G:A	S223F	1.000
18:12817193:G:T	S223Y	1.000
18:12817196:C:A	R222L	1.000
18:12817196:C:G	R222P	1.000
18:12817196:C:T	R222H	1.000
18:12817197:G:A	R222C	1.000
18:12817197:G:C	R222G	1.000
18:12817197:G:T	R222S	1.000
18:12817199:C:A	G221V	1.000
18:12817199:C:G	G221A	1.000
18:12817199:C:T	G221E	1.000
18:12817200:C:A	G221W	1.000
18:12817200:C:G	G221R	1.000
18:12817200:C:T	G221R	1.000
18:12817202:A:T	I220N	1.000

dbSNP variants (sampled 300 via entrez): RS1000031656 (18:12858726 T>C), RS1000057851 (18:12792505 T>A), RS1000116700 (18:12874819 A>G), RS1000163459 (18:12883694 G>A), RS1000173518 (18:12844752 C>T), RS1000208857 (18:12821132 T>C), RS1000210452 (18:12803342 A>C,G), RS1000232827 (18:12809242 G>T), RS1000245304 (18:12880739 T>C,G), RS1000251607 (18:12864616 T>A), RS1000300441 (18:12868913 G>A), RS1000309935 (18:12880814 A>T), RS1000330338 (18:12798088 G>T), RS1000340578 (18:12881042 A>G), RS1000352460 (18:12796887 G>A)

Disease associations

OMIM: gene MIM:176887 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory syndrome of childhood	Strong	Autosomal dominant

Mondo (1): autoinflammatory syndrome of childhood (MONDO:0957018)

Orphanet (0):

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000554	Uveitis
HP:0000572	Visual loss
HP:0000585	Band keratopathy
HP:0001094	Iridocyclitis
HP:0001155	Abnormality of the hand
HP:0001369	Arthritis
HP:0001370	Rheumatoid arthritis
HP:0001371	Flexion contracture
HP:0001382	Joint hypermobility
HP:0001384	Abnormal hip joint morphology
HP:0001386	Joint swelling
HP:0001387	Joint stiffness
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001530	Mild postnatal growth retardation
HP:0001785	Ankle swelling
HP:0001824	Weight loss
HP:0001832	Abnormal metatarsal morphology
HP:0001903	Anemia
HP:0002716	Lymphadenopathy
HP:0002829	Arthralgia
HP:0002960	Autoimmunity
HP:0003019	Abnormality of the wrist
HP:0003028	Abnormality of the ankle
HP:0003043	Abnormal shoulder morphology
HP:0003319	Abnormality of the cervical spine
HP:0003326	Myalgia
HP:0003493	Antinuclear antibody positivity

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST000038_6	Type 1 diabetes	1.000000e-14
GCST000039_2	Crohn’s disease	3.000000e-08
GCST000042_7	Crohn’s disease	2.000000e-07
GCST000207_7	Crohn’s disease	5.000000e-17
GCST000258_10	Type 1 diabetes	9.000000e-08
GCST000392_5	Type 1 diabetes	4.000000e-15
GCST000612_8	Celiac disease	3.000000e-10
GCST000879_52	Crohn’s disease	1.000000e-14
GCST000965_14	C-reactive protein levels	2.000000e-08
GCST000987_5	Celiac disease or Rheumatoid arthritis	5.000000e-12
GCST001191_22	Type 1 diabetes	4.000000e-13
GCST001454_9	Rheumatoid arthritis	2.000000e-08
GCST001674_6	Esophageal cancer (squamous cell)	2.000000e-11
GCST002318_77	Rheumatoid arthritis	8.000000e-09
GCST002318_93	Rheumatoid arthritis	6.000000e-18
GCST002318_94	Rheumatoid arthritis	2.000000e-11
GCST002783_372	Body mass index	4.000000e-06
GCST002783_505	Body mass index	8.000000e-06
GCST002831_12	Lead levels in blood	2.000000e-07
GCST003814_12	Selective IgA deficiency	1.000000e-06
GCST004131_44	Inflammatory bowel disease	1.000000e-16
GCST004132_21	Crohn’s disease	1.000000e-20
GCST004346_60	Psoriasis	1.000000e-10
GCST004866_16	Alopecia areata	6.000000e-07
GCST005523_36	Celiac disease	2.000000e-10
GCST005528_10	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	1.000000e-12
GCST005528_5	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	5.000000e-07
GCST005536_15	Type 1 diabetes	1.000000e-15
GCST005536_16	Type 1 diabetes	2.000000e-06
GCST005537_39	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-26

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004340	body mass index
EFO:0009933	Thyroid preparation use measurement
EFO:0004509	hemoglobin measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004348	hematocrit
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3807 (SINGLE PROTEIN), CHEMBL5465207 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465229 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 62,800 (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
CHEMBL169	URSOLIC ACID	2	20,825
CHEMBL284616	CHLOROGENIC ACID	2	41,945
CHEMBL5095164	OSUNPROTAFIB	2	22
CHEMBL5314543	TEGEPROTAFIB	2	8

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7234029	PTPN2		0.00	0
rs11664064	PTPN2		0.00	0

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 182 [PMID: 37500611]	Inhibition	9.24	pIC50

Binding affinities (BindingDB)

73 measured of 124 human assays (125 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
({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-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
3-({5-[(N-Acetyl-3-{4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-1-naphthyl}-L-alanyl)amino]pentyl}oxy)-2-naphthoic Acid	KI	22 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
1:1 mixture of diastereomers	KI	76 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
({4-[(4E)-2-(1H-1,2,3-benzotriazol-1-yl)-2,5-diphenylpent-4-en-1-yl]phenyl}difluoromethyl)phosphonic acid	IC50	109 nM
1:1 mixture of diastereomers	KI	120 nM
1:1 mixture of diastereomers	KI	130 nM
4-bromo-3-(carboxymethoxy)-5-[4-(2-formamidoacetic acid)phenyl]thiophene-2-carboxylic acid	KI	140 nM
1:1 mixture of diastereomers	KI	140 nM
[difluoro({4-[3-(4-fluorophenyl)-2-[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-3-oxo-2-[(2E)-3-phenylprop-2-en-1-yl]propyl]phenyl})methyl]phosphonic acid	IC50	163 nM
2-{[2-(2-Carbamoylvinyl)-4-(2-(S)-methanesulfonylamino 2-pentylcarbamoylethyl)phenyl]oxalylamino}-benzoic Acid	KI	170 nM
5-bromo-6-[difluoro(phosphono)methyl]-1-benzothiophene-2-carboxylic acid	IC50	170 nM	US-10150787: TC-PTP inhibitors as APC activators for immunotherapy
1:1 mixture of diastereomers	KI	250 nM
6-bromo-5-[difluoro(phosphono)methyl]-1-benzothiophene-2-carboxylic acid	IC50	260 nM	US-10150787: TC-PTP inhibitors as APC activators for immunotherapy
[(6-bromo-2-carbamoyl-1-benzothiophen-5-yl)-difluoromethyl]phosphonic acid	IC50	280 nM	US-10150787: TC-PTP inhibitors as APC activators for immunotherapy
1:1 mixture of diastereomers	KI	330 nM
5-(carboxymethoxy)-10-{[1-(phenylmethane)sulfonylpiperidin-4-yl]amino}-3,7-dithiatricyclo[6.4.0.0^{2,6}]dodeca-1(8),2(6),4,9,11-pentaene-4-carboxylic acid	KI	370 nM
[[6-bromo-2-(cyanomethyl)-1-benzothiophen-5-yl]-difluoromethyl]phosphonic acid	IC50	370 nM	US-10150787: TC-PTP inhibitors as APC activators for immunotherapy
1:1 mixture of diastereomers	KI	430 nM
[(6-bromo-2-ethoxycarbonyl-1-benzothiophen-5-yl)-difluoromethyl]phosphonic acid	IC50	450 nM	US-10150787: TC-PTP inhibitors as APC activators for immunotherapy
1:1 mixture of diastereomers	KI	470 nM
(3-bromo-7-cyanonaphthalen-2-yl)difluoromethylphosphonic acid	IC50	490 nM	US-10150787: TC-PTP inhibitors as APC activators for immunotherapy
2-{[4-(2-acetamido-2-{[(4-nitrophenyl)methyl]carbamoyl}ethyl)-2-ethylphenyl]amidoformic acid}benzoic acid	KI	540 nM
1:1 mixture of diastereomers	KI	540 nM
[[4-[2-acetamido-3-[[1-amino-6-[(4-ethylbenzoyl)amino]-1-oxohexan-2-yl]amino]-3-oxopropyl]phenyl]-difluoromethyl]phosphonic acid	KI	700 nM	US-9217012: Inhibitors of protein tyrosine phosphatases
1:1 mixture of diastereomers	KI	710 nM
[(5-bromo-2-ethoxycarbonyl-1-benzothiophen-6-yl)-difluoromethyl]phosphonic acid	IC50	740 nM	US-10150787: TC-PTP inhibitors as APC activators for immunotherapy
4-bromo-3-(carboxymethoxy)-5-[4-(pyridine-3-amido)phenyl]thiophene-2-carboxylic acid	KI	820 nM
5-{3-[(1E)-3-[3-hydroxy-2-(methoxycarbonyl)phenoxy]prop-1-en-1-yl]phenyl}-4-(hydroxymethyl)-1,2-oxazole-3-carboxylic acid	KI	920 nM
2-({4-[2-acetamido-2-(pentylcarbamoyl)ethyl]naphthalen-1-yl}amidoformic acid)benzoic acid	KI	1100 nM
2-({4-[2-acetamido-2-(pentylcarbamoyl)ethyl]-2-ethylphenyl}amidoformic acid)benzoic acid	KI	1200 nM
1:1 racemic mixture	KI	1200 nM
2-{[4-(2-{[(4-chlorophenyl)methyl]carbamoyl}-2-acetamidoethyl)-2-ethylphenyl]amidoformic acid}benzoic acid	KI	1200 nM

ChEMBL bioactivities

658 potent at pChembl≥5 of 1009 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.24	IC50	0.58	nM	CHEMBL5619806
9.24	IC50	0.58	nM	CHEMBL6177218
9.22	IC50	0.6	nM	CHEMBL5619806
9.00	IC50	1	nM	CHEMBL5084112
9.00	IC50	1	nM	CHEMBL5076419
9.00	IC50	1	nM	CHEMBL6174300
9.00	Ki	1	nM	CHEMBL6175998
9.00	IC50	1	nM	CHEMBL6175073
9.00	IC50	1	nM	CHEMBL6175327
9.00	IC50	1	nM	TEGEPROTAFIB
9.00	IC50	1	nM	CHEMBL6171763
8.87	IC50	1.34	nM	CHEMBL6176656
8.74	IC50	1.8	nM	OSUNPROTAFIB
8.70	Ki	2	nM	CHEMBL395722
8.70	Ki	2	nM	CHEMBL230862
8.70	Ki	2	nM	CHEMBL230860
8.70	Ki	2	nM	CHEMBL230751
8.70	IC50	2	nM	CHEMBL5618445
8.70	IC50	2	nM	CHEMBL6170604
8.66	IC50	2.2	nM	OSUNPROTAFIB
8.60	IC50	2.5	nM	CHEMBL6165237
8.59	IC50	2.6	nM	CHEMBL5618850
8.55	IC50	2.8	nM	OSUNPROTAFIB
8.52	IC50	3	nM	CHEMBL269166
8.41	IC50	3.9	nM	CHEMBL5619195
8.40	IC50	4	nM	CHEMBL267488
8.40	Ki	4	nM	CHEMBL230645
8.40	IC50	4	nM	CHEMBL6142696
8.39	Ki	4.1	nM	CHEMBL3969776
8.37	Ki	4.3	nM	CHEMBL3969776
8.37	IC50	4.3	nM	CHEMBL5564604
8.37	Ki	4.3	nM	CHEMBL6168592
8.36	IC50	4.4	nM	CHEMBL6147388
8.35	IC50	4.5	nM	CHEMBL5562964
8.35	IC50	4.5	nM	CHEMBL5557812
8.35	IC50	4.5	nM	CHEMBL6172893
8.30	Ki	5	nM	CHEMBL397415
8.30	Ki	5	nM	CHEMBL243267
8.30	Ki	5	nM	CHEMBL541214
8.30	IC50	5	nM	CHEMBL5561163
8.30	Ki	5	nM	CHEMBL5618189
8.30	Ki	5	nM	CHEMBL6166197
8.30	IC50	5	nM	CHEMBL6170036
8.30	IC50	5	nM	CHEMBL6171780
8.25	IC50	5.67	nM	CHEMBL6174930
8.22	Ki	6	nM	CHEMBL387614
8.22	Ki	6	nM	CHEMBL390245
8.22	IC50	6.04	nM	CHEMBL5559694
8.22	IC50	6	nM	CHEMBL6176576
8.15	IC50	7.1	nM	CHEMBL5423615

PubChem BioAssay actives

586 with measured affinity, of 1506 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
5-[1-fluoro-3-hydroxy-7-(3-hydroxy-3-methylbutoxy)naphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0006	uM
5-[7-(1-cyclopropylsulfonylpyrrolidin-3-yl)-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[1-fluoro-3-hydroxy-7-(oxan-3-ylmethoxy)naphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (unknown origin) by Mobility shift assay	ic50	0.0010	uM
5-[7-[2-(azetidin-1-yl)ethylamino]-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (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	1808174: Inhibition of PTPN2 (unknown origin) by Mobility shift assay	ic50	0.0010	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	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0018	uM
5-[4-[2-[(3R)-3-ethylpyrrolidin-1-yl]ethyl]-2-fluoro-6-hydroxyphenyl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0020	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[[2-(trifluoromethyl)phenyl]methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0020	uM
5-[3-[[1-[(2-aminophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]-4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0020	uM
5-[3-[[1-[(2-acetamidophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]-4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0020	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[[2-(methanesulfonamido)phenyl]methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0020	uM
[3-[4-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]phenyl]phosphonic acid	1309448: Inhibition of TCPTP (unknown origin) by UV/Vis spectrophotometry	ic50	0.0030	uM
5-[7-(cyclopropylmethylamino)-1-fluoro-3-hydroxynaphthalen-2-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0039	uM
[[4-[2-(benzotriazol-1-yl)-3-[3-bromo-4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]-difluoromethyl]phosphonic acid	209828: Inhibitory activity against T cell protein tyrosine phosphatase	ic50	0.0040	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-chlorophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0040	uM
5-[3-(2-cyclopropylethyl)-6-fluoro-8-hydroxy-1,2,4,5-tetrahydro-3-benzazepin-7-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084062: Inhibition of human PTPN2 using DiFMUP as substrate by fluorescence based phosphatase assay	ic50	0.0043	uM
5-(6-fluoro-8-hydroxy-3-methyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084062: Inhibition of human PTPN2 using DiFMUP as substrate by fluorescence based phosphatase assay	ic50	0.0045	uM
5-[3-(3-cyclopropylpropyl)-6-fluoro-8-hydroxy-1,2,4,5-tetrahydro-3-benzazepin-7-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084062: Inhibition of human PTPN2 using DiFMUP as substrate by fluorescence based phosphatase assay	ic50	0.0045	uM
5-[3-[(1-benzylsulfonylpiperidin-4-yl)amino]phenyl]-4-bromo-3-(carboxymethoxy)thiophene-2-carboxylic acid	2129504: Binding affinity to PTPN2 (unknown origin) assessed as inhibition constant	ki	0.0050	uM
1-cyclohexyl-3-[3-fluoro-5-hydroxy-4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)phenyl]urea	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0050	uM
5-(6-fluoro-8-hydroxy-4-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084062: Inhibition of human PTPN2 using DiFMUP as substrate by fluorescence based phosphatase assay	ic50	0.0050	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-methylphenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0050	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-methoxyphenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0050	uM
5-[3-(cyclopropylmethyl)-6-fluoro-8-hydroxy-1,2,4,5-tetrahydro-3-benzazepin-7-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084062: Inhibition of human PTPN2 using DiFMUP as substrate by fluorescence based phosphatase assay	ic50	0.0060	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-chlorophenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0060	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2-methylphenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0060	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	2038374: Inhibition of PTPN2 (unknown origin) using pNPP as substrate by spectrophotometric analysis	ic50	0.0071	uM
[(3-bromo-7-cyanonaphthalen-2-yl)-difluoromethyl]phosphonic acid	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0071	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2,6-dimethylphenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0080	uM
[[4-[2-(benzotriazol-1-yl)-2-(3,4-difluorophenyl)-3-[4-[difluoro(phosphono)methyl]phenyl]propyl]phenyl]-difluoromethyl]phosphonic acid	209828: Inhibitory activity against T cell protein tyrosine phosphatase	ic50	0.0080	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	2084082: Binding affinity to human PTPN2 assessed as dissociation constant measured upto 300 secs by SPR analysis	kd	0.0087	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(3-chlorophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0090	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(2,6-dimethylphenyl)carbamoyl]piperidin-4-yl]methylamino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0090	uM
5-(6-fluoro-8-hydroxy-3-propan-2-yl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084062: Inhibition of human PTPN2 using DiFMUP as substrate by fluorescence based phosphatase assay	ic50	0.0092	uM
5-(4-ethyl-6-fluoro-8-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2084062: Inhibition of human PTPN2 using DiFMUP as substrate by fluorescence based phosphatase assay	ic50	0.0097	uM
5-[(3S)-3-(4,4-difluorobutylamino)-5-fluoro-7-hydroxy-3,4-dihydro-2H-thiochromen-6-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0100	uM
5-[2-fluoro-6-hydroxy-4-[(6-methyl-1,4,5,6-tetrahydropyrimidin-2-yl)amino]phenyl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0100	uM
5-[(2R)-2-(3,3-difluoropropylamino)-4-fluoro-6-hydroxy-2,3-dihydro-1H-indol-5-yl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2129506: Inhibition of PTPN2 (unknown origin)	ic50	0.0100	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[(4-chlorophenyl)methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0100	uM
[[4-[(E)-2-(benzotriazol-1-yl)-5-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpent-4-enyl]phenyl]-difluoromethyl]phosphonic acid	209828: Inhibitory activity against T cell protein tyrosine phosphatase	ic50	0.0100	uM
[[4-[2-(benzotriazol-1-yl)-3-[4-[difluoro(phosphono)methyl]phenyl]-2-phenylpropyl]phenyl]-difluoromethyl]phosphonic acid	209828: Inhibitory activity against T cell protein tyrosine phosphatase	ic50	0.0100	uM
5-(7-bromo-1-fluoro-3-hydroxynaphthalen-2-yl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one	2038378: Inhibition of PTPN2 (unknown origin) using DiFMUP as substrate by absorbance based assay	ic50	0.0114	uM
4-bromo-3-(carboxymethoxy)-5-[3-[[1-[[2-(ethylcarbamoylamino)phenyl]methylsulfonyl]piperidin-4-yl]amino]phenyl]thiophene-2-carboxylic acid	297807: Inhibition of human recombinant TCPTP	ki	0.0120	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, decreases expression	3
bisphenol A	decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Hydrogen Peroxide	increases expression, decreases activity, increases oxidation, affects cotreatment, increases chemical synthesis (+1 more)	2
Nickel	increases expression	2
Vanadates	decreases activity, decreases reaction, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
quinone	affects cotreatment, increases chemical synthesis, increases metabolic processing, affects binding, decreases activity (+1 more)	1
nitrophenylphosphate	increases hydrolysis, decreases reaction	1
titanium dioxide	increases methylation	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
plumbagin	affects binding, decreases activity	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	increases phosphorylation	1
anthranilic acid	decreases activity, affects binding	1
hydroquinone	affects cotreatment, decreases activity, increases chemical synthesis, increases metabolic processing	1
oxovanadium IV	affects binding, decreases activity	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
bisperoxovanadium	affects reaction, increases expression	1
torcetrapib	increases expression	1
ICG 001	decreases expression	1
salicylideneaniline	affects binding, decreases activity	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1

ChEMBL screening assays

250 unique, capped per target: 246 binding, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1038653	Binding	Inhibition of TC-PTP	Thiazolidinedione derivatives as PTP1B inhibitors with antihyperglycemic and antiobesity effects. — Bioorg Med Chem Lett
CHEMBL4039108	ADMET	Inhibition of human recombinant TCPTP (1 to 317 residues) expressed in Escherichia coli using pNPP as substrate preincubated for 10 mins followed by substrate addition measured after 30 mins	A bromopyrrole-containing diterpene alkaloid from the Okinawan marine sponge Agelas nakamurai activates the insulin pathway in Huh-7 human hepatoma cells by inhibiting protein tyrosine phosphatase 1B. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0Z8	Abcam Jurkat PTPN2 KO	Cancer cell line	Male
CVCL_B8NH	Abcam HCT 116 PTPN2 KO	Cancer cell line	Male
CVCL_B9AV	Abcam MCF-7 PTPN2 KO	Cancer cell line	Female
CVCL_B9QS	Abcam A-549 PTPN2 KO	Cancer cell line	Male
CVCL_D7YZ	Ubigene A-549 PTPN2 KO	Cancer cell line	Male
CVCL_D8UA	Ubigene HCT 116 PTPN2 KO	Cancer cell line	Male
CVCL_D9Q4	Ubigene HEK293 PTPN2 KO	Transformed cell line	Female
CVCL_E0MA	Ubigene HeLa PTPN2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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