PTPN6

Summary

PTPN6 (protein tyrosine phosphatase non-receptor type 6, HGNC:9658) is a protein-coding gene on chromosome 12p13.31, encoding Tyrosine-protein phosphatase non-receptor type 6 (P29350). Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis.

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported.

Source: NCBI Gene 5777 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 98 total
• Phenotypes (HPO): 39
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_002831

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9658
Approved symbol	PTPN6
Name	protein tyrosine phosphatase non-receptor type 6
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	HCP, HCPH, PTP-1C, SHP-1, SHP1
Ensembl gene	ENSG00000111679
Ensembl biotype	protein_coding
OMIM	176883
Entrez	5777

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 11 protein_coding, 6 retained_intron, 6 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000318974, ENST00000399448, ENST00000416215, ENST00000456013, ENST00000534900, ENST00000535462, ENST00000536013, ENST00000536521, ENST00000537533, ENST00000538318, ENST00000538715, ENST00000539029, ENST00000539365, ENST00000540740, ENST00000541698, ENST00000542277, ENST00000542462, ENST00000542761, ENST00000542848, ENST00000543115, ENST00000543120, ENST00000543744, ENST00000545153, ENST00000877771, ENST00000877772, ENST00000877773, ENST00000911913

RefSeq mRNA: 3 — MANE Select: NM_002831 NM_002831, NM_080548, NM_080549

CCDS: CCDS41744, CCDS44820, CCDS44821

Canonical transcript exons

ENST00000318974 — 16 exons

Exon	Start	End
ENSE00001365384	6961126	6961316
ENSE00002317640	6951356	6951520
ENSE00003483795	6960344	6960435
ENSE00003490595	6954805	6954994
ENSE00003512700	6956419	6956568
ENSE00003543362	6957654	6957785
ENSE00003556808	6956142	6956221
ENSE00003580194	6955151	6955267
ENSE00003609788	6960088	6960239
ENSE00003637807	6951983	6952177
ENSE00003638374	6955372	6955485
ENSE00003639748	6960806	6960945
ENSE00003645346	6959927	6959994
ENSE00003670762	6955660	6955756
ENSE00003681310	6957919	6958073
ENSE00003695232	6951609	6951731

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.8649 / max 1018.8852, expressed in 1081 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123855	21.0613	504
123854	2.8655	419
123851	1.6358	637
123850	1.3856	545
123853	0.9785	290
123866	0.4077	162
123852	0.1739	84
123856	0.1645	84
123867	0.1278	58
123857	0.0497	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.47	gold quality
spleen	UBERON:0002106	99.04	gold quality
monocyte	CL:0000576	99.02	gold quality
leukocyte	CL:0000738	98.99	gold quality
mononuclear cell	CL:0000842	98.96	gold quality
blood	UBERON:0000178	98.63	gold quality
bone marrow cell	CL:0002092	98.16	gold quality
vermiform appendix	UBERON:0001154	97.98	gold quality
lymph node	UBERON:0000029	97.68	gold quality
bone marrow	UBERON:0002371	96.53	gold quality
mucosa of transverse colon	UBERON:0004991	96.18	gold quality
caecum	UBERON:0001153	96.00	gold quality
right lung	UBERON:0002167	95.76	gold quality
upper lobe of left lung	UBERON:0008952	95.70	gold quality
upper lobe of lung	UBERON:0008948	94.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.76	gold quality
trabecular bone tissue	UBERON:0002483	94.02	gold quality
small intestine	UBERON:0002108	93.01	gold quality
right adrenal gland	UBERON:0001233	92.73	gold quality
right adrenal gland cortex	UBERON:0035827	92.62	gold quality
rectum	UBERON:0001052	92.28	gold quality
right uterine tube	UBERON:0001302	92.23	gold quality
left adrenal gland cortex	UBERON:0035825	92.10	gold quality
right lobe of liver	UBERON:0001114	91.99	gold quality
left adrenal gland	UBERON:0001234	91.98	gold quality
tonsil	UBERON:0002372	91.96	gold quality
gall bladder	UBERON:0002110	91.81	gold quality
metanephros cortex	UBERON:0010533	91.60	gold quality
transverse colon	UBERON:0001157	91.33	gold quality
adrenal cortex	UBERON:0001235	91.29	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	23.93
E-MTAB-6701	yes	20.93
E-CURD-112	yes	11.45
E-HCAD-6	no	143.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, DNMT1, ESR1, FLT3, FOS, FOXC1, HNF1A, HNF4A, JUN, MBD2, NFKB1, NPM1, NR0B2, PAX1, PBX1, PKNOX1, RELA, RFX1, SPI1, STAT1, STAT3, TCF12, TCF3, TFAP4, TFCP2, TP53, USF1, USF2

miRNA regulators (miRDB)

12 targeting PTPN6, 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-6764-5P	99.75	67.89	2304
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-7156-3P	98.25	67.66	859

Literature-anchored findings (GeneRIF, showing 40)

• The Lyn/CD22/SHP-1 pathway is important in autoimmunity. Naive and tolerant B-cells differ in their calcium signaling in response to antigenic stimulation. (PMID:11826756)
• peripheral blood monocytes treated for 5–8 days with GM-CSF (i.e. mature Mphi) acquired the capacity to assemble tyrosine phosphatase SHP-1 with CD9, alpha3-beta1 integrin and their CD46. (PMID:11858824)
• SHP-1 is recruited to the NK cell immune synapse within 1 min in both cytolytic and noncytolytic conjugates, allowing clear distinction between noncytolytic and cytolytic interactions at this early time. (PMID:11907066)
• interacts with siglec-11 (PMID:11986327)
• evidence of cytokine-regulated SHP-1 nuclear localization mediated by a bipartite nuclear localization signal, suggesting that SHP-1 regulates nuclear signaling in cell growth control. (PMID:11987243)
• ILT2 triggering on cutaneous T-cell lymphoma (CTCL) cells leads to the recruitment of SHP-1 and to the specific inhibition of CTCL malignant cell proliferation in Sezary syndrome induced by CD3/T-cell receptor. (TCR) stimulation. (PMID:12130517)
• In the T cell line HUT-78, JAK3 was found to be highly phosphorylated. These results suggest that SHP-1 might be involved in maintaining the IL-2R/JAK3 signaling pathway under control and point towards a role of SHP-1 in the pathogenesis of the disease. (PMID:12145687)
• Functional loss of SHP1 is associated with the pathogenesis of leukemias/lymphomas. (PMID:12438221)
• participation in regulation of Stat6 dephosphorylation (PMID:12459556)
• crystal structure of the C-terminal truncated human SHP-1 in the inactive conformation at 2.8-A resolution and refined the structure to a crystallographic R-factor of 24.0% (PMID:12482860)
• SHP-1 may be involved in the regulation of beta-catenin transcriptional function and in the negative control of intestinal epithelial cell proliferation (PMID:12571228)
• show the existence of multiple transcripts of SHP-1 in human transformed T cells and normal PBMCs and give evidence supporting the concept that SHP-1 can negatively regulate growth of malignant T cells (PMID:12591278)
• SHP-1 plays a pivotal role in reorganization of cytoskeletal architecture by inducing actin dephosphorylation. (PMID:12646642)
• A blockade in early signaling events observed with TCR antagonists occurs via a negative intracellular signal that is mediated by SHP-1. (PMID:12734331)
• Associates with phosphorylated Fc gamma RIIa to modulate signaling events in myeloid cells (PMID:12832410)
• Vav1 trapping was independent of actin polymerization, suggesting that inhibition of cellular cytotoxicity occurs through an early dephosphorylation of Vav1 by SHP-1, which blocks actin-dependent activation signals. (PMID:12917349)
• SHP-1 inhibits PRL receptor and EPO receptor signaling by recruitment and targeting of SOCS-1 to Jak2, highlighting a new mechanism of SHP-1 regulation of cytokine-receptor signaling. (PMID:14551136)
• Down-regulation of SHP1 is associated with adult T-cell leukemia (PMID:14630083)
• SHP1 gene silencing is one of the events critical to the onset of malignant lymphomas/leukemias in humans. (PMID:14691303)
• hypermethylated in multiple myeloma (PMID:14976049)
• SHP-1 can dephosphorylate alpha-actinin in vitro and in vivo. (PMID:15070900)
• CNS myelination was significantly reduced in SHP-1-deficient mice relative to their normal littermates at multiple times during the active period of myelination. (PMID:15197735)
• Mice lacking SHIP-1 have defects in the erythroid and myeloid compartments similar to those in mice lacking Lyn or SHP-1. (PMID:15339845)
• inactivation of Ros by SHP-1-mediated dephosphorylation plays a role in the regulation of complex stability (PMID:15456853)
• TFG is a novel protein able to modulate SHP-1 activity. (PMID:15557341)
• transformation of TF-1 cells with FLT3/ITD mutations suppressed the activity of SHP-1 by approximately 3-fold (PMID:15574429)
• SHP-1 may be a novel target molecule to sensitize erythropoietin action in hemodialysis patients with hyporesponsive anemia (PMID:15579525)
• SHP-1 acts at multiple stages of hematopoietic differentiation to alter lineage balance. Expression of WT SHP-1 reduced myeloid colony numbers while increasing the numbers of secondary embryoid bodies and mixed hematopoietic colonies obtained (PMID:15701718)
• SRIF inhibitory effects on thyroid medullary carcinoma cell proliferation are mediated, at least in part, by SHP-1, which acts through a MAPK-dependent mechanism (PMID:15746253)
• STAT3 may transform cells by inducing epigenetic silencing of SHP-1 in cooperation with DNMT1 and histone deacetylase 1 (PMID:15870198)
• Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 (PMID:16326706)
• Our results suggest an alteration of the SHP-1 modulation by GM-CSF in lipid rafts of PMN with aging. These alterations could contribute to the decreased GM-CSF effects on PMN. (PMID:16501054)
• SHP1 activation, association with Src and dephosphorylation of specific proteins were dependent on extracellular calcium and maintenance of a higher cytosolic calcium plateau. (PMID:17046078)
• Protein phosphatase 6 specifically down-regulates transforming growth factor beta-activated kinase 1 (TAK1) through dephosphorylation of threonine-187 in the activation loop, suppressing inflammatory responses via TAK1 signaling pathways. (PMID:17079228)
• increased activity of inhibitory molecules, such as Src homology domain-containing protein tyrosine phosphatase-1 (SHP-1) and suppressors of cytokine signalling (SOCS), is responsible for age-related failure of GM-CSF to stimulate neutrophil functions (PMID:17142110)
• findings provide an insight into the structure of the hematopoietic cell-specific P2 promoter of the SHP-1 gene and identify PU.1 as the transcriptional activator of the P2 promoter (PMID:17218319)
• These data suggest a mechanism of IC-mediated inhibition of IFN-gamma signaling, which requires the ITAM-containing FcgammaRI, as well as the ITIM-dependent phosphatase SHP-1, ultimately resulting in the suppression of STAT1 phosphorylation. (PMID:17227821)
• SHP-1 loss correlates with, and may contribute to, progression of cutaneous T-cell lymphoma (PMID:17239936)
• novel mechanism regulating GH signaling in which estrogen receptor modulators enhance GH activation of the JAK2/STAT5 pathway in a cell-type-dependent manner by attenuating protein tyrosine phosphatase activities (PMID:17272397)
• In human erythrocytes SHP-1 is present in membranes from resting cells, but in 5% of the protein amount. SHP-1 ensures band 3 dephosphorylation. (PMID:17404032)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpn6	ENSDARG00000089043
mus_musculus	Ptpn6	ENSMUSG00000004266
rattus_norvegicus	Ptpn6	ENSRNOG00000014294

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), 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), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Tyrosine-protein phosphatase non-receptor type 6 — P29350 (reviewed: P29350)

Alternative names: Hematopoietic cell protein-tyrosine phosphatase, Protein-tyrosine phosphatase 1C, Protein-tyrosine phosphatase SHP-1, SH-PTP1

All UniProt accessions (10): P29350, F5GXD4, F5GY79, F5H0N8, F5H1V7, F5H1Z8, F5H4Z1, F5H5H9, Q53XS4, U3KQS1

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis. Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities. When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events. Modulates the signaling of several cytokine receptors including IL-4 receptor. Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling. Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Also acts as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A.

Subunit / interactions. Monomer. Interacts with MTUS1. Interacts with MILR1 (tyrosine-phosphorylated). Interacts with KIT. Interacts with SIRPA/PTPNS1. Interacts with LILRB1 and LILRB2. Interacts with LILRB4. Interacts with FCRL2 and FCRL4. Interacts with FCRL3 and FCRL6 (tyrosine phosphorylated form). Interacts with CD84. Interacts with CD300LF. Interacts with CDK2. Interacts with KIR2DL1; the interaction is enhanced by ARRB2. Interacts (via SH2 1 domain) with ROS1; the interaction is direct and promotes ROS1 dephosphorylation. Interacts with EGFR; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with the tyrosine phosphorylated form of PDPK1. Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent. Interacts with MPIG6B (via ITIM motif). Interacts with KLRI1 and KLRI2. Interacts with moesin/MSN. Interacts with CLEC12B (via ITIM motif). Interacts with polymerase II components POLR2C and POLR2J; these interactions recruit RNA polymerase II to the PCK1 promoter. Interacts with TNFRSF10A; this interaction enables the inhibition of T-cell receptor signaling via LCK. (Microbial infection) Interacts with HIV-1 Vif; this interaction promotes the suppression of cytokine production.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Isoform 1 is expressed in hematopoietic cells. Isoform 2 is expressed in non-hematopoietic cells.

Post-translational modifications. Phosphorylated on tyrosine residues. Binding of KITLG/SCF to KIT increases tyrosine phosphorylation. Phosphorylation at Tyr-564 by LYN enhances phosphatase activity. Phosphorylation at Thr-394 by TAOK3 leads to polyubiquitination and subsequent proteasomal degradation. Ubiquitinated after phosphorylation by TAOK3. Ubiquitinated by a cooperation between ITCH and WWP2 via ‘Lys-27’-mediated polyubiquitin chains resulting in the reduction of its association with LCK.

Domain organisation. The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P29350-1	1, Long	yes
P29350-3	2
P29350-2	3, Short
P29350-4	4, 70-kDa, SHP-1L

RefSeq proteins (3): NP_002822, NP_536858, NP_536859 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR000980	SH2	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR012152	Tyr_Pase_non-rcpt_typ-6/11	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR052123	Non-rcpt_Tyr_Phosphatase	Family

Pfam: PF00017, 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 (86 total): strand 37, helix 17, modified residue 7, splice variant 4, mutagenesis site 4, domain 3, sequence conflict 3, turn 3, binding site 3, chain 1, cross-link 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
4GRZ	X-RAY DIFFRACTION	1.37
4HJP	X-RAY DIFFRACTION	1.4
4GRY	X-RAY DIFFRACTION	1.7
8YHI	X-RAY DIFFRACTION	1.75
4GS0	X-RAY DIFFRACTION	1.8
4HJQ	X-RAY DIFFRACTION	1.8
1FPR	X-RAY DIFFRACTION	2.5
1GWZ	X-RAY DIFFRACTION	2.5
6SM5	X-RAY DIFFRACTION	2.75
2B3O	X-RAY DIFFRACTION	2.8
3PS5	X-RAY DIFFRACTION	3.1
1X6C	SOLUTION NMR
2RMX	SOLUTION NMR
2YU7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29350-F1	86.54	0.68

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): 453 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 419; 453–459; 500

Post-translational modifications (8): 10, 57, 64, 377, 394, 536, 564, 308

Mutagenesis-validated functional residues (4):

Position	Phenotype
308	almost complete loss of ubiquitination by itch and wwp2.
419	no loss in substrate binding but impaired activity.
453	stabilizes the association between phosphatase and substrates.
564	complete loss of phosphorylation by lyn.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1433559	Regulation of KIT signaling
R-HSA-201556	Signaling by ALK
R-HSA-210990	PECAM1 interactions
R-HSA-389948	Co-inhibition by PD-1
R-HSA-391160	Signal regulatory protein family interactions
R-HSA-432142	Platelet sensitization by LDL
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5690714	CD22 mediated BCR regulation
R-HSA-6798695	Neutrophil degranulation
R-HSA-877300	Interferon gamma signaling
R-HSA-877312	Regulation of IFNG signaling
R-HSA-9008059	Interleukin-37 signaling
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-912526	Interleukin receptor SHC signaling
R-HSA-912694	Regulation of IFNA/IFNB signaling
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer
R-HSA-982772	Growth hormone receptor signaling
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-9927353	Co-inhibition by BTLA

MSigDB gene sets: 0 (showing top):

GO Biological Process (51): MAPK cascade (GO:0000165), mitotic cell cycle (GO:0000278), hematopoietic progenitor cell differentiation (GO:0002244), negative regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002924), protein dephosphorylation (GO:0006470), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), negative regulation of angiogenesis (GO:0016525), peptidyl-tyrosine phosphorylation (GO:0018108), cytokine-mediated signaling pathway (GO:0019221), cell differentiation (GO:0030154), platelet formation (GO:0030220), T cell costimulation (GO:0031295), negative regulation of lipopolysaccharide-mediated signaling pathway (GO:0031665), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of mast cell activation involved in immune response (GO:0033007), positive regulation of cell adhesion mediated by integrin (GO:0033630), peptidyl-tyrosine dephosphorylation (GO:0035335), megakaryocyte development (GO:0035855), T cell proliferation (GO:0042098), T cell activation (GO:0042110), negative regulation of T cell proliferation (GO:0042130), natural killer cell mediated cytotoxicity (GO:0042267), regulation of apoptotic process (GO:0042981), negative regulation of MAPK cascade (GO:0043409), regulation of B cell differentiation (GO:0045577), negative regulation of innate immune response (GO:0045824), T cell receptor signaling pathway (GO:0050852), B cell receptor signaling pathway (GO:0050853), negative regulation of B cell receptor signaling pathway (GO:0050859), negative regulation of T cell receptor signaling pathway (GO:0050860), regulation of release of sequestered calcium ion into cytosol (GO:0051279), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), regulation of type I interferon-mediated signaling pathway (GO:0060338), regulation of ERK1 and ERK2 cascade (GO:0070372), platelet aggregation (GO:0070527), negative regulation of inflammatory response to wounding (GO:0106015), CD27 signaling pathway (GO:0160162)

GO Molecular Function (12): phosphotyrosine residue binding (GO:0001784), protein tyrosine phosphatase activity (GO:0004725), non-membrane spanning protein tyrosine phosphatase activity (GO:0004726), transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), SH3 domain binding (GO:0017124), protein kinase binding (GO:0019901), SH2 domain binding (GO:0042169), cell adhesion molecule binding (GO:0050839), phosphorylation-dependent protein binding (GO:0140031), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (14): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), membrane (GO:0016020), protein-containing complex (GO:0032991), specific granule lumen (GO:0035580), alpha-beta T cell receptor complex (GO:0042105), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-19 pathways:

Category	Pathways
Signaling by the B Cell Receptor (BCR)	2
Interferon Signaling	2
Platelet activation, signaling and aggregation	1
Signaling by SCF-KIT	1
Signaling by Receptor Tyrosine Kinases	1
Cell surface interactions at the vascular wall	1
Regulation of T cell activation by CD28 family	1
Cell-Cell communication	1
Platelet homeostasis	1
Signaling by Interleukins	1
Innate Immune System	1
Interferon gamma signaling	1
Interleukin-1 family signaling	1
Interleukin-2 family signaling	1
Interleukin-3, Interleukin-5 and GM-CSF signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell population proliferation	2
regulation of cell population proliferation	2
protein tyrosine phosphatase activity	2
protein domain specific binding	2
nuclear lumen	2
intracellular signaling cassette	1
cell cycle	1
mitotic nuclear division	1
hemopoiesis	1
cell differentiation	1
humoral immune response mediated by circulating immunoglobulin	1
negative regulation of immunoglobulin mediated immune response	1
negative regulation of humoral immune response	1
regulation of humoral immune response mediated by circulating immunoglobulin	1
dephosphorylation	1
protein modification process	1
G protein-coupled receptor activity	1
signal transduction	1
positive regulation of cellular process	1
negative regulation of cellular process	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cellular developmental process	1
myeloid cell differentiation	1
platelet morphogenesis	1
anatomical structure formation involved in morphogenesis	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
negative regulation of response to biotic stimulus	1
negative regulation of signal transduction	1
lipopolysaccharide-mediated signaling pathway	1
regulation of lipopolysaccharide-mediated signaling pathway	1
negative regulation of response to external stimulus	1
negative regulation of cytokine production	1

Protein interactions and networks

STRING

2856 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN6	CD22	P20273	873
PTPN6	SRC	P12931	817
PTPN6	LILRB1	Q8NHL6	785
PTPN6	INPP5D	Q92835	779
PTPN6	SYK	P43405	773
PTPN6	STAT3	P40763	762
PTPN6	EPOR	P19235	724
PTPN6	CD72	P21854	719
PTPN6	LYN	P07948	708
PTPN6	LAIR1	Q6GTX8	693
PTPN6	SIRPA	P78324	693
PTPN6	JAK1	P23458	684
PTPN6	JAK2	O60674	672
PTPN6	CD300C	Q08708	669
PTPN6	PTS	Q03393	665

IntAct

187 interactions, top by confidence:

A	B	Type	Score
CD33	PTPN6	psi-mi:“MI:0915”(physical association)	0.820
PTPN6	CD33	psi-mi:“MI:0914”(association)	0.820
PTPN6	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.820
PTPN6	KIR2DL3	psi-mi:“MI:0407”(direct interaction)	0.820
PTPN6	KIR2DL3	psi-mi:“MI:0914”(association)	0.820
PTPN6	EPOR	psi-mi:“MI:0915”(physical association)	0.800
EPOR	PTPN6	psi-mi:“MI:0915”(physical association)	0.800
PTPN6	EPOR	psi-mi:“MI:0407”(direct interaction)	0.800

BioGRID (368): PTPN6 (Two-hybrid), PTPN6 (Affinity Capture-MS), AIMP1 (Co-fractionation), DARS (Co-fractionation), PTPN2 (Co-fractionation), PTPN6 (Co-fractionation), TRIP6 (Co-fractionation), VARS (Co-fractionation), OLIG1 (Two-hybrid), PTK2 (Two-hybrid), PTK2 (Affinity Capture-Luminescence), PTPN6 (Affinity Capture-MS), LAT (Affinity Capture-Western), PTPN6 (Affinity Capture-Western), PTPN6 (FRET)

ESM2 similar proteins: A6QNM2, A9CB74, G5ECY0, O14936, O59781, O70589, P08487, P10686, P16885, P19174, P24135, P26285, P29350, P34722, P35991, P49697, P53355, P54936, P70290, Q00013, Q03526, Q06187, Q09506, Q0VC68, Q17QN6, Q24210, Q4V339, Q4V8Q1, Q5RDW4, Q5ZJ00, Q62077, Q623S8, Q62915, Q6DNF7, Q6FIR8, Q6P7F1, Q758X6, Q8CIH5, Q8IUF1, Q8JH64

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

73 interactions.

A	Effect	B	Mechanism
PTPN6	down-regulates	ROS1	dephosphorylation
PTPN6	“down-regulates activity”	LCK	dephosphorylation
PTPN6	down-regulates	CSF2RB	dephosphorylation
PTPN6	up-regulates	SOCS1	binding
PTPN6	down-regulates	JAK1	dephosphorylation
PTPN6	down-regulates	TYK2
SRC	up-regulates	PTPN6	phosphorylation
PRKCA	down-regulates	PTPN6	phosphorylation
PTPN6	down-regulates	SH3BP2	dephosphorylation
PTPN6	down-regulates	STAT3	dephosphorylation
ABL1	“up-regulates activity”	PTPN6	phosphorylation
ABL1	unknown	PTPN6	phosphorylation
PTPN6	“down-regulates activity”	NFAT5	dephosphorylation
PTPN6	“up-regulates activity”	SRC	dephosphorylation
PTPN6	“down-regulates activity”	KDR	dephosphorylation
PTPN6	unknown	KDR	dephosphorylation
PTPN6	“up-regulates activity”	CASP8	dephosphorylation
LYN	“up-regulates activity”	PTPN6	phosphorylation
PKNOX1	“up-regulates quantity by expression”	PTPN6	“transcriptional regulation”
FLT3	“down-regulates quantity”	PTPN6	“transcriptional regulation”
FLT3	“down-regulates quantity by repression”	PTPN6	“transcriptional regulation”
“8-oxo-7-[(6-sulfo-2-naphthalenyl)hydrazinylidene]-5-quinolinesulfonic acid”	“down-regulates activity”	PTPN6	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
PI3K events in ERBB2 signaling	6	63.0×	3e-08
Signaling by ERBB2 ECD mutants	5	52.5×	1e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	6	48.7×	1e-07
Regulation of KIT signaling	5	47.0×	2e-06
Signaling by ERBB2 KD Mutants	7	46.3×	1e-08
SHC1 events in ERBB2 signaling	6	44.6×	2e-07
Signaling by ERBB2 TMD/JMD mutants	6	44.6×	2e-07
Downregulation of ERBB2 signaling	5	29.7×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	9	48.0×	6e-11
immune response-regulating signaling pathway	7	40.4×	6e-08
cell surface receptor protein tyrosine kinase signaling pathway	12	26.4×	1e-11
cellular response to epidermal growth factor stimulus	6	24.1×	2e-05
negative regulation of T cell proliferation	5	20.9×	3e-04
receptor internalization	5	20.5×	3e-04
protein autophosphorylation	11	20.2×	1e-09
epidermal growth factor receptor signaling pathway	6	18.8×	7e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — DLBCLNOS, MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	8
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

3060 predictions. Top by Δscore:

Variant	Effect	Δscore
12:6946736:GTGG:G	donor_gain	1.0000
12:6952042:AT:A	acceptor_gain	1.0000
12:6952175:GAG:G	donor_gain	1.0000
12:6952176:AGGT:A	donor_loss	1.0000
12:6952178:GTGAG:G	donor_loss	1.0000
12:6952179:T:A	donor_loss	1.0000
12:6953417:GAGGC:G	donor_gain	1.0000
12:6953461:G:GT	donor_gain	1.0000
12:6953465:G:GT	donor_gain	1.0000
12:6954801:CTA:C	acceptor_loss	1.0000
12:6954802:TA:T	acceptor_loss	1.0000
12:6954803:A:AG	acceptor_gain	1.0000
12:6954803:AGGT:A	acceptor_gain	1.0000
12:6954804:G:GG	acceptor_gain	1.0000
12:6954804:GGTG:G	acceptor_gain	1.0000
12:6954993:AGGT:A	donor_loss	1.0000
12:6954995:G:GC	donor_loss	1.0000
12:6954996:T:A	donor_loss	1.0000
12:6955147:CCAG:C	acceptor_loss	1.0000
12:6955148:CAG:C	acceptor_loss	1.0000
12:6955149:A:AG	acceptor_gain	1.0000
12:6955149:AG:A	acceptor_gain	1.0000
12:6955149:AGGGT:A	acceptor_gain	1.0000
12:6955150:G:A	acceptor_gain	1.0000
12:6955150:G:GT	acceptor_gain	1.0000
12:6955150:GGGT:G	acceptor_gain	1.0000
12:6955150:GGGTG:G	acceptor_gain	1.0000
12:6955235:G:GT	donor_gain	1.0000
12:6955245:GCGCC:G	donor_gain	1.0000
12:6955365:A:AG	acceptor_gain	1.0000

AlphaMissense

3932 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:6951610:T:A	W4R	1.000
12:6951610:T:C	W4R	1.000
12:6951653:T:A	L18H	1.000
12:6951653:T:C	L18P	1.000
12:6951679:T:C	F27L	1.000
12:6951680:T:C	F27S	1.000
12:6951681:C:A	F27L	1.000
12:6951681:C:G	F27L	1.000
12:6951683:T:A	L28Q	1.000
12:6951683:T:C	L28P	1.000
12:6951686:C:A	A29D	1.000
12:6951715:T:C	F39L	1.000
12:6951717:C:A	F39L	1.000
12:6951717:C:G	F39L	1.000
12:6951722:T:A	L41H	1.000
12:6951722:T:C	L41P	1.000
12:6951724:T:C	S42P	1.000
12:6951725:C:A	S42Y	1.000
12:6951725:C:T	S42F	1.000
12:6951728:T:A	V43D	1.000
12:6952002:C:G	H51D	1.000
12:6952002:C:T	H51Y	1.000
12:6952003:A:G	H51R	1.000
12:6952004:T:A	H51Q	1.000
12:6952004:T:G	H51Q	1.000
12:6952006:T:A	I52N	1.000
12:6952006:T:G	I52S	1.000
12:6952012:T:A	I54N	1.000
12:6952012:T:C	I54T	1.000
12:6952012:T:G	I54S	1.000

dbSNP variants (sampled 300 via entrez): RS1000361901 (12:6954817 C>G,T), RS1000760899 (12:6947679 A>C), RS1002029822 (12:6948260 G>A), RS1002156478 (12:6953904 G>A), RS1002167967 (12:6954229 A>G), RS1002451261 (12:6948661 C>T), RS1002699325 (12:6951218 G>A,T), RS1002761008 (12:6945587 G>A,C), RS1002898246 (12:6959418 T>C), RS1003107717 (12:6961571 G>A), RS1003124748 (12:6955195 C>A), RS1003424214 (12:6961433 C>T), RS1004177738 (12:6951747 G>A), RS1004494517 (12:6946368 C>G,T), RS1004552506 (12:6950555 T>A)

Disease associations

OMIM: gene MIM:176883 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000271	Abnormality of the face
HP:0000464	Abnormality of the neck
HP:0001061	Acne
HP:0001155	Abnormality of the hand
HP:0001644	Dilated cardiomyopathy
HP:0001903	Anemia
HP:0001974	Increased total leukocyte count
HP:0002037	Inflammation of the large intestine
HP:0002664	Neoplasm
HP:0002719	Recurrent infections
HP:0002829	Arthralgia
HP:0003002	Breast carcinoma
HP:0003326	Myalgia
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0004377	Hematological neoplasm
HP:0004808	Acute myeloid leukemia
HP:0005550	Chronic lymphatic leukemia
HP:0008066	Abnormal blistering of the skin
HP:0011117	Abnormal circulating interleukin concentration
HP:0011118	Abnormality of tumor necrosis factor secretion
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011897	Increased total neutrophil count
HP:0011944	Small vessel vasculitis
HP:0012490	Panniculitis
HP:0012531	Pain
HP:0020169	Abnormal drug response
HP:0025452	Pyoderma gangrenosum
HP:0025474	Erythematous plaque
HP:0025616	Sterile abscess
HP:0030350	Erythematous papule

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002712_10	Red blood cell fatty acid levels	3.000000e-30
GCST002712_13	Red blood cell fatty acid levels	3.000000e-49
GCST005992_34	Mean corpuscular hemoglobin concentration	4.000000e-10
GCST010002_206	Refractive error	3.000000e-62

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006807	linoleic acid measurement
EFO:0006810	oleic acid measurement
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3166 (SINGLE PROTEIN), CHEMBL6066056 (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: 52,191 (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
CHEMBL1756	ESTRAMUSTINE PHOSPHATE	4	56
CHEMBL169	URSOLIC ACID	2	20,825
CHEMBL230006	ENOXOLONE	2	24,361
CHEMBL3351077	CEFSULODIN	2	6,949

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

Binding affinities (BindingDB)

25 measured of 53 human assays (53 total across all organisms); most potent 25 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Sodium orthovanadate (SOV)	IC50	25.4 nM
(3Z)-3-[2-(2-carboxyphenyl)hydrazin-1-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid	IC50	1500 nM
4-{2-[(3Z)-5-(benzylsulfamoyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	2500 nM
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	IC50	2900 nM	US-9522881: Hydroxyindole carboxylic acid based inhibitors for oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)
4-{2-[(3Z)-5-{[(4-chlorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	7500 nM
4-{2-[(3Z)-2-oxo-5-(propan-2-ylsulfamoyl)-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	9300 nM
(3Z)-N-[(4-chlorophenyl)methyl]-3-[2-(2-nitrophenyl)hydrazin-1-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide	IC50	9800 nM
3-{2-[(3Z)-5-{[(4-methylphenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	11300 nM
4-{2-[(3Z)-5-{[(4-fluorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	11400 nM
4-{2-[(3Z)-5-{[(2-chlorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	11700 nM
3-{2-[(3Z)-5-{[(4-fluorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	14500 nM
3-{2-[(3Z)-5-{[(3-chlorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	15400 nM
3-{2-[(3Z)-5-{[(4-chlorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	18800 nM
3-{2-[(3Z)-5-{[2-(2,4-dichlorophenyl)ethyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	19300 nM
3-{2-[(3Z)-5-{[(2-chlorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	19400 nM
CHEMBL5192811	IC50	22000 nM
2-{2-[(3Z)-5-({[4-chloro-3-(trifluoromethyl)phenyl]methyl}sulfamoyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	25700 nM
4-{2-[(3Z)-5-({[4-chloro-3-(trifluoromethyl)phenyl]methyl}sulfamoyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	32800 nM
3-{2-[(3Z)-2-oxo-5-(propan-2-ylsulfamoyl)-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	37100 nM
(3Z)-3-[2-(3-carboxyphenyl)hydrazin-1-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-carboxylic acid	IC50	38200 nM
3-{2-[(3Z)-5-{[(3-chloro-4-fluorophenyl)methyl]sulfamoyl}-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	54900 nM
3-{2-[(3Z)-5-({[4-chloro-3-(trifluoromethyl)phenyl]methyl}sulfamoyl)-2-oxo-2,3-dihydro-1H-indol-3-ylidene]hydrazin-1-yl}benzoic acid	IC50	63100 nM
US8987474, NSC-87877	IC50	84500 nM	US-8987474: Inhibition of Shp2/PTPN11 protein tyrosine phosphatase by NSC-87877, NSC-117199 and their analogs
(3Z)-3-[2-(2-nitrophenyl)hydrazin-1-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid	IC50	96700 nM
(3Z)-3-[2-(2-nitrophenyl)hydrazin-1-ylidene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide	IC50	157000 nM

ChEMBL bioactivities

116 potent at pChembl≥5 of 288 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.96	Kd	110	nM	CHEMBL262382
6.92	Kd	120	nM	CHEMBL274087
6.89	IC50	130	nM	CHEMBL4750435
6.80	Kd	160	nM	CHEMBL413215
6.68	Kd	210	nM	CHEMBL408337
6.64	Kd	230	nM	CHEMBL2371862
6.62	Kd	240	nM	CHEMBL413215
6.60	Kd	250	nM	CHEMBL412186
6.57	Kd	270	nM	CHEMBL2371864
6.54	Kd	290	nM	CHEMBL413492
6.54	IC50	290	nM	CHEMBL3322530
6.47	IC50	335	nM	CHEMBL472004
6.47	IC50	335	nM	CHEMBL1650889
6.45	IC50	355	nM	CHEMBL472004
6.44	IC50	360	nM	CHEMBL472004
6.42	IC50	378	nM	CHEMBL1650891
6.39	IC50	408	nM	CHEMBL1650892
6.31	IC50	486	nM	CHEMBL1650893
6.28	Kd	530	nM	CHEMBL269042
6.16	Kd	690	nM	CHEMBL273780
6.15	IC50	710	nM	CHEMBL507502
6.12	IC50	760	nM	CHEMBL2316908
6.07	IC50	850	nM	CHEMBL4175748
6.05	Kd	900	nM	CHEMBL2371863
6.05	IC50	890	nM	CHEMBL499413
6.04	IC50	910	nM	CHEMBL2396718
6.00	Kd	1000	nM	CHEMBL386749
5.97	Kd	1080	nM	CHEMBL386769
5.96	IC50	1090	nM	CHEMBL4164960
5.96	IC50	1110	nM	CHEMBL4475724
5.90	IC50	1250	nM	SODIUM ORTHOVANAD
5.84	IC50	1440	nM	CHEMBL3319356
5.84	Kd	1440	nM	CHEMBL371014
5.82	IC50	1520	nM	CHEMBL4445615
5.75	IC50	1800	nM	CHEMBL4757579
5.75	IC50	1800	nM	CHEMBL5270661
5.71	IC50	1970	nM	TANSHINONE I
5.68	IC50	2080	nM	CHEMBL4762771
5.68	IC50	2070	nM	CHEMBL6172329
5.67	IC50	2140	nM	TANSHINONE IIA
5.67	IC50	2140	nM	CHEMBL4780471
5.66	Ki	2200	nM	CHEMBL574813
5.64	IC50	2300	nM	CHEMBL2316902
5.64	IC50	2300	nM	CHEMBL2316906
5.64	IC50	2310	nM	CHEMBL3593818
5.64	IC50	2310	nM	CHEMBL3634592
5.63	IC50	2340	nM	CHEMBL6169038
5.61	IC50	2450	nM	CHEMBL3822604
5.61	IC50	2430	nM	CHEMBL1823762
5.60	IC50	2490	nM	CHEMBL2316907

PubChem BioAssay actives

116 with measured affinity, of 731 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[(7R,10R,13S,16S)-16-[[(2S)-2-[[2-[[(2S)-2-amino-4-carboxybutanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-10-(2-methylsulfanylethyl)-2,5,9,12,15-pentaoxo-13-[(4-phosphonooxyphenyl)methyl]-1,3,8,11,14-pentazacycloicosane-7-carbonyl]amino]-4-methylpentanoic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.1100	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.1200	uM
4-[1-(4-methoxyphenyl)-3-(2-oxochromen-7-yl)pyrrolo[2,3-b]pyridin-5-yl]benzoic acid	1706919: Inhibition of PTPN6 (unknown origin) pre-incubated for 20 mins followed by fluorescence substrate addition and measured after 120 mins by DiFMUP assay	ic50	0.1300	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-phenylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.1600	uM
(2S)-2-[[(8R,11R,14S,17S)-17-[[(2S)-2-[[2-[[(2S)-2-amino-4-carboxybutanoyl]amino]acetyl]amino]-4-methylpentanoyl]amino]-11-(2-methylsulfanylethyl)-2,5,10,13,16-pentaoxo-14-[(4-phosphonooxyphenyl)methyl]-1,3,9,12,15-pentazacyclohenicosane-8-carbonyl]amino]-4-methylpentanoic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.2100	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.2300	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.2500	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-phenylbutanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.2700	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxy-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.2900	uM
2-(4-acetylanilino)-3-chloronaphthalene-1,4-dione	1870724: Inhibition of human SHP1	ic50	0.2900	uM
6-hydroxy-2-(4-methoxyphenyl)-3-[1-[4-(naphthalen-1-ylamino)-4-oxobutyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566823: Inhibition of Shp1	ic50	0.3350	uM
8-hydroxy-7-[(6-sulfonaphthalen-2-yl)diazenyl]quinoline-5-sulfonic acid	1937997: Inhibition of SHP1 (unknown origin)	ic50	0.3350	uM
3-[1-[4-[(4-chloronaphthalen-1-yl)amino]-4-oxobutyl]triazol-4-yl]-6-hydroxy-2-(4-methylphenyl)-1-benzofuran-5-carboxylic acid	566823: Inhibition of Shp1	ic50	0.3780	uM
6-hydroxy-2-(4-methylphenyl)-3-[1-[4-(naphthalen-1-ylamino)-4-oxobutyl]triazol-4-yl]-1-benzofuran-5-carboxylic acid	566823: Inhibition of Shp1	ic50	0.4080	uM
6-hydroxy-3-[1-[4-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-4-oxobutyl]triazol-4-yl]-2-(3-methylphenyl)-1-benzofuran-5-carboxylic acid	566823: Inhibition of Shp1	ic50	0.4860	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.5300	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.6900	uM
2-[5-[(4aR,6aR,6aS,6bR,8aR,10S,12aR,14bR)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicen-4a-yl]pentanoylamino]-3-(1,3-benzodioxol-5-yl)propanoic acid	409688: Inhibition of human recombinant SHP1	ic50	0.7100	uM
6-hydroxy-3-[2-(4-phenoxyphenyl)ethynyl]-2-phenyl-1-benzofuran-5-carboxylic acid	725278: Inhibition of SHP1 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	0.7600	uM
5-[[2,5-diethoxy-4-(methanesulfonamido)phenyl]methylcarbamoylamino]-N-(3,4-dimethoxyphenyl)-2-ethoxybenzamide	1351466: Inhibition of human GST-tagged SHP1 (244 to 570 residues) expressed in Escherichia coli BL21-CondenPlus (DE3) using pNNP as substrate	ic50	0.8500	uM
4-[[(3S,4aR,6aR,6bS,8aR,12aR,14aR,14bR)-8a-[5-[[(1S)-1-carboxy-2-phenylethyl]amino]-5-oxopentyl]-4,4,6a,6b,11,11,14b-heptamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxymethyl]benzoic acid	409688: Inhibition of human recombinant SHP1	ic50	0.8900	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-phenylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	0.9000	uM
3-[2-(3-chlorophenyl)ethynyl]-6-hydroxy-2-[4-[2-oxo-2-(propylamino)ethoxy]phenyl]-1-benzofuran-5-carboxylic acid	755779: Inhibition of recombinant SHP-1 (unknown origin) using pNPP as substrate by spectrophotometric analysis	ic50	0.9100	uM
bis(4-chloro-2-(phenyliminomethyl)phenol);oxovanadium	1800517: PTP inhibition assay from Article 10.1039/c2dt30198a: “Synthesis and evaluation of oxovanadium(IV) complexes of Schiff-base condensates from 5-substituted-2-hydroxybenzaldehyde and 2-substituted-benzenamine as selective inhibitors of protein tyrosine phosphatase 1B.”	ic50	1.0000	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	1.0000	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxy-3-phenylpropanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	1.0800	uM
methyl 5-[[2,5-diethoxy-4-(methanesulfonamido)phenyl]methylcarbamoylamino]-2-ethoxybenzoate	1351466: Inhibition of human GST-tagged SHP1 (244 to 570 residues) expressed in Escherichia coli BL21-CondenPlus (DE3) using pNNP as substrate	ic50	1.0900	uM
2-[(5Z)-5-[[6-[(4-bromophenyl)methoxy]naphthalen-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-(1H-indol-3-yl)propanoic acid	1551282: Inhibition of human recombinant GST-tagged SHP1 (catalytic domain 244 to 570 residues) expressed in Escherichia coli BL21 (DE3) using pNPP as substrate measured for 2 mins by colorimetric analysis	ic50	1.1100	uM
(2S)-2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-3-(4-phosphonooxyphenyl)propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]pentanedioic acid	238135: Dissociation constant for the interaction with the GST-N-SH2 domain of SHP-1	kd	1.4400	uM
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	1182544: Inhibition of SHP1 (unknown origin)	ic50	1.4400	uM
2-[(5Z)-5-[[6-[(4-fluorophenyl)methoxy]naphthalen-2-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]-3-(1H-indol-3-yl)propanoic acid	1551282: Inhibition of human recombinant GST-tagged SHP1 (catalytic domain 244 to 570 residues) expressed in Escherichia coli BL21 (DE3) using pNPP as substrate measured for 2 mins by colorimetric analysis	ic50	1.5200	uM
4-[[2-(4-ethoxycarbonylphenyl)-5-(4-nitrophenyl)-3-oxo-1H-pyrazol-4-yl]diazenyl]benzenesulfonic acid	1674077: Inhibition of N-terminal His6-tagged TEV cleavage site-fused human SHP1 (222 to 535 residues) expressed in Escherichia coli BL21(DE3)RILcodon+ or BL21(DE3)RPcodon+ using 4-nitrophenylphosphate as substrate	ic50	1.8000	uM
4-[(2Z)-2-[1-(4-ethoxycarbonylphenyl)-3-(4-nitrophenyl)-5-oxopyrazolidin-4-ylidene]hydrazinyl]benzenesulfonic acid	1937997: Inhibition of SHP1 (unknown origin)	ic50	1.8000	uM
2-[(2-hydroxy-5-nitrophenyl)methylideneamino]benzoic acid;oxo(dioxonio)vanadium	1800517: PTP inhibition assay from Article 10.1039/c2dt30198a: “Synthesis and evaluation of oxovanadium(IV) complexes of Schiff-base condensates from 5-substituted-2-hydroxybenzaldehyde and 2-substituted-benzenamine as selective inhibitors of protein tyrosine phosphatase 1B.”	ic50	1.9000	uM
1,6-dimethylnaphtho[1,2-g][1]benzofuran-10,11-dione	772620: Inhibition of GST-tagged SHP1 PTP domain (unknown origin) using phospho-EGFR Asp-Ala-Asp-Glu-Tyr[PO3H2]-Leu-Ile-Pro-Gln-Gln-Gly as substrate preincubated for 30 mins before substrate addition measured after 30 mins by phosphatase activity assay	ic50	1.9700	uM
4-[[2,5-bis(4-nitrophenyl)-3-oxo-1H-pyrazol-4-yl]diazenyl]benzenesulfonic acid	1674076: Inhibition of SHP1 (unknown origin) using 6,8-difluoro-4-methylum-belliferylphosphate as substrate preincubated for 1 hr followed by substrate by fluorescence method	ic50	2.0800	uM
4-[[2-(4-methoxyphenyl)-5-(4-nitrophenyl)-3-oxo-1H-pyrazol-4-yl]diazenyl]benzenesulfonic acid	1674076: Inhibition of SHP1 (unknown origin) using 6,8-difluoro-4-methylum-belliferylphosphate as substrate preincubated for 1 hr followed by substrate by fluorescence method	ic50	2.1400	uM
1,6,6-trimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione	772620: Inhibition of GST-tagged SHP1 PTP domain (unknown origin) using phospho-EGFR Asp-Ala-Asp-Glu-Tyr[PO3H2]-Leu-Ile-Pro-Gln-Gln-Gly as substrate preincubated for 30 mins before substrate addition measured after 30 mins by phosphatase activity assay	ic50	2.1400	uM
(5Z)-5-[[2-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-5-bromophenyl]methylidene]-1,3-thiazolidine-2,4-dione	440907: Inhibition of SHP1 catalytic domain expressed in Escherichia coli	ki	2.2000	uM
6-hydroxy-2-phenyl-3-[2-[3-(trifluoromethyl)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725278: Inhibition of SHP1 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	2.3000	uM
3-[2-(3,5-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725278: Inhibition of SHP1 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	2.3000	uM
1-(4-bromophenyl)-3-[[2,5-diethoxy-4-(methanesulfonamido)phenyl]methyl]urea	1234946: Inhibition of SHP1 (unknown origin) using pNPP as substrate	ic50	2.3100	uM
methyl 2-[4-[[4-[[benzyl(methylsulfonyl)amino]methyl]-N-(4-ethoxyphenyl)sulfonylanilino]methyl]-N-methylsulfonylanilino]acetate	1256605: Inhibition of SHP1 (unknown origin) assessed as hydrolysis of pNPP to pNP after 30 mins	ic50	2.3100	uM
2-[[(E)-3-(2-chlorophenyl)prop-2-enoyl]amino]-3-[6-[(2-fluorophenyl)methoxy]naphthalen-2-yl]propanoic acid	615389: Inhibition of human recombinant SHP1 in Tris buffer at pH 8 using OMPF as substrate	ic50	2.4300	uM
methyl 5-[benzylsulfonyl-[[4-[(2-methoxy-2-oxoethyl)-methylsulfonylamino]phenyl]methyl]amino]-2-[(4-methylphenyl)methoxy]benzoate	1310313: Inhibition of human SHP1 using pNPP as substrate incubated for 30 mins	ic50	2.4500	uM
6-hydroxy-2-phenyl-3-[2-[4-(trifluoromethoxy)phenyl]ethynyl]-1-benzofuran-5-carboxylic acid	725278: Inhibition of SHP1 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	2.4900	uM
bis(4-nitro-2-(phenyliminomethyl)phenol);oxovanadium	1800517: PTP inhibition assay from Article 10.1039/c2dt30198a: “Synthesis and evaluation of oxovanadium(IV) complexes of Schiff-base condensates from 5-substituted-2-hydroxybenzaldehyde and 2-substituted-benzenamine as selective inhibitors of protein tyrosine phosphatase 1B.”	ic50	2.5000	uM
3,4-dibromo-5-[5-[4-(4-propan-2-ylphenoxy)phenyl]-1,3-oxazol-2-yl]benzene-1,2-diol	1602023: Inhibition of SHP1 (unknown origin)	ic50	2.5400	uM
3-[2-(2,4-difluorophenyl)ethynyl]-6-hydroxy-2-phenyl-1-benzofuran-5-carboxylic acid	725278: Inhibition of SHP1 (unknown origin) expressed in Escherichia coli using pNPP substrate after 5 mins by spectrophotometric analysis	ic50	2.6000	uM
7-[[(1R,2S,4aS,8aS)-1,2,4a,5-tetramethyl-2,3,4,7,8,8a-hexahydronaphthalen-1-yl]methyl]-1,3-benzoxazol-5-ol	1616399: Inhibition of SHP1 (unknown origin)	ic50	2.8000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases phosphorylation, affects cotreatment, increases expression, decreases methylation, decreases reaction (+1 more)	6
Decitabine	affects cotreatment, increases expression, decreases methylation	4
Arsenic	affects methylation, decreases expression, increases expression	2
Benzo(a)pyrene	decreases methylation, affects methylation	2
Hydrogen Peroxide	affects expression, decreases reaction, increases expression	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Valproic Acid	decreases expression, increases expression, increases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
tubocapsenolide A	increases activity, affects reaction, decreases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
potassium perchlorate	increases expression	1
capillarisin	increases expression, affects reaction, decreases phosphorylation, increases cleavage	1
terbufos	increases methylation	1
afimoxifene	decreases activity	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
anthranilic acid	affects binding, decreases activity	1
10-decarbamoylmitomycin C	decreases phosphorylation	1
oxovanadium IV	affects binding, decreases activity	1
pervanadate	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
2-(oxalylamino)benzoic acid	decreases activity	1
16-(4-fluorophenoxy)lipoxin A4	affects binding, increases reaction	1
bisperoxovanadium	affects reaction, increases expression	1
abrine	decreases expression	1

ChEMBL screening assays

158 unique, capped per target: 150 binding, 7 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1038654	Binding	Inhibition of SHP1 catalytic domain expressed in Escherichia coli	Thiazolidinedione derivatives as PTP1B inhibitors with antihyperglycemic and antiobesity effects. — Bioorg Med Chem Lett
CHEMBL2173381	Functional	Agonist activity at SHP1 in human PLC5 cells assessed as increase in SHP1 level at 10 uM after 12 hrs by Western blot analysis	Synthesis and biological activity of obatoclax derivatives as novel and potent SHP-1 agonists. — Eur J Med Chem
CHEMBL4626295	ADMET	Inhibition of SHP1 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method	Highly Potent and Selective N-Aryl Oxamic Acid-Based Inhibitors for Mycobacterium tuberculosis Protein Tyrosine Phosphatase B. — J Med Chem

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_B1AI	Abcam THP-1 PTPN6 KO	Cancer cell line	Male
CVCL_B8NI	Abcam HCT 116 PTPN6 KO	Cancer cell line	Male
CVCL_B9AW	Abcam MCF-7 PTPN6 KO	Cancer cell line	Female
CVCL_B9QT	Abcam A-549 PTPN6 KO	Cancer cell line	Male
CVCL_D7Z0	Ubigene A-549 PTPN6 KO	Cancer cell line	Male
CVCL_D8UB	Ubigene HCT 116 PTPN6 KO	Cancer cell line	Male
CVCL_D9Q5	Ubigene HEK293 PTPN6 KO	Transformed cell line	Female
CVCL_E0MB	Ubigene HeLa PTPN6 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder