Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOWDUNT)

• DOT Name: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)
• Synonyms: EC 3.1.3.16; EC 3.1.3.48; EC 3.1.3.67; Inositol polyphosphate 3-phosphatase; EC 3.1.3.-; Mutated in multiple advanced cancers 1; Phosphatase and tensin homolog
• Gene Name: PTEN
• Related Disease:
  Cowden syndrome 1
  Macrocephaly-autism syndrome
  Proteus syndrome
  PTEN hamartoma tumor syndrome
  Leiomyosarcoma
  Renal cell carcinoma
  Activated PI3K-delta syndrome
  Bannayan-Riley-Ruvalcaba syndrome
  Cowden disease
  Lhermitte-Duclos disease
  Proteus-like syndrome
  Recurrent malignant glioma
• UniProt ID: PTEN_HUMAN
• PDB ID: 1D5R; 2KYL; 4O1V; 5BUG; 5BZX; 5BZZ; 7JTX; 7JUK; 7JUL; 7JVX; 7PC7
• EC Number: 3.1.3.-; 3.1.3.16; 3.1.3.48; 3.1.3.67
• Pfam ID: PF10409 ; PF00102
• Sequence:
  MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSK
  HKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVA
  AIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY
  LLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMY
  FEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEI
  DSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEAS
  SSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV
• Function: Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also functions as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring of PtdIns(3,4,5)P3/phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4)P2/phosphatidylinositol 3,4-diphosphate and PtdIns3P/phosphatidylinositol 3-phosphate with a preference for PtdIns(3,4,5)P3. Furthermore, this enzyme can also act as a cytosolic inositol 3-phosphatase acting on Ins(1,3,4,5,6)P5/inositol 1,3,4,5,6 pentakisphosphate and possibly Ins(1,3,4,5)P4/1D-myo-inositol 1,3,4,5-tetrakisphosphate. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation. Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability ; [Isoform alpha]: Functional kinase, like isoform 1 it antagonizes the PI3K-AKT/PKB signaling pathway. Plays a role in mitochondrial energetic metabolism by promoting COX activity and ATP production, via collaboration with isoform 1 in increasing protein levels of PINK1.
• Tissue Specificity: Expressed at a relatively high level in all adult tissues, including heart, brain, placenta, lung, liver, muscle, kidney and pancreas.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  FoxO sig.ling pathway (hsa04068)
  Phosphatidylinositol sig.ling system (hsa04070)
  Sphingolipid sig.ling pathway (hsa04071)
  p53 sig.ling pathway (hsa04115)
  Autophagy - animal (hsa04140)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  Cellular senescence (hsa04218)
  Focal adhesion (hsa04510)
  Insulin resistance (hsa04931)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Pathways in cancer (hsa05200)
  MicroR.s in cancer (hsa05206)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Small cell lung cancer (hsa05222)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Central carbon metabolism in cancer (hsa05230)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204)
  Negative regulation of the PI3K/AKT network (R-HSA-199418)
  Downstream TCR signaling (R-HSA-202424)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
  PTEN Loss of Function in Cancer (R-HSA-5674404)
  Ub-specific processing proteases (R-HSA-5689880)
  Ovarian tumor domain proteases (R-HSA-5689896)
  Regulation of PTEN mRNA translation (R-HSA-8943723)
  Regulation of PTEN localization (R-HSA-8948747)
  Regulation of PTEN stability and activity (R-HSA-8948751)
  Transcriptional Regulation by MECP2 (R-HSA-8986944)
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)
• BioCyc Pathway: MetaCyc:HS10404-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cowden syndrome 1	DISSZB0N	Definitive	Autosomal dominant	[1]
Macrocephaly-autism syndrome	DISPGWOW	Definitive	Autosomal dominant	[2]
Proteus syndrome	DISJ3VXH	Definitive	Somatic mosaicism	[3]
PTEN hamartoma tumor syndrome	DISR6ULG	Definitive	Autosomal dominant	[4]
Leiomyosarcoma	DIS6COXM	Moderate	Autosomal recessive	[5]
Renal cell carcinoma	DISQZ2X8	Moderate	Autosomal dominant	[6]
Activated PI3K-delta syndrome	DISRL9M9	Supportive	Autosomal dominant	[7]
Bannayan-Riley-Ruvalcaba syndrome	DIS99DFP	Supportive	Autosomal dominant	[8]
Cowden disease	DISMYKCE	Supportive	Autosomal dominant	[9]
Lhermitte-Duclos disease	DIS87XW7	Supportive	Autosomal dominant	[10]
Proteus-like syndrome	DIS19G36	Supportive	Autosomal dominant	[11]
Recurrent malignant glioma	DISOZ01W	Limited	Autosomal dominant	[1]

This DOT Affected the Drug Response of 12 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cytarabine	DMZD5QR	Approved	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of Cytarabine.	[71]
Etoposide	DMNH3PG	Approved	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of Etoposide.	[72]
Daunorubicin	DMQUSBT	Approved	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of Daunorubicin.	[73]
GDC0941	DM1YAK6	Phase 2	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of GDC0941.	[74]
BEZ235	DMKBRDL	Phase 2	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of BEZ235.	[75]
GDC-0980/RG7422	DMF3MV1	Phase 2	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of GDC-0980/RG7422.	[76]
LY294002	DMY1AFS	Phase 1	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) affects the response to substance of LY294002.	[56]
Palomid-529	DM428Y3	Phase 1	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) decreases the response to substance of Palomid-529.	[77]
PMID28460551-Compound-2	DM4DOUB	Patented	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of PMID28460551-Compound-2.	[78]
[3H]methyltrienolone	DMTSGOW	Investigative	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) decreases the response to substance of [3H]methyltrienolone.	[35]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) decreases the response to substance of Rapamycin Immunosuppressant Drug.	[79]
TGX-221	DMM0LRE	Investigative	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) increases the response to substance of TGX-221.	[80]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[25]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[27]
EHT-1864	DMYAMP5	Terminated	EHT-1864 decreases the phosphorylation of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[58]

64 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the activity of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the activity of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[17]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[21]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[22]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[23]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[24]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[26]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[28]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[29]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[30]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[31]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the activity of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[14]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[23]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[32]
Gemcitabine	DMSE3I7	Approved	Gemcitabine affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[26]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[33]
Thalidomide	DM70BU5	Approved	Thalidomide increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[34]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the activity of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[35]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[36]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[37]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[38]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[39]
Cantharidin	DMBP5N3	Approved	Cantharidin increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[40]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[41]
Fludarabine	DMVRLT7	Approved	Fludarabine increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[36]
Digitoxin	DMWVIGP	Approved	Digitoxin increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[42]
Cladribine	DM3JDRP	Approved	Cladribine increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[36]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[44]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[45]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[46]
Triptolide	DMCMDVR	Phase 3	Triptolide increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[47]
5-methoxypsoralen	DME2A8X	Phase 3	5-methoxypsoralen increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[48]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[49]
PF-04691502	DMS610L	Phase 2	PF-04691502 increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[50]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[51]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[52]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[53]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[54]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[55]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[56]
Calphostin C	DM9X2D0	Terminated	Calphostin C increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[59]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[60]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[61]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[52]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[63]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[52]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[64]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[65]
OLEANOLIC_ACID	DMWDMJ3	Investigative	OLEANOLIC_ACID increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[66]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[52]
propylpyrazoletriol	DMTCP8K	Investigative	propylpyrazoletriol increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[67]
Flavanone	DMNWIYM	Investigative	Flavanone increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[68]
LUPEOL	DM4ZLUH	Investigative	LUPEOL increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[69]
diarylpropionitril	DM14X29	Investigative	diarylpropionitril increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[67]
GOSSYPETIN	DMMT05U	Investigative	GOSSYPETIN increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[70]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Sorbitol	DMAN0DE	Approved	Sorbitol affects the localization of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[43]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the secretion of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN).	[62]

References

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• [8] PTEN Hamartoma Tumor Syndrome. 2001 Nov 29 [updated 2021 Feb 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
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