Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMS7KP)

• DTT Name: Protein-tyrosine phosphatase 1B (PTP1B)
• Synonyms: Tyrosine-protein phosphatase non-receptor type 1; PTP-1B
• Gene Name: PTPN1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: PTN1_HUMAN
• TTD ID: T16347
• EC Number: EC 3.1.3.48
• Sequence:
  MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLH
  QEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLK
  CAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWP
  DFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKD
  PSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLE
  PPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYG
  IESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLT
  AGAYLCYRFLFNSNT
• Function: Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response.
• KEGG Pathway:
  Adherens junction (hsa04520)
  Insulin signaling pathway (hsa04910)
• Reactome Pathway:
  Regulation of IFNG signaling (R-HSA-877312)
  Regulation of IFNA signaling (R-HSA-912694)
  Growth hormone receptor signaling (R-HSA-982772)
  Integrin alphaIIb beta3 signaling (R-HSA-354192)

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IONIS-PTP1BRX	DMGTJUP	Type-2 diabetes	5A11	Phase 2	[1]
TTP-814	DMH9RGV	Diabetic complication	5A2Y	Phase 1/2	[2]
KQ-791	DMK0BTN	Type-2 diabetes	5A11	Phase 1	[1]
Trodusquemine	DMQ7UN6	Breast cancer	2C60-2C65	Phase 1	[3]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JTT-551	DM48HVI	Type-2 diabetes	5A11	Terminated	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	9.44E-01	7.21E-03	0.08

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Tyrosine-protein phosphatase non-receptor 1 (PTP1B) DME Info
• Gene Name: PTPN1

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-nitrophenyl phosphate	DMBX4UJ	Discovery agent	N.A.	Investigative	[5]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Protein tyrosine phosphatase 1B (PTP-1B; PTPN1). SciBX 5(7); doi:10.1038/scibx.2012.176. Feb. 16 2012
• [3] Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring). 2010 Aug;18(8):1516-23.
• [4] Pharmacological effects of JTT-551, a novel protein tyrosine phosphatase 1B inhibitor, in diet-induced obesity mice. J Diabetes Res. 2014;2014:680348.
• [5] Residues distant from the active site influence protein-tyrosine phosphatase 1B inhibitor binding. J Biol Chem. 2006 Feb 24;281(8):5258-66.