Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7WUAV)

• DTT Name: Protein-tyrosine phosphatase SHP-2 (PTPN11)
• Synonyms: Tyrosine-protein phosphatase non-receptor type 11; SHPTP2; SHP2; SHP-2; SH-PTP3; SH-PTP2; Protein-tyrosine phosphatase SHP2; Protein-tyrosine phosphatase 2C; Protein-tyrosine phosphatase 1D; PTP2C; PTP-2C; PTP-1D
• Gene Name: PTPN11
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: PTN11_HUMAN
• TTD ID: T13057
• EC Number: EC 3.1.3.48
• Sequence:
  MTSRRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTG
  DYYDLYGGEKFATLAELVQYYMEHHGQLKEKNGDVIELKYPLNCADPTSERWFHGHLSGK
  EAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKGESNDGKSKVTHVMIRCQELKYD
  VGGGERFDSLTDLVEHYKKNPMVETLGTVLQLKQPLNTTRINAAEIESRVRELSKLAETT
  DKVKQGFWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNEP
  VSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEV
  ERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHF
  RTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHCSAGIGRTGTFIVIDILIDIIR
  EKGVDCDIDVPKTIQMVRSQRSGMVQTEAQYRFIYMAVQHYIETLQRRIEEEQKSKRKGH
  EYTNIKYSLADQTSGDQSPLPPCTPTPPCAEMREDSARVYENVGLMQQQKSFR
• Function: Positively regulates MAPK signal transduction pathway. Dephosphorylates GAB1, ARHGAP35 and EGFR. Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulatation of its RhoA binding activity. Dephosphorylates CDC73. Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Jak-STAT signaling pathway (hsa04630)
  Natural killer cell mediated cytotoxicity (hsa04650)
  Leukocyte transendothelial migration (hsa04670)
  Neurotrophin signaling pathway (hsa04722)
  Adipocytokine signaling pathway (hsa04920)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Herpes simplex infection (hsa05168)
  Proteoglycans in cancer (hsa05205)
  Renal cell carcinoma (hsa05211)
  Chronic myeloid leukemia (hsa05220)
• Reactome Pathway:
  PI3K Cascade (R-HSA-109704)
  MAPK3 (ERK1) activation (R-HSA-110056)
  MAPK1 (ERK2) activation (R-HSA-112411)
  GPVI-mediated activation cascade (R-HSA-114604)
  Prolactin receptor signaling (R-HSA-1170546)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Spry regulation of FGF signaling (R-HSA-1295596)
  GAB1 signalosome (R-HSA-180292)
  PECAM1 interactions (R-HSA-210990)
  Tie2 Signaling (R-HSA-210993)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Costimulation by the CD28 family (R-HSA-388841)
  CTLA4 inhibitory signaling (R-HSA-389513)
  PD-1 signaling (R-HSA-389948)
  Signal regulatory protein (SIRP) family interactions (R-HSA-391160)
  Netrin mediated repulsion signals (R-HSA-418886)
  Platelet sensitization by LDL (R-HSA-432142)
  Interleukin-3, 5 and GM-CSF signaling (R-HSA-512988)
  PI-3K cascade (R-HSA-5654689)
  FRS-mediated FGFR1 signaling (R-HSA-5654693)
  PI-3K cascade (R-HSA-5654695)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  FRS-mediated FGFR3 signaling (R-HSA-5654706)
  PI-3K cascade (R-HSA-5654710)
  FRS-mediated FGFR4 signaling (R-HSA-5654712)
  SHC-mediated cascade (R-HSA-5654719)
  PI-3K cascade (R-HSA-5654720)
  Negative regulation of FGFR1 signaling (R-HSA-5654726)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Negative regulation of FGFR3 signaling (R-HSA-5654732)
  Negative regulation of FGFR4 signaling (R-HSA-5654733)
  Regulation of IFNG signaling (R-HSA-877312)
  Interferon alpha/beta signaling (R-HSA-909733)
  Regulation of IFNA signaling (R-HSA-912694)
  Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon (R-HSA-936964)
  Interleukin-6 signaling (R-HSA-1059683)

Molecular Interaction Atlas (MIA) of This DTT

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JAB-3312	DMNMV0D	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
A380	DMXOZDP	Aggressive cancer	2A00-2F9Z	Phase 1	[3]
BBP-398	DM572ZL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
JAB-3068	DMSGEU6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]
PF-07284892	DMQ6F8X	Aggressive cancer	2A00-2F9Z	Phase 1	[5]
RG6433	DMZM06U	Aggressive cancer	2A00-2F9Z	Phase 1	[6]
RLY-1971	DMUT4YZ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
SAR442720	DMTAOPC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
TNO155	DMZ60X4	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NSC-87877	DMEYKXL	Discovery agent	N.A.	Patented	[9]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dodecane-Trimethylamine	DMUPMCZ	Discovery agent	N.A.	Investigative	[10]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Clinical pipeline report, company report or official report of AbbVie.
• [3] Clinical pipeline report, company report or official report of Klus Pharma
• [4] ClinicalTrials.gov (NCT04528836) First-in-Human Study of the SHP2 Inhibitor BBP-398 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
• [5] SHP2 Inhibition Sensitizes Diverse Oncogene-Addicted Solid Tumors to Re-treatment with Targeted Therapy. Cancer Discov. 2023 Aug 4;13(8):1789-1801.
• [6] Clinical pipeline report, company report or official report of Roche
• [7] Clinical pipeline report, company report or official report of Relay Therapeutics.
• [8] Clinical pipeline report, company report or official report of Revolution Medicines.
• [9] Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. J Med Chem. 2008 Aug 28;51(16):4948-56.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.