Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEYRJ9)

• DTT Name: GRB2 messenger RNA (GRB2 mRNA)
• Synonyms: SH2/SH3 adapter GRB2 (mRNA); Protein Ash (mRNA); Growth factor receptor-bound protein 2 (mRNA); Adapter protein GRB2 (mRNA); ASH (mRNA)
• Gene Name: GRB2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: mRNA target
• UniProt ID: GRB2_HUMAN
• TTD ID: T30926
• Sequence:
  MEAIAKYDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIEMKPHPW
  FFGKIPRAKAEEMLSKQRHDGAFLIRESESAPGDFSLSVKFGNDVQHFKVLRDGAGKYFL
  WVVKFNSLNELVDYHRSTSVSRNQQIFLRDIEQVPQQPTYVQALFDFDPQEDGELGFRRG
  DFIHVMDNSDPNWWKGACHGQTGMFPRNYVTPVNRNV
• Function: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.
• KEGG Pathway:
  EGFR tyrosine kinase inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  MAPK signaling pathway (hsa04010)
  ErbB signaling pathway (hsa04012)
  Ras signaling pathway (hsa04014)
  Chemokine signaling pathway (hsa04062)
  FoxO signaling pathway (hsa04068)
  Phospholipase D signaling pathway (hsa04072)
  mTOR signaling pathway (hsa04150)
  PI3K-Akt signaling pathway (hsa04151)
  Osteoclast differentiation (hsa04380)
  Focal adhesion (hsa04510)
  Gap junction (hsa04540)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  JAK-STAT signaling pathway (hsa04630)
  Natural killer cell mediated cytotoxicity (hsa04650)
  T cell receptor signaling pathway (hsa04660)
  B cell receptor signaling pathway (hsa04662)
  Fc epsilon RI signaling pathway (hsa04664)
  Thermogenesis (hsa04714)
  Neurotrophin signaling pathway (hsa04722)
  Insulin signaling pathway (hsa04910)
  GnRH signaling pathway (hsa04912)
  Estrogen signaling pathway (hsa04915)
  Prolactin signaling pathway (hsa04917)
  Relaxin signaling pathway (hsa04926)
  Growth hormone synthesis, secretion and action (hsa04935)
  Alcoholism (hsa05034)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Human cytomegalovirus infection (hsa05163)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Proteoglycans in cancer (hsa05205)
  MicroRNAs in cancer (hsa05206)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Colorectal cancer (hsa05210)
  Renal cell carcinoma (hsa05211)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Chronic myeloid leukemia (hsa05220)
  Acute myeloid leukemia (hsa05221)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  SOS-mediated signalling (R-HSA-112412)
  Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382)
  SHC1 events in ERBB2 signaling (R-HSA-1250196)
  SHC1 events in ERBB4 signaling (R-HSA-1250347)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Spry regulation of FGF signaling (R-HSA-1295596)
  Signaling by SCF-KIT (R-HSA-1433557)
  Regulation of KIT signaling (R-HSA-1433559)
  Signalling to RAS (R-HSA-167044)
  GRB2 events in EGFR signaling (R-HSA-179812)
  GAB1 signalosome (R-HSA-180292)
  SHC1 events in EGFR signaling (R-HSA-180336)
  EGFR downregulation (R-HSA-182971)
  Signaling by cytosolic FGFR1 fusion mutants (R-HSA-1839117)
  Downstream signal transduction (R-HSA-186763)
  GRB2 events in ERBB2 signaling (R-HSA-1963640)
  PI3K events in ERBB2 signaling (R-HSA-1963642)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  Tie2 Signaling (R-HSA-210993)
  EGFR Transactivation by Gastrin (R-HSA-2179392)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  DAP12 signaling (R-HSA-2424491)
  SHC-related events triggered by IGF1R (R-HSA-2428933)
  Role of LAT2/NTAL/LAB on calcium mobilization (R-HSA-2730905)
  FCERI mediated MAPK activation (R-HSA-2871796)
  FCERI mediated Ca+2 mobilization (R-HSA-2871809)
  GRB2 (R-HSA-354194)
  NCAM signaling for neurite out-growth (R-HSA-375165)
  Costimulation by the CD28 family (R-HSA-388841)
  CD28 dependent Vav1 pathway (R-HSA-389359)
  Signal regulatory protein family interactions (R-HSA-391160)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)
  Constitutive Signaling by EGFRvIII (R-HSA-5637810)
  SHC-mediated cascade (R-HSA-5654688)
  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)
  SHC-mediated cascade (R-HSA-5654704)
  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)
  Signaling by FGFR2 in disease (R-HSA-5655253)
  Signaling by FGFR4 in disease (R-HSA-5655291)
  Signaling by FGFR1 in disease (R-HSA-5655302)
  Signaling by FGFR3 in disease (R-HSA-5655332)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Negative regulation of MET activity (R-HSA-6807004)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Signal attenuation (R-HSA-74749)
  Insulin receptor signalling cascade (R-HSA-74751)
  MET activates RAS signaling (R-HSA-8851805)
  MET activates PI3K/AKT signaling (R-HSA-8851907)
  RET signaling (R-HSA-8853659)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  MET activates PTPN11 (R-HSA-8865999)
  InlB-mediated entry of Listeria monocytogenes into host cell (R-HSA-8875360)
  MET activates RAP1 and RAC1 (R-HSA-8875555)
  MET receptor recycling (R-HSA-8875656)
  Interleukin-15 signaling (R-HSA-8983432)
  RHOU GTPase cycle (R-HSA-9013420)
  Activated NTRK2 signals through RAS (R-HSA-9026519)
  Erythropoietin activates RAS (R-HSA-9027284)
  Activated NTRK2 signals through PI3K (R-HSA-9028335)
  Activated NTRK2 signals through FRS2 and FRS3 (R-HSA-9028731)
  Activated NTRK3 signals through RAS (R-HSA-9034864)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Regulation of signaling by CBL (R-HSA-912631)
  FLT3 Signaling (R-HSA-9607240)
  Constitutive Signaling by Overexpressed ERBB2 (R-HSA-9634285)
  STAT5 Activation (R-HSA-9645135)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Signaling by ERBB2 KD Mutants (R-HSA-9664565)
  Signaling by ERBB2 ECD mutants (R-HSA-9665348)
  Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686)
  Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439)
  Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants (R-HSA-9673767)
  Signaling by PDGFRA extracellular domain mutants (R-HSA-9673770)
  Signaling by CSF3 (G-CSF) (R-HSA-9674555)
  STAT5 activation downstream of FLT3 ITD mutants (R-HSA-9702518)
  Signaling by FLT3 fusion proteins (R-HSA-9703465)
  Signaling by FLT3 ITD and TKD mutants (R-HSA-9703648)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Antigen activates B Cell Receptor (BCR) leading to generation of second messenger (R-HSA-983695)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BP-100-1-01	DMKDGI8	Acute lymphoblastic leukaemia	2A85	Phase 2	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Myelodysplastic syndrome	2C82	Bone marrow	2.27E-04	0.2	0.94

References

• [1] ClinicalTrials.gov (NCT01159028) Clinical Trial of BP1001 (L-Grb-2 Antisense Oligonucleotide) in CML, AML, ALL & MDS. U.S. National Institutes of Health.