Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT15SL0)

• DTT Name: Proheparin-binding EGF-like growth factor (HBEGF)
• Synonyms: Proheparinbinding EGFlike growth factor; Heparinbinding EGFlike growth factor; Heparin-binding EGF-like growth factor; HEGFL; HB-EGF; Diphtheria toxin receptor; DTS; DTR; DT-R
• Gene Name: HBEGF
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Growth factor
• UniProt ID: HBEGF_HUMAN
• TTD ID: T76093
• Sequence:
  MKLLPSVVLKLFLAAVLSALVTGESLERLRRGLAAGTSNPDPPTVSTDQLLPLGGGRDRK
  VRDLQEADLDLLRVTLSSKPQALATPNKEEHGKRKKKGKGLGKKRDPCLRKYKDFCIHGE
  CKYVKELRAPSCICHPGYHGERCHGLSLPVENRLYTYDHTTILAVVAVVLSSVCLLVIVG
  LLMFRYHRRGGYDVENEEKVKLGMTNSH
• Function: Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor. Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4.
• KEGG Pathway:
  ErbB signaling pathway (hsa04012)
  GnRH signaling pathway (hsa04912)
  Estrogen signaling pathway (hsa04915)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Proteoglycans in cancer (hsa05205)
• Reactome Pathway:
  PI3K events in ERBB4 signaling (R-HSA-1250342)
  SHC1 events in ERBB4 signaling (R-HSA-1250347)
  Nuclear signaling by ERBB4 (R-HSA-1251985)
  PIP3 activates AKT signaling (R-HSA-1257604)
  GRB2 events in ERBB2 signaling (R-HSA-1963640)
  PI3K events in ERBB2 signaling (R-HSA-1963642)
  EGFR Transactivation by Gastrin (R-HSA-2179392)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  RAF/MAP kinase cascade (R-HSA-5673001)
  SHC1 events in ERBB2 signaling (R-HSA-1250196)

Molecular Interaction Atlas (MIA) of This DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP0598	DM9QUCH	Chronic tympanic membrane perforation	AB13	Phase 1	[2]
KHK-2866	DMR7EF6	Ovarian cancer	2C73	Phase 1	[1]
U3-1565	DMWOE62	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Ovarian cancer	2C82	Ovarian tissue	3.92E-01	0.06	0.12

References

• [1] ClinicalTrials.gov (NCT01279291) Study of Anti-HB-EGF Antibody KHK2866 in Subjects With Advanced Solid Tumors and Ovarian Cancer. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT04305184) A Phase 1/2, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of ASP0598 Otic Solution Following Topical Application Into the Ear in Subjects With Chronic Tympanic Membrane Perforation (CTMP). U.S.National Institutes of Health.
• [3] J Clin Oncol 31, 2013 (suppl; abstr 2519).