Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3CPZW)

• DTT Name: Human papillomavirus protein E7 (HPV E7)
• Synonyms: Protein E7; E7
• Gene Name: HPV E7
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Papillomaviridae E protein
• UniProt ID: VE7_HPV16
• TTD ID: T85072
• Sequence:
  MHGDTPTLHEYMLDLQPETTDLYCYEQLNDSSEEEDEIDGPAGQAEPDRAHYNIVTFCCK
  CDSTLRLCVQSTHVDIRTLEDLLMGTLGIVCPICSQKP
• Function: E7 protein has both transforming and trans-activating activities. Disrupts the function of host retinoblastoma protein RB1/pRb, which is a key regulator of the cell cycle. Induces the disassembly of the E2F1 transcription factors from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. Interferes with histone deacetylation mediated by HDAC1 and HDAC2, leading to activation of transcription.

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VGX-3100	DMMQ2U9	Cervical Intraepithelial neoplasia	2E66.1	Phase 3	[1]
ADXS-HPV	DMC8NAO	Cervical cancer	2C77.0	Phase 2	[2]
Tipapkinogene sovacivec	DM5XRMA	Cervical Intraepithelial neoplasia	2E66.1	Phase 2	[3]
CIGB-228	DMJFPK6	Human papillomavirus infection	1A9Y	Phase 1	[4]
KITE-439	DMUB3H9	Cervical cancer	2C77.0	Phase 1	[5]

References

• [1] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [2] ADXS11-001 immunotherapy targeting HPV-E7: updated survival and safety data from a phase 2 study in Indian women with recurrent/refractory cervical cancer. Journal for ImmunoTherapy of Cancer, 2013, 1(Suppl 1):P231.
• [3] Immune therapy for human papillomaviruses-related cancers
• [4] Safety and Immunogenicity of a Human Papillomavirus Peptide Vaccine (CIGB-228) in Women with High-Grade Cervical Intraepithelial Neoplasia: First-in-Human, Proof-of-Concept Trial. ISRN Obstet Gynecol. 2011; 2011: 292951.
• [5] ClinicalTrials.gov (NCT03912831) Safety and Efficacy of KITE-439 in HLA-A*02:01+ Adults With Relapsed/Refractory HPV16+ Cancers. U.S. National Institutes of Health.