Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEC2T3)

• DTT Name: Human immunodeficiency virus Envelope glycoprotein gp160 (HIV env)
• Synonyms: Envelope glycoprotein gp160; Env polyprotein
• Gene Name: HIV env
• DTT Type: Clinical trial target; [1]
• Related Disease: Human immunodeficiency virus disease [ICD-11: 1C60-1C62]
• UniProt ID: ENV_HV1H2
• TTD ID: T02591
• Sequence:
  MRVKEKYQHLWRWGWRWGTMLLGMLMICSATEKLWVTVYYGVPVWKEATTTLFCASDAKA
  YDTEVHNVWATHACVPTDPNPQEVVLVNVTENFNMWKNDMVEQMHEDIISLWDQSLKPCV
  KLTPLCVSLKCTDLKNDTNTNSSSGRMIMEKGEIKNCSFNISTSIRGKVQKEYAFFYKLD
  IIPIDNDTTSYKLTSCNTSVITQACPKVSFEPIPIHYCAPAGFAILKCNNKTFNGTGPCT
  NVSTVQCTHGIRPVVSTQLLLNGSLAEEEVVIRSVNFTDNAKTIIVQLNTSVEINCTRPN
  NNTRKRIRIQRGPGRAFVTIGKIGNMRQAHCNISRAKWNNTLKQIASKLREQFGNNKTII
  FKQSSGGDPEIVTHSFNCGGEFFYCNSTQLFNSTWFNSTWSTEGSNNTEGSDTITLPCRI
  KQIINMWQKVGKAMYAPPISGQIRCSSNITGLLLTRDGGNSNNESEIFRPGGGDMRDNWR
  SELYKYKVVKIEPLGVAPTKAKRRVVQREKRAVGIGALFLGFLGAAGSTMGAASMTLTVQ
  ARQLLSGIVQQQNNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQQLLGIWGCSG
  KLICTTAVPWNASWSNKSLEQIWNHTTWMEWDREINNYTSLIHSLIEESQNQQEKNEQEL
  LELDKWASLWNWFNITNWLWYIKLFIMIVGGLVGLRIVFAVLSIVNRVRQGYSPLSFQTH
  LPTPRGPDRPEGIEEEGGERDRDRSIRLVNGSLALIWDDLRSLCLFSYHRLRDLLLIVTR
  IVELLGRRGWEALKYWWNLLQYWSQELKNSAVSLLNATAIAVAEGTDRVIEVVQGACRAI
  RHIPRRIRQGLERILL
• Function: Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.
• Reactome Pathway:
  Budding and maturation of HIV virion (R-HSA-162588)
  Synthesis and processing of ENV and VPU (R-HSA-171286)
  Binding and entry of HIV virion (R-HSA-173107)
  Assembly Of The HIV Virion (R-HSA-175474)
  Dectin-2 family (R-HSA-5621480)
  Alpha-defensins (R-HSA-1462054)

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
Ad35-GRIN/ENV	DMG82ZA	Human immunodeficiency virus infection	1C62	Phase 1	[2]
Ad5-ENVA-48	DMMBQV3	Human immunodeficiency virus-1 infection	1C62	Phase 1	[1]
MGD014	DMZN5QX	Human immunodeficiency virus-1 infection	1C62	Phase 1	[3]
PENNVAX-6	DM0BNLC	Human immunodeficiency virus infection	1C62	Phase 1	[4]
TBC-M4	DM9CDPO	Human immunodeficiency virus infection	1C62	Phase 1	[5]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GPG	DMYR7LO	Human immunodeficiency virus infection	1C62	Discontinued in Phase 1/2	[6]

References

• [1] ClinicalTrials.gov (NCT00695877) Safety and Immune Response to a Recombinant Adenovirus HIV-1 Vaccine in Healthy Adults. U.S. National Institutes of Health.
• [2] A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults. PLoS One. 2012;7(8):e41936.
• [3] Clinical pipeline report, company report or official report of MacroGenics.
• [4] Company report (Inovio)
• [5] A Phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C-modified vaccinia Ankara virus vaccine candidate in Indian volunteers. AIDS Res Hum Retroviruses. 2009 Nov;25(11):1107-16.
• [6] GPG-NH2 acts via the metabolite alphaHGA to target HIV-1 Env to the ER-associated protein degradation pathway. Retrovirology 2010, 7:20.