Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5FH9Y)

• DTT Name: Human immunodeficiency virus Integrase (HIV IN)
• Synonyms: HIV IN
• Gene Name: HIV IN
• DTT Type: Successful target; [1]
• BioChemical Class: Integrase
• UniProt ID: POL_HV1B1
• TTD ID: T39087
• EC Number: EC 2.7.7.-
• Sequence:
  FLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGI
  WQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSN
  FTSATVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAV
  FIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAK
  LLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED
• Function: Gag-Pol polyprotein: Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bictegravir, emtricitabine and tenofovir alafenamide	DMG0H8K	Human immunodeficiency virus infection	1C62	Approved	[2]
Dolutegravir	DMCZGRE	Human immunodeficiency virus infection	1C62	Approved	[1]
Elvitegravir	DMG9B1U	Human immunodeficiency virus infection	1C62	Approved	[1]
Raltegravir	DMYURI6	Human immunodeficiency virus infection	1C62	Approved	[3]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK1265744	DMT8J0I	Human immunodeficiency virus infection	1C62	Phase 3	[4]
S-1360	DM9KTSG	Human immunodeficiency virus infection	1C62	Phase 2	[5]
S-364735	DMU7ZMH	Human immunodeficiency virus infection	1C62	Phase 2	[6]
Acriflavine	DMKVE8X	Human immunodeficiency virus infection	1C62	Phase 1	[7]
C-2507	DMOFT1V	Human immunodeficiency virus infection	1C62	Phase 1	[8]
S-265744 LAP	DMDQRWT	Human immunodeficiency virus infection	1C62	Phase 1	[9]
VH4524184	DM1FS0F	Human immunodeficiency virus infection	1C62	Phase 1	[10]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JTK-656	DMEADBG	Human immunodeficiency virus infection	1C62	Discontinued in Phase 1	[11]
AR177	DMHU1E8	Human immunodeficiency virus infection	1C62	Terminated	[12]
GS-9160	DMQSMB1	Human immunodeficiency virus infection	1C62	Terminated	[13]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dicaffeoylquinic acids	DM4I5Z3	Human immunodeficiency virus infection	1C62	Investigative	[14]
Dicaffeoyltartaric acids	DMAV0BX	Human immunodeficiency virus infection	1C62	Investigative	[14]
L-708,906	DMWYIJ3	Discovery agent	N.A.	Investigative	[12]
L-731,988	DM7YVUT	Discovery agent	N.A.	Investigative	[12]
L17	DMZ4KO0	Discovery agent	N.A.	Investigative	[12]
Purpurin	DMYWRL6	Discovery agent	N.A.	Investigative	[15]
V-165	DM8SWVN	Discovery agent	N.A.	Investigative	[16]

References

• [1] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [2] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [3] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] HIV-1 integrase inhibitors: an emerging clinical reality. Drugs R D. 2007;8(3):155-68.
• [6] The naphthyridinone GSK364735 is a novel, potent human immunodeficiency virus type 1 integrase inhibitor and antiretroviral. Antimicrob Agents Chemother. 2008 Mar;52(3):901-8.
• [7] Why have ten or so nontoxic, retrovirus integrase inhibitors not been made available for AIDS treatment. Biomed Pharmacother. 1999 Dec;53(10):484-6.
• [8] Elvitegravir: a new HIV integrase inhibitor. Antivir Chem Chemother. 2009 Oct 19;20(2):79-85.
• [9] Long-acting shot prevents infection with HIV analogue. Nature. doi:10.1038/nature.2014.14819. 04 March 2014
• [10] Clinical pipeline report, company report or official report of ViiV Healthcare
• [11] US patent application no. 8,497,270, Macrocyclic integrase inhibitors.
• [12] Specific inhibition of human immunodeficiency virus type 1 (HIV-1) integration in cell culture: putative inhibitors of HIV-1 integrase. Antimicrob Agents Chemother. 2001 Sep;45(9):2510-6.
• [13] Preclinical evaluation of GS-9160, a novel inhibitor of human immunodeficiency virus type 1 integrase. Antimicrob Agents Chemother. 2009 Mar;53(3):1194-203.
• [14] Dicaffeoylquinic and dicaffeoyltartaric acids are selective inhibitors of human immunodeficiency virus type 1 integrase. Antimicrob Agents Chemother. 1998 Jan;42(1):140-6.
• [15] Identification of HIV-1 integrase inhibitors based on a four-point pharmacophore. Antivir Chem Chemother. 1998 Nov;9(6):461-72.
• [16] New class of HIV integrase inhibitors that block viral replication in cell culture. Curr Biol. 2002 Jul 23;12(14):1169-77.