Target General Infomation
Target ID
T56915
Former ID
TTDS00320
Target Name
HIV protease
Gene Name
gag-pol
Synonyms
HIV-1 Retropepsin; HIV-1 peptidase; Retropepsin; gag-pol
Target Type
Successful
Disease HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2]
HIV-1 infection [ICD9: 001-139, 042; ICD10: B20-B24]
Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26]
Viral infections [ICD9: 054.0, 054.1, 054.2, 054.3, 075, 771.2, 052, 053; ICD10: B01, B02, A60, B00, B27, G05.1, P35.2]
Unspecified [ICD code not available]
Function
Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre- integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bpduplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.
BioChemical Class
Peptidase
Target Validation
T56915
UniProt ID
EC Number
EC 3.4.23.16
Sequence
PQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPGRWKPKMIGGIGGFIKVRQYD
QILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNF
Structure
1A9M; 1AJV; 1AJX; 1AXA; 1BQM; 1BQN; 1D4H; 1D4I; 1D4J; 1DLO; 1DW6; 1EBK; 1EBW; 1EBY; 1EBZ; 1EC0; 1EC1; 1EC2; 1EC3; 1EET; 1G35; 1GNM; 1GNN; 1GNO; 1HAR; 1HBV; 1HEF; 1HEG; 1HIH; 1HMV; 1HNI; 1HNV; 1HOS; 1HPS; 1HPZ; 1HQE; 1HQU; 1HRH; 1HTE; 1HTF; 1HTG; 1HVI; 1HVK; 1HVP; 1HVU; 1HYS; 1IKV; 1IKW; 1IKX; 1IKY; 1J5O; 1KJH; 1MER; 1MES; 1MET; 1MEU; 1N5Y; 1N6Q; 1NPA; 1NPV; 1NPW; 1QE1; 1QMC;1R0A; 1RDH; 1RTD; 1RVL; 1RVM; 1RVN; 1RVO; 1RVP; 1RVQ; 1RVR; 1S6P; 1S6Q; 1S9E; 1S9G; 1SBG; 1SUQ; 1SV5; 1T03; 1T05; 1T7K; 1TV6; 1TVR; 1UWB; 1W5V; 1W5W; 1W5X; 1W5Y; 1YT9; 1ZP8; 1ZPA; 1ZSF; 1ZSR; 2AQU; 2B5J; 2B6A; 2BAN; 2BBB; 2BE2; 2EXF; 2G69; 2HB3; 2HMI; 2HNZ; 2HS1; 2HS2; 2I4D; 2I4U; 2I4V; 2I4W; 2I4X; 2I5J; 2IAJ; 2IC3; 2IDW; 2IEO; 2JZW; 2L45; 2L46; 2L4L; 2UXZ; 2UY0; 2VG5; 2VG6; 2VG7; 2X4U; 2YKM; 2YKN; 2ZD1; 2ZE2; 3AVI; 3BGR; 3DLK; 3GGA; 3GGV; 3GGX; 3HVT; 3IG1; 3IRX; 3IS9; 3ISN; 3ITH; 3JSM; 3JYT; 3K2P; 3K4V; 3KLE; 3KLF; 3KLG; 3KLH; 3KLI; 3NDT; 3NU3; 3NU4; 3NU5; 3NU6; 3NU9; 3NUJ; 3NUO; 3OK9; 3PSU;3QAA; 3QLH; 3QO9; 3TKG; 3TKW; 3TL9; 3TLH; 3V4I; 3V6D; 3V81; 3ZPS; 3ZPT; 3ZPU; 4COE; 4CP7; 4CPQ; 4CPR; 4CPS; 4CPT; 4CPU; 4CPW; 4CPX; 4DG1; 4G1Q; 4G8G; 4G8I; 4G9D; 4G9F; 4H4M; 4H4O; 4I2P; 4I2Q; 4ICL; 4ID5; 4IDK; 4IFV; 4IFY; 4IG0; 4IG3; 4KFB; 4KKO; 4KO0; 4LSL; 4LSN; 4MFB; 4O44; 4O4G; 4OJR; 4PQU; 4PUO; 4PWD; 4Q0B; 4QAG; 4U8W; 4WE1
Drugs and Mode of Action
Drug(s) Amprenavir Drug Info Approved Human immunodeficiency virus infection [536361]
Atazanavir Drug Info Approved Human immunodeficiency virus infection [536361]
Darunavir Drug Info Approved Human immunodeficiency virus infection [536361]
Fosamprenavir Drug Info Approved Human immunodeficiency virus infection [550326]
Indinavir Drug Info Approved Human immunodeficiency virus infection [550326]
Ritonavir Drug Info Approved Human immunodeficiency virus infection [536361]
Saquinavir Drug Info Approved Human immunodeficiency virus infection [468045], [550326]
Tipranavir Drug Info Approved Human immunodeficiency virus infection [536361]
BI 201335 Drug Info Phase 3 HCV infection [550385]
ABT-450 Drug Info Phase 2 HCV infection [550189]
ACH-1625 Drug Info Phase 2 HCV infection [550195]
BMS 650032 Drug Info Phase 2 HCV infection [550384]
Danoprevir Drug Info Phase 2 HCV infection [551039]
DG-17 Drug Info Phase 2 Human immunodeficiency virus infection [550282]
GS-9256 Drug Info Phase 2 HCV infection [550812]
KNI-272 Drug Info Phase 2 Human immunodeficiency virus infection [544490]
MK-5172 Drug Info Phase 2 HCV infection [551141]
TMC-310911 Drug Info Phase 2 Human immunodeficiency virus infection [522572]
Vaniprevir Drug Info Phase 2 HCV infection [551141]
BIT225 Drug Info Phase 1 HCV infection [550378]
CTP-298 Drug Info Phase 1 Human immunodeficiency virus infection [523670]
PF-04776548 Drug Info Phase 1 Human immunodeficiency virus infection [522912]
VX-500 Drug Info Phase 1 HCV infection [551770]
PPL-100 Drug Info Preclinical Human immunodeficiency virus infection [547190]
A-75925 Drug Info Discontinued in Phase 2 Viral infections [545458]
BRECANAVIR Drug Info Discontinued in Phase 2 Human immunodeficiency virus infection [547500]
MK-944a Drug Info Discontinued in Phase 2 Human immunodeficiency virus infection [547117]
MOZENAVIR MESILATE Drug Info Discontinued in Phase 2 Human immunodeficiency virus infection [545709]
R-87366 Drug Info Discontinued in Phase 2 Human immunodeficiency virus infection [546555]
Telinavir Drug Info Discontinued in Phase 2 Human immunodeficiency virus infection [545455]
GS-9005 Drug Info Discontinued in Phase 1/2 Human immunodeficiency virus infection [547700]
A-80987 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [545217]
CGP-53437 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [545200]
DMP-851 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [546493]
DPC-681 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [547252]
DPC-684 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [547253]
KNI-764 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [546821]
LASINAVIR Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [546180]
R-944 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [547553]
SPI-256 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [548265]
U-103017 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [546040]
U-96988 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [545725]
XM-323 Drug Info Discontinued in Phase 1 Human immunodeficiency virus infection [545218]
AG-1284 Drug Info Terminated Human immunodeficiency virus infection [545853]
AG-1350 Drug Info Terminated Human immunodeficiency virus infection [545680]
BAY-793 Drug Info Terminated Human immunodeficiency virus infection [545325]
BMS-182193 Drug Info Terminated Human immunodeficiency virus infection [545338]
BMS-186318 Drug Info Terminated HIV-1 infection [545817]
CGP-70726 Drug Info Terminated HIV-1 infection [546368]
Droxinavir hydrochloride Drug Info Terminated Human immunodeficiency virus infection [545796]
GE-20372A Drug Info Terminated Human immunodeficiency virus infection [545909]
GS-2992 Drug Info Terminated Human immunodeficiency virus infection [545882]
KNI-102 Drug Info Terminated Human immunodeficiency virus infection [545221]
Palinavir Drug Info Terminated Human immunodeficiency virus infection [545948]
PD-153103 Drug Info Terminated HIV-1 infection [545855]
SB-206343 Drug Info Terminated HIV-1 infection [545968]
U-75875 Drug Info Terminated Human immunodeficiency virus infection [545091]
Inhibitor A-75925 Drug Info [534596]
A-80987 Drug Info [534168]
ABT-450 Drug Info [550189]
ACH-1625 Drug Info [550195]
AG-1350 Drug Info [551632], [551871]
Amprenavir Drug Info [537180]
BI 201335 Drug Info [550385]
BIT225 Drug Info [550378]
BMS 650032 Drug Info [550384]
BMS-232632 Drug Info [535120]
CGP-53437 Drug Info [533961]
CTP-298 Drug Info [550016]
Danoprevir Drug Info [551039]
DG-17 Drug Info [544059]
DMP-851 Drug Info [534751], [551871]
DPC-681 Drug Info [526167], [551871]
DPC-684 Drug Info [526167], [551871]
Fosamprenavir Drug Info [537453]
GE-20372A Drug Info [550896]
GS-9005 Drug Info [550938]
GS-9256 Drug Info [550812]
Indinavir Drug Info [537031]
LASINAVIR Drug Info [534465], [551871]
MK-5172 Drug Info [551141]
MK-944a Drug Info [525865]
MOZENAVIR MESILATE Drug Info [534206]
PPL-100 Drug Info [528026]
R-87366 Drug Info [534336], [551871]
R-944 Drug Info [550855]
Ritonavir Drug Info [535213], [536999]
Saquinavir Drug Info [536954]
SPI-256 Drug Info [544193]
Telinavir Drug Info [534397]
TMC-310911 Drug Info [551655]
U-103017 Drug Info [534077]
U-96988 Drug Info [533813]
Vaniprevir Drug Info [551141]
VX-500 Drug Info [551770]
XM-323 Drug Info [533902]
Modulator AG-1284 Drug Info [534231]
Atazanavir Drug Info [556264]
BAY-793 Drug Info [533674]
BMS-182193 Drug Info [533713]
BMS-186318 Drug Info [534225]
BRECANAVIR Drug Info
CGP-70726 Drug Info [525842]
Darunavir Drug Info [528715]
Droxinavir hydrochloride Drug Info [534332]
GS-2992 Drug Info [550896]
JG-365 Drug Info
KH-164 Drug Info
KNI-102 Drug Info [529151]
KNI-272 Drug Info
KNI-764 Drug Info
Palinavir Drug Info [534383]
PD-153103 Drug Info [550896]
PF-04776548 Drug Info [522912]
SB-206343 Drug Info [533812]
Tipranavir Drug Info [556264]
U-75875 Drug Info [533613]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
DRM DRM Info
References
Ref 468045(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4813).
Ref 522572ClinicalTrials.gov (NCT00838162) A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients. U.S. National Institutes of Health.
Ref 522912ClinicalTrials.gov (NCT01045317) A Study To Investigate The Clearance Of PF-04776548 From The Body Following A Very Low (Micro) Dose Of The Compound Using A Low Level Of Radiotracer To Help Quantify Expected Low Concentrations Of PF-04776548 In The Body. U.S. National Institutes of Health.
Ref 523670ClinicalTrials.gov (NCT01458769) Pharmacokinetics, Safety & Tolerability of Isotopologs of Atazanavir (ATV), With Pharmacokinetic Comparison to Reyataz. U.S. National Institutes of Health.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 544490Metabolic Characterization of a Tripeptide Human Immunodeficiency Virus Type 1 Protease Inhibitor, KNI-272, in Rat Liver Microsomes. Antimicrob Agents Chemother. 1999 March; 43(3): 549-556.
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Ref 546493Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008536)
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Ref 546821Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010459)
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Ref 547252Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014480)
Ref 547253Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014481)
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Ref 550189Clinical pipeline report, company report or official report of Abbott Laboratories (2011)
Ref 550195Clinical pipeline report, company report or official report of Achillion (2011).
Ref 550282Narhex Life Sciences Limited announced a successful capital raising via a combined Rights Issue and Placement offering. 21 May 2007.
Ref 550326Approved antiretroviral drugs. Antiretroviral Drugs. Company report of AVERT. 2009.
Ref 5503782011 Pipeline of Biotron.
Ref 5503842011 Pipeline of Bristol-Myers Squibb.
Ref 5503852011 Pipeline of Boehringer Ingelheim Pharma.
Ref 550812Clinical pipeline report, company report or official report of Gilead (2011).
Ref 5510392011 Pipeline of InterMune.
Ref 551141Clinical pipeline report, company report or official report of Merck (2011).
Ref 5517702011 Pipeline of Vertex.
Ref 522912ClinicalTrials.gov (NCT01045317) A Study To Investigate The Clearance Of PF-04776548 From The Body Following A Very Low (Micro) Dose Of The Compound Using A Low Level Of Radiotracer To Help Quantify Expected Low Concentrations Of PF-04776548 In The Body. U.S. National Institutes of Health.
Ref 525842Oral bioavailability of a poorly water soluble HIV-1 protease inhibitor incorporated into pH-sensitive particles: effect of the particle size and nutritional state. J Control Release. 2000 Aug 10;68(2):291-8.
Ref 525865Identification of MK-944a: a second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors. J Med Chem. 2000 Sep 7;43(18):3386-99.
Ref 526167DPC 681 and DPC 684: potent, selective inhibitors of human immunodeficiency virus protease active against clinically relevant mutant variants. Antimicrob Agents Chemother. 2001 Nov;45(11):3021-8.
Ref 528026Antiviral activity and cross-resistance profile of P-1946, a novel human immunodeficiency virus type 1 protease inhibitor. Antiviral Res. 2006 Jun;70(2):17-20. Epub 2006 Jan 20.
Ref 5287152006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
Ref 529151KNI-102, a novel tripeptide HIV protease inhibitor containing allophenylnorstatine as a transition-state mimic. Chem Pharm Bull (Tokyo). 1991 Nov;39(11):3088-90.
Ref 533613Effects of U-75875, a peptidomimetic inhibitor of retroviral proteases, on simian immunodeficiency virus infection in rhesus monkeys. Antimicrob Agents Chemother. 1994 Jun;38(6):1277-83.
Ref 533674HIV protease inhibitor HOE/BAY 793, structure-activity relationships in a series of C2-symmetric diols. Bioorg Med Chem. 1995 May;3(5):559-71.
Ref 533713Antiviral properties of aminodiol inhibitors against human immunodeficiency virus and protease. Antimicrob Agents Chemother. 1995 Feb;39(2):374-9.
Ref 533812Rational design, synthesis, and crystallographic analysis of a hydroxyethylene-based HIV-1 protease inhibitor containing a heterocyclic P1'--P2' amide bond isostere. J Med Chem. 1994 Sep 16;37(19):3100-7.
Ref 533813Structure-based design of HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors. J Med Chem. 1994 Sep 30;37(20):3200-4.
Ref 533902In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor. Antimicrob Agents Chemother. 1993 Dec;37(12):2606-11.
Ref 533961CGP 53437, an orally bioavailable inhibitor of human immunodeficiency virus type 1 protease with potent antiviral activity. Antimicrob Agents Chemother. 1993 Oct;37(10):2087-92.
Ref 534077Structure-based design of sulfonamide-substituted non-peptidic HIV protease inhibitors. J Med Chem. 1995 Dec 22;38(26):4968-71.
Ref 534168Human serum alpha 1 acid glycoprotein reduces uptake, intracellular concentration, and antiviral activity of A-80987, an inhibitor of the human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother. 1996 Jun;40(6):1491-7.
Ref 534206Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450. Chem Biol. 1996 Apr;3(4):301-14.
Ref 534225Determination of BMS-186318 in dog, rat and monkey plasma by liquid chromatography-ionspray mass spectrometry. J Pharm Biomed Anal. 1995 Dec;14(1-2):43-8.
Ref 534231Exploring the energy landscapes of molecular recognition by a genetic algorithm: analysis of the requirements for robust docking of HIV-1 protease and FKBP-12 complexes. Proteins. 1996 Jul;25(3):342-53.
Ref 534332A mutation in human immunodeficiency virus type 1 protease at position 88, located outside the active site, confers resistance to the hydroxyethylurea inhibitor SC-55389A. Antimicrob Agents Chemother. 1997 Mar;41(3):515-22.
Ref 534336In vitro and ex vivo anti-human immunodeficiency virus (HIV) activities of a new water-soluble HIV protease inhibitor, R-87366, containing (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid. Biol Pharm Bull. 1997 Feb;20(2):175-80.
Ref 534383Antiviral properties of palinavir, a potent inhibitor of the human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother. 1997 May;41(5):965-71.
Ref 534397Improvement of bioavailability of the HIV protease inhibitor SC-52151 in the beagle dog by coadministration of the CYP3A4 inhibitor, ketoconazole. Xenobiotica. 1997 May;27(5):489-97.
Ref 534465Quantitative determination of CGP 61755, a protease inhibitor, in plasma and urine by high-performance liquid chromatography and fluorescence detection. J Chromatogr B Biomed Sci Appl. 1997 Aug 15;696(1):123-30.
Ref 534596Solvation studies of DMP323 and A76928 bound to HIV protease: analysis of water sites using grand canonical Monte Carlo simulations. Protein Sci. 1998 Mar;7(3):573-9.
Ref 534751Design and selection of DMP 850 and DMP 851: the next generation of cyclic urea HIV protease inhibitors. Chem Biol. 1998 Oct;5(10):597-608.
Ref 535120Hollow-fiber unit evaluation of a new human immunodeficiency virus type 1 protease inhibitor, BMS-232632, for determination of the linked pharmacodynamic variable. J Infect Dis. 2001 Apr 1;183(7):1126-9. Epub 2001 Mar 1.
Ref 535213Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J Biol Chem. 2001 Sep 7;276(36):33309-12. Epub 2001 Jul 20.
Ref 536954PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. J Med Virol. 2008 Dec;80(12):2053-63.
Ref 536999Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20. Epub 2008 Dec 23.
Ref 537031Quantification of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cell lysate using liquid chromatography coupled with tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Feb 15;877(5-6):575-80. Epub 2009 Jan 14.
Ref 537180Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503. doi: 10.2165/00003495-200969040-00007.
Ref 537453Fosamprenavir/ritonavir in advanced HIV disease (TRIAD): a randomized study of high-dose, dual-boosted or standard dose fosamprenavir/ritonavir in HIV-1-infected patients with antiretroviral resistance. J Antimicrob Chemother. 2009 Aug;64(2):398-410. Epub 2009 Jun 10.
Ref 544059Highly drug-resistant HIV-1 clinical isolates are cross-resistant to many antiretroviral compounds in current clinical development. AIDS. 1999 April 16; 13(6): 661-667.
Ref 544193Current and Novel Inhibitors of HIV Protease. Viruses. 2009 December; 1(3): 1209-1239.
Ref 550016Avanir Licenses Concert's Deuterium-Modified Dextromethorphan Products in Potential US$200 M Deal. Vol 2012 Issue 3 Page(38).
Ref 550189Clinical pipeline report, company report or official report of Abbott Laboratories (2011)
Ref 550195Clinical pipeline report, company report or official report of Achillion (2011).
Ref 5503782011 Pipeline of Biotron.
Ref 5503842011 Pipeline of Bristol-Myers Squibb.
Ref 5503852011 Pipeline of Boehringer Ingelheim Pharma.
Ref 550812Clinical pipeline report, company report or official report of Gilead (2011).
Ref 550855CN patent application no. 101115713, Hiv protease inhibitors.
Ref 550896US patent application no. 2008,0161,324, Compositions and methods for treatment of viral diseases.
Ref 550938WO patent application no. 2003,0906,90, Cellular accumulation of phosphonate analogs of hiv protease inhibitor compounds and the compounds as such.
Ref 5510392011 Pipeline of InterMune.
Ref 551141Clinical pipeline report, company report or official report of Merck (2011).
Ref 551632Ly316340: A potent HIV-1 protease inhibitor containing a high affinity octahydrothienopyridine hydroxyethylamine isostere. Bioorganic & Medicinal Chemistry Letters Volume 5, Issue 23, 7 December 1995, Pages 2885-2890.
Ref 551655Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates. Chemistry & Biology Volume 21, Issue 9, 18 September 2014, Pages 1115-1142.
Ref 5517702011 Pipeline of Vertex.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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