Target Information

Target General Information

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Target ID

T56915 (Former ID: TTDS00320)

Target Name

Human immunodeficiency virus Protease (HIV PR)

Synonyms

HIV Retropepsin; HIV PR

Click to Show/Hide

Gene Name

HIV PR

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Human immunodeficiency virus disease [ICD-11: 1C60-1C62]

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.

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BioChemical Class

Peptidase

UniProt ID

POL_HV1B1

EC Number

EC 3.4.23.16

Sequence

PQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPGRWKPKMIGGIGGFIKVRQYD
QILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNF

Click to Show/Hide

3D Structure

Click to Show 3D Structure of This Target

PDB

Drugs and Modes of Action

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Approved Drug(s)

[+] 8 Approved Drugs

Amprenavir

Drug Info

Approved

Human immunodeficiency virus infection

[2]

Atazanavir

Drug Info

Approved

Human immunodeficiency virus infection

[2]

Darunavir

Drug Info

Approved

Human immunodeficiency virus infection

[2]

Fosamprenavir

Drug Info

Approved

Human immunodeficiency virus infection

[3]

Indinavir

Drug Info

Approved

Human immunodeficiency virus infection

[3]

Ritonavir

Drug Info

Approved

Human immunodeficiency virus infection

[2]

Saquinavir

Drug Info

Approved

Human immunodeficiency virus infection

[3], [4]

Tipranavir

Drug Info

Approved

Human immunodeficiency virus infection

[2]

Clinical Trial Drug(s)

[+] 16 Clinical Trial Drugs

BI 201335

Drug Info

Phase 3

Hepatitis C virus infection

[5]

ABT-450

Drug Info

Phase 2

Hepatitis C virus infection

[6]

ACH-1625

Drug Info

Phase 2

Hepatitis C virus infection

[7]

BMS 650032

Drug Info

Phase 2

Hepatitis C virus infection

[8]

Danoprevir

Drug Info

Phase 2

Hepatitis C virus infection

[9]

DG-17

Drug Info

Phase 2

Human immunodeficiency virus infection

[10]

GS-9256

Drug Info

Phase 2

Hepatitis C virus infection

[11]

KNI-272

Drug Info

Phase 2

Human immunodeficiency virus infection

[12]

MK-5172

Drug Info

Phase 2

Hepatitis C virus infection

[13]

TMC-310911

Drug Info

Phase 2

Human immunodeficiency virus infection

[14]

Vaniprevir

Drug Info

Phase 2

Hepatitis C virus infection

[13]

BIT225

Drug Info

Phase 1

Hepatitis C virus infection

[15]

CTP-298

Drug Info

Phase 1

Human immunodeficiency virus infection

[16]

PF-04776548

Drug Info

Phase 1

Human immunodeficiency virus infection

[17]

PPL-100

Drug Info

Phase 1

Human immunodeficiency virus infection

[18]

VX-500

Drug Info

Phase 1

Hepatitis C virus infection

[19]

Discontinued Drug(s)

[+] 33 Discontinued Drugs

A-75925

Drug Info

Discontinued in Phase 2

Virus infection

[20]

BRECANAVIR

Drug Info

Discontinued in Phase 2

Human immunodeficiency virus infection

[21]

MK-944a

Drug Info

Discontinued in Phase 2

Human immunodeficiency virus infection

[22]

Mozenavir

Drug Info

Discontinued in Phase 2

Human immunodeficiency virus infection

[23]

R-87366

Drug Info

Discontinued in Phase 2

Human immunodeficiency virus infection

[24]

Telinavir

Drug Info

Discontinued in Phase 2

Human immunodeficiency virus infection

[25]

GS-9005

Drug Info

Discontinued in Phase 1/2

Human immunodeficiency virus infection

[26]

A-80987

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[27]

CGP-53437

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[28]

DMP-851

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[29]

DPC-681

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[30]

DPC-684

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[31]

KNI-764

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[32]

LASINAVIR

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[33]

R-944

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[34]

SPI-256

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[35]

U-103017

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[36]

U-96988

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[37]

XM-323

Drug Info

Discontinued in Phase 1

Human immunodeficiency virus infection

[38]

AG-1284

Drug Info

Terminated

Human immunodeficiency virus infection

[39]

AG-1350

Drug Info

Terminated

Human immunodeficiency virus infection

[40]

BAY-793

Drug Info

Terminated

Human immunodeficiency virus infection

[41]

BMS-182193

Drug Info

Terminated

Human immunodeficiency virus infection

[42]

BMS-186318

Drug Info

Terminated

Human immunodeficiency virus-1 infection

[43]

CGP-70726

Drug Info

Terminated

Human immunodeficiency virus-1 infection

[44]

Droxinavir hydrochloride

Drug Info

Terminated

Human immunodeficiency virus infection

[45]

GE-20372A

Drug Info

Terminated

Human immunodeficiency virus infection

[46]

GS-2992

Drug Info

Terminated

Human immunodeficiency virus infection

[47]

KNI-102

Drug Info

Terminated

Human immunodeficiency virus infection

[48]

Palinavir

Drug Info

Terminated

Human immunodeficiency virus infection

[49]

PD-153103

Drug Info

Terminated

Human immunodeficiency virus-1 infection

[50]

SB-206343

Drug Info

Terminated

Human immunodeficiency virus-1 infection

[51]

U-75875

Drug Info

Terminated

Human immunodeficiency virus infection

[52]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 38 Inhibitor drugs

Amprenavir

Drug Info

[53]

Fosamprenavir

Drug Info

[57]

Indinavir

Drug Info

[1]

Ritonavir

Drug Info

[58], [59]

Saquinavir

Drug Info

[60]

BI 201335

Drug Info

[5]

ABT-450

Drug Info

[6]

ACH-1625

Drug Info

[7]

BMS 650032

Drug Info

[8]

Danoprevir

Drug Info

[9]

DG-17

Drug Info

[61]

GS-9256

Drug Info

[11]

MK-5172

Drug Info

[13]

TMC-310911

Drug Info

[63]

Vaniprevir

Drug Info

[13]

BIT225

Drug Info

[15]

CTP-298

Drug Info

[64]

PPL-100

Drug Info

[65]

VX-500

Drug Info

[19]

A-75925

Drug Info

[66]

MK-944a

Drug Info

[68]

Mozenavir

Drug Info

[69]

R-87366

Drug Info

[70], [71]

Telinavir

Drug Info

[72]

GS-9005

Drug Info

[73]

A-80987

Drug Info

[74]

CGP-53437

Drug Info

[75]

DMP-851

Drug Info

[71], [76]

DPC-681

Drug Info

[71], [77]

DPC-684

Drug Info

[71], [77]

LASINAVIR

Drug Info

[71], [79]

R-944

Drug Info

[80]

SPI-256

Drug Info

[81]

U-103017

Drug Info

[82]

U-96988

Drug Info

[83]

XM-323

Drug Info

[84]

AG-1350

Drug Info

[71], [86]

GE-20372A

Drug Info

[92]

Modulator

[+] 21 Modulator drugs

Atazanavir

Drug Info

[54], [55]

Darunavir

Drug Info

[56]

Tipranavir

Drug Info

[55]

KNI-272

Drug Info

[62]

PF-04776548

Drug Info

[17]

BRECANAVIR

Drug Info

[67]

KNI-764

Drug Info

[78]

AG-1284

Drug Info

[85]

BAY-793

Drug Info

[87]

BMS-182193

Drug Info

[88]

BMS-186318

Drug Info

[89]

CGP-70726

Drug Info

[90]

Droxinavir hydrochloride

Drug Info

[91]

GS-2992

Drug Info

[92]

KNI-102

Drug Info

[93]

Palinavir

Drug Info

[94]

PD-153103

Drug Info

[92]

SB-206343

Drug Info

[95]

U-75875

Drug Info

[96]

JG-365

Drug Info

[97]

KH-164

Drug Info

[98]

Drug Binding Sites of Target

Top

Ligand Name: Saquinavir

Ligand Info

Structure Description

crystal structure of HIV protease model precursor/Saquinavir complex

PDB:3TL9

Method

X-ray diffraction

Resolution

1.32 Å

Mutation

[99]

PDB Sequence

PQITLWKRPL

¹⁰

VTIKIGGQLK

²⁰

EALLDTGADD

³⁰

TVIEEMSLPG

⁴⁰

RWKPKMIGGI

⁵⁰

GGFIKVRQYD

⁶⁰

QIIIEIAGHK

⁷⁰

AIGTVLVGPT

⁸⁰

PVNIIGRNLL

⁹⁰

TQIGATLNF

Residue

Distance (Å)

LEU23

4.019

ASP25

2.578

GLY27

3.398

ALA28

3.602

ASP29

2.943

ASP30

3.058

VAL32

4.680

ILE47

3.755

Residue

Distance (Å)

GLY48

3.037

GLY49

3.696

ILE50

3.290

PHE53

4.919

THR80

3.555

PRO81

3.681

VAL82

3.903

ILE84

3.640

Click to View More Binding Site Information of This Target and Ligand Pair

Ligand Name: Amprenavir

Ligand Info

Structure Description

Crystal Structure of HIV-1 Protease Mutant I84V with Antiviral Drug Amprenavir

PDB:3NU9

Method

X-ray diffraction

Resolution

1.85 Å

Mutation

Yes

[100]

PDB Sequence

PQITLWKRPL

¹⁰

VTIKIGGQLK

²⁰

EALLDTGADD

³⁰

TVIEEMSLPG

⁴⁰

RWKPKMIGGI

⁵⁰

GGFIKVRQYD

⁶⁰

QIIIEIAGHK

⁷⁰

AIGTVLVGPT

⁸⁰

PVNVIGRNLL

⁹⁰

TQIGATLNF

Residue

Distance (Å)

ARG8

4.032

LEU23

4.085

ASP25

2.585

GLY27

3.613

ALA28

3.352

ASP29

3.977

ASP30

3.269

VAL32

3.428

ILE47

4.205

Residue

Distance (Å)

GLY48

3.544

GLY49

3.174

ILE50

3.559

LEU76

4.380

THR80

4.958

PRO81

3.643

VAL82

3.554

VAL84

4.180

Click to View More Binding Site Information of This Target with Different Ligands

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Profiles in Patients

Top

Drug Resistance
Mutation (DRM)

Drug Resistance Mutation Info

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

Target QSAR Model

References

Top

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Quantification of HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in peripheral blood mononuclear cell lysate using liq... J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Feb 15;877(5-6):575-80.

REF 2

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 3

Approved antiretroviral drugs. Antiretroviral Drugs. Company report of AVERT. 2009.

REF 4

URL: 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 5

2011 Pipeline of Boehringer Ingelheim Pharma.

REF 6

Clinical pipeline report, company report or official report of Abbott Laboratories (2011)

REF 7

Clinical pipeline report, company report or official report of Achillion (2011).

REF 8

2011 Pipeline of Bristol-Myers Squibb.

REF 9

2011 Pipeline of InterMune.

REF 10

Narhex Life Sciences Limited announced a successful capital raising via a combined Rights Issue and Placement offering. 21 May 2007.

REF 11

Clinical pipeline report, company report or official report of Gilead (2011).

REF 12

Metabolic 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.

REF 13

Clinical pipeline report, company report or official report of Merck (2011).

REF 14

ClinicalTrials.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 15

2011 Pipeline of Biotron.

REF 16

ClinicalTrials.gov (NCT01458769) Pharmacokinetics, Safety & Tolerability of Isotopologs of Atazanavir (ATV), With Pharmacokinetic Comparison to Reyataz. U.S. National Institutes of Health.

REF 17

ClinicalTrials.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 18

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 19

2011 Pipeline of Vertex.

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003337)

REF 21

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016864)

REF 22

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013179)

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004305)

REF 24

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008914)

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003330)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018518)

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002482)

REF 28

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002438)

REF 29

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008536)

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014480)

REF 31

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014481)

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010459)

REF 33

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006772)

REF 34

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017230)

REF 35

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023938)

REF 36

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006008)

REF 37

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004387)

REF 38

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002483)

REF 39

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005055)

REF 40

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004154)

REF 41

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002843)

REF 42

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002890)

REF 43

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004898)

REF 44

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007747)

REF 45

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004768)

REF 46

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005311)

REF 47

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005194)

REF 48

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002506)

REF 49

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005466)

REF 50

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005066)

REF 51

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005565)

REF 52

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002095)

REF 53

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Hollow-fiber unit evaluation of a new human immunodeficiency virus type 1 protease inhibitor, BMS-232632, for determination of the linked pharmacod... J Infect Dis. 2001 Apr 1;183(7):1126-9.

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Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.

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Fosamprenavir/ritonavir in advanced HIV disease (TRIAD): a randomized study of high-dose, dual-boosted or standard dose fosamprenavir/ritonavir in ... J Antimicrob Chemother. 2009 Aug;64(2):398-410.

REF 58

Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20.

REF 59

Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J Biol Chem. 2001 Sep 7;276(36):33309-12.

REF 60

PL-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.

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Highly 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.

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Oxidative modifications of kynostatin-272, a potent human immunodeficiency virus type 1 protease inhibitor: potential mechanism for altered activit... Antimicrob Agents Chemother. 2002 Feb;46(2):402-8.

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Oral 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.

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Avanir Licenses Concert's Deuterium-Modified Dextromethorphan Products in Potential US$200 M Deal. Vol 2012 Issue 3 Page(38).

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Antiviral 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.

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Solvation 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.

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Safety and pharmacokinetics of brecanavir, a novel human immunodeficiency virus type 1 protease inhibitor, following repeat administration with and without ritonavir in healthy adult subjects.Antimicrob Agents Chemother.2007 Apr;51(4):1202-8.

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Identification 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.

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Improved 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.

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In 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.

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Improvement 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.

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WO patent application no. 2003,0906,90, Cellular accumulation of phosphonate analogs of hiv protease inhibitor compounds and the compounds as such.

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Human 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.

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CGP 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.

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JE-2147: a dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1. Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8675-80.

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Quantitative 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.

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CN patent application no. 101115713, Hiv protease inhibitors.

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Current and Novel Inhibitors of HIV Protease. Viruses. 2009 December; 1(3): 1209-1239.

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Structure-based design of sulfonamide-substituted non-peptidic HIV protease inhibitors. J Med Chem. 1995 Dec 22;38(26):4968-71.

REF 83

Structure-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 84

In vitro anti-human immunodeficiency virus (HIV) activity of XM323, a novel HIV protease inhibitor. Antimicrob Agents Chemother. 1993 Dec;37(12):2606-11.

REF 85

Exploring 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 86

Ly316340: 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 87

HIV 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 88

Antiviral properties of aminodiol inhibitors against human immunodeficiency virus and protease. Antimicrob Agents Chemother. 1995 Feb;39(2):374-9.

REF 89

Determination 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 90

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