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Version 2.5
Creation Date 2007-05-16 17:43:23
Update Date 2009-06-23 18:06:14
Primary Accession Number DB01264
Secondary Accession Number
  • EXPT00002
Name Darunavir
Drug Type
  • Approved
  • Small Molecule
Description Darunavir is a protease inhibitor used to treat HIV. It acts on the HIV aspartyl protease which the virus needs to cleave the HIV polyprotein into its functional fragments.
Synonyms
  1. AIDS073035
  2. Darunavirum [INN-latin]
  3. TMC-114
  4. TMC114
  5. UIC-94017
Brand Names
  1. Prezista
Brand Mixtures Not Available
Chemical IUPAC Name [(3R,3aS,6aR)-2,3,3a,4,5,6a-hexahydrofuro[5,4-b]furan-3-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
Chemical Formula C27H37N3O7S
Chemical Structure Structure
CAS Registry Number 206361-99-1
InChI Identifier InChI=1/C27H37N3O7S/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32)/t22-,23-,24+,25-,26+/m0/s1/f/h29H
InChI Key CJBJHOAVZSMMDJ-QSHSPGAWDK
KEGG Drug D03656 Link Image
KEGG Compound Not Available
PubChem Compound 213039 Link Image
PubChem Substance 17397753 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02284057 Link Image
RxList Link http://www.rxlist.com/cgi/generic/prezista.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Darunavir Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 547.6640
Monoisotopic Molecular Weight 547.2352
State Solid
Melting Point Not Available
Experimental Water Solubility Approximately 0.15 mg/mL at 20°C as ethanolate salt Source: PhysProp
Predicted Water Solubility 6.68e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.8 Source: PhysProp
Predicted LogP 1.89 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -3.91 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CO[C@H]2OCC[C@@H]12)S(=O)(=O)C1=CC=C(N)C=C1
Canonical SMILES CC(C)CN(CC(O)C(CC1=CC=CC=C1)NC(=O)OC1COC2OCCC12)S(=O)(=O)C1=CC=C(N)C=C1
Drug Category
  • Antiviral Agents
  • HIV Protease Inhibitors
ATC Codes
AHFS Codes
  • 08:18.08.08
Indication Darunavir, co-administered with ritonavir, and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.
Pharmacology Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006). Darunavir is used as an adjunct therapy with low dose ritonavir, which inhibits cytochrome P450 3A (CYP3A) which increases the bioavailability and half life of darunavir.
Mechanism of Action Darunavir is a HIV protease inhibitor which prevents HIV replication by cleaving HIV encoded Gag-Pol polyproteins in infected cells, reducing viral maturation, load and increasing CD4 T lymphocytes. HIV destroys CD4 T lymphocytes which are an integral part of the immune system.
Absorption The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.
Toxicity Not Available
Protein Binding Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).
Biotransformation Hepatic. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.
Half Life The terminal elimination half-life of darunavir was approximately 15 hours when combined with ritonavir.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Clarithromycin Increased levels of clarithromycin
Lidocaine Possible increase in lidocaine levels
Lopinavir Decreased levels of darunavir
Saquinavir Decreased levels of darunavir
Food Interactions
  • Take with food - better absorption (+30%).
Pathways Not Available
General References
  1. Back D, Sekar V, Hoetelmans RM: Darunavir: pharmacokinetics and drug interactions. Antivir Ther. 2008;13(1):1-13. [PubMed Link Image]
  2. Medilexicon Link Image
  3. Company Website Link Image
  4. Wikipedia Link Image
  5. RxList Link Image
Organisms Affected
  • Human Immunodeficiency Virus
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. HIV-1 protease
  2. Gag-Pol polyprotein
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 731
Target 1 Name HIV-1 protease
Target 1 Synonyms
  1. Fragment
Target 1 Gene Name HIV-1 protease
Target 1 Protein Sequence >HIV-1 protease 
PQVTLWQRPIVTIKIGGQLKEALLDTGADDTVLEEMSLPGKWKPKMIGGIGGFIKVRQYD
QVSIEICGHKAIGTVLIGPTPVNIIGRNLLTQLGCTLNF
Target 1 Number of Residues 100
Target 1 Molecular Weight 10725
Target 1 Theoretical pI 8.77
Target 1 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
aspartic-type endopeptidase activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
Not Available
Target 1 General Function Involved in aspartic-type endopeptidase activity
Target 1 Specific Function Not Available
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 4377614 Link Image
Target 1 UniProtKB/Swiss-Prot ID O90777 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name O90777_9PLVG Link Image
Target 1 PDB ID 1ODW Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >297 bp 
CCTCAGGTCACTCTTTGGCAACGACCCATAGTCACAATAAAGATAGGGGGGCAACTAAAG
GAAGCTCTATTAGATACAGGAGCAGATGATACAGTATTAGAAGAAATGAGTTTGCCAGGA
AAATGGAAACCAAAAATGATAGGGGGAATTGGAGGTTTTATCAAAGTAAGACAGTATGAT
CAGGTATCCATAGAAATCTGCGGACATAAAGCTATAGGTACAGTATTAATAGGACCTACA
CCTGTCAACATAATTGGAAGGAATCTGTTGACTCAGCTTGGCTGCACTTTAAATTTT
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Servais J, Lambert C, Fontaine E, Plesseria JM, Robert I, Arendt V, Staub T, Schneider F, Hemmer R, Burtonboy G, Schmit JC: Comparison of DNA sequencing and a line probe assay for detection of human immunodeficiency virus type 1 drug resistance mutations in patients failing highly active antiretroviral therapy. J Clin Microbiol. 2001 Feb;39(2):454-9. [PubMed Link Image]
  2. Servais J, Lambert C, Fontaine E, Plesseria JM, Robert I, Arendt V, Staub T, Schneider F, Hemmer R, Burtonboy G, Schmit JC: Variant human immunodeficiency virus type 1 proteases and response to combination therapy including a protease inhibitor. Antimicrob Agents Chemother. 2001 Mar;45(3):893-900. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
  3. Wang YF, Tie Y, Boross PI, Tozser J, Ghosh AK, Harrison RW, Weber IT: Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. J Med Chem. 2007 Sep 6;50(18):4509-15. Epub 2007 Aug 16. [PubMed Link Image]
  4. Ghosh AK, Dawson ZL, Mitsuya H: Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. Bioorg Med Chem. 2007 Sep 14;. [PubMed Link Image]
  5. Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to HIV-1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Oct 10;. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 3722
Target 2 Name Gag-Pol polyprotein
Target 2 Synonyms
  1. CA
  2. Capsid protein p24
  3. EC 2.7.7.49
  4. EC 2.7.7.7
  5. EC 3.1.26.4
  6. EC 3.4.23.16
  7. IN]
  8. Integrase
  9. MA
  10. NC
  11. Nucleocapsid protein p7
  12. PR
  13. Pr160Gag-Pol[Contains: Matrix protein p17
  14. Protease
  15. Retropepsin
  16. Reverse transcriptase/ribonuclease H
  17. Spacer peptide p2
  18. TF
  19. Transframe peptide
  20. p15
  21. p51 RT
  22. p6*
  23. p6-pol
  24. p66 RT
Target 2 Gene Name gag-pol
Target 2 Protein Sequence >Gag-Pol polyprotein 
MGARASVLSGGELDRWEKIRLRPGGKKKYKLKHIVWASRELERFAVNPGLLETSEGCRQI
LGQLQPSLQTGSEELRSLYNTVATLYCVHQRIEIKDTKEALDKIEEEQNKSKKKAQQAAA
DTGHSSQVSQNYPIVQNIQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGAT
PQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRVHPVHAGPIAPGQMREPRGSDIAGTT
STLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRF
YKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKA
RVLAEAMSQVTNTATIMMQRGNFRNQRKMVKCFNCGKEGHTARNCRAPRKKGCWKCGKEG
HQMKDCTERQANFLREDLAFLQGKAREFSSEQTRANSPTISSEQTRANSPTRRELQVWGR
DNNSPSEAGADRQGTVSFNFPQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMSLPG
RWKPKMIGGIGGFIKVRQYDQILIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFP
ISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVF
AIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLD
EDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVIY
QYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTV
QPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAEL
ELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAH
TNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPP
LVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNKGRQKVVPLTNTTNQKTELQA
IYLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHKG
IGGNEQVDKLVSAGIRKILFLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCD
KCQLKGEAMHGQVDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFL
LKLAGRWPVKTIHTDNGSNFTSATVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKI
IGQVRDQAEHLKTAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQ
NFRVYYRDSRNPLWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCV
ASRQDED
Target 2 Number of Residues 1471
Target 2 Molecular Weight 163290
Target 2 Theoretical pI 9.11
Target 2 GO Classification
Function
hydrolase activity, acting on ester bonds
nuclease activity
endonuclease activity
endoribonuclease activity
endoribonuclease activity, producing 5'-phosphomonoesters
ribonuclease H activity
hydrolase activity
peptidase activity
endopeptidase activity
aspartic-type endopeptidase activity
structural molecule activity
ion binding
cation binding
transition metal ion binding
zinc ion binding
DNA binding
integrase activity
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleotidyltransferase activity
RNA-directed DNA polymerase activity
binding
nucleic acid binding
RNA binding
Process
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
DNA integration
DNA recombination
viral life cycle
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
DNA replication
RNA-dependent DNA replication
Component
Not Available
Target 2 General Function Not Available
Target 2 Specific Function Integrase performs the integration of the newly synthesized dsDNA copy of the viral genome into the host chromosome. The integrated DNA is called provirus
Target 2 Pathways
Name SMPDB Link KEGG Link
Purine metabolism SMP00050 Link Image map00230 Link Image
Target 2 Reactions
  • Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 326388 Link Image
Target 2 UniProtKB/Swiss-Prot ID P03366 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name POL_HV1B1 Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Nucleus. Cytoplasm (By similarity). Note=Following virus entry, the nuclear localization signal (NLS
Target 2 Gene Sequence >1539 bp 
ATGGGTGCGAGAGCGTCAGTATTAAGCGGGGGAGAATTAGATCGATGGGAAAAAATTCGG
TTAAGGCCAGGGGGAAAGAAAAAATATAAATTAAAACATATAGTATGGGCAAGCAGGGAG
CTAGAACGATTCGCAGTTAATCCTGGCCTGTTAGAAACATCAGAAGGCTGTAGACAAATA
CTGGGACAGCTACAACCATCCCTTCAGACAGGATCAGAAGAACTTAGATCATTATATAAT
ACAGTAGCAACCCTCTATTGTGTGCATCAAAGGATAGAGATAAAAGACACCAAGGAAGCT
TTAGACAAGATAGAGGAAGAGCAAAACAAAAGTAAGAAAAAAGCACAGCAAGCAGCAGCT
GACACAGGACACAGCAGTCAGGTCAGCCAAAATTACCCTATAGTGCAGAACATCCAGGGG
CAAATGGTACATCAGGCCATATCACCTAGAACTTTAAATGCATGGGTAAAAGTAGTAGAA
GAGAAGGCTTTCAGCCCAGAAGTAATACCCATGTTTTCAGCATTATCAGAAGGAGCCACC
CCACAAGATTTAAACACCATGCTAAACACAGTGGGGGGACATCAAGCAGCCATGCAAATG
TTAAAAGAGACCATCAATGAGGAAGCTGCAGAATGGGATAGAGTACATCCAGTGCATGCA
GGGCCTATTGCACCAGGCCAGATGAGAGAACCAAGGGGAAGTGACATAGCAGGAACTACT
AGTACCCTTCAGGAACAAATAGGATGGATGACAAATAATCCACCTATCCCAGTAGGAGAA
ATTTATAAAAGATGGATAATCCTGGGATTAAATAAAATAGTAAGAATGTATAGCCCTACC
AGCATTCTGGACATAAGACAAGGACCAAAAGAACCTTTTAGAGACTATGTAGACCGGTTC
TATAAAACTCTAAGAGCCGAGCAAGCTTCACAGGAGGTAAAAAATTGGATGACAGAAACC
TTGTTGGTCCAAAATGCGAACCCAGATTGTAAGACTATTTTAAAAGCATTGGGACCAGCG
GCTACACTAGAAGAAATGATGACAGCATGTCAGGGAGTAGGAGGACCCGGCCATAAGGCA
AGAGTTTTGGCTGAAGCAATGAGCCAAGTAACAAATACAGCTACCATAATGATGCAGAGA
GGCAATTTTAGGAACCAAAGAAAGATGGTTAAGTGTTTCAATTGTGGCAAAGAAGGGCAC
ACAGCCAGAAATTGCAGGGCCCCTAGGAAAAAGGGCTGTTGGAAATGTGGAAAGGAAGGA
CACCAAATGAAAGATTGTACTGAGAGACAGGCTAATTTTTTAGGGAAGATCTGGCCTTCC
TACAAGGGAAGGCCAGGGAATTTTCTTCAGAGCAGACCAGAGCCAACAGCCCCACCATTT
CTTCAGAGCAGACCAGAGCCAACAGCCCCACCAGAAGAGAGCTTCAGGTCTGGGGTAGAG
ACAACAACTCCCCCTCAGAAGCAGGAGCCGATAGACAAGGAACTGTATCCTTTAACTTCC
CTCAGATCACTCTTTGGCAACGACCCCTCGTCACAATAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID Not Available
Target 2 HGNC ID Not Available
Target 2 Chromosome Location Not Available
Target 2 Locus Not Available
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Sarafianos SG, Das K, Clark AD Jr, Ding J, Boyer PL, Hughes SH, Arnold E: Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10027-32. [PubMed Link Image]
  2. Sluis-Cremer N, Arion D, Kaushik N, Lim H, Parniak MA: Mutational analysis of Lys65 of HIV-1 reverse transcriptase. Biochem J. 2000 May 15;348 Pt 1:77-82. [PubMed Link Image]
  3. Sarafianos SG, Clark AD Jr, Das K, Tuske S, Birktoft JJ, Ilankumaran P, Ramesha AR, Sayer JM, Jerina DM, Boyer PL, Hughes SH, Arnold E: Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA. EMBO J. 2002 Dec 2;21(23):6614-24. [PubMed Link Image]
  4. Tachedjian G, Aronson HE, de los Santos M, Seehra J, McCoy JM, Goff SP: Role of residues in the tryptophan repeat motif for HIV-1 reverse transcriptase dimerization. J Mol Biol. 2003 Feb 14;326(2):381-96. [PubMed Link Image]
  5. Koval'skii DB, Kanibolotskii DS, Dubina VN, Korneliuk AI: [Conformational changes in HIV-1 proteinase: effect of protonation of the active center on conformation of HIV-1 proteinase in water] Ukr Biokhim Zh. 2002 Nov-Dec;74(6):135-8. [PubMed Link Image]
  6. Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA: Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science. 1992 Jun 26;256(5065):1783-90. [PubMed Link Image]
  7. Davies JF 2nd, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA: Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase. Science. 1991 Apr 5;252(5002):88-95. [PubMed Link Image]
  8. Wohrl BM, Volkmann S, Moelling K: Mutations of a conserved residue within HIV-1 ribonuclease H affect its exo- and endonuclease activities. J Mol Biol. 1991 Aug 5;220(3):801-18. [PubMed Link Image]
  9. Jupp RA, Phylip LH, Mills JS, Le Grice SF, Kay J: Mutating P2 and P1 residues at cleavage junctions in the HIV-1 pol polyprotein. Effects on hydrolysis by HIV-1 proteinase. FEBS Lett. 1991 Jun 3;283(2):180-4. [PubMed Link Image]
  10. Erickson J, Neidhart DJ, VanDrie J, Kempf DJ, Wang XC, Norbeck DW, Plattner JJ, Rittenhouse JW, Turon M, Wideburg N, et al.: Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease. Science. 1990 Aug 3;249(4968):527-33. [PubMed Link Image]
  11. 2476069 Mizrahi V, Lazarus GM, Miles LM, Meyers CA, Debouck C: Recombinant HIV-1 reverse transcriptase: purification, primary structure, and polymerase/ribonuclease H activities. Arch Biochem Biophys. 1989 Sep;273(2):347-58.
  12. 2537531 Weber IT, Miller M, Jaskolski M, Leis J, Skalka AM, Wlodawer A: Molecular modeling of the HIV-1 protease and its substrate binding site. Science. 1989 Feb 17;243(4893):928-31.
  13. 2578615 Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, et al.: Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24-30;313(6000):277-84.
  14. 2982104 Muesing MA, Smith DH, Cabradilla CD, Benton CV, Lasky LA, Capon DJ: Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7-13;313(6002):450-8.
  15. 7532306 Rodgers DW, Gamblin SJ, Harris BA, Ray S, Culp JS, Hellmig B, Woolf DJ, Debouck C, Harrison SC: The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6.
  16. 7542140 Ding J, Das K, Tantillo C, Zhang W, Clark AD Jr, Jessen S, Lu X, Hsiou Y, Jacobo-Molina A, Andries K, et al.: Structure of HIV-1 reverse transcriptase in a complex with the non-nucleoside inhibitor alpha-APA R 95845 at 2.8 A resolution. Structure. 1995 Apr 15;3(4):365-79.
  17. 7545077 Ding J, Das K, Moereels H, Koymans L, Andries K, Janssen PA, Hughes SH, Arnold E: Structure of HIV-1 RT/TIBO R 86183 complex reveals similarity in the binding of diverse nonnucleoside inhibitors. Nat Struct Biol. 1995 May;2(5):407-15.
  18. 7552753 Eijkelenboom AP, Lutzke RA, Boelens R, Plasterk RH, Kaptein R, Hard K: The DNA-binding domain of HIV-1 integrase has an SH3-like fold. Nat Struct Biol. 1995 Sep;2(9):807-10.
  19. 7613867 Priestle JP, Fassler A, Rosel J, Tintelnot-Blomley M, Strop P, Grutter MG: Comparative analysis of the X-ray structures of HIV-1 and HIV-2 proteases in complex with CGP 53820, a novel pseudosymmetric inhibitor. Structure. 1995 Apr 15;3(4):381-9.
  20. 7687065 Jacobo-Molina A, Ding J, Nanni RG, Clark AD Jr, Lu X, Tantillo C, Williams RL, Kamer G, Ferris AL, Clark P, et al.: Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 A resolution shows bent DNA. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6320-4.
  21. 8805568 Hsiou Y, Ding J, Das K, Clark AD Jr, Hughes SH, Arnold E: Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms. Structure. 1996 Jul 15;4(7):853-60.
  22. 9111014 Palaniappan C, Wisniewski M, Jacques PS, Le Grice SF, Fay PJ, Bambara RA: Mutations within the primer grip region of HIV-1 reverse transcriptase result in loss of RNase H function. J Biol Chem. 1997 Apr 25;272(17):11157-64.
  23. 9450540 Hong L, Zhang XJ, Foundling S, Hartsuck JA, Tang J: Structure of a G48H mutant of HIV-1 protease explains how glycine-48 replacements produce mutants resistant to inhibitor drugs. FEBS Lett. 1997 Dec 22;420(1):11-6.
  24. 9533880 Gao HQ, Boyer PL, Arnold E, Hughes SH: Effects of mutations in the polymerase domain on the polymerase, RNase H and strand transfer activities of human immunodeficiency virus type 1 reverse transcriptase. J Mol Biol. 1998 Apr 3;277(3):559-72.
  25. 9813120 Hsiou Y, Das K, Ding J, Clark AD Jr, Kleim JP, Rosner M, Winkler I, Riess G, Hughes SH, Arnold E: Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance. J Mol Biol. 1998 Nov 27;284(2):313-23.
  26. 9831551 Huang H, Chopra R, Verdine GL, Harrison SC: Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science. 1998 Nov 27;282(5394):1669-75.
  27. 9878383 Turner BG, Summers MF: Structural biology of HIV. J Mol Biol. 1999 Jan 8;285(1):1-32.
Target 2 Drug References Not Available

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.