CA2725227A1 - Antiviral cell penetrating peptides - Google Patents
Antiviral cell penetrating peptides Download PDFInfo
- Publication number
- CA2725227A1 CA2725227A1 CA2725227A CA2725227A CA2725227A1 CA 2725227 A1 CA2725227 A1 CA 2725227A1 CA 2725227 A CA2725227 A CA 2725227A CA 2725227 A CA2725227 A CA 2725227A CA 2725227 A1 CA2725227 A1 CA 2725227A1
- Authority
- CA
- Canada
- Prior art keywords
- amino acids
- peptide
- seq
- nyad
- mammal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 title abstract description 9
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 title abstract description 9
- 230000000840 anti-viral effect Effects 0.000 title description 12
- 241000725303 Human immunodeficiency virus Species 0.000 claims abstract description 32
- 238000011282 treatment Methods 0.000 claims abstract description 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 128
- 235000001014 amino acid Nutrition 0.000 claims description 113
- 150000001413 amino acids Chemical class 0.000 claims description 110
- 238000000034 method Methods 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 38
- 241000124008 Mammalia Species 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 30
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 24
- 235000004279 alanine Nutrition 0.000 claims description 24
- 208000015181 infectious disease Diseases 0.000 claims description 20
- 230000010076 replication Effects 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 238000006467 substitution reaction Methods 0.000 claims description 11
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 101100533890 Hypocrea jecorina (strain QM6a) sor3 gene Proteins 0.000 claims description 3
- 101100533874 Hypocrea jecorina (strain QM6a) sor5 gene Proteins 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- 239000003443 antiviral agent Substances 0.000 claims description 2
- 229940024606 amino acid Drugs 0.000 description 95
- 210000004027 cell Anatomy 0.000 description 82
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 53
- 102000004196 processed proteins & peptides Human genes 0.000 description 53
- 210000000234 capsid Anatomy 0.000 description 49
- 241000700605 Viruses Species 0.000 description 45
- 230000003612 virological effect Effects 0.000 description 32
- 239000002245 particle Substances 0.000 description 30
- 102000004169 proteins and genes Human genes 0.000 description 27
- 108090000623 proteins and genes Proteins 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 25
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 20
- 239000000539 dimer Substances 0.000 description 17
- 230000035800 maturation Effects 0.000 description 17
- 231100000135 cytotoxicity Toxicity 0.000 description 16
- 230000003013 cytotoxicity Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 101710205625 Capsid protein p24 Proteins 0.000 description 14
- 101710177166 Phosphoprotein Proteins 0.000 description 14
- 101710149279 Small delta antigen Proteins 0.000 description 14
- 102100022563 Tubulin polymerization-promoting protein Human genes 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 102100034347 Integrase Human genes 0.000 description 12
- -1 atoms hydrogen Chemical class 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 235000002639 sodium chloride Nutrition 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 11
- 239000004365 Protease Substances 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 108091005804 Peptidases Proteins 0.000 description 9
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 210000004899 c-terminal region Anatomy 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 150000002430 hydrocarbons Chemical class 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 208000030507 AIDS Diseases 0.000 description 7
- 108090000565 Capsid Proteins Proteins 0.000 description 7
- 239000004215 Carbon black (E152) Substances 0.000 description 7
- 102100023321 Ceruloplasmin Human genes 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 230000002458 infectious effect Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 230000004850 protein–protein interaction Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 5
- 208000031886 HIV Infections Diseases 0.000 description 5
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 5
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012737 fresh medium Substances 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 101710177291 Gag polyprotein Proteins 0.000 description 4
- 108010061833 Integrases Proteins 0.000 description 4
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 238000006471 dimerization reaction Methods 0.000 description 4
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 4
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 235000018977 lysine Nutrition 0.000 description 4
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 4
- 239000000816 peptidomimetic Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 3
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 3
- 108010032976 Enfuvirtide Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 208000037357 HIV infectious disease Diseases 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- IRHXGOXEBNJUSN-YOXDLBRISA-N Saquinavir mesylate Chemical compound CS(O)(=O)=O.C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 IRHXGOXEBNJUSN-YOXDLBRISA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 3
- 238000005865 alkene metathesis reaction Methods 0.000 description 3
- 230000003466 anti-cipated effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 229960003277 atazanavir Drugs 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000034303 cell budding Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000002983 circular dichroism Methods 0.000 description 3
- 238000001142 circular dichroism spectrum Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine mesylate Natural products CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 229960002656 didanosine Drugs 0.000 description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 235000019800 disodium phosphate Nutrition 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000001493 electron microscopy Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 229940124524 integrase inhibitor Drugs 0.000 description 3
- 239000002850 integrase inhibitor Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 3
- 150000002669 lysines Chemical class 0.000 description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
- 229960000884 nelfinavir Drugs 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 3
- 235000004400 serine Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 235000014393 valine Nutrition 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 2
- 101710170658 Endogenous retrovirus group K member 10 Gag polyprotein Proteins 0.000 description 2
- 101710186314 Endogenous retrovirus group K member 21 Gag polyprotein Proteins 0.000 description 2
- 101710162093 Endogenous retrovirus group K member 24 Gag polyprotein Proteins 0.000 description 2
- 101710094596 Endogenous retrovirus group K member 8 Gag polyprotein Proteins 0.000 description 2
- 101710177443 Endogenous retrovirus group K member 9 Gag polyprotein Proteins 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 101710203526 Integrase Proteins 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 101710125418 Major capsid protein Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 2
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 2
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 2
- 229960004748 abacavir Drugs 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- PMDQGYMGQKTCSX-HQROKSDRSA-L calcium;[(2r,3s)-1-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-[[(3s)-oxolan-3-yl]oxycarbonylamino]-4-phenylbutan-2-yl] phosphate Chemical compound [Ca+2].C([C@@H]([C@H](OP([O-])([O-])=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 PMDQGYMGQKTCSX-HQROKSDRSA-L 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 2
- 229960003586 elvitegravir Drugs 0.000 description 2
- JUZYLCPPVHEVSV-LJQANCHMSA-N elvitegravir Chemical compound COC1=CC=2N([C@H](CO)C(C)C)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1F JUZYLCPPVHEVSV-LJQANCHMSA-N 0.000 description 2
- 229960002062 enfuvirtide Drugs 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 229960003142 fosamprenavir Drugs 0.000 description 2
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 2
- 108700004026 gag Genes Proteins 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960001627 lamivudine Drugs 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 229940113354 lexiva Drugs 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- GSNHKUDZZFZSJB-QYOOZWMWSA-N maraviroc Chemical compound CC(C)C1=NN=C(C)N1[C@@H]1C[C@H](N2CC[C@H](NC(=O)C3CCC(F)(F)CC3)C=3C=CC=CC=3)CC[C@H]2C1 GSNHKUDZZFZSJB-QYOOZWMWSA-N 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 108091005601 modified peptides Proteins 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 2
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 238000006384 oligomerization reaction Methods 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 2
- 229960002169 plerixafor Drugs 0.000 description 2
- 229940068917 polyethylene glycols Drugs 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229940107904 reyataz Drugs 0.000 description 2
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 2
- 235000008521 threonine Nutrition 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 231100000607 toxicokinetics Toxicity 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000024275 uncoating of virus Effects 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 210000002845 virion Anatomy 0.000 description 2
- 229960000523 zalcitabine Drugs 0.000 description 2
- 229960002555 zidovudine Drugs 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- NUBQKPWHXMGDLP-UHFFFAOYSA-N 1-[4-benzyl-2-hydroxy-5-[(2-hydroxy-2,3-dihydro-1h-inden-1-yl)amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;sulfuric acid Chemical compound OS(O)(=O)=O.C1CN(CC(O)CC(CC=2C=CC=CC=2)C(=O)NC2C3=CC=CC=C3CC2O)C(C(=O)NC(C)(C)C)CN1CC1=CC=CN=C1 NUBQKPWHXMGDLP-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 1
- JDDWRLPTKIOUOF-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-[[4-[2-[bis(4-methylphenyl)methylamino]-2-oxoethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]carbamate Chemical compound COC1=CC(OC)=CC=C1C(C=1C=CC(OCC(=O)NC(C=2C=CC(C)=CC=2)C=2C=CC(C)=CC=2)=CC=1)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 JDDWRLPTKIOUOF-UHFFFAOYSA-N 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 241000712891 Arenavirus Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 108010061299 CXCR4 Receptors Proteins 0.000 description 1
- 102000012000 CXCR4 Receptors Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N Cyclohexylamine Natural products NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
- 108010072220 Cyclophilin A Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 208000001490 Dengue Diseases 0.000 description 1
- 206010012310 Dengue fever Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 241000713800 Feline immunodeficiency virus Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- 241000710781 Flaviviridae Species 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 229940126656 GS-4224 Drugs 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229940033330 HIV vaccine Drugs 0.000 description 1
- 229940126544 HIV-1 protease inhibitor Drugs 0.000 description 1
- 241000711549 Hepacivirus C Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 description 1
- 241001136003 Human T-lymphotropic virus 3 Species 0.000 description 1
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 1
- 108700020129 Human immunodeficiency virus 1 p31 integrase Proteins 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- OFFWOVJBSQMVPI-RMLGOCCBSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O.N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 OFFWOVJBSQMVPI-RMLGOCCBSA-N 0.000 description 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001115401 Marburgvirus Species 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 241000150452 Orthohantavirus Species 0.000 description 1
- 241000712464 Orthomyxoviridae Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 description 1
- 241000150350 Peribunyaviridae Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000713311 Simian immunodeficiency virus Species 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000004006 Tick-borne encephalitis Diseases 0.000 description 1
- 241000710924 Togaviridae Species 0.000 description 1
- 241000711517 Torovirus Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 108010065667 Viral Matrix Proteins Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 101710165741 Virion-associated protein Proteins 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- GLWHPRRGGYLLRV-XLPZGREQSA-N [[(2s,3s,5r)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](N=[N+]=[N-])C1 GLWHPRRGGYLLRV-XLPZGREQSA-N 0.000 description 1
- WMHSRBZIJNQHKT-FFKFEZPRSA-N abacavir sulfate Chemical compound OS(O)(=O)=O.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 WMHSRBZIJNQHKT-FFKFEZPRSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009830 antibody antigen interaction Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000011225 antiretroviral therapy Methods 0.000 description 1
- 229940124522 antiretrovirals Drugs 0.000 description 1
- 239000003903 antiretrovirus agent Substances 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
- HOQPTLCRWVZIQZ-UHFFFAOYSA-H bis[[2-(5-hydroxy-4,7-dioxo-1,3,2$l^{2}-dioxaplumbepan-5-yl)acetyl]oxy]lead Chemical compound [Pb+2].[Pb+2].[Pb+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HOQPTLCRWVZIQZ-UHFFFAOYSA-H 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940014461 combivir Drugs 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 229940088900 crixivan Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 125000001295 dansyl group Chemical group [H]C1=C([H])C(N(C([H])([H])[H])C([H])([H])[H])=C2C([H])=C([H])C([H])=C(C2=C1[H])S(*)(=O)=O 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 229960000475 delavirdine mesylate Drugs 0.000 description 1
- MEPNHSOMXMALDZ-UHFFFAOYSA-N delavirdine mesylate Chemical compound CS(O)(=O)=O.CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 MEPNHSOMXMALDZ-UHFFFAOYSA-N 0.000 description 1
- 208000025729 dengue disease Diseases 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- 238000010218 electron microscopic analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 108700004025 env Genes Proteins 0.000 description 1
- 229940072253 epivir Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 229940099052 fuzeon Drugs 0.000 description 1
- 101150098622 gag gene Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000011984 grubbs catalyst Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229960004243 indinavir sulfate Drugs 0.000 description 1
- NUBQKPWHXMGDLP-BDEHJDMKSA-N indinavir sulfate Chemical compound OS(O)(=O)=O.C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 NUBQKPWHXMGDLP-BDEHJDMKSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940088976 invirase Drugs 0.000 description 1
- 229940111682 isentress Drugs 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 229940112586 kaletra Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940120922 lopinavir and ritonavir Drugs 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229960004710 maraviroc Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 230000003641 microbiacidal effect Effects 0.000 description 1
- 229940124561 microbicide Drugs 0.000 description 1
- 239000002855 microbicide agent Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 229940072250 norvir Drugs 0.000 description 1
- 229940042404 nucleoside and nucleotide reverse transcriptase inhibitor Drugs 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229940114930 potassium stearate Drugs 0.000 description 1
- IFUKBHBISRAZTF-UHFFFAOYSA-M potassium;4-[(4-fluorophenyl)methylcarbamoyl]-1-methyl-2-[2-[(5-methyl-1,3,4-oxadiazole-2-carbonyl)amino]propan-2-yl]-6-oxopyrimidin-5-olate Chemical compound [K+].O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C([O-])C(=O)N1C IFUKBHBISRAZTF-UHFFFAOYSA-M 0.000 description 1
- ANBFRLKBEIFNQU-UHFFFAOYSA-M potassium;octadecanoate Chemical compound [K+].CCCCCCCCCCCCCCCCCC([O-])=O ANBFRLKBEIFNQU-UHFFFAOYSA-M 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960004742 raltegravir Drugs 0.000 description 1
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 229940063627 rescriptor Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229940064914 retrovir Drugs 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- QEKVQYCTJHJBOF-UHFFFAOYSA-L ruthenium(2+);styrene;triphenylphosphane;dichloride Chemical compound Cl[Ru]Cl.C=CC1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QEKVQYCTJHJBOF-UHFFFAOYSA-L 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- 229960003542 saquinavir mesylate Drugs 0.000 description 1
- 229940031307 selzentry Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 229960001203 stavudine Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229940054565 sustiva Drugs 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960001355 tenofovir disoproxil Drugs 0.000 description 1
- 229960004693 tenofovir disoproxil fumarate Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229940043263 traditional drug Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229940111527 trizivir Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 229940023080 viracept Drugs 0.000 description 1
- 230000007486 viral budding Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000029302 virus maturation Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000012982 x-ray structure analysis Methods 0.000 description 1
- 229940087450 zerit Drugs 0.000 description 1
- 229940052255 ziagen Drugs 0.000 description 1
- 229940120938 zidovudine and lamivudine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16211—Human Immunodeficiency Virus, HIV concerning HIV gagpol
- C12N2740/16222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5095508P | 2008-05-06 | 2008-05-06 | |
| US61/050,955 | 2008-05-06 | ||
| PCT/US2009/042913 WO2009137532A1 (en) | 2008-05-06 | 2009-05-05 | Antiviral cell penetrating peptides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2725227A1 true CA2725227A1 (en) | 2009-11-12 |
Family
ID=40957984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2725227A Abandoned CA2725227A1 (en) | 2008-05-06 | 2009-05-05 | Antiviral cell penetrating peptides |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US8324153B2 (enExample) |
| EP (1) | EP2283033A1 (enExample) |
| JP (1) | JP2011522796A (enExample) |
| AU (1) | AU2009244400B2 (enExample) |
| CA (1) | CA2725227A1 (enExample) |
| WO (1) | WO2009137532A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010505831A (ja) * | 2006-10-05 | 2010-02-25 | ニューヨーク ブラッド センター, インコーポレイテッド | 安定化した、治療用の小型のヘリックス性抗ウイルスペプチド |
| US8937154B2 (en) | 2006-10-05 | 2015-01-20 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| CA2677045C (en) | 2007-01-31 | 2016-10-18 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| KR101623985B1 (ko) | 2007-03-28 | 2016-05-25 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 스티칭된 폴리펩티드 |
| EP2283033A1 (en) * | 2008-05-06 | 2011-02-16 | New York Blood Center | Antiviral cell penetrating peptides |
| KR102104762B1 (ko) | 2010-08-13 | 2020-04-24 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
| WO2012137036A1 (en) * | 2011-04-04 | 2012-10-11 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| CA2834657A1 (en) * | 2011-04-29 | 2012-11-01 | Kinemed, Inc. | Chemical modification of apolipoprotein mimetic peptides for the production of therapeutic agents |
| CN108929375A (zh) | 2011-10-18 | 2018-12-04 | 爱勒让治疗公司 | 拟肽大环化合物 |
| KR102112373B1 (ko) | 2012-02-15 | 2020-05-18 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티드모방체 마크로사이클 |
| EP2819688A4 (en) | 2012-02-15 | 2015-10-28 | Aileron Therapeutics Inc | PEPTIDOMIMETIC MACROCYCLES CROSS-LINKED WITH TRIAZOLE AND THIOETHER |
| WO2014053880A1 (en) | 2012-10-04 | 2014-04-10 | Centre National De La Recherche Scientifique | Cell penetrating peptides for intracellular delivery of molecules |
| KR20150082307A (ko) | 2012-11-01 | 2015-07-15 | 에일러론 테라퓨틱스 인코포레이티드 | 이치환 아미노산 및 이의 제조 및 사용 방법 |
| SG10201902598VA (en) | 2014-09-24 | 2019-04-29 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and formulations thereof |
| CN106999541A (zh) | 2014-09-24 | 2017-08-01 | 艾瑞朗医疗公司 | 拟肽大环化合物及其用途 |
| CN105622732B (zh) * | 2014-10-30 | 2019-10-25 | 中国科学院武汉病毒研究所 | 猴病毒40衣壳蛋白vp1在作为细胞穿膜蛋白中的应用 |
| LT3237436T (lt) | 2014-12-24 | 2019-09-25 | Aadigen, Llc | Peptidai ir nanodalelės, skirti molekulių įvedimui į ląstelę |
| MX2017011834A (es) | 2015-03-20 | 2018-04-11 | Aileron Therapeutics Inc | Macrociclos peptidomimeticos y usos de los mismos. |
| JP2018528217A (ja) | 2015-09-10 | 2018-09-27 | エルロン・セラピューティクス・インコーポレイテッドAileron Therapeutics,Inc. | Mcl−1のモジュレーターとしてのペプチド模倣大環状分子 |
| WO2019118893A1 (en) | 2017-12-15 | 2019-06-20 | Dana-Farber Cancer Institute, Inc. | Stabilized peptide-mediated targeted protein degradation |
| EP3749678A1 (en) | 2018-02-07 | 2020-12-16 | Dana Farber Cancer Institute, Inc. | Cell-permeable stapled peptide modules for cellular delivery |
| CN114302735B (zh) * | 2019-06-07 | 2025-03-18 | 密苏里大学管理者 | 抑制hiv衣壳的肽抑制剂 |
| CA3173973A1 (en) * | 2020-03-04 | 2021-09-10 | Dana-Farber Cancer Institute, Inc. | Antiviral structurally-stabilized sars-cov-2 peptides and uses thereof |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6187548B1 (en) | 1993-05-23 | 2001-02-13 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Methods using human calcium sensor protein, fragments thereof and DNA encoding same |
| US6239270B1 (en) | 1993-05-24 | 2001-05-29 | Rhone-Poulenc Rorer S.A. | Nucleic acids encoding human calcium sensor protein |
| EP0972198B2 (de) * | 1997-03-10 | 2013-12-11 | Roche Diagnostics GmbH | Verfahren zur simultanen bestimmung von hiv-antigenen und hiv-antikörpern |
| ES2535961T3 (es) | 1999-04-09 | 2015-05-19 | Zoetis P&U Llc | Bacteria pasteurelácea atenuada que tiene una mutación en un gen de virulencia |
| US6790950B2 (en) | 1999-04-09 | 2004-09-14 | Pharmacia & Upjohn Company | Anti-bacterial vaccine compositions |
| US7192713B1 (en) * | 1999-05-18 | 2007-03-20 | President And Fellows Of Harvard College | Stabilized compounds having secondary structure motifs |
| AUPQ776100A0 (en) | 2000-05-26 | 2000-06-15 | Australian National University, The | Synthetic molecules and uses therefor |
| US20020115606A1 (en) | 2000-10-17 | 2002-08-22 | Myriad Genetics, Inc. | Protein-protein interactions in neurodegenerative diseases |
| WO2005044839A2 (en) | 2003-11-05 | 2005-05-19 | Dana-Farber Cancer Institute, Inc. | Stabilized alpha helical peptides and uses thereof |
| WO2008008998A2 (en) | 2006-07-13 | 2008-01-17 | Cell Signaling Technology, Inc. | Reagents for the detection of protein phosphorylation in signaling pathways |
| US20100159477A1 (en) | 2006-07-13 | 2010-06-24 | Peter Hornbeck | Reagents for the detection of protein phosphorylation in signaling pathways |
| CN101600447A (zh) | 2006-09-11 | 2009-12-09 | 伊利诺斯大学理事会 | 铜氧还蛋白衍生肽类的修饰物及其使用方法 |
| JP2010505831A (ja) | 2006-10-05 | 2010-02-25 | ニューヨーク ブラッド センター, インコーポレイテッド | 安定化した、治療用の小型のヘリックス性抗ウイルスペプチド |
| US8937154B2 (en) | 2006-10-05 | 2015-01-20 | New York Blood Center, Inc. | Stabilized therapeutic small helical antiviral peptides |
| CA2677045C (en) | 2007-01-31 | 2016-10-18 | Dana-Farber Cancer Institute, Inc. | Stabilized p53 peptides and uses thereof |
| JP5078401B2 (ja) * | 2007-03-27 | 2012-11-21 | 株式会社Adeka | 防水シート |
| WO2009042237A2 (en) | 2007-09-26 | 2009-04-02 | Dana Farber Cancer Institute | Methods and compositions for modulating bcl-2 family polypeptides |
| CA2713089C (en) | 2008-01-23 | 2017-11-21 | Dana Farber Cancer Institute | Compositions and methods for the treatment of viral infections |
| EP2283033A1 (en) * | 2008-05-06 | 2011-02-16 | New York Blood Center | Antiviral cell penetrating peptides |
| EP3401684B1 (en) | 2008-10-10 | 2022-03-16 | Dana Farber Cancer Institute, Inc. | Chemical modulators of pro-apoptotic bax and bcl-2 polypeptides |
-
2009
- 2009-05-05 EP EP09743518A patent/EP2283033A1/en not_active Withdrawn
- 2009-05-05 CA CA2725227A patent/CA2725227A1/en not_active Abandoned
- 2009-05-05 WO PCT/US2009/042913 patent/WO2009137532A1/en not_active Ceased
- 2009-05-05 US US12/436,080 patent/US8324153B2/en not_active Expired - Fee Related
- 2009-05-05 AU AU2009244400A patent/AU2009244400B2/en not_active Ceased
- 2009-05-05 JP JP2011508615A patent/JP2011522796A/ja active Pending
-
2012
- 2012-10-31 US US13/664,699 patent/US8933019B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2011522796A (ja) | 2011-08-04 |
| US20130059776A1 (en) | 2013-03-07 |
| EP2283033A1 (en) | 2011-02-16 |
| AU2009244400A2 (en) | 2010-11-11 |
| AU2009244400A1 (en) | 2009-11-12 |
| US8933019B2 (en) | 2015-01-13 |
| AU2009244400B2 (en) | 2012-12-20 |
| US20090281041A1 (en) | 2009-11-12 |
| WO2009137532A1 (en) | 2009-11-12 |
| US8324153B2 (en) | 2012-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009244400B2 (en) | Antiviral cell penetrating peptides | |
| JP2011522796A5 (enExample) | ||
| ES2387827T3 (es) | Péptidos antivirales helicoidales, de pequeño tamaño, terapéuticos estabilizados | |
| Zhang et al. | Dual-acting stapled peptides target both HIV-1 entry and assembly | |
| JP2024531265A (ja) | ウイルス膜融合阻害剤を最適化する方法、および広域スペクトルの抗コロナウイルスリポペプチドとその応用 | |
| US9724383B2 (en) | Stabilized trimeric HIV-1 GP41 fusion inhibitor polypeptides comprising the N-terminal heptad repeat (NHR) and foldon (FD) trimerization motif | |
| CN106749558B (zh) | 广谱抑制hiv的脂肽、其衍生物、其药物组合物及其用途 | |
| JP2020517741A (ja) | Hivを強力に阻害するためのリポペプチド、その誘導体、その医薬組成物及びその使用 | |
| US8937154B2 (en) | Stabilized therapeutic small helical antiviral peptides | |
| EP2291392B1 (en) | Bifunctional molecules for inhibiting hiv entry | |
| WO2005007831A2 (en) | Compositions of protein mimetics and methods of using same against hiv-1, sars-cov and the like | |
| Geng et al. | Characterization of novel HIV fusion-inhibitory lipopeptides with the MT hook structure | |
| CA2766417A1 (en) | Stabilized therapeutic small helical antiviral peptides | |
| Spensiero | Design and synthesis of new integrase inhibitors | |
| AU2012200580A1 (en) | Stabilized therapeutic small helical antiviral peptides | |
| Bailey | The mechanism of HIV-1 virolytic inactivation by Env-targeting peptide triazole thiols | |
| Zhang | Interaction-mediating sequences within class I viral fusion glycoproteins: their roles in viral infection and in applications | |
| Simin | Interaction-Mediating Sequences within Class I Viral Fusion Glycoproteins: Their Roles in Viral Infection and in Applications | |
| Tien et al. | Understanding regulation of HIV-1 protease precursor autoprocessing | |
| WO2005068492A2 (en) | Peptide inhibitors of retroviral integrase useful for the treatment of retroviral infection | |
| Poe | Bimolecular fluorescence complementation reveals that HIV-1 Nef oligomerization is essential for CD4 downregulation and viral replication | |
| Suntoke | HIV entry: a biophysical and mutational analysis of gp41-mediated membrane fusion and its inhibition | |
| OA19487A (en) | Potent HIV inhibiting lipopeptide, derivative thereof, pharmaceutical composition thereof and use thereof. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20150505 |