JP2000509394A

JP2000509394A - 細胞膜を横切って物質を輸送するためのポリペプチド結合体

細胞膜を横切って物質を輸送するためのポリペプチド結合体

Info

Publication number: JP2000509394A
Authority: JP; Japan
Prior art keywords: polypeptide; acid; composition; compound; terminus
Prior art date: 1996-05-01
Legal status : Ceased

Application number

JP9539221A

Other languages

English (en)

Japanese (ja)

Other versions

JP2000509394A5 (2

Inventor

イー．サマートン，ジェームス

ディー．ウェラー，ドワイト

Original Assignee

アンティバイラルズインコーポレイテッド

Priority date

1996-05-01

Filing date

1997-04-30

Publication date

2000-07-25

1997-04-30 Application filed by アンティバイラルズインコーポレイテッド filed Critical アンティバイラルズインコーポレイテッド

2000-07-25 Publication of JP2000509394A publication Critical patent/JP2000509394A/ja

2004-12-09 Publication of JP2000509394A5 publication Critical patent/JP2000509394A5/ja

Status Ceased legal-status Critical Current

Links

108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 318
102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 297
229920001184 polypeptide Polymers 0.000 title claims abstract description 291
210000000170 cell membrane Anatomy 0.000 title description 19
239000000126 substance Substances 0.000 title description 9
150000001875 compounds Chemical class 0.000 claims abstract description 142
239000000203 mixture Substances 0.000 claims abstract description 134
229920000642 polymer Polymers 0.000 claims abstract description 73
230000007704 transition Effects 0.000 claims abstract description 57
230000002441 reversible effect Effects 0.000 claims abstract description 9
210000004027 cell Anatomy 0.000 claims description 103
238000000034 method Methods 0.000 claims description 85
239000002253 acid Substances 0.000 claims description 72
150000002632 lipids Chemical class 0.000 claims description 66
229940024606 amino acid Drugs 0.000 claims description 61
235000001014 amino acid Nutrition 0.000 claims description 59
150000001413 amino acids Chemical class 0.000 claims description 57
210000000172 cytosol Anatomy 0.000 claims description 53
239000003999 initiator Substances 0.000 claims description 46
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 33
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 33
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 33
239000004220 glutamic acid Substances 0.000 claims description 27
235000013922 glutamic acid Nutrition 0.000 claims description 26
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 25
230000002378 acidificating effect Effects 0.000 claims description 21
-1 Soleucine Natural products 0.000 claims description 20
125000000539 amino acid group Chemical group 0.000 claims description 20
230000008569 process Effects 0.000 claims description 20
150000002148 esters Chemical class 0.000 claims description 18
238000011282 treatment Methods 0.000 claims description 18
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 17
230000015572 biosynthetic process Effects 0.000 claims description 16
238000005192 partition Methods 0.000 claims description 16
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 15
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 15
229940000635 beta-alanine Drugs 0.000 claims description 15
238000009826 distribution Methods 0.000 claims description 15
235000005772 leucine Nutrition 0.000 claims description 15
229960001592 paclitaxel Drugs 0.000 claims description 13
230000037317 transdermal delivery Effects 0.000 claims description 13
QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 claims description 12
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 12
235000004279 alanine Nutrition 0.000 claims description 12
229960001265 ciclosporin Drugs 0.000 claims description 12
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 11
229920002643 polyglutamic acid Polymers 0.000 claims description 11
210000000434 stratum corneum Anatomy 0.000 claims description 11
229930012538 Paclitaxel Natural products 0.000 claims description 10
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 10
108010036949 Cyclosporine Proteins 0.000 claims description 9
235000003704 aspartic acid Nutrition 0.000 claims description 9
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 8
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 8
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 8
108010020346 Polyglutamic Acid Proteins 0.000 claims description 8
230000001580 bacterial effect Effects 0.000 claims description 8
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 8
208000002925 dental caries Diseases 0.000 claims description 8
235000019253 formic acid Nutrition 0.000 claims description 8
229930182817 methionine Natural products 0.000 claims description 8
235000006109 methionine Nutrition 0.000 claims description 8
238000003786 synthesis reaction Methods 0.000 claims description 8
SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 claims description 7
SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 claims description 7
108020004707 nucleic acids Proteins 0.000 claims description 7
150000007523 nucleic acids Chemical class 0.000 claims description 7
102000039446 nucleic acids Human genes 0.000 claims description 7
241000894006 Bacteria Species 0.000 claims description 6
229930105110 Cyclosporin A Natural products 0.000 claims description 6
QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 claims description 6
229930182912 cyclosporin Natural products 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 5
208000015181 infectious disease Diseases 0.000 claims description 5
150000002634 lipophilic molecules Chemical class 0.000 claims description 5
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 5
COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 5
210000004881 tumor cell Anatomy 0.000 claims description 5
OQEBBZSWEGYTPG-UHFFFAOYSA-N 3-aminobutanoic acid Chemical compound CC(N)CC(O)=O OQEBBZSWEGYTPG-UHFFFAOYSA-N 0.000 claims description 4
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 claims description 4
108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 4
102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 4
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 4
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 claims description 4
229960003942 amphotericin b Drugs 0.000 claims description 4
239000003242 anti bacterial agent Substances 0.000 claims description 4
239000002246 antineoplastic agent Substances 0.000 claims description 4
210000002744 extracellular matrix Anatomy 0.000 claims description 4
239000004474 valine Substances 0.000 claims description 4
230000001013 cariogenic effect Effects 0.000 claims description 3
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 2
230000000259 anti-tumor effect Effects 0.000 claims description 2
229940034982 antineoplastic agent Drugs 0.000 claims description 2
125000002091 cationic group Chemical group 0.000 claims description 2
210000004051 gastric juice Anatomy 0.000 claims description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
229960000310 isoleucine Drugs 0.000 claims description 2
230000001737 promoting effect Effects 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 2
125000001142 dicarboxylic acid group Chemical group 0.000 claims 2
244000003416 Asparagus officinalis Species 0.000 claims 1
235000005340 Asparagus officinalis Nutrition 0.000 claims 1
150000001991 dicarboxylic acids Chemical group 0.000 claims 1
238000011321 prophylaxis Methods 0.000 claims 1
238000000926 separation method Methods 0.000 claims 1
ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 claims 1
230000001419 dependent effect Effects 0.000 abstract description 7
229940079593 drug Drugs 0.000 description 57
239000003814 drug Substances 0.000 description 57
239000000047 product Substances 0.000 description 54
239000012528 membrane Substances 0.000 description 47
210000004379 membrane Anatomy 0.000 description 46
KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 43
230000032258 transport Effects 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 30
230000012202 endocytosis Effects 0.000 description 29
239000000243 solution Substances 0.000 description 29
210000001163 endosome Anatomy 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 23
230000000692 anti-sense effect Effects 0.000 description 23
229910052739 hydrogen Inorganic materials 0.000 description 22
239000001257 hydrogen Substances 0.000 description 22
239000002609 medium Substances 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 21
229960002989 glutamic acid Drugs 0.000 description 20
230000009545 invasion Effects 0.000 description 20
239000011347 resin Substances 0.000 description 19
229920005989 resin Polymers 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
238000000746 purification Methods 0.000 description 14
238000000638 solvent extraction Methods 0.000 description 14
230000004709 cell invasion Effects 0.000 description 13
230000000694 effects Effects 0.000 description 13
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 13
238000002360 preparation method Methods 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
150000001412 amines Chemical class 0.000 description 12
239000000872 buffer Substances 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
238000002474 experimental method Methods 0.000 description 12
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
108060001084 Luciferase Proteins 0.000 description 11
239000005089 Luciferase Substances 0.000 description 11
229960003136 leucine Drugs 0.000 description 11
229960003767 alanine Drugs 0.000 description 10
150000001408 amides Chemical class 0.000 description 10
210000004899 c-terminal region Anatomy 0.000 description 10
210000003527 eukaryotic cell Anatomy 0.000 description 10
230000001965 increasing effect Effects 0.000 description 10
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
150000008575 L-amino acids Chemical class 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
229920003002 synthetic resin Polymers 0.000 description 9
239000000057 synthetic resin Substances 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
230000008901 benefit Effects 0.000 description 8
210000002889 endothelial cell Anatomy 0.000 description 8
230000002132 lysosomal effect Effects 0.000 description 8
TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 8
230000035515 penetration Effects 0.000 description 8
239000012071 phase Substances 0.000 description 8
210000003491 skin Anatomy 0.000 description 8
238000003756 stirring Methods 0.000 description 8
102000004190 Enzymes Human genes 0.000 description 7
108090000790 Enzymes Proteins 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
230000007423 decrease Effects 0.000 description 7
229940088598 enzyme Drugs 0.000 description 7
229940049906 glutamate Drugs 0.000 description 7
229930195712 glutamate Natural products 0.000 description 7
239000000463 material Substances 0.000 description 7
230000004048 modification Effects 0.000 description 7
238000012986 modification Methods 0.000 description 7
239000002904 solvent Substances 0.000 description 7
OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-N 0.000 description 6
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
150000008574 D-amino acids Chemical class 0.000 description 6
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
230000004888 barrier function Effects 0.000 description 6
239000002585 base Substances 0.000 description 6
230000008499 blood brain barrier function Effects 0.000 description 6
210000001218 blood-brain barrier Anatomy 0.000 description 6
210000004323 caveolae Anatomy 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
235000018417 cysteine Nutrition 0.000 description 6
230000001086 cytosolic effect Effects 0.000 description 6
230000002121 endocytic effect Effects 0.000 description 6
OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 6
238000009472 formulation Methods 0.000 description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
230000003834 intracellular effect Effects 0.000 description 6
239000003446 ligand Substances 0.000 description 6
230000007935 neutral effect Effects 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
230000000750 progressive effect Effects 0.000 description 6
238000007614 solvation Methods 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
239000000232 Lipid Bilayer Substances 0.000 description 5
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
239000004472 Lysine Substances 0.000 description 5
108091034117 Oligonucleotide Proteins 0.000 description 5
238000002835 absorbance Methods 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
239000003623 enhancer Substances 0.000 description 5
238000002825 functional assay Methods 0.000 description 5
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
206010021143 Hypoxia Diseases 0.000 description 4
206010028980 Neoplasm Diseases 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
125000003275 alpha amino acid group Chemical group 0.000 description 4
239000012062 aqueous buffer Substances 0.000 description 4
210000004958 brain cell Anatomy 0.000 description 4
150000007942 carboxylates Chemical class 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
230000021615 conjugation Effects 0.000 description 4
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 4
229960003957 dexamethasone Drugs 0.000 description 4
229940126534 drug product Drugs 0.000 description 4
238000010828 elution Methods 0.000 description 4
238000011156 evaluation Methods 0.000 description 4
238000000799 fluorescence microscopy Methods 0.000 description 4
238000004108 freeze drying Methods 0.000 description 4
239000001963 growth medium Substances 0.000 description 4
238000004255 ion exchange chromatography Methods 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000011068 loading method Methods 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
239000011159 matrix material Substances 0.000 description 4
230000037361 pathway Effects 0.000 description 4
239000008188 pellet Substances 0.000 description 4
239000000825 pharmaceutical preparation Substances 0.000 description 4
238000011160 research Methods 0.000 description 4
230000007017 scission Effects 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000007787 solid Substances 0.000 description 4
210000002784 stomach Anatomy 0.000 description 4
150000003568 thioethers Chemical class 0.000 description 4
239000011782 vitamin Substances 0.000 description 4
235000013343 vitamin Nutrition 0.000 description 4
229940088594 vitamin Drugs 0.000 description 4
229930003231 vitamin Natural products 0.000 description 4
ZPZHKIOMBYYVRD-CPEWUTAISA-N (6s,9s,12r,15s,18s,30s)-33-[(e,1r,2r)-1,6-dihydroxy-2-methylhex-4-enyl]-30-ethyl-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,2 Chemical compound CC[C@@H]1NC(=O)C([C@H](O)[C@H](C)C\C=C\CO)N(C)C(=O)C(C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O ZPZHKIOMBYYVRD-CPEWUTAISA-N 0.000 description 3
RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 3
NJYVEMPWNAYQQN-UHFFFAOYSA-N 5-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C21OC(=O)C1=CC(C(=O)O)=CC=C21 NJYVEMPWNAYQQN-UHFFFAOYSA-N 0.000 description 3
102000000844 Cell Surface Receptors Human genes 0.000 description 3
108010001857 Cell Surface Receptors Proteins 0.000 description 3
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
239000004471 Glycine Substances 0.000 description 3
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 3
102100021904 Potassium-transporting ATPase alpha chain 1 Human genes 0.000 description 3
108010083204 Proton Pumps Proteins 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
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 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000008351 acetate buffer Substances 0.000 description 3
230000009471 action Effects 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 3
150000001720 carbohydrates Chemical class 0.000 description 3
235000014633 carbohydrates Nutrition 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
238000004090 dissolution Methods 0.000 description 3
150000002019 disulfides Chemical class 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
150000004665 fatty acids Chemical class 0.000 description 3
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
235000019152 folic acid Nutrition 0.000 description 3
229960000304 folic acid Drugs 0.000 description 3
239000011724 folic acid Substances 0.000 description 3
230000002209 hydrophobic effect Effects 0.000 description 3
230000001146 hypoxic effect Effects 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000000977 initiatory effect Effects 0.000 description 3
239000002502 liposome Substances 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
229960004452 methionine Drugs 0.000 description 3
239000003961 penetration enhancing agent Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
229960005190 phenylalanine Drugs 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
238000012545 processing Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000008279 sol Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
230000031998 transcytosis Effects 0.000 description 3
238000012546 transfer Methods 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 2
IBKQQKPQRYUGBJ-UHFFFAOYSA-N 1-(3,4,5-trihydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(O)=C(O)C(O)=C1 IBKQQKPQRYUGBJ-UHFFFAOYSA-N 0.000 description 2
AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
LINBWYYLPWJQHE-UHFFFAOYSA-N 3-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)NCCC(=O)O)C3=CC=CC=C3C2=C1 LINBWYYLPWJQHE-UHFFFAOYSA-N 0.000 description 2
BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical group C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
102000003939 Membrane transport proteins Human genes 0.000 description 2
108090000301 Membrane transport proteins Proteins 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
229920000805 Polyaspartic acid Polymers 0.000 description 2
239000004743 Polypropylene Substances 0.000 description 2
102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 2
108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
229940041181 antineoplastic drug Drugs 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
150000004657 carbamic acid derivatives Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
210000002421 cell wall Anatomy 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
210000004748 cultured cell Anatomy 0.000 description 2
230000009089 cytolysis Effects 0.000 description 2
230000000593 degrading effect Effects 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
229960004679 doxorubicin Drugs 0.000 description 2
238000001035 drying Methods 0.000 description 2
235000013399 edible fruits Nutrition 0.000 description 2
210000002615 epidermis Anatomy 0.000 description 2
210000002919 epithelial cell Anatomy 0.000 description 2
230000008029 eradication Effects 0.000 description 2
230000004927 fusion Effects 0.000 description 2
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
239000011521 glass Substances 0.000 description 2
229920001519 homopolymer Polymers 0.000 description 2
230000036571 hydration Effects 0.000 description 2
238000006703 hydration reaction Methods 0.000 description 2
150000002433 hydrophilic molecules Chemical class 0.000 description 2
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
238000007654 immersion Methods 0.000 description 2
230000001976 improved effect Effects 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
210000005229 liver cell Anatomy 0.000 description 2
210000003712 lysosome Anatomy 0.000 description 2
230000001868 lysosomic effect Effects 0.000 description 2
210000004962 mammalian cell Anatomy 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
230000009061 membrane transport Effects 0.000 description 2
108020004999 messenger RNA Proteins 0.000 description 2
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
230000003204 osmotic effect Effects 0.000 description 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
239000013612 plasmid Substances 0.000 description 2
108010064470 polyaspartate Proteins 0.000 description 2
229920001155 polypropylene Polymers 0.000 description 2
230000002265 prevention Effects 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
238000004366 reverse phase liquid chromatography Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000012679 serum free medium Substances 0.000 description 2
230000001568 sexual effect Effects 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
241000894007 species Species 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000012916 structural analysis Methods 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000003396 thiol group Chemical group [H]S* 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
238000013519 translation Methods 0.000 description 2
210000003956 transport vesicle Anatomy 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 2
125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
238000005406 washing Methods 0.000 description 2
OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
QUGODPAQMQMGRN-UHFFFAOYSA-N (2,3-dinitrophenyl) hydrogen carbonate Chemical compound OC(=O)OC1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O QUGODPAQMQMGRN-UHFFFAOYSA-N 0.000 description 1
FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
PXUVMGHJTJYCDF-UHFFFAOYSA-N (6-amino-2-morpholin-4-ylpurin-6-yl)-phenylmethanone Chemical compound N1=C2N=CN=C2C(N)(C(=O)C=2C=CC=CC=2)N=C1N1CCOCC1 PXUVMGHJTJYCDF-UHFFFAOYSA-N 0.000 description 1
GYPCWHHQAVLMKO-XXKQIVDLSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-[(e)-n-[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-ylidene)amino]-c-methylcarbonimidoyl]-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical group Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\N=C1CC(C)(C)N(O)C(C)(C)C1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 GYPCWHHQAVLMKO-XXKQIVDLSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
CTTUQCIBNSCQRH-UHFFFAOYSA-N 2,3,4-trimethylpentan-3-amine Chemical compound CC(C)C(C)(N)C(C)C CTTUQCIBNSCQRH-UHFFFAOYSA-N 0.000 description 1
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
FQVKLEDFFUPTQP-UHFFFAOYSA-N 2-[bis(1-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)C(C)P(C(C)C(O)=O)C(C)C(O)=O FQVKLEDFFUPTQP-UHFFFAOYSA-N 0.000 description 1
OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
JHRPHASLIZOEBJ-UHFFFAOYSA-N 2-methylpyridine-3-carbaldehyde Chemical compound CC1=NC=CC=C1C=O JHRPHASLIZOEBJ-UHFFFAOYSA-N 0.000 description 1
UBDUXVILYVIFKH-UHFFFAOYSA-N 2-morpholin-4-ylbutanedioic acid Chemical compound OC(=O)CC(C(O)=O)N1CCOCC1 UBDUXVILYVIFKH-UHFFFAOYSA-N 0.000 description 1
IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 1
UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
SIVJYKAWVLZRSX-UHFFFAOYSA-N 5-morpholin-4-yl-1h-pyrimidine-2,4-dione Chemical group O=C1NC(=O)NC=C1N1CCOCC1 SIVJYKAWVLZRSX-UHFFFAOYSA-N 0.000 description 1
KSPBSYDKMUWKEX-UHFFFAOYSA-N 6-benzoyl-4-(morpholin-4-ylamino)-1H-pyrimidin-2-one Chemical compound C=1C(NN2CCOCC2)=NC(=O)NC=1C(=O)C1=CC=CC=C1 KSPBSYDKMUWKEX-UHFFFAOYSA-N 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
241000186046 Actinomyces Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 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
108010017384 Blood Proteins Proteins 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
208000003174 Brain Neoplasms Diseases 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
DIKAQUXQCRWVOB-UHFFFAOYSA-N CCN=C=NCCCN(C)C.CO Chemical compound CCN=C=NCCCN(C)C.CO DIKAQUXQCRWVOB-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 1
DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 description 1
AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 1
108020004414 DNA Proteins 0.000 description 1
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
241000255925 Diptera Species 0.000 description 1
241000611421 Elia Species 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
102400001368 Epidermal growth factor Human genes 0.000 description 1
101800003838 Epidermal growth factor Proteins 0.000 description 1
239000004386 Erythritol Substances 0.000 description 1
UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
108090000331 Firefly luciferases Proteins 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 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
241000720950 Gluta Species 0.000 description 1
102100027685 Hemoglobin subunit alpha Human genes 0.000 description 1
108091005902 Hemoglobin subunit alpha Proteins 0.000 description 1
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
229930010555 Inosine Natural products 0.000 description 1
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-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
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-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
108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
102000014944 Lysosome-Associated Membrane Glycoproteins Human genes 0.000 description 1
108010064171 Lysosome-Associated Membrane Glycoproteins Proteins 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
NPPQSCRMBWNHMW-UHFFFAOYSA-N Meprobamate Chemical group NC(=O)OCC(C)(CCC)COC(N)=O NPPQSCRMBWNHMW-UHFFFAOYSA-N 0.000 description 1
241000907681 Morpho Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
241001024099 Olla Species 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
240000007594 Oryza sativa Species 0.000 description 1
235000007164 Oryza sativa Nutrition 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
241000288049 Perdix perdix Species 0.000 description 1
BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
229920000608 Polyaspartic Polymers 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
239000012614 Q-Sepharose Substances 0.000 description 1
241000277331 Salmonidae Species 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
239000004098 Tetracycline Substances 0.000 description 1
JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
241000700605 Viruses Species 0.000 description 1
HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
230000009056 active transport Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000011543 agarose gel Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001335 aliphatic alkanes Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
235000020661 alpha-linolenic acid Nutrition 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
229960003022 amoxicillin Drugs 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
238000005571 anion exchange chromatography Methods 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
230000003409 anti-rejection Effects 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
239000000074 antisense oligonucleotide Substances 0.000 description 1
238000012230 antisense oligonucleotides Methods 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
150000001510 aspartic acids Chemical class 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
108010042854 bacteria histone-like protein HU Proteins 0.000 description 1
230000008955 bacterial trafficking Effects 0.000 description 1
210000002469 basement membrane Anatomy 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
239000011616 biotin Substances 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
HKJFYVRDQXGPPK-UHFFFAOYSA-N bis(4-nitrophenyl) butanedioate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)CCC(=O)OC1=CC=C([N+]([O-])=O)C=C1 HKJFYVRDQXGPPK-UHFFFAOYSA-N 0.000 description 1
IOIJXIHQQRSQDS-UHFFFAOYSA-N bis(4-nitrophenyl) pentanedioate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)CCCC(=O)OC1=CC=C([N+]([O-])=O)C=C1 IOIJXIHQQRSQDS-UHFFFAOYSA-N 0.000 description 1
150000001621 bismuth Chemical class 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000036770 blood supply Effects 0.000 description 1
238000006664 bond formation reaction Methods 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
210000004781 brain capillary Anatomy 0.000 description 1
201000008211 brain sarcoma Diseases 0.000 description 1
239000012267 brine Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000005587 carbonate group Chemical group 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000033077 cellular process Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
229940106189 ceramide Drugs 0.000 description 1
150000001783 ceramides Chemical class 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
229960003260 chlorhexidine Drugs 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
BHYOQNUELFTYRT-DPAQBDIFSA-N cholesterol sulfate Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 BHYOQNUELFTYRT-DPAQBDIFSA-N 0.000 description 1
229940080277 cholesteryl sulfate Drugs 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
229960002626 clarithromycin Drugs 0.000 description 1
238000010835 comparative analysis Methods 0.000 description 1
230000000536 complexating effect Effects 0.000 description 1
229940125810 compound 20 Drugs 0.000 description 1
239000012059 conventional drug carrier Substances 0.000 description 1
238000005520 cutting process Methods 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
150000001945 cysteines Chemical class 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000003795 desorption Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
YXVFQADLFFNVDS-UHFFFAOYSA-N diammonium citrate Chemical compound [NH4+].[NH4+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O YXVFQADLFFNVDS-UHFFFAOYSA-N 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
235000019800 disodium phosphate Nutrition 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
125000002228 disulfide group Chemical group 0.000 description 1
239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
229940088679 drug related substance Drugs 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
230000004651 endocytosis pathway Effects 0.000 description 1
230000001159 endocytotic effect Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
229940116977 epidermal growth factor Drugs 0.000 description 1
229940009714 erythritol Drugs 0.000 description 1
UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
235000019414 erythritol Nutrition 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000007850 fluorescent dye Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
235000021588 free fatty acids Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
239000003292 glue Substances 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
150000002307 glutamic acids Chemical class 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
KMXTYZBQPJXGNK-UHFFFAOYSA-N hexadecan-1-amine;hydron;fluoride Chemical compound F.CCCCCCCCCCCCCCCCN KMXTYZBQPJXGNK-UHFFFAOYSA-N 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000012678 infectious agent Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
229960003786 inosine Drugs 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229960004488 linolenic acid Drugs 0.000 description 1
KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
150000004668 long chain fatty acids Chemical class 0.000 description 1
239000006210 lotion Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000002483 medication Methods 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
229960000282 metronidazole Drugs 0.000 description 1
VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
238000000302 molecular modelling Methods 0.000 description 1
239000003068 molecular probe Substances 0.000 description 1
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
230000004942 nuclear accumulation Effects 0.000 description 1
QGSCPWWHMSCFOV-UHFFFAOYSA-N octadec-9-enylazanium;fluoride Chemical compound F.CCCCCCCCC=CCCCCCCCCN QGSCPWWHMSCFOV-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
229960000381 omeprazole Drugs 0.000 description 1
238000005457 optimization Methods 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
238000001139 pH measurement Methods 0.000 description 1
YVOFTMXWTWHRBH-UHFFFAOYSA-N pentanedioyl dichloride Chemical compound ClC(=O)CCCC(Cl)=O YVOFTMXWTWHRBH-UHFFFAOYSA-N 0.000 description 1
239000007793 ph indicator Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
229960003531 phenolsulfonphthalein Drugs 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
230000008884 pinocytosis Effects 0.000 description 1
229920000447 polyanionic polymer Polymers 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
238000012805 post-processing Methods 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
XXPDBLUZJRXNNZ-UHFFFAOYSA-N promethazine hydrochloride Chemical compound Cl.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 XXPDBLUZJRXNNZ-UHFFFAOYSA-N 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
235000019192 riboflavin Nutrition 0.000 description 1
229960002477 riboflavin Drugs 0.000 description 1
239000002151 riboflavin Substances 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
229940085605 saccharin sodium Drugs 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
239000000523 sample Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000008299 semisolid dosage form Substances 0.000 description 1
125000005629 sialic acid group Chemical group 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000002002 slurry Substances 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000004960 subcellular localization Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
229940014800 succinic anhydride Drugs 0.000 description 1
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
230000008093 supporting effect Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
230000008685 targeting Effects 0.000 description 1
238000011191 terminal modification Methods 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
235000019157 thiamine Nutrition 0.000 description 1
KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
229960003495 thiamine Drugs 0.000 description 1
239000011721 thiamine Substances 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
238000001269 time-of-flight mass spectrometry Methods 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
230000005945 translocation Effects 0.000 description 1
230000032895 transmembrane transport Effects 0.000 description 1
229960003500 triclosan Drugs 0.000 description 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
229940038773 trisodium citrate Drugs 0.000 description 1
229960004799 tryptophan Drugs 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1