CN102151261A - [3.2.0]杂环化合物及其类似物在癌症、炎症和感染性疾病治疗中的应用 - Google Patents
[3.2.0]杂环化合物及其类似物在癌症、炎症和感染性疾病治疗中的应用 Download PDFInfo
- Publication number
- CN102151261A CN102151261A CN2010102534518A CN201010253451A CN102151261A CN 102151261 A CN102151261 A CN 102151261A CN 2010102534518 A CN2010102534518 A CN 2010102534518A CN 201010253451 A CN201010253451 A CN 201010253451A CN 102151261 A CN102151261 A CN 102151261A
- Authority
- CN
- China
- Prior art keywords
- chemical compound
- formula
- group
- cell
- amino
- 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.)
- Pending
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 68
- 201000011510 cancer Diseases 0.000 title claims abstract description 50
- 208000035473 Communicable disease Diseases 0.000 title abstract description 18
- 150000002391 heterocyclic compounds Chemical class 0.000 title abstract description 5
- 206010061218 Inflammation Diseases 0.000 title description 27
- 230000004054 inflammatory process Effects 0.000 title description 27
- 241001465754 Metazoa Species 0.000 claims abstract description 32
- 241000124008 Mammalia Species 0.000 claims abstract description 5
- 241000283984 Rodentia Species 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 480
- -1 amino, amino carbonyl Chemical group 0.000 claims description 104
- 239000003814 drug Substances 0.000 claims description 89
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 238000002360 preparation method Methods 0.000 claims description 59
- 239000001257 hydrogen Substances 0.000 claims description 53
- 150000002431 hydrogen Chemical class 0.000 claims description 46
- 125000002252 acyl group Chemical group 0.000 claims description 43
- 229910052801 chlorine Inorganic materials 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 41
- 239000001301 oxygen Substances 0.000 claims description 41
- 229910052794 bromium Inorganic materials 0.000 claims description 37
- 229910052731 fluorine Inorganic materials 0.000 claims description 37
- 229910052740 iodine Inorganic materials 0.000 claims description 37
- 239000011737 fluorine Substances 0.000 claims description 31
- 229940079593 drug Drugs 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 108090000623 proteins and genes Proteins 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 229920006395 saturated elastomer Polymers 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 102000004169 proteins and genes Human genes 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000004423 acyloxy group Chemical group 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- SETHSKIRVBKZTB-UHFFFAOYSA-N NC([O])=O Chemical compound NC([O])=O SETHSKIRVBKZTB-UHFFFAOYSA-N 0.000 claims description 18
- 125000004414 alkyl thio group Chemical group 0.000 claims description 18
- 125000005110 aryl thio group Chemical group 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 15
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 15
- 238000010572 single replacement reaction Methods 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 230000004913 activation Effects 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 230000014509 gene expression Effects 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 201000003076 Angiosarcoma Diseases 0.000 claims description 2
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 claims description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 claims description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 201000005619 esophageal carcinoma Diseases 0.000 claims description 2
- 201000011066 hemangioma Diseases 0.000 claims description 2
- 201000007433 ureter carcinoma Diseases 0.000 claims description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 1
- 102100021339 Multidrug resistance-associated protein 1 Human genes 0.000 claims 1
- 230000005775 apoptotic pathway Effects 0.000 claims 1
- 108010066052 multidrug resistance-associated protein 1 Proteins 0.000 claims 1
- NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 abstract description 164
- 229950002736 marizomib Drugs 0.000 abstract description 157
- NGWSFRIPKNWYAO-UHFFFAOYSA-N salinosporamide A Natural products N1C(=O)C(CCCl)C2(C)OC(=O)C21C(O)C1CCCC=C1 NGWSFRIPKNWYAO-UHFFFAOYSA-N 0.000 abstract description 157
- 238000000034 method Methods 0.000 abstract description 98
- 208000015181 infectious disease Diseases 0.000 abstract description 27
- RBLXHLSQRPDVQD-UHFFFAOYSA-N 7-oxa-4-azabicyclo[3.2.0]heptane-3,6-dione Chemical compound C1C(=O)NC2C(=O)OC21 RBLXHLSQRPDVQD-UHFFFAOYSA-N 0.000 abstract 1
- 230000004968 inflammatory condition Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 239
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 149
- 230000000694 effects Effects 0.000 description 138
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 95
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 81
- 239000000203 mixture Substances 0.000 description 79
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 76
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 75
- 108010057466 NF-kappa B Proteins 0.000 description 69
- 102000003945 NF-kappa B Human genes 0.000 description 69
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- 238000004458 analytical method Methods 0.000 description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 44
- 102000035195 Peptidases Human genes 0.000 description 43
- 108091005804 Peptidases Proteins 0.000 description 43
- 239000000460 chlorine Substances 0.000 description 42
- 201000010099 disease Diseases 0.000 description 42
- 239000000243 solution Substances 0.000 description 42
- 244000005700 microbiome Species 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 238000002474 experimental method Methods 0.000 description 38
- 239000000758 substrate Substances 0.000 description 38
- 230000000845 anti-microbial effect Effects 0.000 description 37
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 36
- 239000004365 Protease Substances 0.000 description 34
- 239000002585 base Substances 0.000 description 34
- 235000019419 proteases Nutrition 0.000 description 34
- 210000004881 tumor cell Anatomy 0.000 description 32
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 31
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 31
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 31
- 230000012010 growth Effects 0.000 description 31
- 230000005764 inhibitory process Effects 0.000 description 31
- 239000011630 iodine Substances 0.000 description 31
- 238000012360 testing method Methods 0.000 description 31
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 30
- 239000000523 sample Substances 0.000 description 30
- 238000012545 processing Methods 0.000 description 29
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- 239000001963 growth medium Substances 0.000 description 28
- 238000000746 purification Methods 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 108060001084 Luciferase Proteins 0.000 description 27
- 239000005089 Luciferase Substances 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 27
- 238000004128 high performance liquid chromatography Methods 0.000 description 27
- 238000004519 manufacturing process Methods 0.000 description 27
- 241001597008 Nomeidae Species 0.000 description 26
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 25
- 239000003153 chemical reaction reagent Substances 0.000 description 24
- 150000002148 esters Chemical class 0.000 description 23
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 22
- 239000003005 anticarcinogenic agent Substances 0.000 description 22
- 238000010790 dilution Methods 0.000 description 22
- 239000012895 dilution Substances 0.000 description 22
- 230000002401 inhibitory effect Effects 0.000 description 22
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 21
- 230000001939 inductive effect Effects 0.000 description 21
- 238000002347 injection Methods 0.000 description 21
- 239000007924 injection Substances 0.000 description 21
- 239000007788 liquid Substances 0.000 description 21
- 229940002612 prodrug Drugs 0.000 description 21
- 239000000651 prodrug Substances 0.000 description 21
- 238000003860 storage Methods 0.000 description 21
- 238000005336 cracking Methods 0.000 description 20
- 239000003112 inhibitor Substances 0.000 description 20
- 241000193738 Bacillus anthracis Species 0.000 description 19
- 102100025566 Chymotrypsin-like protease CTRL-1 Human genes 0.000 description 19
- 101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 19
- 241000283973 Oryctolagus cuniculus Species 0.000 description 19
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 19
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 19
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 19
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 19
- 230000003110 anti-inflammatory effect Effects 0.000 description 19
- 230000003013 cytotoxicity Effects 0.000 description 19
- 231100000135 cytotoxicity Toxicity 0.000 description 19
- 239000000376 reactant Substances 0.000 description 19
- 125000001424 substituent group Chemical group 0.000 description 19
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 18
- 102000003952 Caspase 3 Human genes 0.000 description 18
- 108090000397 Caspase 3 Proteins 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 210000004369 blood Anatomy 0.000 description 16
- 239000008280 blood Substances 0.000 description 16
- 239000002054 inoculum Substances 0.000 description 16
- 239000008194 pharmaceutical composition Substances 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 238000011160 research Methods 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 206010035226 Plasma cell myeloma Diseases 0.000 description 15
- 238000011156 evaluation Methods 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 102000008379 I-kappa B Proteins Human genes 0.000 description 14
- 108010021699 I-kappa B Proteins Proteins 0.000 description 14
- 208000034578 Multiple myelomas Diseases 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 14
- 239000000872 buffer Substances 0.000 description 14
- 230000004083 survival effect Effects 0.000 description 14
- FWPWHHUJACGNMZ-NBBQQVJHSA-N (1s,2r,5r)-5-[(1s)-1-hydroxy-2-methylpropyl]-2-methyl-7-oxa-4-azabicyclo[3.2.0]heptane-3,6-dione Chemical compound N1C(=O)[C@H](C)[C@@H]2OC(=O)[C@@]21[C@@H](O)C(C)C FWPWHHUJACGNMZ-NBBQQVJHSA-N 0.000 description 13
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 230000037012 chymotrypsin-like activity Effects 0.000 description 13
- 231100000433 cytotoxic Toxicity 0.000 description 13
- 230000001472 cytotoxic effect Effects 0.000 description 13
- 125000005842 heteroatom Chemical group 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 239000011734 sodium Substances 0.000 description 13
- 206010006187 Breast cancer Diseases 0.000 description 12
- 208000026310 Breast neoplasm Diseases 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 102000018745 NF-KappaB Inhibitor alpha Human genes 0.000 description 12
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- 210000002540 macrophage Anatomy 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 108090000227 Chymases Proteins 0.000 description 11
- 102000003858 Chymases Human genes 0.000 description 11
- 241000426682 Salinispora Species 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 102100040247 Tumor necrosis factor Human genes 0.000 description 11
- 230000030833 cell death Effects 0.000 description 11
- 230000008859 change Effects 0.000 description 11
- 239000012531 culture fluid Substances 0.000 description 11
- 231100000673 dose–response relationship Toxicity 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 239000006166 lysate Substances 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 206010033128 Ovarian cancer Diseases 0.000 description 10
- 206010061535 Ovarian neoplasm Diseases 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 230000006907 apoptotic process Effects 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 201000008275 breast carcinoma Diseases 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 238000000855 fermentation Methods 0.000 description 10
- 230000004151 fermentation Effects 0.000 description 10
- 201000001441 melanoma Diseases 0.000 description 10
- 235000015097 nutrients Nutrition 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 201000001514 prostate carcinoma Diseases 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 229920005989 resin Polymers 0.000 description 10
- 239000011347 resin Substances 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 239000003053 toxin Substances 0.000 description 10
- 231100000765 toxin Toxicity 0.000 description 10
- 206010059866 Drug resistance Diseases 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
- 210000003743 erythrocyte Anatomy 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 210000004969 inflammatory cell Anatomy 0.000 description 9
- 230000001665 lethal effect Effects 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- 230000000813 microbial effect Effects 0.000 description 9
- 230000002969 morbid Effects 0.000 description 9
- 230000026731 phosphorylation Effects 0.000 description 9
- 238000006366 phosphorylation reaction Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 230000001988 toxicity Effects 0.000 description 9
- 231100000419 toxicity Toxicity 0.000 description 9
- 238000001262 western blot Methods 0.000 description 9
- 206010009944 Colon cancer Diseases 0.000 description 8
- 108700008625 Reporter Genes Proteins 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 8
- 230000001093 anti-cancer Effects 0.000 description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 description 8
- 229920001429 chelating resin Polymers 0.000 description 8
- 239000000975 dye Substances 0.000 description 8
- DOGIDQKFVLKMLQ-JTHVHQAWSA-N epoxomicin Chemical compound CC[C@H](C)[C@H](N(C)C(C)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1 DOGIDQKFVLKMLQ-JTHVHQAWSA-N 0.000 description 8
- 108700002672 epoxomicin Proteins 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 238000007912 intraperitoneal administration Methods 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 231100000518 lethal Toxicity 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 8
- 229960004169 mitoxantrone hydrochloride Drugs 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000002674 ointment Substances 0.000 description 8
- 150000002924 oxiranes Chemical class 0.000 description 8
- UVFAEQZFLBGVRM-MSMWPWNWSA-N succinyl-Leu-Leu-Val-Tyr-7-amino-4-methylcoumarin Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CCC(O)=O)CC(C)C)C(=O)NC=1C=C2OC(=O)C=C(C)C2=CC=1)C1=CC=C(O)C=C1 UVFAEQZFLBGVRM-MSMWPWNWSA-N 0.000 description 8
- 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 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 102400001093 PAK-2p27 Human genes 0.000 description 7
- 102000011195 Profilin Human genes 0.000 description 7
- 108050001408 Profilin Proteins 0.000 description 7
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 7
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- 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 7
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 230000010261 cell growth Effects 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 7
- 230000003203 everyday effect Effects 0.000 description 7
- 230000004927 fusion Effects 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 7
- 239000002502 liposome Substances 0.000 description 7
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 7
- 244000052769 pathogen Species 0.000 description 7
- 230000001717 pathogenic effect Effects 0.000 description 7
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229910052710 silicon Inorganic materials 0.000 description 7
- 239000010703 silicon Substances 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- 239000011593 sulfur Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- 102000011727 Caspases Human genes 0.000 description 6
- 108010076667 Caspases Proteins 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 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 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229930012538 Paclitaxel Natural products 0.000 description 6
- 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 6
- 150000001412 amines Chemical class 0.000 description 6
- 230000001640 apoptogenic effect Effects 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 238000012258 culturing Methods 0.000 description 6
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 6
- 238000001647 drug administration Methods 0.000 description 6
- 238000000105 evaporative light scattering detection Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000002458 infectious effect Effects 0.000 description 6
- 238000011081 inoculation Methods 0.000 description 6
- 230000004060 metabolic process Effects 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 229960001592 paclitaxel Drugs 0.000 description 6
- 230000036377 pgph activity Effects 0.000 description 6
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 6
- 210000002381 plasma Anatomy 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 235000019833 protease Nutrition 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 239000011550 stock solution Substances 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 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 description 6
- 230000001810 trypsinlike Effects 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 5
- 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 5
- 241000233866 Fungi Species 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
- 241000222722 Leishmania <genus> Species 0.000 description 5
- 229930195725 Mannitol Natural products 0.000 description 5
- 241000224016 Plasmodium Species 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 229940089468 hydroxyethylpiperazine ethane sulfonic acid Drugs 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 229930014626 natural product Natural products 0.000 description 5
- 230000001613 neoplastic effect Effects 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 239000002423 protozoacide Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 238000005556 structure-activity relationship Methods 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 229940099039 velcade Drugs 0.000 description 5
- 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 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- 206010008190 Cerebrovascular accident Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- 239000001888 Peptone Substances 0.000 description 4
- 108010080698 Peptones Proteins 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 4
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940124660 anti-multiple myeloma Drugs 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004104 aryloxy group Chemical group 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 235000014633 carbohydrates Nutrition 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 235000013351 cheese Nutrition 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 201000010989 colorectal carcinoma Diseases 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 239000006196 drop Substances 0.000 description 4
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 4
- 238000003810 ethyl acetate extraction Methods 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 231100000682 maximum tolerated dose Toxicity 0.000 description 4
- 230000010534 mechanism of action Effects 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000012821 model calculation Methods 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 235000019319 peptone Nutrition 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000010926 purge Methods 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 210000000664 rectum Anatomy 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000013207 serial dilution Methods 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 4
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- FOYHOBVZPWIGJM-KCHLEUMXSA-N (4s)-4-[[(2s)-4-methyl-2-[[(2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]-5-[(4-methyl-2-oxochromen-7-yl)amino]-5-oxopentanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NC=1C=C2OC(=O)C=C(C)C2=CC=1)C(=O)OCC1=CC=CC=C1 FOYHOBVZPWIGJM-KCHLEUMXSA-N 0.000 description 3
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 3
- 102000016736 Cyclin Human genes 0.000 description 3
- 108050006400 Cyclin Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- DAQAKHDKYAWHCG-UHFFFAOYSA-N Lactacystin Natural products CC(=O)NC(C(O)=O)CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O DAQAKHDKYAWHCG-UHFFFAOYSA-N 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 3
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 229940079156 Proteasome inhibitor Drugs 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000002421 anti-septic effect Effects 0.000 description 3
- 239000004599 antimicrobial Substances 0.000 description 3
- 230000000680 avirulence Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 3
- 239000000287 crude extract Substances 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000002532 enzyme inhibitor Substances 0.000 description 3
- 229940125532 enzyme inhibitor Drugs 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000010408 film Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 229910017053 inorganic salt Inorganic materials 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 229960004768 irinotecan Drugs 0.000 description 3
- 230000002147 killing effect Effects 0.000 description 3
- DAQAKHDKYAWHCG-RWTHQLGUSA-N lactacystin Chemical compound CC(=O)N[C@H](C(O)=O)CSC(=O)[C@]1([C@@H](O)C(C)C)NC(=O)[C@H](C)[C@@H]1O DAQAKHDKYAWHCG-RWTHQLGUSA-N 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 239000003207 proteasome inhibitor Substances 0.000 description 3
- 229930189723 salinosporamide Natural products 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 201000003365 uterine corpus sarcoma Diseases 0.000 description 3
- 210000001215 vagina Anatomy 0.000 description 3
- 239000012138 yeast extract Substances 0.000 description 3
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- VUGZQVCBBBEZQE-MIZDRFBCSA-N 2-[2-[3-[[(2r)-4-[[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethylsulfanylcarbonyl]butanoic acid Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C(C(O)=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 VUGZQVCBBBEZQE-MIZDRFBCSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 101001027327 Bos taurus Growth-regulated protein homolog alpha Proteins 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 238000007445 Chromatographic isolation Methods 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 108090000317 Chymotrypsin Proteins 0.000 description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 2
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 2
- 208000004232 Enteritis Diseases 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 229920001503 Glucan Polymers 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- 102000001284 I-kappa-B kinase Human genes 0.000 description 2
- 108060006678 I-kappa-B kinase Proteins 0.000 description 2
- 230000004950 I-kappaB phosphorylation Effects 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
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 229940124647 MEK inhibitor Drugs 0.000 description 2
- 101150024075 Mapk1 gene Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 241000872931 Myoporum sandwicense Species 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-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
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 101710194807 Protective antigen Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 108700005075 Regulator Genes Proteins 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 206010070834 Sensitisation Diseases 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
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229940050528 albumin Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000002924 anti-infective effect Effects 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 230000001851 biosynthetic effect Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- CRFNGMNYKDXRTN-CITAKDKDSA-N butyryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CRFNGMNYKDXRTN-CITAKDKDSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 230000032823 cell division Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000010668 complexation reaction Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 2
- 229960001305 cysteine hydrochloride Drugs 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- LJOQGZACKSYWCH-UHFFFAOYSA-N dihydro quinine Natural products C1=C(OC)C=C2C(C(O)C3CC4CCN3CC4CC)=CC=NC2=C1 LJOQGZACKSYWCH-UHFFFAOYSA-N 0.000 description 2
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 238000013100 final test Methods 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 235000010492 gellan gum Nutrition 0.000 description 2
- 239000000216 gellan gum Substances 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 238000009499 grossing Methods 0.000 description 2
- 230000009422 growth inhibiting effect Effects 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229910000358 iron sulfate Inorganic materials 0.000 description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960001855 mannitol Drugs 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 2
- 229960004961 mechlorethamine Drugs 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000004531 microgranule Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000003791 organic solvent mixture Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000006174 pH buffer Substances 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 201000010174 renal carcinoma Diseases 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- JXOHGGNKMLTUBP-HSUXUTPPSA-N shikimic acid Chemical compound O[C@@H]1CC(C(O)=O)=C[C@@H](O)[C@H]1O JXOHGGNKMLTUBP-HSUXUTPPSA-N 0.000 description 2
- JXOHGGNKMLTUBP-JKUQZMGJSA-N shikimic acid Natural products O[C@@H]1CC(C(O)=O)=C[C@H](O)[C@@H]1O JXOHGGNKMLTUBP-JKUQZMGJSA-N 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 229940073490 sodium glutamate Drugs 0.000 description 2
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical class [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 2
- 239000004324 sodium propionate Substances 0.000 description 2
- 235000010334 sodium propionate Nutrition 0.000 description 2
- 229960003212 sodium propionate Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 238000010023 transfer printing Methods 0.000 description 2
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 239000012137 tryptone Substances 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- 238000001291 vacuum drying Methods 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- URLVCROWVOSNPT-XOTOMLERSA-N (2s)-4-[(13r)-13-hydroxy-13-[(2r,5r)-5-[(2r,5r)-5-[(1r)-1-hydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2h-furan-5-one Chemical compound O1[C@@H]([C@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCCCCC=2C(O[C@@H](C)C=2)=O)CC1 URLVCROWVOSNPT-XOTOMLERSA-N 0.000 description 1
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 1
- IEXUMDBQLIVNHZ-YOUGDJEHSA-N (8s,11r,13r,14s,17s)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(O)CCCO)[C@@]2(C)C1 IEXUMDBQLIVNHZ-YOUGDJEHSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- ZOAMZFNAPHWBEN-UHFFFAOYSA-N 2-$l^{1}-oxidanylpropane Chemical compound CC(C)[O] ZOAMZFNAPHWBEN-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 description 1
- XVKFDCVTYBMNRZ-UHFFFAOYSA-N 3-methylidenecyclohexene Chemical compound C=C1CCCC=C1 XVKFDCVTYBMNRZ-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 229930195573 Amycin Natural products 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102100034613 Annexin A2 Human genes 0.000 description 1
- 108090000668 Annexin A2 Proteins 0.000 description 1
- 101100046775 Arabidopsis thaliana TPPA gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- ZKAISLGYPWGEAE-UHFFFAOYSA-N C(C)(=O)OC.C(C(=C)C)(=O)O Chemical compound C(C)(=O)OC.C(C(=C)C)(=O)O ZKAISLGYPWGEAE-UHFFFAOYSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 102000007590 Calpain Human genes 0.000 description 1
- 108010032088 Calpain Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108010031896 Cell Cycle Proteins Proteins 0.000 description 1
- 102000005483 Cell Cycle Proteins Human genes 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 240000001817 Cereus hexagonus Species 0.000 description 1
- 108010014419 Chemokine CXCL1 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 244000050510 Cunninghamia lanceolata Species 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 108010074922 Cytochrome P-450 CYP1A2 Proteins 0.000 description 1
- 108010026925 Cytochrome P-450 CYP2C19 Proteins 0.000 description 1
- 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 description 1
- 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 description 1
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 1
- 102100026533 Cytochrome P450 1A2 Human genes 0.000 description 1
- 102100029363 Cytochrome P450 2C19 Human genes 0.000 description 1
- 102100029358 Cytochrome P450 2C9 Human genes 0.000 description 1
- 102100021704 Cytochrome P450 2D6 Human genes 0.000 description 1
- 102100039205 Cytochrome P450 3A4 Human genes 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 101100285410 Danio rerio eng2b gene Proteins 0.000 description 1
- 241001269238 Data Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 229930189413 Esperamicin Natural products 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- VUGZQVCBBBEZQE-VRQRJWBYSA-N Ethylmalonyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSC(=O)C(C(O)=O)CC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 VUGZQVCBBBEZQE-VRQRJWBYSA-N 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 240000004859 Gamochaeta purpurea Species 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-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
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000031662 Noncommunicable disease Diseases 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- 101000924984 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) 3-dehydroquinate dehydratase Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 244000062793 Sorghum vulgare Species 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000006859 Swern oxidation reaction Methods 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 1
- 102000008233 Toll-Like Receptor 4 Human genes 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 102100040411 Tripeptidyl-peptidase 2 Human genes 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms 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
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- FZCYKCCPXTYLLE-UHFFFAOYSA-L [Br+].[Br-].[Na+].[Br-] Chemical compound [Br+].[Br-].[Na+].[Br-] FZCYKCCPXTYLLE-UHFFFAOYSA-L 0.000 description 1
- DWDAZFJBSZTCCM-UHFFFAOYSA-N [O]C1CCCCC1 Chemical compound [O]C1CCCCC1 DWDAZFJBSZTCCM-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- QUHYUSAHBDACNG-UHFFFAOYSA-N acerogenin 3 Natural products C1=CC(O)=CC=C1CCCCC(=O)CCC1=CC=C(O)C=C1 QUHYUSAHBDACNG-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 230000001780 adrenocortical effect Effects 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229940098174 alkeran Drugs 0.000 description 1
- 125000000033 alkoxyamino group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- PZZYQPZGQPZBDN-UHFFFAOYSA-N aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003817 anthracycline antibiotic agent Substances 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 210000001229 azygos vein Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000003180 beta-lactone group Chemical group 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000036983 biotransformation 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
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000007767 bonding agent Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000004611 cancer cell death Effects 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- NGPGYVQZGRJHFJ-UHFFFAOYSA-N chembl1604790 Chemical compound OC1=CC(O)=CC=C1N=NC1=CC=C([N+]([O-])=O)C=C1 NGPGYVQZGRJHFJ-UHFFFAOYSA-N 0.000 description 1
- 239000012829 chemotherapy agent Substances 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000037011 constitutive activity Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 235000001671 coumarin Nutrition 0.000 description 1
- KFWWCMJSYSSPSK-PAXLJYGASA-N crotonoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)/C=C/C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 KFWWCMJSYSSPSK-PAXLJYGASA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
- 150000001934 cyclohexanes Chemical class 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- URLVCROWVOSNPT-QTTMQESMSA-N desacetyluvaricin Natural products O=C1C(CCCCCCCCCCCC[C@@H](O)[C@H]2O[C@@H]([C@@H]3O[C@@H]([C@@H](O)CCCCCCCCCC)CC3)CC2)=C[C@H](C)O1 URLVCROWVOSNPT-QTTMQESMSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 231100000284 endotoxic Toxicity 0.000 description 1
- 230000002346 endotoxic effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- LJQQFQHBKUKHIS-WJHRIEJJSA-N esperamicin Chemical compound O1CC(NC(C)C)C(OC)CC1OC1C(O)C(NOC2OC(C)C(SC)C(O)C2)C(C)OC1OC1C(\C2=C/CSSSC)=C(NC(=O)OC)C(=O)C(OC3OC(C)C(O)C(OC(=O)C=4C(=CC(OC)=C(OC)C=4)NC(=O)C(=C)OC)C3)C2(O)C#C\C=C/C#C1 LJQQFQHBKUKHIS-WJHRIEJJSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013360 fish flour Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 206010017758 gastric cancer Diseases 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
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000054896 human PML Human genes 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229960000811 hydroquinidine Drugs 0.000 description 1
- 229960004251 hydroquinine Drugs 0.000 description 1
- FAHBNUUHRFUEAI-UHFFFAOYSA-M hydroxidooxidoaluminium Chemical compound O[Al]=O FAHBNUUHRFUEAI-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000004715 keto acids Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000019713 millet Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 208000010753 nasal discharge Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 230000037360 nucleotide metabolism Effects 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229950011093 onapristone Drugs 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 239000008183 oral pharmaceutical preparation Substances 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 201000003733 ovarian melanoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical compound O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000012985 polymerization agent Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 238000011112 process operation Methods 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000002212 purine nucleoside Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 102000037983 regulatory factors Human genes 0.000 description 1
- 108091008025 regulatory factors Proteins 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000012807 shake-flask culturing Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- FQZYTYWMLGAPFJ-OQKDUQJOSA-N tamoxifen citrate Chemical compound [H+].[H+].[H+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 FQZYTYWMLGAPFJ-OQKDUQJOSA-N 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000004654 triazenes Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 108010039189 tripeptidyl-peptidase 2 Proteins 0.000 description 1
- XZZNDPSIHUTMOC-UHFFFAOYSA-N triphenyl phosphate Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)(=O)OC1=CC=CC=C1 XZZNDPSIHUTMOC-UHFFFAOYSA-N 0.000 description 1
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 238000007738 vacuum evaporation Methods 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
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US48027003P | 2003-06-20 | 2003-06-20 | |
| US60/480,270 | 2003-06-20 | ||
| US56695204P | 2004-04-30 | 2004-04-30 | |
| US60/566,952 | 2004-04-30 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2004800237100A Division CN1838952A (zh) | 2003-06-20 | 2004-06-18 | [3.2.0]杂环化合物及其类似物在癌症、炎症和感染性疾病治疗中的应用 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102151261A true CN102151261A (zh) | 2011-08-17 |
Family
ID=33567612
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102534518A Pending CN102151261A (zh) | 2003-06-20 | 2004-06-18 | [3.2.0]杂环化合物及其类似物在癌症、炎症和感染性疾病治疗中的应用 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US20050049294A1 (https=) |
| EP (1) | EP1638552B1 (https=) |
| JP (2) | JP2007523862A (https=) |
| KR (1) | KR20060026052A (https=) |
| CN (1) | CN102151261A (https=) |
| AT (1) | ATE499934T1 (https=) |
| AU (1) | AU2004253478A1 (https=) |
| BR (1) | BRPI0411677A (https=) |
| CA (1) | CA2532066C (https=) |
| DE (1) | DE602004031614D1 (https=) |
| IL (1) | IL172705A (https=) |
| MX (1) | MXPA05013982A (https=) |
| NZ (1) | NZ544588A (https=) |
| WO (1) | WO2005002572A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115006532A (zh) * | 2021-03-05 | 2022-09-06 | 广州医科大学 | 蛋白酶体抑制剂的应用 |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2429163C (en) * | 2000-11-16 | 2013-02-12 | The Regents Of The University Of California | Marine actinomycete taxon for drug fermentation and product discovery |
| US7176232B2 (en) | 2002-06-24 | 2007-02-13 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| US7179834B2 (en) * | 2002-06-24 | 2007-02-20 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| AU2004253478A1 (en) | 2003-06-20 | 2005-01-13 | Nereus Pharmaceuticals, Inc. | Use of [3.2.0] heterocyclic compounds and analogs thereof for the treatment of cancer, inflammation and infectious diseases |
| ZA200600473B (en) * | 2003-06-20 | 2007-04-25 | Univ California | Salinosporamides and methods for use thereof |
| JP4691041B2 (ja) | 2003-11-20 | 2011-06-01 | チルドレンズ ホスピタル メディカル センター | Gtpアーゼ阻害剤および使用方法 |
| WO2005099687A2 (en) | 2004-04-09 | 2005-10-27 | President And Fellows Of Harvard College | Analogs of salinosporamide a |
| US7579371B2 (en) | 2004-04-30 | 2009-08-25 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| EP2266988A1 (en) * | 2004-04-30 | 2010-12-29 | Nereus Pharmaceuticals, Inc. | [3.2.0] Heterocyclic compounds and methods of using the same |
| CN101133022A (zh) * | 2004-07-12 | 2008-02-27 | 拜尔农作物科学股份公司 | 用作杀真菌剂和杀虫剂的取代的2-吡咯烷酮衍生物 |
| MX2007006523A (es) * | 2004-12-03 | 2007-09-11 | Nereus Pharmaceuticals Inc | Metodos para utilizar compuestos heterociclicos [3.2.0] y sus analogos. |
| EP1830838B1 (en) * | 2004-12-03 | 2012-10-03 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating neoplastic diseases |
| WO2007016539A2 (en) | 2005-07-29 | 2007-02-08 | Children's Hospital Medical Center | Gtpase inhibitors and methods of use and crystal structure of rac-1 gtpase |
| US7691896B2 (en) | 2005-08-10 | 2010-04-06 | President And Fellows Of Harvard College | Analogs of salinosporamide A |
| WO2007021897A1 (en) * | 2005-08-10 | 2007-02-22 | President And Fellows Of Harvard College | Analogs of salinosporamide a |
| US7572606B1 (en) | 2005-09-09 | 2009-08-11 | Nereus Pharmaceuticals, Inc. | Biosyntheses of salinosporamide A and its analogs and related methods of making salinosporamide A and its analogs |
| US7465720B2 (en) | 2005-09-12 | 2008-12-16 | President And Fellows Of Harvard College | Proteasome inhibiting β-lactam compounds |
| BRPI0618198A2 (pt) * | 2005-11-04 | 2018-06-26 | Nereus Pharmaceuticals Inc | métodos de tratamento, prevenção ou inibição de câncer e de linfoma, composição, kit, e, método de tratamento de câncer resistente a terapia |
| CN101460457B (zh) | 2006-04-06 | 2012-07-18 | 尼瑞斯药品公司 | Salinosporamide a及其类似物的全合成 |
| WO2008097249A2 (en) * | 2006-06-14 | 2008-08-14 | Children's Medical Center Corporation | Method for the treatment of anthrax toxicity |
| US8986971B2 (en) | 2006-09-22 | 2015-03-24 | Triphase Research And Development I Corp. | Salt formulations for the fermentation of marine microorganisms |
| WO2008095195A2 (en) | 2007-02-02 | 2008-08-07 | Nereus Pharmaceuticals, Inc. | Lyophilized formulations of salinosporamide a |
| US20080280968A1 (en) * | 2007-05-04 | 2008-11-13 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof for treating infectious diseases |
| US8394816B2 (en) | 2007-12-07 | 2013-03-12 | Irene Ghobrial | Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia |
| EP2088205A1 (en) | 2008-02-11 | 2009-08-12 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | PSMB10: A diagnosis marker and therapeutic target of chronic rejection. |
| NZ587985A (en) | 2008-03-07 | 2012-07-27 | Nereus Pharmaceuticals Inc | Total synthesis of salinosporamide a and analogs thereof |
| US20090285836A1 (en) * | 2008-04-14 | 2009-11-19 | Nereus Pharmaceuticals, Inc. | Use of salinosporamide a to inhibit metastasis |
| WO2009140287A1 (en) | 2008-05-12 | 2009-11-19 | Nereus Pharmaceuticals, Inc. | Salinosporamide derivatives as proteasome inhibitors |
| US20110111417A1 (en) | 2008-05-14 | 2011-05-12 | Millennium Pharmaceuticals, Inc. | Methods and kits for monitoring the effects of immunomodulators on adaptive immunity |
| US8315815B2 (en) | 2008-12-30 | 2012-11-20 | The Invention Science Fund I, Llc | Computational methods and systems for suggesting modulators of CYP450 as treatment options |
| US8321151B2 (en) | 2008-12-30 | 2012-11-27 | The Invention Science Fund I, Llc | Computational methods and systems for treatment in relation to modulation of CYP450 enzyme activity |
| US8073633B2 (en) * | 2008-12-30 | 2011-12-06 | The Invention Science Fund I, Llc | Computational methods and systems for suggesting modulators of CYP450 as treatment options |
| WO2010096574A1 (en) | 2009-02-20 | 2010-08-26 | Lisanti Michael P | A method of diagnosis or prognosis of a neoplasm comprising determining the level of expression of a protein in stromal cells adjacent to the neoplasm |
| US9126997B1 (en) | 2010-09-07 | 2015-09-08 | Northwestern University | Synergistic effect of glucocorticoid receptor agonists in combination with proteosome inhibitors for treating leukemia and myeloma |
| WO2012135528A2 (en) * | 2011-03-29 | 2012-10-04 | Texas Tech University System | Galectin-3c combination therapy for human cancer |
| EP2771489B1 (en) | 2011-10-28 | 2018-07-04 | Millennium Pharmaceuticals, Inc. | Biomarkers of response to nae inhibitors |
| CA2855368A1 (en) | 2011-11-11 | 2013-05-16 | Millennium Pharmaceuticals, Inc. | Biomarkers of response to proteasome inhibitors |
| JP6215235B2 (ja) | 2012-01-24 | 2017-10-18 | ミレニアム ファーマシューティカルズ, インコーポレイテッドMillennium Pharmaceuticals, Inc. | 癌の治療方法 |
| GB2523211B (en) | 2012-01-27 | 2020-03-18 | Univ Jefferson | MCT protein inhibitor-related prognostic and therapeutic methods |
| WO2014055543A2 (en) | 2012-10-01 | 2014-04-10 | Millennium Pharmaceuticals, Inc. | Biomarkers and methods to predict response to inhibitors and uses thereof |
| BR112015010504A2 (pt) | 2012-11-09 | 2017-12-05 | Univ Cornell | uso de inibidores de molécula pequena de malt1, método de identificação de um modulador de molécula pequena de malt1, e composição farmacêutica |
| WO2014172627A1 (en) | 2013-04-19 | 2014-10-23 | Thomas Jefferson University | Caveolin-1 related methods for treating glioblastoma with temozolomide |
| US10028503B2 (en) | 2014-06-18 | 2018-07-24 | Children's Hospital Medical Center | Platelet storage methods and compositions for same |
| US20170348284A1 (en) | 2016-06-01 | 2017-12-07 | Celgene Tri A Holdings Ltd. | Use of marizomib for the treatment of central nervous system (cns) cancers |
| WO2018033631A1 (en) | 2016-08-19 | 2018-02-22 | Celgene International Ii Sàrl | Morphic forms of marizomib and uses thereof |
| KR101953671B1 (ko) * | 2017-08-21 | 2019-03-04 | 충남대학교산학협력단 | 프로테아좀 억제제를 유효성분으로 함유하는 아토피성 피부질환의 예방, 개선 또는 치료용 조성물 |
| EP3546447A1 (en) * | 2018-03-29 | 2019-10-02 | Heidelberg Pharma GmbH | Synthesis of (2s,3r,4r)-4,5-dihydroxyisoleucine and derivatives |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5133974A (en) * | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US5276182A (en) * | 1990-07-09 | 1994-01-04 | The Dow Chemical Company | Process for preparing polyurea oligomers |
| DE4039602A1 (de) * | 1990-12-12 | 1992-06-17 | Bauer Kurt Heinz Prof Dr | Pharmazeutische formulierungen |
| KR100221695B1 (ko) * | 1991-08-12 | 1999-09-15 | 그린 마틴, 브라이언 쥐 테슬리 | 약학적 구상 제형 |
| US5683676A (en) * | 1991-12-12 | 1997-11-04 | Glaxo Group Limited | Canister containing aerosol formulations containing P134a and particulate medicaments |
| ES2224200T3 (es) * | 1992-11-27 | 2005-03-01 | Mayne Pharma (Usa) Inc. | Composicion inyectable estable de paclitaxel. |
| EP0684829A4 (en) | 1993-02-10 | 1997-05-21 | Harvard College | THE ROLE OF ATP-UBIQUITIN-DEPENDENT PROTEOLYSIS IN MHC-1 DEPENDENT ANTIGENT PRESENTATION AND RELATED INHIBITORS. |
| US5654286A (en) * | 1993-05-12 | 1997-08-05 | Hostetler; Karl Y. | Nucleotides for topical treatment of psoriasis, and methods for using same |
| CZ301771B6 (cs) * | 1993-10-01 | 2010-06-16 | Syntex (U.S.A.) Llc. | Farmaceutický prostredek ve forme suchého granulátu obsahující mofetil mykofenolát nebo kyselinu mykofenolovou a zpusob jeho prípravy |
| US5707641A (en) * | 1994-10-13 | 1998-01-13 | Pharmaderm Research & Development Ltd. | Formulations comprising therapeutically-active proteins or polypeptides |
| IE80468B1 (en) * | 1995-04-04 | 1998-07-29 | Elan Corp Plc | Controlled release biodegradable nanoparticles containing insulin |
| US6838477B2 (en) * | 1995-04-12 | 2005-01-04 | President And Fellows Of Harvard College | Lactacystin analogs |
| US6335358B1 (en) * | 1995-04-12 | 2002-01-01 | President And Fellows Of Harvard College | Lactacystin analogs |
| US5653987A (en) * | 1995-05-16 | 1997-08-05 | Modi; Pankaj | Liquid formulations for proteinic pharmaceuticals |
| US5726181A (en) * | 1995-06-05 | 1998-03-10 | Bionumerik Pharmaceuticals, Inc. | Formulations and compositions of poorly water soluble camptothecin derivatives |
| US5667809A (en) * | 1995-06-07 | 1997-09-16 | Alliance Pharmaceutical Corp. | Continuous fluorochemical microdispersions for the delivery of lipophilic pharmaceutical agents |
| US5874443A (en) * | 1995-10-19 | 1999-02-23 | Trega Biosciences, Inc. | Isoquinoline derivatives and isoquinoline combinatorial libraries |
| US5886210A (en) * | 1996-08-22 | 1999-03-23 | Rohm And Haas Company | Method for preparing aromatic compounds |
| US6271199B2 (en) | 1997-02-15 | 2001-08-07 | Millennium Pharmaceuticals, Inc. | Treatment of infarcts |
| AU6764398A (en) | 1997-03-20 | 1998-10-12 | Variagenics, Inc. | Target genes for allele-specific drugs |
| US5922683A (en) * | 1997-05-29 | 1999-07-13 | Abbott Laboratories | Multicyclic erythromycin derivatives |
| US6333358B1 (en) * | 1997-08-04 | 2001-12-25 | Taisho Pharmaceutical Co., Ltd. | Aryloxyaniline derivatives |
| US6133308A (en) * | 1997-08-15 | 2000-10-17 | Millennium Pharmaceuticals, Inc. | Synthesis of clasto-lactacystin beta-lactone and analogs thereof |
| CN1271342A (zh) | 1997-08-15 | 2000-10-25 | F·索西 | 裂-乳胱氨酸-β-内脂及其类似物的合成 |
| US20010051654A1 (en) * | 1997-09-25 | 2001-12-13 | Elliott Peter J. | Treatment of inflammatory and autoimmune diseases |
| EP1017398A1 (en) | 1997-09-25 | 2000-07-12 | Proscript, Inc. | Proteasome inhibitors, ubiquitin pathway inhibitors or agents that interfere with the activation of nf-kb via the ubiquitin proteasome pathway to treat inflammatory and autoimmune diseases |
| CA2219867A1 (en) | 1997-10-31 | 1999-04-30 | Jiangping Wu | The use of proteasome inhibitors for treating cancer, inflammation, autoimmune disease, graft rejection and septic shock |
| EP2201945B1 (en) * | 1997-11-21 | 2013-03-06 | Purdue Neuroscience Company | Use of substituted 2-aminoacetamides for treating or ameliorating anxiety |
| US6617171B2 (en) * | 1998-02-27 | 2003-09-09 | The General Hospital Corporation | Methods for diagnosing and treating autoimmune disease |
| PL343249A1 (en) * | 1998-03-26 | 2001-07-30 | Shionogi & Co | Indole derivatives with antiviral activity |
| US6509331B1 (en) * | 1998-06-22 | 2003-01-21 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds |
| BR9914648A (pt) * | 1998-10-20 | 2001-11-27 | Millennium Pharm Inc | Processo para monitorar ação medicamentosa deinibidor de proteasoma |
| FR2784988B1 (fr) * | 1998-10-23 | 2002-09-20 | Adir | Nouveaux composes dihydro et tetrahydroquinoleiniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| AU1930900A (en) | 1998-12-04 | 2000-06-26 | University Of Maryland Biotechnology Institute | Use of protease inhibitors to modulate cellular pathways, immunity and therapiesassociated therewith |
| US20020049157A1 (en) * | 1999-08-25 | 2002-04-25 | Jiangping Wu | Use of proteasome inhibitors for treating cancer, inflammation, autoimmune disease, graft rejection and septic shock |
| ATE338564T1 (de) * | 2000-10-12 | 2006-09-15 | Viromics Gmbh | Proteasome inhibitoren zur behandlung von hepatitis-virus infektionen |
| CA2429163C (en) * | 2000-11-16 | 2013-02-12 | The Regents Of The University Of California | Marine actinomycete taxon for drug fermentation and product discovery |
| DE50313092D1 (de) * | 2002-04-05 | 2010-10-28 | Virologik Gmbh | Mittel zur behandlung von flaviviridae-infektionen |
| US7179834B2 (en) * | 2002-06-24 | 2007-02-20 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| US7176232B2 (en) * | 2002-06-24 | 2007-02-13 | The Regents Of The University Of California | Salinosporamides and methods for use thereof |
| WO2004004749A1 (en) | 2002-07-03 | 2004-01-15 | Charite - Universitätsmedizin Berlin | Proteaseome inhibitors for the treatment of herpesviridae infected individuals |
| ES2421516T3 (es) | 2002-11-06 | 2013-09-03 | Dana Farber Cancer Inst Inc | Composiciones para tratar el cáncer usando el inhibidor de proteasomas PS-341 |
| EP1597262B1 (en) * | 2003-02-14 | 2009-11-11 | InterMed Discovery GmbH | Substituted heterocycles |
| ZA200600473B (en) * | 2003-06-20 | 2007-04-25 | Univ California | Salinosporamides and methods for use thereof |
| AU2004253478A1 (en) * | 2003-06-20 | 2005-01-13 | Nereus Pharmaceuticals, Inc. | Use of [3.2.0] heterocyclic compounds and analogs thereof for the treatment of cancer, inflammation and infectious diseases |
| US7371875B2 (en) * | 2004-03-12 | 2008-05-13 | Miikana Therapeutics, Inc. | Cytotoxic agents and methods of use |
| WO2005099687A2 (en) * | 2004-04-09 | 2005-10-27 | President And Fellows Of Harvard College | Analogs of salinosporamide a |
| US7183417B2 (en) * | 2004-04-09 | 2007-02-27 | President And Fellows Of Harvard College | Simple stereocontrolled synthesis of salinosporamide A |
| EP2266988A1 (en) * | 2004-04-30 | 2010-12-29 | Nereus Pharmaceuticals, Inc. | [3.2.0] Heterocyclic compounds and methods of using the same |
| US7579371B2 (en) * | 2004-04-30 | 2009-08-25 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| US20060264495A1 (en) * | 2004-04-30 | 2006-11-23 | Michael Palladino | Methods of using [3.2.0] heterocyclic compounds and analogs thereof |
| EP1830838B1 (en) * | 2004-12-03 | 2012-10-03 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating neoplastic diseases |
| WO2006124902A2 (en) * | 2005-05-16 | 2006-11-23 | Sloan-Kettering Institute For Cancer Research | Synthesis of salinosporamide a and analogues thereof |
| US7572606B1 (en) * | 2005-09-09 | 2009-08-11 | Nereus Pharmaceuticals, Inc. | Biosyntheses of salinosporamide A and its analogs and related methods of making salinosporamide A and its analogs |
| DE102005046344A1 (de) * | 2005-09-28 | 2007-03-29 | Saltigo Gmbh | Verfahren zur Kupplung von Benzylaminen mit Halogenaromaten |
| BRPI0618198A2 (pt) * | 2005-11-04 | 2018-06-26 | Nereus Pharmaceuticals Inc | métodos de tratamento, prevenção ou inibição de câncer e de linfoma, composição, kit, e, método de tratamento de câncer resistente a terapia |
| GB0605217D0 (en) * | 2006-03-15 | 2006-04-26 | Novartis Ag | Method and compositions for assessing acute rejection |
| CN101460457B (zh) | 2006-04-06 | 2012-07-18 | 尼瑞斯药品公司 | Salinosporamide a及其类似物的全合成 |
| US8088923B2 (en) * | 2006-07-07 | 2012-01-03 | The Texas A&M University System | Cyclic-fused beta-lactones and their synthesis |
| US20080280968A1 (en) * | 2007-05-04 | 2008-11-13 | Nereus Pharmaceuticals, Inc. | Methods of using [3.2.0] heterocyclic compounds and analogs thereof for treating infectious diseases |
| US8394816B2 (en) * | 2007-12-07 | 2013-03-12 | Irene Ghobrial | Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia |
| EP2088205A1 (en) | 2008-02-11 | 2009-08-12 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | PSMB10: A diagnosis marker and therapeutic target of chronic rejection. |
| NZ587985A (en) | 2008-03-07 | 2012-07-27 | Nereus Pharmaceuticals Inc | Total synthesis of salinosporamide a and analogs thereof |
| WO2009140287A1 (en) * | 2008-05-12 | 2009-11-19 | Nereus Pharmaceuticals, Inc. | Salinosporamide derivatives as proteasome inhibitors |
-
2004
- 2004-06-18 AU AU2004253478A patent/AU2004253478A1/en not_active Abandoned
- 2004-06-18 EP EP04776757A patent/EP1638552B1/en not_active Expired - Lifetime
- 2004-06-18 US US10/871,368 patent/US20050049294A1/en not_active Abandoned
- 2004-06-18 BR BRPI0411677-1A patent/BRPI0411677A/pt not_active IP Right Cessation
- 2004-06-18 AT AT04776757T patent/ATE499934T1/de not_active IP Right Cessation
- 2004-06-18 DE DE602004031614T patent/DE602004031614D1/de not_active Expired - Lifetime
- 2004-06-18 CA CA2532066A patent/CA2532066C/en not_active Expired - Lifetime
- 2004-06-18 CN CN2010102534518A patent/CN102151261A/zh active Pending
- 2004-06-18 KR KR1020057024503A patent/KR20060026052A/ko not_active Ceased
- 2004-06-18 NZ NZ544588A patent/NZ544588A/en not_active IP Right Cessation
- 2004-06-18 MX MXPA05013982A patent/MXPA05013982A/es not_active Application Discontinuation
- 2004-06-18 WO PCT/US2004/019543 patent/WO2005002572A2/en not_active Ceased
- 2004-06-18 JP JP2006517404A patent/JP2007523862A/ja not_active Withdrawn
-
2005
- 2005-12-20 IL IL172705A patent/IL172705A/en active IP Right Grant
-
2008
- 2008-06-10 US US12/136,688 patent/US8168803B2/en not_active Expired - Lifetime
-
2011
- 2011-10-28 JP JP2011238014A patent/JP2012031198A/ja not_active Withdrawn
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115006532A (zh) * | 2021-03-05 | 2022-09-06 | 广州医科大学 | 蛋白酶体抑制剂的应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ544588A (en) | 2010-06-25 |
| IL172705A (en) | 2017-06-29 |
| DE602004031614D1 (de) | 2011-04-14 |
| MXPA05013982A (es) | 2006-05-25 |
| JP2007523862A (ja) | 2007-08-23 |
| CA2532066C (en) | 2015-07-28 |
| US8168803B2 (en) | 2012-05-01 |
| JP2012031198A (ja) | 2012-02-16 |
| IL172705A0 (en) | 2006-04-10 |
| BRPI0411677A (pt) | 2006-08-29 |
| WO2005002572A3 (en) | 2005-05-12 |
| AU2004253478A1 (en) | 2005-01-13 |
| US20090182027A1 (en) | 2009-07-16 |
| ATE499934T1 (de) | 2011-03-15 |
| CA2532066A1 (en) | 2005-01-13 |
| US20050049294A1 (en) | 2005-03-03 |
| EP1638552B1 (en) | 2011-03-02 |
| EP1638552A2 (en) | 2006-03-29 |
| WO2005002572A2 (en) | 2005-01-13 |
| KR20060026052A (ko) | 2006-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102151261A (zh) | [3.2.0]杂环化合物及其类似物在癌症、炎症和感染性疾病治疗中的应用 | |
| US12122756B2 (en) | Biflavone compound against I-type herpes simplex virus, and preparation method therefor and use thereof | |
| AU2005311572A1 (en) | Methods of using (3.2.0) heterocyclic compounds and analogs thereof | |
| US20070004676A1 (en) | Methods of using [3.2.0] heterocyclic compounds and analogs thereof | |
| CN108623607B (zh) | 5,5,6-多环含特特拉姆酸大环内酰胺类化合物及其制备方法和用途 | |
| US10759831B2 (en) | Peptide compound, production method therefor, and use thereof | |
| CN114573537B (zh) | 具有抗神经退行性改变活性的化合物、制备方法及其应用 | |
| CN104557909B (zh) | 3-酰氧基取代右旋去氧娃儿藤宁衍生物、其制法和药物组合物与用途 | |
| CN103002892B (zh) | 含有大环内酯菌素a及其衍生物作为有效成分的具有抗血管生成效果的组合物 | |
| Bu et al. | Cocrystallization-driven self-assembly with vanillic acid offers a new opportunity for surmounting fast and excessive absorption issues of antifungal drug 5-fluorocytosine: a combined theoretical and experimental research | |
| CN113143913A (zh) | 一种桉烷型倍半萜类化合物在制备抗胰腺癌药物中的应用 | |
| CN103553888B (zh) | 厚朴酚衍生物及其制备方法和在制备抗肿瘤药物中的应用 | |
| CN103183722B (zh) | 一种乙二醛酶i抑制剂及其制备方法和医药用途 | |
| US8598313B2 (en) | Compositions for ameliorating cell proliferative disorders and methods of making and using them | |
| CN106188242A (zh) | 一种新型环肽化合物在制备抑制结核杆菌的药物中的应用 | |
| CN106995368B (zh) | 一种非atp竞争性fgfr1抑制剂及其应用 | |
| EP3326631B1 (en) | Compound pac-1 or salt thereof, and pharmaceutical composition comprising same | |
| CN109867657B (zh) | 二羟二苯并[b,f][1,5]二氧杂辛环类化合物、制备方法及其药用组合物和应用 | |
| CN102485735A (zh) | 6-果糖氨-4-芳胺基喹唑啉衍生物及其用途 | |
| ZA200600536B (en) | Use of [3.2.0] heterocyclic compounds and analogs thereof for the treatment of cancer, inflammation and infectious diseases | |
| Okino | Heterocycles from cyanobacteria | |
| KR100327155B1 (ko) | 화합물 kr-15012를 함유하는 항암제 | |
| CN118344426A (zh) | 五环三萜类异硫氰酸酯衍生物及其制备方法和应用 | |
| US20100179324A1 (en) | Anti-tumor agent comprising sulphostin or sulphostin-related compound as the active ingredient | |
| CN106924233A (zh) | 二氢苯并呋喃二聚阿魏酸单甲酯木质素在制备抗肿瘤药物增敏剂中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110817 |