JP4428727B2 - 癌の成長を抑制する方法 - Google Patents
癌の成長を抑制する方法 Download PDFInfo
- Publication number
- JP4428727B2 JP4428727B2 JP53443498A JP53443498A JP4428727B2 JP 4428727 B2 JP4428727 B2 JP 4428727B2 JP 53443498 A JP53443498 A JP 53443498A JP 53443498 A JP53443498 A JP 53443498A JP 4428727 B2 JP4428727 B2 JP 4428727B2
- Authority
- JP
- Japan
- Prior art keywords
- cmt
- tetracycline
- dimethylamino
- cancer
- pharmaceutical composition
- 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.)
- Expired - Fee Related
Links
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 32
- 230000005907 cancer growth Effects 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title abstract description 73
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 188
- 239000004098 Tetracycline Substances 0.000 claims abstract description 135
- 235000019364 tetracycline Nutrition 0.000 claims abstract description 134
- 229960002180 tetracycline Drugs 0.000 claims abstract description 119
- 229930101283 tetracycline Natural products 0.000 claims abstract description 118
- 201000011510 cancer Diseases 0.000 claims abstract description 96
- -1 tetracycline compounds Chemical class 0.000 claims abstract description 81
- 206010027476 Metastases Diseases 0.000 claims abstract description 33
- 230000009401 metastasis Effects 0.000 claims abstract description 31
- 241000124008 Mammalia Species 0.000 claims abstract description 30
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 21
- 201000001441 melanoma Diseases 0.000 claims abstract description 14
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 9
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 5
- 230000000694 effects Effects 0.000 claims description 76
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 56
- 150000003522 tetracyclines Chemical class 0.000 claims description 54
- XCCHQGIGHCRZOS-KBKZQPOHSA-N (4as,5as,6s,12ar)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@@](C)(O)[C@@H](C[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)C3)(O)C3=O)C3=C(O)C2=C1O XCCHQGIGHCRZOS-KBKZQPOHSA-N 0.000 claims description 53
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 37
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims description 31
- MWUTTXATIMURBN-VSAOOKSHSA-N (4aS,5aS,6S,12aR)-3,6,10,11-tetrahydroxy-6-methyl-1,12-dioxo-4a,5,5a,12a-tetrahydro-4H-tetracene-2-carboxamide Chemical compound C[C@]1(O)[C@H]2C[C@H]3CC(O)=C(C(N)=O)C(=O)[C@H]3C(=O)C2=C(O)c2c(O)cccc12 MWUTTXATIMURBN-VSAOOKSHSA-N 0.000 claims description 23
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- 230000014509 gene expression Effects 0.000 claims description 21
- 229940079593 drug Drugs 0.000 claims description 20
- 210000004072 lung Anatomy 0.000 claims description 20
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 17
- 102000013382 Gelatinases Human genes 0.000 claims description 16
- 108010026132 Gelatinases Proteins 0.000 claims description 16
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 claims description 14
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 claims description 12
- 230000001394 metastastic effect Effects 0.000 claims description 9
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 9
- 201000009030 Carcinoma Diseases 0.000 claims description 8
- 210000002307 prostate Anatomy 0.000 claims description 8
- 230000010261 cell growth Effects 0.000 claims description 7
- 208000009956 adenocarcinoma Diseases 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 6
- 210000001550 testis Anatomy 0.000 claims description 6
- 206010039491 Sarcoma Diseases 0.000 claims description 5
- 230000002147 killing effect Effects 0.000 claims description 5
- 210000001672 ovary Anatomy 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 5
- 201000005296 lung carcinoma Diseases 0.000 claims description 3
- 208000005623 Carcinogenesis Diseases 0.000 claims description 2
- 230000036952 cancer formation Effects 0.000 claims description 2
- 231100000504 carcinogenesis Toxicity 0.000 claims description 2
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 claims 2
- 230000009400 cancer invasion Effects 0.000 claims 1
- 210000002429 large intestine Anatomy 0.000 claims 1
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 230000003013 cytotoxicity Effects 0.000 abstract description 26
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 26
- 230000012010 growth Effects 0.000 abstract description 18
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 13
- 230000004663 cell proliferation Effects 0.000 abstract description 9
- 206010006187 Breast cancer Diseases 0.000 abstract description 7
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 7
- 208000029742 colonic neoplasm Diseases 0.000 abstract description 6
- 230000001939 inductive effect Effects 0.000 abstract description 4
- 201000005202 lung cancer Diseases 0.000 abstract description 2
- 208000020816 lung neoplasm Diseases 0.000 abstract description 2
- NBRQRXRBIHVLGI-OWXODZSWSA-N (4as,5ar,12ar)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=CC=CC(O)=C2C(O)=C(C2=O)[C@@H]1C[C@@H]1[C@@]2(O)C(O)=C(C(=O)N)C(=O)C1 NBRQRXRBIHVLGI-OWXODZSWSA-N 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 170
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 67
- 229960003722 doxycycline Drugs 0.000 description 67
- 150000001875 compounds Chemical class 0.000 description 41
- 210000004881 tumor cell Anatomy 0.000 description 36
- 241001465754 Metazoa Species 0.000 description 28
- 238000000338 in vitro Methods 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 27
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 24
- 241000700159 Rattus Species 0.000 description 24
- 238000003556 assay Methods 0.000 description 23
- 238000002474 experimental method Methods 0.000 description 21
- 230000004614 tumor growth Effects 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- BVFDLIAWTKFZQD-JXVDNWKRSA-N cmt-8 Chemical compound O=C1C2=C(O)C=CC=C2C(C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)C[C@@H]1C2O BVFDLIAWTKFZQD-JXVDNWKRSA-N 0.000 description 18
- 230000005764 inhibitory process Effects 0.000 description 16
- 229940040944 tetracyclines Drugs 0.000 description 16
- 230000001472 cytotoxic effect Effects 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 13
- 231100000433 cytotoxic Toxicity 0.000 description 13
- 239000002609 medium Substances 0.000 description 13
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 231100000673 dose–response relationship Toxicity 0.000 description 11
- 239000000499 gel Substances 0.000 description 11
- 230000001629 suppression Effects 0.000 description 11
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 10
- 239000012228 culture supernatant Substances 0.000 description 10
- 230000007246 mechanism Effects 0.000 description 10
- 230000007423 decrease Effects 0.000 description 9
- 230000000477 gelanolytic effect Effects 0.000 description 9
- 239000008273 gelatin Substances 0.000 description 9
- 229920000159 gelatin Polymers 0.000 description 9
- 230000000845 anti-microbial effect Effects 0.000 description 8
- 230000009545 invasion Effects 0.000 description 8
- 230000003902 lesion Effects 0.000 description 8
- 230000008901 benefit Effects 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000012679 serum free medium Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 6
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 6
- 206010027458 Metastases to lung Diseases 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 239000001110 calcium chloride Substances 0.000 description 6
- 229910001628 calcium chloride Inorganic materials 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 210000002744 extracellular matrix Anatomy 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 235000011852 gelatine desserts Nutrition 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 229960004023 minocycline Drugs 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
- NCQJBPXXRXOIJD-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-naphthalen-2-ylpropanoic acid Chemical compound C1=CC=CC2=CC(C(CC(O)=O)NC(=O)OC(C)(C)C)=CC=C21 NCQJBPXXRXOIJD-UHFFFAOYSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- 102000029816 Collagenase Human genes 0.000 description 5
- 108060005980 Collagenase Proteins 0.000 description 5
- 108010047956 Nucleosomes Proteins 0.000 description 5
- 230000001093 anti-cancer Effects 0.000 description 5
- 230000003115 biocidal effect Effects 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 5
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 5
- 230000004709 cell invasion Effects 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 230000002354 daily effect Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 230000009036 growth inhibition Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 108010082117 matrigel Proteins 0.000 description 5
- 210000001623 nucleosome Anatomy 0.000 description 5
- 208000023958 prostate neoplasm Diseases 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 230000005748 tumor development Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 238000011579 SCID mouse model Methods 0.000 description 4
- 229960002424 collagenase Drugs 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 238000003304 gavage Methods 0.000 description 4
- 238000002513 implantation Methods 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 238000000134 MTT assay Methods 0.000 description 3
- 231100000002 MTT assay Toxicity 0.000 description 3
- 102000005741 Metalloproteases Human genes 0.000 description 3
- 108010006035 Metalloproteases Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010061309 Neoplasm progression Diseases 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000000118 anti-neoplastic effect Effects 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 229940034982 antineoplastic agent Drugs 0.000 description 3
- 238000003782 apoptosis assay Methods 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000009702 cancer cell proliferation Effects 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- VCROZLOYPNVPSH-DCKQLXEASA-N cmt-5 Chemical compound N1N=C2C3=C(O)C=CC=C3[C@@](C)(O)C3C2=C1[C@]1(O)C(=O)C(C(N)=O)=C(O)CC1C3 VCROZLOYPNVPSH-DCKQLXEASA-N 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000001085 cytostatic effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000000099 in vitro assay Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000009101 premedication Methods 0.000 description 3
- 230000005522 programmed cell death Effects 0.000 description 3
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 3
- 210000001095 prostate stromal cell Anatomy 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 210000002536 stromal cell Anatomy 0.000 description 3
- 230000005751 tumor progression Effects 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 238000007805 zymography Methods 0.000 description 3
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 108010085895 Laminin Proteins 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108010005246 Tissue Inhibitor of Metalloproteinases Proteins 0.000 description 2
- 102000005876 Tissue Inhibitor of Metalloproteinases Human genes 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229940124650 anti-cancer therapies Drugs 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000011319 anticancer therapy Methods 0.000 description 2
- 210000002469 basement membrane Anatomy 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000005880 cancer cell killing Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 239000003636 conditioned culture medium Substances 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 238000011613 copenhagen rat Methods 0.000 description 2
- 239000000824 cytostatic agent Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000000834 fixative Substances 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 230000000762 glandular Effects 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 201000001514 prostate carcinoma Diseases 0.000 description 2
- 210000005267 prostate cell Anatomy 0.000 description 2
- 210000000064 prostate epithelial cell Anatomy 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000000611 regression analysis Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 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 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 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 2
- 229940072172 tetracycline antibiotic Drugs 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 231100000167 toxic agent Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- DVWJFTGEISXVSH-CWVFEVJCSA-N (1R,3S,5S,7Z,11R,12S,13Z,15Z,17Z,19Z,21R,23S,24R,25S)-21-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-12-ethyl-1,3,5,25-tetrahydroxy-11-methyl-9-oxo-10,27-dioxabicyclo[21.3.1]heptacosa-7,13,15,17,19-pentaene-24-carboxylic acid Chemical compound CC[C@H]1\C=C/C=C\C=C/C=C\[C@@H](C[C@@H]2O[C@@](O)(C[C@H](O)[C@H]2C(O)=O)C[C@@H](O)C[C@@H](O)C\C=C/C(=O)O[C@@H]1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](N)[C@@H]1O DVWJFTGEISXVSH-CWVFEVJCSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
- 102000017304 72kDa type IV collagenases Human genes 0.000 description 1
- 108050005269 72kDa type IV collagenases Proteins 0.000 description 1
- 208000000058 Anaplasia Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 1
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 108050005238 Collagenase 3 Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 231100001074 DNA strand break Toxicity 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 102000008887 Membrane-Associated Matrix Metalloproteinases Human genes 0.000 description 1
- 108010088571 Membrane-Associated Matrix Metalloproteinases Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- 101710118230 Neutrophil collagenase Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 101710108790 Stromelysin-1 Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000007640 basal medium Substances 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000004791 biological behavior Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000006041 cell recruitment Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical class C1=CC(Cl)=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)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 1
- 210000003040 circulating cell Anatomy 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- ZXFCRFYULUUSDW-LANRQRAVSA-N cmt-3 Chemical compound C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)[C@@]2(O)C1CC(O)=C(C(=O)N)C2=O ZXFCRFYULUUSDW-LANRQRAVSA-N 0.000 description 1
- 230000003366 colagenolytic effect Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000276 dose-dependent cytotoxicity Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- SFNALCNOMXIBKG-UHFFFAOYSA-N ethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCO SFNALCNOMXIBKG-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003538 lonidamine Drugs 0.000 description 1
- WDRYRZXSPDWGEB-UHFFFAOYSA-N lonidamine Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl WDRYRZXSPDWGEB-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000022886 mitochondrial translation Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 108010067415 progelatinase Proteins 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 229940000207 selenious acid Drugs 0.000 description 1
- MCAHWIHFGHIESP-UHFFFAOYSA-N selenous acid Chemical compound O[Se](O)=O MCAHWIHFGHIESP-UHFFFAOYSA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 238000005549 size reduction Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 229930183279 tetramycin Natural products 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000001262 western blot Methods 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
- A61K31/65—Tetracyclines
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/783,655 | 1997-01-15 | ||
| US08/783,655 US5837696A (en) | 1997-01-15 | 1997-01-15 | Method of inhibiting cancer growth |
| PCT/US1998/000332 WO1998031224A1 (en) | 1997-01-15 | 1998-01-15 | Method of inhibiting cancer growth |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001508794A JP2001508794A (ja) | 2001-07-03 |
| JP2001508794A5 JP2001508794A5 (https=) | 2005-05-12 |
| JP4428727B2 true JP4428727B2 (ja) | 2010-03-10 |
Family
ID=25130005
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP53443498A Expired - Fee Related JP4428727B2 (ja) | 1997-01-15 | 1998-01-15 | 癌の成長を抑制する方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US5837696A (https=) |
| EP (1) | EP0971585B1 (https=) |
| JP (1) | JP4428727B2 (https=) |
| KR (1) | KR20000070212A (https=) |
| AT (1) | ATE321452T1 (https=) |
| AU (1) | AU729886B2 (https=) |
| CA (1) | CA2277865C (https=) |
| DE (1) | DE69834024T2 (https=) |
| ES (1) | ES2262221T3 (https=) |
| PT (1) | PT971585E (https=) |
| WO (1) | WO1998031224A1 (https=) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5837696A (en) * | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
| US6429204B1 (en) | 1997-01-15 | 2002-08-06 | University Of Miami | Method of inhibiting cancer growth |
| AU2001599A (en) * | 1997-12-19 | 1999-07-05 | New York University | Method for inhibiting cyclooxygenase-2 and tumor necrosis factor alpha |
| US6277061B1 (en) | 1998-03-31 | 2001-08-21 | The Research Foundation Of State University Of New York | Method of inhibiting membrane-type matrix metalloproteinase |
| US6015804A (en) * | 1998-09-11 | 2000-01-18 | The Research Foundation Of State University Of New York | Method of using tetracycline compounds to enhance interleukin-10 production |
| US5977091A (en) * | 1998-09-21 | 1999-11-02 | The Research Foundation Of State University Of New York | Method of preventing acute lung injury |
| US6833373B1 (en) | 1998-12-23 | 2004-12-21 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| BR9916536A (pt) * | 1998-12-23 | 2002-01-02 | Searle & Co | Método para o tratamento ou prevenção de um distúrbio de neoplasia em um mamìfero em necessidade deste tratamento ou prevenção, e, combinação |
| US6858598B1 (en) | 1998-12-23 | 2005-02-22 | G. D. Searle & Co. | Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| US6984619B1 (en) * | 1999-03-19 | 2006-01-10 | Arch Development Corporation | Method for protection against tumor metastasis formation |
| DE10032256C2 (de) * | 2000-07-03 | 2003-06-05 | Infineon Technologies Ag | Chip-ID-Register-Anordnung |
| EP2311440A1 (en) * | 2001-04-05 | 2011-04-20 | Collagenex Pharmaceuticals, Inc. | Controlled delivery of tetracycline compounds and tetracycline derivatives |
| EP2327409A1 (en) | 2001-07-13 | 2011-06-01 | Paratek Pharmaceuticals, Inc. | Tetracycline compound having target therapeutic activities |
| US20060194773A1 (en) * | 2001-07-13 | 2006-08-31 | Paratek Pharmaceuticals, Inc. | Tetracyline compounds having target therapeutic activities |
| RU2300380C2 (ru) * | 2001-10-05 | 2007-06-10 | Тетрадженекс Фармасьютикалс, Инк. | Производные тетрациклина и способы их применения |
| PE20030701A1 (es) * | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
| ES2551708T3 (es) | 2002-01-08 | 2015-11-23 | Paratek Pharmaceuticals, Inc. | Compuestos de 4-desdimetilamino tetraciclina |
| EP2311451A1 (en) | 2002-03-08 | 2011-04-20 | Paratek Pharmaceuticals, Inc. | Amino-methyl substituted tetracycline compounds |
| EP1503981A4 (en) | 2002-03-21 | 2007-08-15 | Paratek Pharm Innc | SUBSTITUTED TETRACYCLINE COMPOUNDS |
| JP2005526114A (ja) * | 2002-05-06 | 2005-09-02 | コッラジェネックス ファーマシューチカルス インコーポレイテッド | 粘膜炎及び真菌感染症の同時治療方法 |
| JP2005533766A (ja) * | 2002-05-20 | 2005-11-10 | コッラジェネックス ファーマシューチカルス インコーポレイテッド | アレルギー反応の治療方法 |
| AU2003261161B2 (en) | 2002-07-12 | 2009-09-10 | Paratek Pharmaceuticals, Inc | 3, 10, and 12a substituted tetracycline compounds |
| CA2503446C (en) | 2002-10-24 | 2012-12-18 | Paratek Pharmaceuticals, Inc. | Methods of using substituted tetracycline compounds to modulate rna |
| WO2004091483A2 (en) | 2003-04-07 | 2004-10-28 | Shire Laboratories, Inc. | Once daily formulations of tetracyclines |
| US20050143352A1 (en) | 2003-07-09 | 2005-06-30 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| AU2004259661B2 (en) | 2003-07-09 | 2011-11-10 | Paratek Pharmaceuticals, Inc. | Prodrugs of 9-aminomethyl tetracycline compounds |
| JP5010284B2 (ja) * | 2004-01-15 | 2012-08-29 | パラテック ファーマシューティカルズ インコーポレイテッド | テトラサイクリン化合物の芳香族ａ環誘導体 |
| EP2033950A1 (en) | 2004-10-25 | 2009-03-11 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds |
| EP1805134B1 (en) | 2004-10-25 | 2012-06-20 | Paratek Pharmaceuticals, Inc. | 4-aminotetracyclines and methods of use thereof |
| US20070093455A1 (en) * | 2005-07-21 | 2007-04-26 | Paul Abato | 10-substituted tetracyclines and methods of use thereof |
| WO2008079339A2 (en) | 2006-12-21 | 2008-07-03 | Paratek Pharmaceuticals, Inc. | Tetracycline derivatives for the treatment of bacterial, viral and parasitic infections |
| CA2892739A1 (en) | 2006-12-21 | 2008-07-03 | Paratek Pharmaceuticals, Inc. | Substituted tetracycline compounds for treatment of inflammatory skin disorders |
| EP2216323A3 (en) * | 2007-04-27 | 2010-12-29 | Paratek Pharmaceuticals, Inc. | Methods for synthesizing and purifying aminoalkyl tetracycline compounds |
| EP2176216B1 (en) * | 2007-07-06 | 2012-04-25 | Paratek Pharmaceuticals, Inc. | Methods for synthesizing 9-substituted minocycline |
| TWI680117B (zh) | 2008-05-19 | 2019-12-21 | 派洛泰克藥物股份有限公司 | 四環素化合物之甲苯磺酸鹽及同素異形體 |
| KR101746795B1 (ko) | 2008-08-08 | 2017-06-13 | 테트라페이즈 파마슈티컬스, 인코포레이티드 | Ｃ７-플루오로 치환된 테트라시클린 화합물 |
| WO2010129057A2 (en) | 2009-05-08 | 2010-11-11 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| NO2470500T3 (https=) | 2009-08-28 | 2018-03-03 | ||
| WO2011109899A1 (en) * | 2010-03-10 | 2011-09-15 | University Health Network | Use of tigecycline for treatment of cancer |
| DK2552890T3 (en) | 2010-03-31 | 2017-04-03 | Tetraphase Pharmaceuticals Inc | POLYCYCLIC TETRACYCLINE COMPOUNDS |
| CA2883238C (en) | 2012-08-31 | 2021-11-23 | Tetraphase Pharmaceuticals, Inc. | Tetracycline compounds |
| CN105142631A (zh) * | 2013-01-14 | 2015-12-09 | 健康诊所有限公司 | 抗癌药物和用途 |
| HUE066360T2 (hu) | 2016-10-19 | 2024-07-28 | Tetraphase Pharmaceuticals Inc | Eravaciklin kristályformái |
| US11197872B2 (en) | 2017-04-21 | 2021-12-14 | Lunella Biotech, Inc. | Vitamin C and doxycycline: a synthetic lethal combination therapy for eradicating cancer stem cells (CSCs) |
| CA3060509A1 (en) | 2017-04-21 | 2018-10-25 | Federica Sotgia | Targeting hypoxic cancer stem cells (cscs) with doxycycline: implications for improving anti-angiogenic therapy |
| US12006553B2 (en) | 2017-05-19 | 2024-06-11 | Lunella Biotech, Inc. | Companion diagnostics for mitochondrial inhibitors |
| KR20200010343A (ko) | 2017-05-19 | 2020-01-30 | 루넬라 바이오테크 인코포레이티드 | 안티미토신: 암 줄기 세포를 근절하기 위한 미토콘드리아 생물발생의 표적화 억제제 |
| US12570604B2 (en) | 2018-11-09 | 2026-03-10 | Tetraphase Pharmaceuticals, Inc. | Polymorphic forms of a tetracycline compound and uses thereof |
| CN115006411A (zh) * | 2022-07-26 | 2022-09-06 | 中南大学湘雅医院 | 依拉环素类化合物的应用、药物及其制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5308839A (en) * | 1989-12-04 | 1994-05-03 | The Research Foundation Of State University Of New York | Composition comprising non-steroidal anti-inflammatory agent tenidap and effectively non-antibacterial tetracycline |
| JP3016587B2 (ja) * | 1989-12-04 | 2000-03-06 | ザ・リサーチ・ファンデーション・オブ・ステート・ユニバーシティ・オブ・ニューヨーク | 非ステロイド抗炎症剤及びテトラサイクリンの配合 |
| AU1411992A (en) * | 1991-01-15 | 1992-08-27 | Robert A Bok | A composition containing a tetracycline and use for inhibiting angiogenesis |
| US5668122A (en) * | 1993-07-28 | 1997-09-16 | Fife; Rose S. | Method to treat cancer with tetracyclines |
| US5574026A (en) * | 1994-12-13 | 1996-11-12 | American Cyanamid Company | Methods for inhibiting angiogenesis proliferation of endothelial or tumor cells and tumor growth |
| US5567693A (en) * | 1994-12-13 | 1996-10-22 | American Cyanamid Company | Method for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
| US5563130A (en) * | 1994-12-13 | 1996-10-08 | American Cyanamid Company | Methods for inhibiting angiogenesis, proliferation of endothelial or tumor cells and tumor growth |
| US5837696A (en) * | 1997-01-15 | 1998-11-17 | The Research Foundation Of State University Of New York | Method of inhibiting cancer growth |
-
1997
- 1997-01-15 US US08/783,655 patent/US5837696A/en not_active Expired - Lifetime
-
1998
- 1998-01-15 WO PCT/US1998/000332 patent/WO1998031224A1/en not_active Ceased
- 1998-01-15 PT PT98902437T patent/PT971585E/pt unknown
- 1998-01-15 JP JP53443498A patent/JP4428727B2/ja not_active Expired - Fee Related
- 1998-01-15 DE DE69834024T patent/DE69834024T2/de not_active Expired - Lifetime
- 1998-01-15 EP EP98902437A patent/EP0971585B1/en not_active Expired - Lifetime
- 1998-01-15 AU AU59104/98A patent/AU729886B2/en not_active Ceased
- 1998-01-15 KR KR1019997006438A patent/KR20000070212A/ko not_active Ceased
- 1998-01-15 CA CA002277865A patent/CA2277865C/en not_active Expired - Fee Related
- 1998-01-15 US US09/007,645 patent/US6100248A/en not_active Expired - Lifetime
- 1998-01-15 ES ES98902437T patent/ES2262221T3/es not_active Expired - Lifetime
- 1998-01-15 AT AT98902437T patent/ATE321452T1/de active
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998031224A1 (en) | 1998-07-23 |
| EP0971585A4 (en) | 2001-01-24 |
| DE69834024T2 (de) | 2006-12-07 |
| EP0971585A1 (en) | 2000-01-19 |
| JP2001508794A (ja) | 2001-07-03 |
| KR20000070212A (ko) | 2000-11-25 |
| ATE321452T1 (de) | 2006-04-15 |
| PT971585E (pt) | 2006-08-31 |
| US6100248A (en) | 2000-08-08 |
| US5837696A (en) | 1998-11-17 |
| CA2277865A1 (en) | 1998-07-23 |
| DE69834024D1 (de) | 2006-05-18 |
| ES2262221T3 (es) | 2006-11-16 |
| CA2277865C (en) | 2009-06-02 |
| EP0971585B1 (en) | 2006-03-29 |
| AU5910498A (en) | 1998-08-07 |
| AU729886B2 (en) | 2001-02-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4428727B2 (ja) | 癌の成長を抑制する方法 | |
| AU748870B2 (en) | Method of inhibiting membrane-type matrix metalloproteinase | |
| KR100554859B1 (ko) | 일산화질소 생산을 억제하기 위한 테트라사이클린 화합물을 포함하는 약제학적 조성물 | |
| KR100691654B1 (ko) | 테트라시클린 화합물을 이용한 인터루킨-10 생성을촉진하는 방법 | |
| AU755871B2 (en) | Combination of bisphosphonate and tetracycline | |
| US6429204B1 (en) | Method of inhibiting cancer growth | |
| EP0586020A1 (en) | Tetracyclines alone or in combination with NSAID for treating tissue destruction | |
| JPH0780774B2 (ja) | 薬剤組成物 | |
| JPH03227931A (ja) | 非ステロイド抗炎症剤及びテトラサイクリンの配合 | |
| JP2011168613A (ja) | ざ瘡の治療方法 | |
| RO122247B1 (ro) | Compoziţii farmaceutice de tizoxanidă şi nitazoxanidă | |
| MXPA99006554A (en) | Method of inhibiting cancer growth | |
| Schneider et al. | Tetracyclines inhibit intracellular muscle proteolysis in vitro | |
| JP2003535140A (ja) | 抗真菌薬剤としての非抗細菌性テトラサイクリン |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040820 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040820 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080507 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080807 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080912 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081107 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20081107 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20091208 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20091215 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121225 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121225 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131225 Year of fee payment: 4 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |