CA2388674C - Inhibitors of endo-exonuclease activity for treating cancer - Google Patents
Inhibitors of endo-exonuclease activity for treating cancer Download PDFInfo
- Publication number
- CA2388674C CA2388674C CA002388674A CA2388674A CA2388674C CA 2388674 C CA2388674 C CA 2388674C CA 002388674 A CA002388674 A CA 002388674A CA 2388674 A CA2388674 A CA 2388674A CA 2388674 C CA2388674 C CA 2388674C
- Authority
- CA
- Canada
- Prior art keywords
- endo
- exonuclease
- pentamidine
- agent
- compound
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 133
- 108010051357 endoexonuclease Proteins 0.000 title claims abstract description 94
- 201000011510 cancer Diseases 0.000 title claims abstract description 81
- 230000000694 effects Effects 0.000 title claims abstract description 80
- 239000003112 inhibitor Substances 0.000 title description 4
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 claims abstract description 124
- 229960004448 pentamidine Drugs 0.000 claims abstract description 121
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 230000004614 tumor growth Effects 0.000 claims abstract description 38
- 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 claims abstract description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 29
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 25
- 229960004857 mitomycin Drugs 0.000 claims abstract description 21
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims abstract description 20
- 229960004316 cisplatin Drugs 0.000 claims abstract description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 53
- 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 claims description 30
- 230000035755 proliferation Effects 0.000 claims description 30
- 229940009456 adriamycin Drugs 0.000 claims description 15
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 8
- 229960002949 fluorouracil Drugs 0.000 claims description 8
- 239000000693 micelle Substances 0.000 claims description 7
- 108010006654 Bleomycin Proteins 0.000 claims description 6
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 6
- 229930012538 Paclitaxel Natural products 0.000 claims description 6
- 230000000692 anti-sense effect Effects 0.000 claims description 6
- 229960001561 bleomycin Drugs 0.000 claims description 6
- 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 claims description 6
- 229960005243 carmustine Drugs 0.000 claims description 6
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 6
- 229960001924 melphalan Drugs 0.000 claims description 6
- 229960001592 paclitaxel Drugs 0.000 claims 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 claims description 6
- 239000002502 liposome Substances 0.000 claims description 5
- -1 vesicles Substances 0.000 claims 3
- 238000000034 method Methods 0.000 abstract description 32
- 229940079593 drug Drugs 0.000 abstract description 28
- 239000003814 drug Substances 0.000 abstract description 28
- 239000000203 mixture Substances 0.000 abstract description 14
- 238000011282 treatment Methods 0.000 abstract description 13
- 210000002966 serum Anatomy 0.000 abstract description 6
- 230000008439 repair process Effects 0.000 abstract description 4
- 231100000419 toxicity Toxicity 0.000 abstract description 4
- 230000001988 toxicity Effects 0.000 abstract description 4
- 238000012544 monitoring process Methods 0.000 abstract description 2
- 230000002195 synergetic effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 111
- 241001465754 Metazoa Species 0.000 description 29
- 108020004414 DNA Proteins 0.000 description 27
- 238000002474 experimental method Methods 0.000 description 22
- 239000002246 antineoplastic agent Substances 0.000 description 17
- 239000012528 membrane Substances 0.000 description 17
- 239000000872 buffer Substances 0.000 description 16
- 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 16
- 241000699670 Mus sp. Species 0.000 description 15
- 230000001093 anti-cancer Effects 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 14
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 13
- 229960005420 etoposide Drugs 0.000 description 13
- UPBAOYRENQEPJO-UHFFFAOYSA-N n-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide Chemical compound CN1C=C(NC=O)C=C1C(=O)NC1=CN(C)C(C(=O)NC2=CN(C)C(C(=O)NCCC(N)=N)=C2)=C1 UPBAOYRENQEPJO-UHFFFAOYSA-N 0.000 description 13
- 206010027476 Metastases Diseases 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 239000007943 implant Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- 229940127089 cytotoxic agent Drugs 0.000 description 9
- 230000012010 growth Effects 0.000 description 9
- 210000004072 lung Anatomy 0.000 description 9
- 229920000642 polymer Polymers 0.000 description 9
- 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 7
- 229930192392 Mitomycin Natural products 0.000 description 7
- 230000005782 double-strand break Effects 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000005855 radiation Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 6
- 238000004113 cell culture Methods 0.000 description 6
- 229940044683 chemotherapy drug Drugs 0.000 description 6
- XNYZHCFCZNMTFY-UHFFFAOYSA-N diminazene Chemical compound C1=CC(C(=N)N)=CC=C1N\N=N\C1=CC=C(C(N)=N)C=C1 XNYZHCFCZNMTFY-UHFFFAOYSA-N 0.000 description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 108010042747 stallimycin Proteins 0.000 description 6
- 229950009902 stallimycin Drugs 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 206010027458 Metastases to lung Diseases 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 4
- 208000002151 Pleural effusion Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 208000009956 adenocarcinoma Diseases 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 238000009643 clonogenic assay Methods 0.000 description 4
- 231100000096 clonogenic assay Toxicity 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 208000003849 large cell carcinoma Diseases 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 235000020183 skimmed milk Nutrition 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 230000033616 DNA repair Effects 0.000 description 3
- 230000004543 DNA replication Effects 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 101150006234 RAD52 gene Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000005783 single-strand break Effects 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000011547 Bouin solution Substances 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 102000016911 Deoxyribonucleases Human genes 0.000 description 2
- 108010053770 Deoxyribonucleases Proteins 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 102100022760 Stress-70 protein, mitochondrial Human genes 0.000 description 2
- 101710183280 Topoisomerase Proteins 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000002001 anti-metastasis Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229940064804 betadine Drugs 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000005880 cancer cell killing Effects 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000003021 clonogenic effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000006846 excision repair Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 229940127084 other anti-cancer agent Drugs 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 239000013610 patient sample Substances 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 238000011886 postmortem examination Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 231100000925 very toxic Toxicity 0.000 description 2
- OZDAOHVKBFBBMZ-UHFFFAOYSA-N 2-aminopentanedioic acid;hydrate Chemical compound O.OC(=O)C(N)CCC(O)=O OZDAOHVKBFBBMZ-UHFFFAOYSA-N 0.000 description 1
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 description 1
- LVSPDZAGCBEQAV-UHFFFAOYSA-N 4-chloronaphthalen-1-ol Chemical compound C1=CC=C2C(O)=CC=C(Cl)C2=C1 LVSPDZAGCBEQAV-UHFFFAOYSA-N 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101150031823 HSP70 gene Proteins 0.000 description 1
- 101150101832 HSPA9 gene Proteins 0.000 description 1
- 108060003951 Immunoglobulin 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
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000204031 Mycoplasma Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 101710111177 Stress-70 protein, mitochondrial Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 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
- 239000002253 acid Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 101150052825 dnaK gene Proteins 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229940084362 forane Drugs 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 108010072187 mortalin Proteins 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000404 nontoxic agent Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000003007 single stranded DNA break Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000011537 solubilization buffer Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011255 standard chemotherapy Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229910000811 surgical stainless steel Inorganic materials 0.000 description 1
- 239000010966 surgical stainless steel Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- 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)
- Inorganic Chemistry (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002483352A CA2483352A1 (en) | 1999-11-16 | 2000-11-16 | Inhibitors of endo-exonuclease activity for treating cancer |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16568899P | 1999-11-16 | 1999-11-16 | |
| US60/165,688 | 1999-11-16 | ||
| PCT/CA2000/001355 WO2001035935A2 (en) | 1999-11-16 | 2000-11-16 | Inhibitors of endo-exonuclease activity such as pentamidine for the treatment of cancer |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002483352A Division CA2483352A1 (en) | 1999-11-16 | 2000-11-16 | Inhibitors of endo-exonuclease activity for treating cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2388674A1 CA2388674A1 (en) | 2001-05-25 |
| CA2388674C true CA2388674C (en) | 2005-01-25 |
Family
ID=22600019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002388674A Expired - Fee Related CA2388674C (en) | 1999-11-16 | 2000-11-16 | Inhibitors of endo-exonuclease activity for treating cancer |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US20060276548A1 (enExample) |
| EP (1) | EP1231910B1 (enExample) |
| JP (1) | JP2003515534A (enExample) |
| AT (1) | ATE431734T1 (enExample) |
| AU (1) | AU780538B2 (enExample) |
| CA (1) | CA2388674C (enExample) |
| CY (1) | CY1110503T1 (enExample) |
| DE (1) | DE60042245D1 (enExample) |
| DK (1) | DK1231910T3 (enExample) |
| ES (1) | ES2327313T3 (enExample) |
| PT (1) | PT1231910E (enExample) |
| WO (1) | WO2001035935A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014008592A1 (en) * | 2012-07-13 | 2014-01-16 | Oncozyme Pharma Inc. | Combinations comprising diamidine compounds and parp inhibitors for use iν treating cancer |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001097794A2 (en) * | 2000-06-21 | 2001-12-27 | Georgetown University | Inhibitors of matriptase for the treatment of cancer |
| US6569853B1 (en) | 2000-11-06 | 2003-05-27 | Combinatorx, Incorporated | Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders |
| US6693125B2 (en) | 2001-01-24 | 2004-02-17 | Combinatorx Incorporated | Combinations of drugs (e.g., a benzimidazole and pentamidine) for the treatment of neoplastic disorders |
| US8053477B2 (en) * | 2002-03-29 | 2011-11-08 | University Of Maryland, Baltimore | Inhibitors of the S100-p53 protein-protein interaction and method of inhibiting cancer employing the same |
| ITMI20021455A1 (it) * | 2002-07-02 | 2004-01-02 | Ugo Raffaello Citernesi | Formulazioni fosfolipidiche di lexitropsine loro preparazione ed impiego terapeutico |
| US20050054708A1 (en) * | 2003-07-28 | 2005-03-10 | Nichols Matthew James | Combinations of drugs for the treatment of neoplasms |
| US20100028339A1 (en) | 2004-03-29 | 2010-02-04 | Cheng Jin Q | Compositions including triciribine and trastuzumab and methods of use thereof |
| US20110008327A1 (en) | 2004-03-29 | 2011-01-13 | Cheng Jin Q | Compositions including triciribine and epidermal growth factor receptor inhibitor compounds or salts thereof and methods of use thereof |
| EP1737472B1 (en) | 2004-03-29 | 2014-08-13 | University Of South Florida | Effective treatment of tumors and cancer with triciribine |
| US20100009928A1 (en) | 2004-03-29 | 2010-01-14 | Cheng Jin Q | Compositions including triciribine and taxanes and methods of use thereof |
| US20100009929A1 (en) | 2004-03-29 | 2010-01-14 | Cheng Jin Q | Compositions including triciribine and bortezomib and derivatives thereof and methods of use thereof |
| US20100173864A1 (en) | 2004-03-29 | 2010-07-08 | Cheng Jin Q | Compositions including triciribine and one or more platinum compounds and methods of use thereof |
| JPWO2006062072A1 (ja) * | 2004-12-10 | 2008-08-07 | テムリック株式会社 | 転移癌治療剤および癌転移抑制剤 |
| WO2009086485A1 (en) | 2007-12-28 | 2009-07-09 | Server Technology, Inc. | Power distribution, management, and monitoring systems and methods |
| JP2012525371A (ja) * | 2009-05-01 | 2012-10-22 | オンコザイム・ファーマ・インコーポレイテッド | 癌を治療するためのペンタミジンの組み合わせ |
| EP3724161B1 (en) | 2017-11-16 | 2025-01-01 | Montdorex Inc. | Mono- and di-amidine endo-exonuclease inhibitors and methods for inhibiting endo-exonuclease activity |
| CN111671904B (zh) * | 2020-04-15 | 2022-12-06 | 四川大学华西第二医院 | 一种含有抑制核酸内切酶功能的药物及其抗肿瘤的用途 |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2145528C3 (de) * | 1971-09-11 | 1981-12-17 | Heinrich Mack Nachf., 7918 Illertissen | Exonuclease und diese enthaltendes cytostatisches Mittel |
| DE3750106T3 (de) * | 1986-08-06 | 1999-04-22 | Ajinomoto Co., Inc., Tokio/Tokyo | Rekombinanter B-Zell-Differenzierungsfaktor. |
| EP0309519B1 (en) * | 1987-04-09 | 1992-07-08 | FISONS plc | Pharmaceutical compositions containing pentamidine |
| US5204113A (en) * | 1987-04-09 | 1993-04-20 | Fisons Plc | Pharmaceutical compositions containing pentamidine |
| US5166140A (en) * | 1987-05-05 | 1992-11-24 | City Of Hope | Use of certain nucleoside analogs to attenuate cancer cell resistance to DNA damaging chemotherapy |
| US5585363A (en) * | 1987-05-05 | 1996-12-17 | City Of Hope | Circumvention of human tumor drug resistance |
| US4856528A (en) * | 1987-06-26 | 1989-08-15 | John Hopkins University | Tumor volume determination |
| US5204352A (en) * | 1987-09-29 | 1993-04-20 | The United States Of America As Represented By The Secretary Of The Army | Compounds exhibiting anti-parasitic activity and a method for their use |
| US5084480A (en) * | 1987-11-06 | 1992-01-28 | Fujisawa Usa, Inc. | Pentamidine salts useful in the treatment of pneumocystis carinii pneumonia |
| US5422120A (en) * | 1988-05-30 | 1995-06-06 | Depotech Corporation | Heterovesicular liposomes |
| MX16687A (es) * | 1988-07-07 | 1994-01-31 | Ciba Geigy Ag | Compuestos de biarilo y procedimiento para su preparacion. |
| US5037758A (en) * | 1989-01-11 | 1991-08-06 | Her Majesty The Queen In Right Of Canada, As Represented By The National Research Council Of Canada | Enhanced production of biosurfactant through the use of a mutated B subtilis strain |
| GB8903438D0 (en) * | 1989-02-15 | 1989-04-05 | May & Baker Ltd | New compositions of matter |
| US5352581A (en) * | 1989-03-24 | 1994-10-04 | United States/National Institutes Of Health | Sensitive yeast genetic system for identifying agents causing double-stranded DNA damage |
| WO1991009954A1 (en) * | 1989-12-27 | 1991-07-11 | Resnick Michael A | Novel system for isolating and producing new genes, gene products and dna sequences |
| US5324830A (en) * | 1991-03-26 | 1994-06-28 | United States Of America | Chimeric protein that has a human RHo Motif and deoxyribonuclease activity |
| US5489524A (en) * | 1991-03-26 | 1996-02-06 | The United States Of America As Represented By The Department Of Health And Human Services | Chimeric protein that has a human Rho motif and deoxyribonuclease activity |
| US5283238A (en) * | 1992-04-24 | 1994-02-01 | Immtech International, Inc. | Methods of treating cancer using modified C-reactive protein |
| US5723288A (en) * | 1994-05-06 | 1998-03-03 | The University Of North Carolina At Chapel Hill | Method of fluorescent detection of nucleic acids and cytoskeleton elements using bis-dicationic aryl furans, and kits useful therefor |
| US5874283A (en) * | 1995-05-30 | 1999-02-23 | John Joseph Harrington | Mammalian flap-specific endonuclease |
| US5643935A (en) * | 1995-06-07 | 1997-07-01 | The University Of North Carolina At Chapel Hill | Method of combatting infectious diseases using dicationic bis-benzimidazoles |
| US5698556A (en) * | 1995-06-07 | 1997-12-16 | Chan; Carcy L. | Methotrexate analogs and methods of using same |
| US5916779A (en) * | 1995-09-21 | 1999-06-29 | Becton, Dickinson And Company | Strand displacement amplification of RNA targets |
| US5935982A (en) * | 1997-02-28 | 1999-08-10 | The University Of North Carolina At Chapel Hill | Methods of treating retroviral infection and compounds useful therefor |
| US5977311A (en) * | 1997-09-23 | 1999-11-02 | Curagen Corporation | 53BP2 complexes |
| EP1375515A3 (en) * | 1997-10-07 | 2004-04-21 | Ono Pharmaceutical Co., Ltd. | Polypeptide, cDNA encoding the same, and use thereof |
| US7115665B1 (en) * | 2000-11-16 | 2006-10-03 | Onocozyme Pharma, Inc. | Inhibitors of endo-exonuclease activity for treating cancer |
| EP3594334A3 (en) * | 2000-03-08 | 2020-03-18 | Novozymes A/S | Variants with altered properties |
| US6569853B1 (en) * | 2000-11-06 | 2003-05-27 | Combinatorx, Incorporated | Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders |
| US6693125B2 (en) * | 2001-01-24 | 2004-02-17 | Combinatorx Incorporated | Combinations of drugs (e.g., a benzimidazole and pentamidine) for the treatment of neoplastic disorders |
| US20040010045A1 (en) * | 2001-09-07 | 2004-01-15 | Taolin Yi | Therapeutic compositions comprised of pentamidine and methods of using same to treat cancer |
| US8053477B2 (en) * | 2002-03-29 | 2011-11-08 | University Of Maryland, Baltimore | Inhibitors of the S100-p53 protein-protein interaction and method of inhibiting cancer employing the same |
-
2000
- 2000-11-16 DK DK00975725T patent/DK1231910T3/da active
- 2000-11-16 AU AU13765/01A patent/AU780538B2/en not_active Ceased
- 2000-11-16 DE DE60042245T patent/DE60042245D1/de not_active Expired - Lifetime
- 2000-11-16 AT AT00975725T patent/ATE431734T1/de active
- 2000-11-16 PT PT00975725T patent/PT1231910E/pt unknown
- 2000-11-16 EP EP00975725A patent/EP1231910B1/en not_active Expired - Lifetime
- 2000-11-16 WO PCT/CA2000/001355 patent/WO2001035935A2/en not_active Ceased
- 2000-11-16 JP JP2001537928A patent/JP2003515534A/ja active Pending
- 2000-11-16 CA CA002388674A patent/CA2388674C/en not_active Expired - Fee Related
- 2000-11-16 ES ES00975725T patent/ES2327313T3/es not_active Expired - Lifetime
-
2006
- 2006-05-25 US US11/420,358 patent/US20060276548A1/en not_active Abandoned
-
2008
- 2008-08-27 US US12/199,603 patent/US20090068094A1/en not_active Abandoned
-
2009
- 2009-08-11 CY CY20091100855T patent/CY1110503T1/el unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014008592A1 (en) * | 2012-07-13 | 2014-01-16 | Oncozyme Pharma Inc. | Combinations comprising diamidine compounds and parp inhibitors for use iν treating cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2388674A1 (en) | 2001-05-25 |
| JP2003515534A (ja) | 2003-05-07 |
| EP1231910A2 (en) | 2002-08-21 |
| WO2001035935A2 (en) | 2001-05-25 |
| AU1376501A (en) | 2001-05-30 |
| DK1231910T3 (da) | 2009-08-31 |
| WO2001035935B1 (en) | 2002-02-07 |
| EP1231910B1 (en) | 2009-05-20 |
| US20060276548A1 (en) | 2006-12-07 |
| PT1231910E (pt) | 2009-08-06 |
| CY1110503T1 (el) | 2015-04-29 |
| WO2001035935A3 (en) | 2002-01-03 |
| ATE431734T1 (de) | 2009-06-15 |
| US20090068094A1 (en) | 2009-03-12 |
| ES2327313T3 (es) | 2009-10-28 |
| DE60042245D1 (de) | 2009-07-02 |
| AU780538B2 (en) | 2005-03-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20090068094A1 (en) | Inhibitors of endo-exonuclease activity for treating cancer | |
| US5541232A (en) | Treatment of multidrug resistant diseases | |
| Kim et al. | Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice | |
| ES2232613T3 (es) | Formulaciones y metodos de utilizacion de agentes mimeticos del oxido nitrico contra un fenotipo celular maligno. | |
| AU2001250221A1 (en) | Formulations and methods of using nitric oxide mimetics against a malignant cell phenotype | |
| US20100056625A1 (en) | Non-toxic anti-cancer drug combining ascorbate, magnesium and a naphthoquinone | |
| JP2000510460A (ja) | スクアラミンを他の抗癌剤と併用する上皮性悪性腫瘍の治療 | |
| JP2012017346A (ja) | ＮＣＣａ−ＡＴＰチャネルを標的とする治療剤およびその使用方法 | |
| Cinatl et al. | Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis. | |
| WO2019109074A1 (en) | Mebendazole cancer therapies and methods of use | |
| Laurie et al. | Targeting MDM2 and MDMX in retinoblastoma | |
| WO1997027848A9 (en) | SENSITIZATION OF HER2/neu OVER-EXPRESSING CANCER CELLS TO CHEMOTHERAPEUTIC DRUGS | |
| US7115665B1 (en) | Inhibitors of endo-exonuclease activity for treating cancer | |
| WO1997027848A1 (en) | SENSITIZATION OF HER2/neu OVER-EXPRESSING CANCER CELLS TO CHEMOTHERAPEUTIC DRUGS | |
| CN113329772B (zh) | 化学疗法与重组齐整小核菌凝集素的联合疗法 | |
| CN111542325A (zh) | 用于治疗恶性肿瘤和癌前病症的组合物及其使用方法和制备药剂的方法 | |
| CA2483352A1 (en) | Inhibitors of endo-exonuclease activity for treating cancer | |
| US20250186438A1 (en) | Treatment of clear cell renal cell carcinoma | |
| US12239617B2 (en) | Mono- and di-amidine endo-exonuclease inhibitors and methods for inhibiting endo-exonuclease activity | |
| JP5393691B2 (ja) | 急性ヒト骨髄性白血病細胞を死滅させるトロンボポエチン受容体作用薬（ＴｐｏＲＡ） | |
| CN110882240B (zh) | 作为急性缺血性中风的治疗剂的多酚衍生物化合物6-cepn | |
| CN104815322A (zh) | 用于头颈部肿瘤联合治疗的制剂及其用途 | |
| JPWO2006035515A1 (ja) | 膀胱表在性癌の治療又は予防用医薬組成物、及びその利用 | |
| KR101316642B1 (ko) | 메틸 피오포바이드를 유효성분으로 포함하는 항암제 내성 극복 의약 조성물 | |
| US20020193319A1 (en) | Use of EGF genistein to prevent development of EGF-receptor expressing cancers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20161116 |