WO1990012321A1 - Radiosensibilisateurs avec ligand d'adn halogene pour la therapie anticancereuse - Google Patents
Radiosensibilisateurs avec ligand d'adn halogene pour la therapie anticancereuse Download PDFInfo
- Publication number
- WO1990012321A1 WO1990012321A1 PCT/AU1990/000122 AU9000122W WO9012321A1 WO 1990012321 A1 WO1990012321 A1 WO 1990012321A1 AU 9000122 W AU9000122 W AU 9000122W WO 9012321 A1 WO9012321 A1 WO 9012321A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- halogenated
- dna
- ligand
- hydroxy
- halogen
- Prior art date
Links
- 239000003446 ligand Substances 0.000 title claims abstract description 55
- 238000011275 oncology therapy Methods 0.000 title claims description 5
- 230000005855 radiation Effects 0.000 claims abstract description 27
- 230000001678 irradiating effect Effects 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 230000002939 deleterious effect Effects 0.000 claims description 12
- -1 halogenated aminoacridine compound Chemical class 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical class C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 238000009830 intercalation Methods 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 abstract 1
- 108020004414 DNA Proteins 0.000 description 48
- 238000003776 cleavage reaction Methods 0.000 description 21
- 230000007017 scission Effects 0.000 description 21
- 239000012634 fragment Substances 0.000 description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- ZGUNSONXLSTYPT-UHFFFAOYSA-N 2-iodo-4-[6-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-benzimidazol-2-yl]phenol Chemical compound CN1CCN(CC1)C1=CC=C2N=C(NC2=C1)C1=CC=C2N=C(NC2=C1)C1=CC=C(O)C(I)=C1 ZGUNSONXLSTYPT-UHFFFAOYSA-N 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 238000012163 sequencing technique Methods 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000006303 photolysis reaction Methods 0.000 description 6
- 230000015843 photosynthesis, light reaction Effects 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 238000001712 DNA sequencing Methods 0.000 description 4
- 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 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 230000037230 mobility Effects 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 231100000489 sensitizer Toxicity 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000000203 mixture Substances 0.000 description 3
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 3
- 229950009268 zinostatin Drugs 0.000 description 3
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 2
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 0 **(CC1)CCN1c(cc1)cc2*1NC(c(cc1)cc3*1N[C@](c(c(*)c(*)c(*)c1*)c1I)N3)N2 Chemical compound **(CC1)CCN1c(cc1)cc2*1NC(c(cc1)cc3*1N[C@](c(c(*)c(*)c(*)c1*)c1I)N3)N2 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- XJGFWWJLMVZSIG-UHFFFAOYSA-N 9-aminoacridine Chemical compound C1=CC=C2C(N)=C(C=CC=C3)C3=NC2=C1 XJGFWWJLMVZSIG-UHFFFAOYSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 231100001074 DNA strand break Toxicity 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 108010059712 Pronase Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229960001441 aminoacridine Drugs 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- HAAZLUGHYHWQIW-KVQBGUIXSA-N dGTP Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 HAAZLUGHYHWQIW-KVQBGUIXSA-N 0.000 description 1
- NHVNXKFIZYSCEB-XLPZGREQSA-N dTTP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C1 NHVNXKFIZYSCEB-XLPZGREQSA-N 0.000 description 1
- 238000005831 deiodination reaction Methods 0.000 description 1
- 238000000326 densiometry Methods 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
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- OBBCSXFCDPPXOL-UHFFFAOYSA-N misonidazole Chemical compound COCC(O)CN1C=CN=C1[N+]([O-])=O OBBCSXFCDPPXOL-UHFFFAOYSA-N 0.000 description 1
- 229950010514 misonidazole Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
Definitions
- HALOGENATED DNA LIGAND RADIOSENSITISERS FOR CANCER THERAPY This invention relates to the use in cancer therapy of halogenated DNA ligands which induce radiation damage in DNA in response to ionising or ultraviolet radiation. More particularly, the invention is concerned with the use of such ligands as radiosensitisers.
- Radiosensitisers are substances which when present during irradiation, enhance the cytotoxic effects of radiation.
- the hypoxic radiosensitiser Misonidazole enhances the cytotoxic effect of X- and ⁇ - radiation.
- the interaction between radiation and radiosensitiser is complex and difficult to predict.
- both the radiosensitiser and the radiation are cytotoxic per se. their use in therapy is limited.
- Photosensitisers are substances which when present, enhance the cytotoxic effects of ultraviolet or visible radiation.
- photosensitisers are included in the term
- ionising radiation is used herein to include photons having enough energy to ionise a bond, such as, a, ⁇ , and ⁇ rays from radioactive nuclei and x-rays.
- Incorporation of a bromine or iodine atom into DNA using BUdR or IUdR is known to sensitise DNA to breakage by ionising or ultraviolet radiation.
- the sensitisation is mediated by the uracilyl free radical formed by dissociation of the carbon-halogen bond in the BUdR or IUdR by UV and the same free radical is formed by a reaction of hydrated electrons produced by ionising radiation. It has been proposed that the uracilyl free radical initiates strand cleavage by abstraction of the hydrogen atom from the 2'-deoxyribose carbon on the adjacent nucleotide.
- iodinated DNA ligand is a potent sensitiser of cell-kill by near UV.
- irradiation with ionising or ultraviolet radiation generates free radicals very close to, but not actually on, the DNA.
- DNA breaks are produced following abstraction of hydrogen atoms from DNA near the binding sites of the halogenated ligand.
- halogenated DNA ligands may also act as sensitisers of ionising radiation.
- Ultraviolet radiation is more effective at producing free radicals than ionising radiation.
- ultraviolet radiation has a low tissue penetration and could only be used in the treatment of superficial tumours or in the specific killing of isolated tumour cells for example, in samples of bone marrow prior to bone marrow transplantation.
- a radiosensitiser for use in cancer therapy which comprises a halogenated DNA ligand.
- a method for enhancing the radiosensitiser for use in cancer therapy which comprises a halogenated DNA ligand.
- a method for inducing radiation damage in DNA which comprises causing or allowing a halogenated DNA ligand to bind to DNA and irradiating the DNA and said bound ligand or the locus thereof with ionising or ultraviolet radiation.
- the DNA ligand may be of any suitable known type e.g. an intercalating ligand such as an aminoacridine or a minor groove binding ligand such as bis-benzimidazole and those described in Baguley, V.C., (1982) J. Mol.
- the ligand (with its attached halogen atom) is of a type which allows enhanced uptake, by endocytosis or other means, of the radiosensitiser into cells.
- the minor groove binding ligand is a halogenated bis-benzimidazole of the general formula:
- R 1 , R 2 , R 3 , R 4 and R 5 which may be the same or different, are selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitro or any other suitable non-deleterious substituent; and
- R 6 is alkyl; phenyl; phenyl optionally substituted with halogen, hydroxy, alkoxy, nitro or any other
- R 1 , R 2 , R 3 , R 4 and R 5 which are either the same or different, are selected from hydrogen, hydroxy, alkoxy, iodo and bromo;
- R 6 is methyl, phenyl or phenylalkyl.
- the halogenated ligand is preferably selected so as to bind at a location near the sugar chain of DNA so that the halogen free radical is sufficiently close to the potential target area in the sugar chain.
- Figure 1 shows the 1.7% agarose gel of UV-B
- FIG. 1 shows the DNA-sequencing gels of
- Figure 3 shows the pBR322 restriction fragment used in the experiments involving higher resolution ( 16% acrylamide) sequencing gels
- Figure 4 shows the relationship between UV-A dose and cell survival when iodoHoescht is added to the cell medium to a concentration of 4 ⁇ M; and Figure 5 shows the analysis of a large number of binding sites of DNA substrates derived from M13 clones of human alpha-DNA.
- the UV spectrum of Hoechst 33258 has an absorption maximum at 338nm which shifts to 356nm upon binding to DNA. Substitution of iodine with the phenyl ring of the bis-benzimidazole shifts the maximum to 345nm.
- UV-A (320-400nm) was used in preference to UV-B which closely coincides with the absorption of the halogenated nucleotides.
- Maxam-Gilbert sequencing tracks regardless of whether or not the photolysis samples are treated with hot
- Example 1 - ( Figure 1) Mixtures containing pBR322 DNA (l ⁇ g) and various amounts of HPLC-purified iodoHoechst 33258, in 20 ⁇ l of
- Example 2 EcoR1-cut pBR322 DNA was 5'- 32 P-end labelled, cut with BamH1 and the 375 bp labelled fragment isolated by preparative polyacrylamide gel electrophoresis. Samples of the labelled fragment were mixed with carrier DNA and iodoHoechst 33258 and photolysed as described in Example 1. The final concentrations of iodoHoechst were l ⁇ M (lane 1), 2.5 ⁇ M (lane 4), and 5 ⁇ M (lanes 2 & 5), 10 ⁇ M
- End-labelled restriction fragments were derived from pBR322.
- the 375 bp fragments were prepared by 3'- or 5'- 32 P end labelling at the EcoR1 site, followed by subsequent cleavage with BamHl and then isolation by preparative polyacrylamide gel electrophoresis.
- the dose-rate delivered to the monolayer was calculated to be approximately 50 ⁇ W cm -2 .
- the flasks were covered with black adhesive vinyl, washed twice with ice cold
- Example 5 - ( Figure 5) Clone alpha 32, which contains a 340 bp insert of human alpha RI-DNA in M13 mp9, was effectively 5'-end labelled as described below and UV irradiated in the presence of iodoHoechst 33258 as described in Example 1. Autoradiographs of DNA sequencing gels were analysed by laser densitometry and damage sites were quantified as very strong (VS), strong (S) or medium (M).
- VS very strong
- S strong
- M medium
- the iodoHoechst 33258 binding site is in capital letters.
- the procedure for effectively 5'-end labelling M13 clone alpha 32 briefly involves pulse labelling the DNA immediately after the 17 bp sequencing primer with
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Saccharide Compounds (AREA)
Abstract
Le radiosensibilisateur décrit, qui est conçu pour être utilisé en radiothérapie, comprend un ligand d'ADN halogéné. On améliore la sensibilité de l'ADN à l'attaque par rayonnement en amenant ou en permettant la liaison du ligand d'ADN halogéné avec l'ADN, avant de soumettre l'ADN ou son site à un rayonnement ionisant ou ultra-violet. On provoque également une attaque par rayonnement de l'ADN en amenant ou en permettant la liaison du ligand d'ADN halogéné avec l'ADN et en exposant l'ADN et le ligand lié ou son site à un rayonnement ionisé ou ultra-violet.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPJ3468 | 1989-03-31 | ||
| AUPJ346889 | 1989-03-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1990012321A1 true WO1990012321A1 (fr) | 1990-10-18 |
Family
ID=3773818
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/AU1990/000122 WO1990012321A1 (fr) | 1989-03-31 | 1990-03-30 | Radiosensibilisateurs avec ligand d'adn halogene pour la therapie anticancereuse |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1990012321A1 (fr) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996006831A1 (fr) * | 1994-08-26 | 1996-03-07 | Auckland Division Cancer Society Of New Zealand Inc. | Nouveaux agents d'alkilation cibles sur l'adn |
| WO1997004776A1 (fr) * | 1995-07-28 | 1997-02-13 | The Inner And Eastern Health Care Network | Radioprotecteurs |
| CN1302777C (zh) * | 2002-04-02 | 2007-03-07 | 内尔维阿诺医学科学有限公司 | 包括取代的丙烯酰偏端霉素衍生物和放射治疗的抗肿瘤联合疗法 |
| US10118920B2 (en) | 2015-04-20 | 2018-11-06 | Cellcentric Ltd | Isoxazolyl substituted benzimidazoles |
| US10428065B2 (en) | 2015-04-20 | 2019-10-01 | Cellcentric Ltd | Isoxazolyl substituted imidazopyridines |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988007986A2 (fr) * | 1987-04-17 | 1988-10-20 | Ire-Celltarg S.A. | Composes utiles notamment pour la radiotherapie ou l'imagerie du cancer |
-
1990
- 1990-03-30 WO PCT/AU1990/000122 patent/WO1990012321A1/fr unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988007986A2 (fr) * | 1987-04-17 | 1988-10-20 | Ire-Celltarg S.A. | Composes utiles notamment pour la radiotherapie ou l'imagerie du cancer |
Non-Patent Citations (4)
| Title |
|---|
| CHEMICAL ABSTRACTS, Volume 106, No. 11, issued 16 March 1987 (Columbus, Ohio, USA); ZEDDA et al.: "Variation of the binding constants in gamma-irridiated DNA-9-aminoacridine complexes", see page 274, column 2, the abstract no. 80890k, APPL. PHYS. COMMUN 1986, 6(2-3), 131-41 (Eng). * |
| CHEMICAL ABSTRACTS, Volume 111, No. 3, issued 17 July 1989 (Columbus, Ohio, USA); KASSIS, AMIN I. et al.: "Radiotoxicity of an iodine-125-labeled DNA intercalator in mammalian cells", see page 308, column 2, the abstract no. 20195x, RADIAT. RES., 1989, 118(2), 283-94 (Eng). * |
| CHEMICAL ABSTRACTS, Volume 96, No. 1, issued 4 January 1982 (Columbus, Ohio, USA); KRUGLYAKOVA, K.E. et al.: "Investigation of the interaction of 9-aminoacridine with DNA damaged by UV light of different wavelength", see page 271, column 1, the abstract no. 2973a, STUD. BIOPHYS. 1981, 85(1), 57-8 (Russ). * |
| INTERNATIONAL JOURNAL OF RADIATION AND RELATED STUDIES IN PHYSICS, CHEMISTRY, AND MEDICINE, Volume 46, No. 4, 1984, p. 331-344, SMITH and ANDERSON: "Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative". See pages 337-341 and 344. * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996006831A1 (fr) * | 1994-08-26 | 1996-03-07 | Auckland Division Cancer Society Of New Zealand Inc. | Nouveaux agents d'alkilation cibles sur l'adn |
| US5968933A (en) * | 1994-08-26 | 1999-10-19 | Auckland Division Cancer Society Of New Zealand Inc. | DNA-targeted alkylating agents |
| WO1997004776A1 (fr) * | 1995-07-28 | 1997-02-13 | The Inner And Eastern Health Care Network | Radioprotecteurs |
| US6194414B1 (en) | 1995-07-28 | 2001-02-27 | The Inner And Eastern Health Care Network | Radioprotectors |
| US6548505B1 (en) | 1995-07-28 | 2003-04-15 | Peter Maccallum Cancer Institute | Radioprotectors |
| CN1302777C (zh) * | 2002-04-02 | 2007-03-07 | 内尔维阿诺医学科学有限公司 | 包括取代的丙烯酰偏端霉素衍生物和放射治疗的抗肿瘤联合疗法 |
| US10118920B2 (en) | 2015-04-20 | 2018-11-06 | Cellcentric Ltd | Isoxazolyl substituted benzimidazoles |
| US10428065B2 (en) | 2015-04-20 | 2019-10-01 | Cellcentric Ltd | Isoxazolyl substituted imidazopyridines |
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