JP2009517403A - Parp−1阻害剤の使用 - Google Patents
Parp−1阻害剤の使用 Download PDFInfo
- Publication number
- JP2009517403A JP2009517403A JP2008542534A JP2008542534A JP2009517403A JP 2009517403 A JP2009517403 A JP 2009517403A JP 2008542534 A JP2008542534 A JP 2008542534A JP 2008542534 A JP2008542534 A JP 2008542534A JP 2009517403 A JP2009517403 A JP 2009517403A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- parp
- inhibitor
- therapeutically effective
- effective amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 39
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 title claims abstract description 19
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 title claims abstract 17
- 239000000203 mixture Substances 0.000 claims abstract description 67
- 238000000034 method Methods 0.000 claims abstract description 20
- 231100000135 cytotoxicity Toxicity 0.000 claims abstract description 17
- 230000003013 cytotoxicity Effects 0.000 claims abstract description 17
- 230000002708 enhancing effect Effects 0.000 claims abstract description 8
- 230000000259 anti-tumor effect Effects 0.000 claims abstract description 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 18
- 210000004881 tumor cell Anatomy 0.000 claims description 17
- 210000004027 cell Anatomy 0.000 claims description 16
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 claims description 9
- 229960003966 nicotinamide Drugs 0.000 claims description 9
- 235000005152 nicotinamide Nutrition 0.000 claims description 9
- 239000011570 nicotinamide Substances 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine group Chemical group [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 6
- LFUJIPVWTMGYDG-UHFFFAOYSA-N isoquinoline-1,5-diol Chemical compound N1=CC=C2C(O)=CC=CC2=C1O LFUJIPVWTMGYDG-UHFFFAOYSA-N 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- -1 (2H) -pyridinyl Chemical group 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical class C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 201000000849 skin cancer Diseases 0.000 claims description 4
- FLYGLPYJEQPCFY-UHFFFAOYSA-N 3-(4-chlorophenyl)quinoxaline-5-carboxamide Chemical class N1=C2C(C(=O)N)=CC=CC2=NC=C1C1=CC=C(Cl)C=C1 FLYGLPYJEQPCFY-UHFFFAOYSA-N 0.000 claims description 3
- GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 claims description 3
- SSMIFVHARFVINF-UHFFFAOYSA-N 4-amino-1,8-naphthalimide Chemical compound O=C1NC(=O)C2=CC=CC3=C2C1=CC=C3N SSMIFVHARFVINF-UHFFFAOYSA-N 0.000 claims description 3
- MDOJTZQKHMAPBK-UHFFFAOYSA-N 4-iodo-3-nitrobenzamide Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 claims description 3
- LQJVOLSLAFIXSV-UHFFFAOYSA-N 4h-thieno[2,3-c]isoquinolin-5-one Chemical compound C12=CC=CC=C2C(=O)NC2=C1C=CS2 LQJVOLSLAFIXSV-UHFFFAOYSA-N 0.000 claims description 3
- FXIZMDFKRKHHGE-UHFFFAOYSA-N 5-iodo-6-nitrochromen-2-one Chemical compound O1C(=O)C=CC2=C(I)C([N+](=O)[O-])=CC=C21 FXIZMDFKRKHHGE-UHFFFAOYSA-N 0.000 claims description 3
- NXOWUXJENKGPDO-UHFFFAOYSA-N 5h-1,7-naphthyridin-6-one Chemical group C1=CN=C2C=NC(=O)CC2=C1 NXOWUXJENKGPDO-UHFFFAOYSA-N 0.000 claims description 3
- WWRAFPGUBABZSD-UHFFFAOYSA-N 6-amino-5-iodochromen-2-one Chemical compound O1C(=O)C=CC2=C(I)C(N)=CC=C21 WWRAFPGUBABZSD-UHFFFAOYSA-N 0.000 claims description 3
- 239000002126 C01EB10 - Adenosine Chemical group 0.000 claims description 3
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims description 3
- 239000005104 Neeliglow 4-amino-1,8-naphthalimide Substances 0.000 claims description 3
- 229960005305 adenosine Drugs 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- SDXBGOVSVBZDFL-UHFFFAOYSA-N cep-6800 Chemical compound NCC1=CC=C2NC3=C(CCC4)C4=C(C(=O)NC4=O)C4=C3C2=C1 SDXBGOVSVBZDFL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 claims description 3
- 229960000572 olaparib Drugs 0.000 claims description 3
- 201000004477 skin sarcoma Diseases 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- RZFVLEJOHSLEFR-UHFFFAOYSA-N phenanthridone Chemical compound C1=CC=C2C(O)=NC3=CC=CC=C3C2=C1 RZFVLEJOHSLEFR-UHFFFAOYSA-N 0.000 claims description 2
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 claims 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 42
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 40
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 40
- 108020004414 DNA Proteins 0.000 description 8
- XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 description 7
- 239000012661 PARP inhibitor Substances 0.000 description 7
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000035945 sensitivity Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 229960000977 trabectedin Drugs 0.000 description 5
- 230000005778 DNA damage Effects 0.000 description 4
- 231100000277 DNA damage Toxicity 0.000 description 4
- 238000002784 cytotoxicity assay Methods 0.000 description 4
- 231100000263 cytotoxicity test Toxicity 0.000 description 4
- 230000010534 mechanism of action Effects 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- VPAHZSUNBOYNQY-DLVGLDQCSA-N zalypsis Chemical compound C([C@H]1C2=C3OCOC3=C(C)C(OC(C)=O)=C2C[C@@H]2N1[C@@H](O)[C@@H]1CC3=CC(C)=C(C(=C3[C@H]2N1C)O)OC)NC(=O)\C=C\C1=CC=CC(C(F)(F)F)=C1 VPAHZSUNBOYNQY-DLVGLDQCSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 101710179684 Poly [ADP-ribose] polymerase Proteins 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
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229940004212 yondelis Drugs 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 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
- HXLGEOKJENBTHE-UHFFFAOYSA-N 5h-phenanthridin-1-one Chemical compound C1=CC=CC2=C3C(=O)C=CC=C3NC=C21 HXLGEOKJENBTHE-UHFFFAOYSA-N 0.000 description 1
- PWJFNRJRHXWEPT-UHFFFAOYSA-N ADP ribose Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)C=O)C(O)C1O PWJFNRJRHXWEPT-UHFFFAOYSA-N 0.000 description 1
- SRNWOUGRCWSEMX-TYASJMOZSA-N ADP-D-ribose Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1OC(O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-TYASJMOZSA-N 0.000 description 1
- 241001260012 Bursa Species 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 108020004703 Cruciform DNA Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 241000798368 Ecteinascidia Species 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 108700041567 MDR Genes Proteins 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010047956 Nucleosomes Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102100030306 TBC1 domain family member 9 Human genes 0.000 description 1
- 241000251555 Tunicata Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000002152 aqueous-organic solution Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical class C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000001623 nucleosome Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 description 1
- 210000001944 turbinate Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73953605P | 2005-11-25 | 2005-11-25 | |
| PCT/US2006/061254 WO2007062413A2 (en) | 2005-11-25 | 2006-11-27 | Use of parp-1 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009517403A true JP2009517403A (ja) | 2009-04-30 |
| JP2009517403A5 JP2009517403A5 (enExample) | 2010-01-14 |
Family
ID=38068066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008542534A Pending JP2009517403A (ja) | 2005-11-25 | 2006-11-27 | Parp−1阻害剤の使用 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20090170860A1 (enExample) |
| EP (1) | EP1962843B1 (enExample) |
| JP (1) | JP2009517403A (enExample) |
| AT (1) | ATE499098T1 (enExample) |
| AU (1) | AU2006318226A1 (enExample) |
| CA (1) | CA2630900A1 (enExample) |
| DE (1) | DE602006020335D1 (enExample) |
| ES (1) | ES2361566T3 (enExample) |
| WO (1) | WO2007062413A2 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY164077A (en) * | 1999-05-13 | 2017-11-30 | Pharma Mar Sa | Compositions and uses of et743 for treating cancer |
| BR0115162A (pt) * | 2000-11-06 | 2003-10-21 | Pharma Mar Sa | Tratamentos antitumorais eficazes |
| GB0117402D0 (en) * | 2001-07-17 | 2001-09-05 | Pharma Mar Sa | New antitumoral derivatives of et-743 |
| US20080255132A1 (en) * | 2003-11-14 | 2008-10-16 | Eric Rowinsky | Combination Therapy Comprising the Use of Et-743 and Paclitaxel for Treating Cancer |
| PL1827500T3 (pl) * | 2004-10-26 | 2009-09-30 | Pharma Mar Sa | Pegylowana liposomalna doksorubicyna w kombinacji z ekteinascydyną 743 |
| DK1658848T3 (da) * | 2004-10-29 | 2007-11-26 | Pharma Mar Sa | Formuleringer omfattende ecteinascidin og et disaccharid |
| GB0522082D0 (en) * | 2005-10-31 | 2005-12-07 | Pharma Mar Sa | Formulations |
| US9486449B2 (en) | 2007-10-09 | 2016-11-08 | Malka COHEN-ARMON | Cancer therapy |
| EP2207548B1 (en) * | 2007-10-09 | 2013-05-22 | Malka Cohen-Armon | Breast cancer therapy |
| AU2008313634A1 (en) * | 2007-10-19 | 2009-04-23 | Pharma Mar, S.A. | Prognostic molecular markers for ET-743 treatment |
| US8871765B2 (en) | 2010-07-27 | 2014-10-28 | Cadila Healthcare Limited | Substituted 4-(4-fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one derivatives as poly (ADP-ribose) polymerase-1 inhibitors |
| EP2870140B8 (en) | 2012-07-09 | 2016-09-28 | Lupin Limited | Tetrahydroquinazolinone derivatives as parp inhibitors |
| SG11201503670YA (en) | 2012-12-31 | 2015-07-30 | Cadila Healthcare Ltd | Substituted phthalazin-1 (2h)-one derivatives as selective inhibitors of poly (adp-ribose) polymerase-1 |
| CN106853252B (zh) * | 2015-12-09 | 2020-03-13 | 江苏恒瑞医药股份有限公司 | 曲贝替定药物组合物及其制备方法 |
| CN108368059B (zh) * | 2016-04-18 | 2022-02-01 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的酞嗪酮化合物及其药物组合物 |
| KR20180097876A (ko) * | 2017-02-24 | 2018-09-03 | 주식회사 온코크로스 | 1,5-이소퀴놀린디올을 포함하는 피부 노화 방지 및 주름 개선용 조성물 |
| JOP20190254A1 (ar) | 2017-04-27 | 2019-10-27 | Pharma Mar Sa | مركبات مضادة للأورام |
| EP3960177A1 (en) * | 2020-08-26 | 2022-03-02 | Anturec Pharmaceuticals GmbH | Composition comprising ttf-ngr for use in treating soft-tissue sarcoma |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004517056A (ja) * | 2000-11-06 | 2004-06-10 | ファルマ・マール・ソシエダード・アノニマ | 効果的な抗腫瘍治療 |
| US20050020595A1 (en) * | 2003-05-28 | 2005-01-27 | Kalish Vincent J. | Compounds, methods and pharmaceutical compositions for inhibiting PARP |
| WO2005012524A1 (en) * | 2003-07-25 | 2005-02-10 | The University Of Sheffield | Use of rnai inhibiting parp activtiy for the manufacture of a medicament for the treatment of cancer |
| WO2005097750A1 (en) * | 2004-03-30 | 2005-10-20 | Aventis Pharmaceuticals Inc. | Substituted pyridones as inhibitors of poly(adp-ribose) polymerase (parp) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6635677B2 (en) * | 1999-08-13 | 2003-10-21 | Case Western Reserve University | Methoxyamine combinations in the treatment of cancer |
| US20050187172A1 (en) * | 2003-12-23 | 2005-08-25 | Masferrer Jaime L. | Combination of a Cox-2 inhibitor and a DNA topoisomerase I inhibitor for treatment of neoplasia |
-
2006
- 2006-11-27 CA CA002630900A patent/CA2630900A1/en not_active Abandoned
- 2006-11-27 ES ES06840026T patent/ES2361566T3/es active Active
- 2006-11-27 WO PCT/US2006/061254 patent/WO2007062413A2/en not_active Ceased
- 2006-11-27 DE DE602006020335T patent/DE602006020335D1/de active Active
- 2006-11-27 AT AT06840026T patent/ATE499098T1/de not_active IP Right Cessation
- 2006-11-27 AU AU2006318226A patent/AU2006318226A1/en not_active Abandoned
- 2006-11-27 EP EP06840026A patent/EP1962843B1/en active Active
- 2006-11-27 JP JP2008542534A patent/JP2009517403A/ja active Pending
- 2006-11-27 US US12/094,744 patent/US20090170860A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004517056A (ja) * | 2000-11-06 | 2004-06-10 | ファルマ・マール・ソシエダード・アノニマ | 効果的な抗腫瘍治療 |
| US20050020595A1 (en) * | 2003-05-28 | 2005-01-27 | Kalish Vincent J. | Compounds, methods and pharmaceutical compositions for inhibiting PARP |
| WO2005012524A1 (en) * | 2003-07-25 | 2005-02-10 | The University Of Sheffield | Use of rnai inhibiting parp activtiy for the manufacture of a medicament for the treatment of cancer |
| WO2005097750A1 (en) * | 2004-03-30 | 2005-10-20 | Aventis Pharmaceuticals Inc. | Substituted pyridones as inhibitors of poly(adp-ribose) polymerase (parp) |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1962843A2 (en) | 2008-09-03 |
| EP1962843A4 (en) | 2009-08-12 |
| US20090170860A1 (en) | 2009-07-02 |
| WO2007062413A3 (en) | 2007-12-27 |
| ATE499098T1 (de) | 2011-03-15 |
| DE602006020335D1 (de) | 2011-04-07 |
| WO2007062413A2 (en) | 2007-05-31 |
| CA2630900A1 (en) | 2007-05-31 |
| AU2006318226A1 (en) | 2007-05-31 |
| EP1962843B1 (en) | 2011-02-23 |
| ES2361566T3 (es) | 2011-06-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2009517403A (ja) | Parp−1阻害剤の使用 | |
| AU2019216351B2 (en) | Combination therapy for the treatment of mastocytosis | |
| CN107087409B (zh) | 苯并杂环化合物及其应用 | |
| JP2021004244A (ja) | 多形神経膠芽腫及び髄芽腫を含む新生物疾患及び癌幹細胞を処置するためのジアンヒドロガラクチトール及び類似体を含めた置換ヘキシトールの使用 | |
| US20150087687A1 (en) | Compositions and methods to improve the therapeutic benefit of indirubin and analogs thereof, including meisoindigo | |
| US20160158186A1 (en) | Use of dianhydrogalactitol and analogs and derivatives thereof to treat recurrent malignant glioma or progressive secondary brain tumor | |
| CN102227221A (zh) | 包含hsp90抑制剂和mtor抑制剂的药物组合 | |
| KR102115047B1 (ko) | 티로신 키나제 억제제들을 갖는 조합 제품 및 그의 용도 | |
| US8691777B2 (en) | Combination therapy | |
| US20140378409A1 (en) | Effect potentiator for antitumor agents | |
| JP2016519684A (ja) | 準最適に投与された薬物療法の有効性を改善するための及び/又は副作用を低減するための方法および組成物 | |
| RU2474612C2 (ru) | Индуцирование гибели клеток путем ингибирования адаптивного теплового шокового ответа | |
| US20210283109A1 (en) | Heterocyclic diamidines | |
| US20130079401A1 (en) | Novel use of isothiocyanates for treating cancer | |
| JP2003525255A (ja) | ファルネシルタンパク質トランスフェラーゼ阻害剤とさらなる抗癌剤との組み合わせ剤 | |
| WO2019207087A1 (en) | Combination therapy including beta-sitosterol in combination with at least one of a braf inhibitor, a mek inhibitor and an erk inhibitor and methods and use thereof | |
| US20070207996A1 (en) | Novel Compositions And Methods Of Treatment | |
| WO2011016952A1 (en) | Compositions and methods for treating cancer | |
| US20130345231A1 (en) | Anticancer therapeutic agents | |
| JP2008526817A (ja) | 新規のピロロジヒドロイソキノリン | |
| CN108853507A (zh) | 一种抗肿瘤的增效药物组合物及其制备方法和用途 | |
| MXPA06014477A (es) | Agente antitumor, fortificador de efecto antitumor y metodo de terapia para cancer. | |
| CN115038440A (zh) | 使用chk抑制剂的癌症联合疗法 | |
| RU2844464C2 (ru) | Фармацевтическая композиция для профилактики или лечения трижды негативного рака молочной железы | |
| US20190247397A1 (en) | Combinatory treatment strategies of cancer based on rna polymerase i inhibition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20090430 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090430 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091117 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20091117 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101102 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120521 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20121105 |