KR20120127709A - 5-fu 또는 이의 프로드럭과 dpd 억제제의 병용물과 관련된 신경독성의 치료 - Google Patents
5-fu 또는 이의 프로드럭과 dpd 억제제의 병용물과 관련된 신경독성의 치료 Download PDFInfo
- Publication number
- KR20120127709A KR20120127709A KR1020127012289A KR20127012289A KR20120127709A KR 20120127709 A KR20120127709 A KR 20120127709A KR 1020127012289 A KR1020127012289 A KR 1020127012289A KR 20127012289 A KR20127012289 A KR 20127012289A KR 20120127709 A KR20120127709 A KR 20120127709A
- Authority
- KR
- South Korea
- Prior art keywords
- eniluracil
- prodrug
- dpd
- administered
- dose
- 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.)
- Withdrawn
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 120
- 229940002612 prodrug Drugs 0.000 title claims abstract description 46
- 239000000651 prodrug Substances 0.000 title claims abstract description 46
- 206010029350 Neurotoxicity Diseases 0.000 title claims description 28
- 206010044221 Toxic encephalopathy Diseases 0.000 title claims description 28
- 231100000228 neurotoxicity Toxicity 0.000 title claims description 28
- 230000007135 neurotoxicity Effects 0.000 title claims description 28
- 229960002949 fluorouracil Drugs 0.000 claims abstract description 250
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims abstract description 249
- 102100022334 Dihydropyrimidine dehydrogenase [NADP(+)] Human genes 0.000 claims abstract description 181
- UEJQGOKMPMUMTO-UHFFFAOYSA-N C(C#C)OC1=NC=C(C(=N1)OCC#C)F Chemical compound C(C#C)OC1=NC=C(C(=N1)OCC#C)F UEJQGOKMPMUMTO-UHFFFAOYSA-N 0.000 claims abstract description 64
- 230000001537 neural effect Effects 0.000 claims abstract description 58
- 238000000034 method Methods 0.000 claims abstract description 55
- 230000000694 effects Effects 0.000 claims abstract description 30
- JOZGNYDSEBIJDH-UHFFFAOYSA-N eniluracil Chemical group O=C1NC=C(C#C)C(=O)N1 JOZGNYDSEBIJDH-UHFFFAOYSA-N 0.000 claims description 160
- 229950010213 eniluracil Drugs 0.000 claims description 157
- 206010028980 Neoplasm Diseases 0.000 claims description 42
- 201000011510 cancer Diseases 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 29
- 238000009472 formulation Methods 0.000 claims description 28
- 239000002246 antineoplastic agent Substances 0.000 claims description 27
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 16
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Natural products O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 14
- 230000008030 elimination Effects 0.000 claims description 14
- 238000003379 elimination reaction Methods 0.000 claims description 14
- -1 5'-deoxy-4 ' Chemical compound 0.000 claims description 13
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 12
- 229960004117 capecitabine Drugs 0.000 claims description 12
- 229940035893 uracil Drugs 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 238000013268 sustained release Methods 0.000 claims description 7
- 239000012730 sustained-release form Substances 0.000 claims description 7
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 claims description 6
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 claims description 6
- WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 claims description 6
- 238000001727 in vivo Methods 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- HAUXRJCZDHHADG-UHFFFAOYSA-N 2,4-dioxo-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC=C(C#N)C(=O)N1 HAUXRJCZDHHADG-UHFFFAOYSA-N 0.000 claims description 4
- CYMBDTMRFAUHRM-UHFFFAOYSA-N 5-(1-chloroethenyl)-1h-pyrimidine-2,4-dione Chemical compound ClC(=C)C1=CNC(=O)NC1=O CYMBDTMRFAUHRM-UHFFFAOYSA-N 0.000 claims description 4
- XFPGPBKTWIFNAA-UHFFFAOYSA-N 5-(2-bromo-1-chloroethenyl)-1h-pyrimidine-2,4-dione Chemical compound BrC=C(Cl)C1=CNC(=O)NC1=O XFPGPBKTWIFNAA-UHFFFAOYSA-N 0.000 claims description 4
- LKTQRCSUYNIRSM-UHFFFAOYSA-N 5-(2-bromoethynyl)-1h-pyrimidine-2,4-dione Chemical compound BrC#CC1=CNC(=O)NC1=O LKTQRCSUYNIRSM-UHFFFAOYSA-N 0.000 claims description 4
- BLXGZIDBSXVMLU-OWOJBTEDSA-N 5-[(e)-2-bromoethenyl]-1h-pyrimidine-2,4-dione Chemical compound Br\C=C\C1=CNC(=O)NC1=O BLXGZIDBSXVMLU-OWOJBTEDSA-N 0.000 claims description 4
- BLXGZIDBSXVMLU-UHFFFAOYSA-N 5-(2-bromoethenyl)-1h-pyrimidine-2,4-dione Chemical compound BrC=CC1=CNC(=O)NC1=O BLXGZIDBSXVMLU-UHFFFAOYSA-N 0.000 claims description 3
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims description 3
- STRZQWQNZQMHQR-UAKXSSHOSA-N 5-fluorocytidine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 STRZQWQNZQMHQR-UAKXSSHOSA-N 0.000 claims description 3
- TUFMBCUUDJKPJB-UHFFFAOYSA-N 5-hex-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CCCCC#CC1=CNC(=O)NC1=O TUFMBCUUDJKPJB-UHFFFAOYSA-N 0.000 claims description 3
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 claims description 3
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 3
- IDYKCXHJJGMAEV-RRKCRQDMSA-N 4-amino-5-fluoro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 IDYKCXHJJGMAEV-RRKCRQDMSA-N 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 108090000790 Enzymes Proteins 0.000 abstract description 5
- 102000004190 Enzymes Human genes 0.000 abstract description 5
- 210000001519 tissue Anatomy 0.000 description 34
- 230000000259 anti-tumor effect Effects 0.000 description 22
- 239000004480 active ingredient Substances 0.000 description 11
- 230000001925 catabolic effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 230000015556 catabolic process Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000002547 new drug Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 5
- 235000008191 folinic acid Nutrition 0.000 description 5
- 239000011672 folinic acid Substances 0.000 description 5
- 229960001691 leucovorin Drugs 0.000 description 5
- 230000002503 metabolic effect Effects 0.000 description 5
- 206010003591 Ataxia Diseases 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000002427 irreversible effect Effects 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 150000003833 nucleoside derivatives Chemical class 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 206010017577 Gait disturbance Diseases 0.000 description 3
- 206010060860 Neurological symptom Diseases 0.000 description 3
- GCQYYIHYQMVWLT-HQNLTJAPSA-N Sorivudine Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(\C=C\Br)=C1 GCQYYIHYQMVWLT-HQNLTJAPSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 208000002173 dizziness Diseases 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 231100000189 neurotoxic Toxicity 0.000 description 3
- 230000002887 neurotoxic effect Effects 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- FBOIBTWYSVRYTJ-VBLCRABPSA-N 5-[(3S,4S,5S)-6-fluoro-3,4,5-trihydroxyoxan-2-yl]-1H-pyrimidine-2,4-dione Chemical compound FC1[C@H]([C@H]([C@@H](C(O1)C=1C(NC(NC=1)=O)=O)O)O)O FBOIBTWYSVRYTJ-VBLCRABPSA-N 0.000 description 2
- ZRYZBEQILKESAW-UHFFFAOYSA-N 5-ethenyl-1h-pyrimidine-2,4-dione Chemical compound C=CC1=CNC(=O)NC1=O ZRYZBEQILKESAW-UHFFFAOYSA-N 0.000 description 2
- 241000220479 Acacia Species 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 208000011644 Neurologic Gait disease Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- FKTHAKABFGARQH-UHFFFAOYSA-N alpha-Fluoro-beta-ureidopropionic acid Chemical compound NC(=O)NCC(F)C(O)=O FKTHAKABFGARQH-UHFFFAOYSA-N 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000006652 catabolic pathway Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 210000004976 peripheral blood cell Anatomy 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 2
- 229960001674 tegafur Drugs 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QLOCVMVCRJOTTM-SDNRWEOFSA-N 1-[(2r,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-prop-1-ynylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CC)=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 QLOCVMVCRJOTTM-SDNRWEOFSA-N 0.000 description 1
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
- RAIRJKWTBBDDAR-UHFFFAOYSA-N 5,6-Dihydro-5-fluorouracil Chemical compound FC1CNC(=O)NC1=O RAIRJKWTBBDDAR-UHFFFAOYSA-N 0.000 description 1
- PASXZRQBIQUQOS-UHFFFAOYSA-N 5-(1-bromoethenyl)-1h-pyrimidine-2,4-dione Chemical compound BrC(=C)C1=CNC(=O)NC1=O PASXZRQBIQUQOS-UHFFFAOYSA-N 0.000 description 1
- LMNPKIOZMGYQIU-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrimidine-2,4-dione Chemical compound FC(F)(F)C1=CNC(=O)NC1=O LMNPKIOZMGYQIU-UHFFFAOYSA-N 0.000 description 1
- POYNHVFBISCPAG-DJLDLDEBSA-N 5-ethynyl-1-[(2r,4s,5r)-4-fluoro-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical class C1[C@H](F)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C#C)=C1 POYNHVFBISCPAG-DJLDLDEBSA-N 0.000 description 1
- LTBQNWHGFBPRNE-UHFFFAOYSA-N 5-ethynyl-1h-pyrimidin-2-one Chemical compound O=C1N=CC(C#C)=CN1 LTBQNWHGFBPRNE-UHFFFAOYSA-N 0.000 description 1
- HFEKDTCAMMOLQP-RRKCRQDMSA-N 5-fluorodeoxyuridine monophosphate Chemical compound O1[C@H](COP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(F)=C1 HFEKDTCAMMOLQP-RRKCRQDMSA-N 0.000 description 1
- 241000490494 Arabis Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- HVSOLIXCBKMTCY-UHFFFAOYSA-N C(=C)C=1C(NC(NC1)=O)=O.N1C(=O)NC(=O)C=C1 Chemical class C(=C)C=1C(NC(NC1)=O)=O.N1C(=O)NC(=O)C=C1 HVSOLIXCBKMTCY-UHFFFAOYSA-N 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010066455 Dihydrouracil Dehydrogenase (NADP) Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033553 Palmar-plantar erythrodysaesthesia syndrome Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical class O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- HKUJAJKSNVIDLX-RRKCRQDMSA-N [(2R,3S,5R)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(F)=C1 HKUJAJKSNVIDLX-RRKCRQDMSA-N 0.000 description 1
- YQOCUTDPKPPQGA-RRKCRQDMSA-N [[(2r,3s,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(F)=C1 YQOCUTDPKPPQGA-RRKCRQDMSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- OJQNRNQELNLWHH-UHFFFAOYSA-N alpha-Fluoro-beta-alanine Chemical compound NCC(F)C(O)=O OJQNRNQELNLWHH-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000008209 arabinosides Chemical class 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012792 core layer Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 231100001264 fatal toxicity Toxicity 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- WLQBZMZTRNPUDL-BBVRLYRLSA-N fudp Chemical compound C1[C@H](F)[C@@H](CO[P@](O)(=O)OP(O)(=O)O)O[C@@H]1N1C(=O)NC(=O)C=C1 WLQBZMZTRNPUDL-BBVRLYRLSA-N 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000000937 inactivator Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229950009279 sorivudine Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229940053867 xeloda Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—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
-
- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25144909P | 2009-10-14 | 2009-10-14 | |
| US61/251,449 | 2009-10-14 | ||
| PCT/US2010/052734 WO2011047195A1 (en) | 2009-10-14 | 2010-10-14 | Treating neurotoxicity associated with combinations of 5 - fu or its prodrugs and dpd inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20120127709A true KR20120127709A (ko) | 2012-11-23 |
Family
ID=43466528
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020127012289A Withdrawn KR20120127709A (ko) | 2009-10-14 | 2010-10-14 | 5-fu 또는 이의 프로드럭과 dpd 억제제의 병용물과 관련된 신경독성의 치료 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8658618B2 (enExample) |
| EP (1) | EP2488182B1 (enExample) |
| JP (2) | JP2013508293A (enExample) |
| KR (1) | KR20120127709A (enExample) |
| CN (1) | CN102811721A (enExample) |
| AU (1) | AU2010306698B2 (enExample) |
| BR (1) | BR112012008951A2 (enExample) |
| CA (1) | CA2777546C (enExample) |
| CO (1) | CO6541596A2 (enExample) |
| EA (1) | EA201270551A1 (enExample) |
| ES (1) | ES2644237T3 (enExample) |
| IL (1) | IL219179A0 (enExample) |
| MX (1) | MX2012004383A (enExample) |
| WO (1) | WO2011047195A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014089004A1 (en) * | 2012-12-04 | 2014-06-12 | Adherex Technologies, Inc. | Methods for treating 5-fluorouracil prodrug non-responsive cancer patients |
| CN106692173A (zh) * | 2015-11-18 | 2017-05-24 | 北京诺普德医药科技有限公司 | 一种抗肿瘤复方组合物及其应用 |
| IL321302A (en) * | 2022-12-06 | 2025-08-01 | Elion Oncology Inc | Combined use of anilouracil and capecitabine for cancer treatment |
| WO2025015267A1 (en) * | 2023-07-13 | 2025-01-16 | Processa Pharmaceuticals, Inc. | Methods of personalizing cancer treatment |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5687599A (en) | 1979-12-19 | 1981-07-16 | Yamasa Shoyu Co Ltd | E 55 22halogenovinyl arabinofuranosyluracil and its preparation |
| GB8629892D0 (en) | 1986-12-15 | 1987-01-28 | Wellcome Found | Antiviral compounds |
| US5157114A (en) | 1988-08-19 | 1992-10-20 | Burroughs Wellcome Co. | 2',3'-dideoxy-3'-fluoro-5-ethyngluridine |
| SG49855A1 (en) * | 1990-07-19 | 1998-06-15 | Wellcome Found | Enzyme inactivators |
| GB9020930D0 (en) * | 1990-09-26 | 1990-11-07 | Wellcome Found | Pharmaceutical combinations |
| US5476855A (en) | 1993-11-02 | 1995-12-19 | Mahmoud H. el Kouni | Enzyme inhibitors, their synthesis and methods for use |
| NZ330360A (en) * | 1997-06-02 | 1999-03-29 | Hoffmann La Roche | 5'-deoxy-cytidine derivatives, their manufacture and use as antitumoral agents |
| US6716452B1 (en) * | 2000-08-22 | 2004-04-06 | New River Pharmaceuticals Inc. | Active agent delivery systems and methods for protecting and administering active agents |
| US20040028687A1 (en) * | 2002-01-15 | 2004-02-12 | Waelti Ernst Rudolf | Methods and compositions for the targeted delivery of therapeutic substances to specific cells and tissues |
| EP1827443A1 (en) | 2004-12-03 | 2007-09-05 | Adherex Technologies, Inc. | Methods for administering dpd inhibitors in combination with 5-fu and 5-fu prodrugs |
-
2010
- 2010-10-14 US US12/904,974 patent/US8658618B2/en active Active
- 2010-10-14 MX MX2012004383A patent/MX2012004383A/es not_active Application Discontinuation
- 2010-10-14 AU AU2010306698A patent/AU2010306698B2/en active Active
- 2010-10-14 JP JP2012534373A patent/JP2013508293A/ja active Pending
- 2010-10-14 WO PCT/US2010/052734 patent/WO2011047195A1/en not_active Ceased
- 2010-10-14 KR KR1020127012289A patent/KR20120127709A/ko not_active Withdrawn
- 2010-10-14 EP EP10768670.1A patent/EP2488182B1/en active Active
- 2010-10-14 CN CN2010800562916A patent/CN102811721A/zh active Pending
- 2010-10-14 EA EA201270551A patent/EA201270551A1/ru unknown
- 2010-10-14 CA CA2777546A patent/CA2777546C/en active Active
- 2010-10-14 ES ES10768670.1T patent/ES2644237T3/es active Active
- 2010-10-14 BR BR112012008951A patent/BR112012008951A2/pt not_active IP Right Cessation
-
2012
- 2012-04-15 IL IL219179A patent/IL219179A0/en unknown
- 2012-05-14 CO CO12078833A patent/CO6541596A2/es not_active Application Discontinuation
-
2015
- 2015-09-29 JP JP2015190757A patent/JP2016014051A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN102811721A (zh) | 2012-12-05 |
| EA201270551A1 (ru) | 2012-12-28 |
| BR112012008951A2 (pt) | 2019-09-24 |
| ES2644237T3 (es) | 2017-11-28 |
| JP2016014051A (ja) | 2016-01-28 |
| JP2013508293A (ja) | 2013-03-07 |
| IL219179A0 (en) | 2012-06-28 |
| WO2011047195A1 (en) | 2011-04-21 |
| EP2488182A1 (en) | 2012-08-22 |
| US8658618B2 (en) | 2014-02-25 |
| CO6541596A2 (es) | 2012-10-16 |
| CA2777546A1 (en) | 2011-04-21 |
| AU2010306698B2 (en) | 2016-05-26 |
| MX2012004383A (es) | 2012-08-23 |
| CA2777546C (en) | 2019-11-05 |
| EP2488182B1 (en) | 2017-07-19 |
| US20110130359A1 (en) | 2011-06-02 |
| AU2010306698A1 (en) | 2012-05-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20130184232A1 (en) | Methods for administering dpd inhibitors in combination with 5-fu and 5-fu prodrugs | |
| Zorzi et al. | A phase I study of histone deacetylase inhibitor, pracinostat (SB939), in pediatric patients with refractory solid tumors: IND203 a trial of the NCIC IND program/C17 pediatric phase I consortium | |
| CZ20021050A3 (cs) | Imunostimulační nukleové kyseliny | |
| CN114727996A (zh) | 用于治疗白血病或骨髓增生异常综合征的与维奈托克、吉瑞替尼、米哚妥林或其他化合物组合的阿扎胞苷 | |
| KR20070104559A (ko) | α,α,α-트리플루오로티미딘과 티미딘포스포릴라아제저해제를 배합한 항암제 | |
| KR20120127709A (ko) | 5-fu 또는 이의 프로드럭과 dpd 억제제의 병용물과 관련된 신경독성의 치료 | |
| JP2007508299A (ja) | 全身性抗癌治療の間の器官保護のための方法、組成物、およびキット | |
| CN108367016A (zh) | 用于治疗异位脂肪堆积的a3腺苷受体配体 | |
| JP2013508293A5 (enExample) | ||
| AU2012200856B2 (en) | Methods for administering DPD inhibitors in combination with 5-FU and 5-FU prodrugs | |
| Padrik et al. | Combination therapy with capecitabine and interferon alfa-2A in patients with advanced renal cell carcinoma: a phase II study | |
| US20080255168A1 (en) | Methods for administering dpd inhibitors in combination with 5-fu and 5-fu prodrugs | |
| WO2008135792A1 (en) | Pm00104 compound for use in cancer therapy | |
| WO2014089004A1 (en) | Methods for treating 5-fluorouracil prodrug non-responsive cancer patients | |
| Yano et al. | 67 In Vitro Characterization of a Novel dUTPase Inhibitor, TAS-114, as a Fluoropyrimidine Enhancer | |
| HK1110531A (en) | Methods for administering dpd inhibitors in combination with 5-fu and 5-fu prodrugs | |
| Favier et al. | Results of a phase I trial of intravenous vinorelbine plus oral capecitabine as first-line chemotherapy of metastatic breast cancer | |
| US20080153858A1 (en) | Antitumorigenic drug combination | |
| Tanaka et al. | 66 Trifluorothymidine Incorporation into DNA is the Primary Mechanism of Action of TAS-102, and Leads to Markedly Prolonged Survival in a Mouse Model | |
| Cats | Maarten J. Deenen, Luc Dewit, Henk Boot, Ria Dubbelman, Jos H. Beijnen, Jan HM Schellens |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20120511 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |