JPH07501810A - 癌治療のレスキュー剤としてのｕｄｐｇの利用 - Google Patents
癌治療のレスキュー剤としてのｕｄｐｇの利用Info
- Publication number
- JPH07501810A JPH07501810A JP5510416A JP51041693A JPH07501810A JP H07501810 A JPH07501810 A JP H07501810A JP 5510416 A JP5510416 A JP 5510416A JP 51041693 A JP51041693 A JP 51041693A JP H07501810 A JPH07501810 A JP H07501810A
- Authority
- JP
- Japan
- Prior art keywords
- pyrimidine
- administered
- administration
- udpg
- tumor
- 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
- HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 title claims description 72
- HSCJRCZFDFQWRP-JZMIEXBBSA-N UDP-alpha-D-glucose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-JZMIEXBBSA-N 0.000 title claims description 71
- 206010028980 Neoplasm Diseases 0.000 title claims description 39
- 201000011510 cancer Diseases 0.000 title claims description 20
- 238000011282 treatment Methods 0.000 title description 15
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 64
- 229960002949 fluorouracil Drugs 0.000 claims description 62
- 229940045145 uridine Drugs 0.000 claims description 57
- 239000003112 inhibitor Substances 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 30
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 29
- 230000000259 anti-tumor effect Effects 0.000 claims description 28
- 239000002246 antineoplastic agent Substances 0.000 claims description 26
- 239000003795 chemical substances by application Substances 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 12
- 231100000331 toxic Toxicity 0.000 claims description 10
- 230000002588 toxic effect Effects 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 230000002503 metabolic effect Effects 0.000 claims description 8
- 239000002243 precursor Substances 0.000 claims description 8
- HFEKDTCAMMOLQP-RRKCRQDMSA-N 5-fluorodeoxyuridine monophosphate Chemical group 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 claims description 5
- 231100000636 lethal dose Toxicity 0.000 claims description 4
- 229940034982 antineoplastic agent Drugs 0.000 claims description 2
- 230000015556 catabolic process Effects 0.000 claims description 2
- 230000001925 catabolic effect Effects 0.000 claims 3
- 230000002303 anti-venom Effects 0.000 claims 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims 1
- 208000025865 Ulcer Diseases 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000003160 anti-catabolic effect Effects 0.000 claims 1
- 230000000235 effect on cancer Effects 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- 230000006824 pyrimidine synthesis Effects 0.000 claims 1
- 231100000397 ulcer Toxicity 0.000 claims 1
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound 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 106
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 53
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 53
- 229940041181 antineoplastic drug Drugs 0.000 description 20
- 231100000419 toxicity Toxicity 0.000 description 15
- 230000001988 toxicity Effects 0.000 description 15
- 238000001802 infusion Methods 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 230000008859 change Effects 0.000 description 10
- 230000036470 plasma concentration Effects 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 210000003462 vein Anatomy 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 5
- 208000021760 high fever Diseases 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 208000001297 phlebitis Diseases 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- 230000001093 anti-cancer Effects 0.000 description 4
- 231100000682 maximum tolerated dose Toxicity 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 210000002381 plasma Anatomy 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 231100000816 toxic dose Toxicity 0.000 description 3
- 206010065553 Bone marrow failure Diseases 0.000 description 2
- 102000009097 Phosphorylases Human genes 0.000 description 2
- 108010073135 Phosphorylases Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 208000026775 severe diarrhea Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- ZZKNRXZVGOYGJT-VKHMYHEASA-N (2s)-2-[(2-phosphonoacetyl)amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CP(O)(O)=O ZZKNRXZVGOYGJT-VKHMYHEASA-N 0.000 description 1
- YDYOYUPJKSJCMF-UHFFFAOYSA-N 1-(2-hydroxyethoxymethyl)pyrimidine-2,4-dione Chemical compound OCCOCN1C=CC(=O)NC1=O YDYOYUPJKSJCMF-UHFFFAOYSA-N 0.000 description 1
- SPJAGILXQBHHSZ-UHFFFAOYSA-N 5-benzyl-1-(2-hydroxyethoxymethyl)uracil Chemical compound O=C1NC(=O)N(COCCO)C=C1CC1=CC=CC=C1 SPJAGILXQBHHSZ-UHFFFAOYSA-N 0.000 description 1
- 101100510615 Caenorhabditis elegans lag-2 gene Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes 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
- 241000282412 Homo Species 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000043141 Nuclear RNA Human genes 0.000 description 1
- 108020003217 Nuclear RNA Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 229940122352 Uridine phosphorylase inhibitor Drugs 0.000 description 1
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 1
- 241000289690 Xenarthra Species 0.000 description 1
- AREUQFTVCMGENT-UAKXSSHOSA-N [[(2r,3s,4r,5r)-5-(5-fluoro-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-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@@H](O)[C@@H]1N1C(=O)NC(=O)C(F)=C1 AREUQFTVCMGENT-UAKXSSHOSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 150000008209 arabinosides Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000037058 blood plasma level Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- UUGITDASWNOAGG-CCXZUQQUSA-N cyclouridine Chemical compound O=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 UUGITDASWNOAGG-CCXZUQQUSA-N 0.000 description 1
- 231100000895 deafness Toxicity 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 208000025426 neoplasm of thorax Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 150000003961 organosilicon compounds Chemical class 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 201000003957 thoracic cancer Diseases 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US1991/007613 WO1993013779A2 (fr) | 1991-12-16 | 1991-12-16 | Utilisation de diphosphoglucose d'uridine en tant qu'antidote electif dans le traitement therapeutique de cancers |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07501810A true JPH07501810A (ja) | 1995-02-23 |
Family
ID=22225879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5510416A Pending JPH07501810A (ja) | 1991-12-16 | 1991-12-16 | 癌治療のレスキュー剤としてのｕｄｐｇの利用 |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0617625A1 (fr) |
| JP (1) | JPH07501810A (fr) |
| AU (1) | AU4100193A (fr) |
| WO (1) | WO1993013779A2 (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPR951101A0 (en) | 2001-12-13 | 2002-01-24 | Centre For Molecular Biology And Medicine | Method of treatment |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1986003678A1 (fr) * | 1984-12-20 | 1986-07-03 | Memorial Hospital For Cancer And Allied Diseases | Composition et procede de traitement de tumeurs avec de l'udpg |
-
1991
- 1991-12-16 WO PCT/US1991/007613 patent/WO1993013779A2/fr not_active Ceased
- 1991-12-16 EP EP93910550A patent/EP0617625A1/fr not_active Withdrawn
- 1991-12-16 JP JP5510416A patent/JPH07501810A/ja active Pending
- 1991-12-16 AU AU41001/93A patent/AU4100193A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1993013779A2 (fr) | 1993-07-22 |
| EP0617625A1 (fr) | 1994-10-05 |
| WO1993013779A3 (fr) | 1993-08-19 |
| AU4100193A (en) | 1993-08-03 |
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