DK1313508T5 - Kombination indeholdende et antifolat og methylmalonsyresænkende middel - Google Patents
Kombination indeholdende et antifolat og methylmalonsyresænkende middel Download PDFInfo
- Publication number
- DK1313508T5 DK1313508T5 DK01948214.0T DK01948214T DK1313508T5 DK 1313508 T5 DK1313508 T5 DK 1313508T5 DK 01948214 T DK01948214 T DK 01948214T DK 1313508 T5 DK1313508 T5 DK 1313508T5
- Authority
- DK
- Denmark
- Prior art keywords
- vitamin
- administered
- acid
- use according
- pharmaceutical derivative
- Prior art date
Links
- 239000004052 folic acid antagonist Substances 0.000 title abstract description 67
- 230000003432 anti-folate effect Effects 0.000 title abstract description 64
- 229940127074 antifolate Drugs 0.000 title abstract description 64
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 title abstract description 41
- 239000003795 chemical substances by application Substances 0.000 title abstract description 36
- 241000124008 Mammalia Species 0.000 claims abstract description 17
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 89
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 80
- 229930003779 Vitamin B12 Natural products 0.000 claims description 73
- 235000019163 vitamin B12 Nutrition 0.000 claims description 73
- 239000011715 vitamin B12 Substances 0.000 claims description 73
- 235000019152 folic acid Nutrition 0.000 claims description 46
- 239000011724 folic acid Substances 0.000 claims description 45
- 239000003814 drug Substances 0.000 claims description 43
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 40
- NYDXNILOWQXUOF-UHFFFAOYSA-L disodium;2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate Chemical compound [Na+].[Na+].C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)NC(CCC([O-])=O)C([O-])=O)C=C1 NYDXNILOWQXUOF-UHFFFAOYSA-L 0.000 claims description 40
- 229960000304 folic acid Drugs 0.000 claims description 40
- 229960003349 pemetrexed disodium Drugs 0.000 claims description 40
- 229940079593 drug Drugs 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 25
- 239000011230 binding agent Substances 0.000 claims description 22
- 230000004614 tumor growth Effects 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 101001039269 Rattus norvegicus Glycine N-methyltransferase Proteins 0.000 claims description 9
- 238000010255 intramuscular injection Methods 0.000 claims description 9
- 239000007927 intramuscular injection Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- YOZNUFWCRFCGIH-BYFNXCQMSA-L hydroxocobalamin Chemical compound O[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O YOZNUFWCRFCGIH-BYFNXCQMSA-L 0.000 claims description 6
- 238000002648 combination therapy Methods 0.000 claims description 5
- 125000003929 folic acid group Chemical group 0.000 claims description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 5
- ZNOVTXRBGFNYRX-OLZOCXBDSA-N (2s)-2-[[4-[[(6r)-2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl]methylamino]benzoyl]amino]pentanedioic acid Chemical compound C([C@H]1N(C=2C(=O)NC(N)=NC=2NC1)C)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-OLZOCXBDSA-N 0.000 claims description 4
- WBSXYJYELWQLCJ-UHFFFAOYSA-K cobalt(3+);[5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] 1-[3-[2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1h-corrin-21-id-3-yl]propanoylamino]propan-2 Chemical compound O.[OH-].[Co+3].OCC1OC(N2C3=CC(C)=C(C)C=C3N=C2)C(O)C1OP([O-])(=O)OC(C)CNC(=O)CCC1(C)C(CC(N)=O)C2[N-]\C1=C(C)/C(C(C\1(C)C)CCC(N)=O)=N/C/1=C\C(C(C/1(CC(N)=O)C)CCC(N)=O)=N\C\1=C(C)/C1=NC2(C)C(C)(CC(N)=O)C1CCC(N)=O WBSXYJYELWQLCJ-UHFFFAOYSA-K 0.000 claims description 4
- 239000011888 foil Substances 0.000 claims description 4
- -1 azidocobalamin Chemical compound 0.000 claims description 3
- 235000004867 hydroxocobalamin Nutrition 0.000 claims description 3
- 239000011704 hydroxocobalamin Substances 0.000 claims description 3
- 229960001103 hydroxocobalamin Drugs 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- BYLXFSREGROOBJ-UVKKECPRSA-K cobalt(3+) [(2R,3S,4R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2R)-1-[3-[(2R,3R,4Z,7S,9Z,12S,13S,14Z,17S,18S,19R)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1H-corrin-21-id-3-yl]propanoylamino]propan-2-yl] phosphate chloride Chemical compound [Cl-].[Co+3].C[C@H](CNC(=O)CC[C@]1(C)[C@@H](CC(N)=O)C2[N-]\C1=C(C)/C1=N/C(=C\C3=N\C(=C(C)/C4=N[C@]2(C)[C@@](C)(CC(N)=O)[C@@H]4CCC(N)=O)\[C@@](C)(CC(N)=O)[C@@H]3CCC(N)=O)/C(C)(C)[C@@H]1CCC(N)=O)OP([O-])(=O)O[C@@H]1[C@@H](CO)O[C@@H]([C@@H]1O)n1cnc2cc(C)c(C)cc12 BYLXFSREGROOBJ-UVKKECPRSA-K 0.000 claims 4
- 102000023732 binding proteins Human genes 0.000 claims 3
- 108091008324 binding proteins Proteins 0.000 claims 3
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 claims 1
- 102000021127 protein binding proteins Human genes 0.000 claims 1
- 108091011138 protein binding proteins Proteins 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 7
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 36
- 229940110282 alimta Drugs 0.000 description 29
- 238000011282 treatment Methods 0.000 description 29
- 231100000419 toxicity Toxicity 0.000 description 21
- 230000001988 toxicity Effects 0.000 description 21
- 206010028980 Neoplasm Diseases 0.000 description 15
- 108010022394 Threonine synthase Proteins 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 11
- 229940088594 vitamin Drugs 0.000 description 10
- 229930003231 vitamin Natural products 0.000 description 10
- 235000013343 vitamin Nutrition 0.000 description 10
- 239000011782 vitamin Substances 0.000 description 10
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 231100000331 toxic Toxicity 0.000 description 8
- 230000002588 toxic effect Effects 0.000 description 8
- 208000010201 Exanthema Diseases 0.000 description 7
- 208000012766 Growth delay Diseases 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- 102000004419 dihydrofolate reductase Human genes 0.000 description 7
- 201000005884 exanthem Diseases 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 206010037844 rash Diseases 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 206010006187 Breast cancer Diseases 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 101000606741 Homo sapiens Phosphoribosylglycinamide formyltransferase Proteins 0.000 description 6
- 102100039654 Phosphoribosylglycinamide formyltransferase Human genes 0.000 description 6
- 102000005497 Thymidylate Synthase Human genes 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 231100000517 death Toxicity 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 206010016256 fatigue Diseases 0.000 description 6
- 229960005079 pemetrexed Drugs 0.000 description 6
- 231100000046 skin rash Toxicity 0.000 description 6
- 239000013589 supplement Substances 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 210000002700 urine Anatomy 0.000 description 5
- 150000003722 vitamin derivatives Chemical class 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 229940014144 folate Drugs 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229960000485 methotrexate Drugs 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 4
- VVIAGPKUTFNRDU-OLZOCXBDSA-N (2s)-2-[[4-[[(6r)-2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl]methylamino]benzoyl]amino]pentanedioic acid Chemical compound C([C@H]1N(C=O)C=2C(=O)N=C(NC=2NC1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-OLZOCXBDSA-N 0.000 description 3
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010028116 Mucosal inflammation Diseases 0.000 description 3
- 201000010927 Mucositis Diseases 0.000 description 3
- 206010037867 Rash macular Diseases 0.000 description 3
- 206010037876 Rash papular Diseases 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 3
- 206010070863 Toxicity to various agents Diseases 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 230000002489 hematologic effect Effects 0.000 description 3
- 231100001225 mammalian toxicity Toxicity 0.000 description 3
- 208000004235 neutropenia Diseases 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 208000012963 papular rash Diseases 0.000 description 3
- 229960004432 raltitrexed Drugs 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 206010043554 thrombocytopenia Diseases 0.000 description 3
- 230000002485 urinary effect Effects 0.000 description 3
- 229940082632 vitamin b12 and folic acid Drugs 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 230000003254 anti-foaming effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 238000009104 chemotherapy regimen Methods 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 231100000226 haematotoxicity Toxicity 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 239000003944 phosphoribosylglycinamide formyltransferase inhibitor Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 2
- 235000019158 vitamin B6 Nutrition 0.000 description 2
- 239000011726 vitamin B6 Substances 0.000 description 2
- 229940011671 vitamin b6 Drugs 0.000 description 2
- 235000019195 vitamin supplement Nutrition 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 101100332563 Caenorhabditis elegans dhfr-1 gene Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241000287107 Passer Species 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037898 Rash vesicular Diseases 0.000 description 1
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-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
- 229960003896 aminopterin Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000002519 antifouling agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003225 biodiesel Substances 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].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 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- FDJOLVPMNUYSCM-IQFXPAJWSA-L cobalt(3+);[5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2s)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahyd Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@H](C)OP([O-])(=O)OC3C(C(OC3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-IQFXPAJWSA-L 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
- 238000013415 human tumor xenograft model Methods 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 231100001106 life-threatening toxicity Toxicity 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 231100000142 low-dose toxicity Toxicity 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 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
- A61K31/33—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nutrition Science (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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Detergent Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21531000P | 2000-06-30 | 2000-06-30 | |
| US23585900P | 2000-09-27 | 2000-09-27 | |
| US28444801P | 2001-04-18 | 2001-04-18 | |
| PCT/US2001/014860 WO2002002093A2 (en) | 2000-06-30 | 2001-06-15 | Combination containing an antifolate and methylmalonic acid lowering agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK1313508T3 DK1313508T3 (da) | 2007-08-06 |
| DK1313508T5 true DK1313508T5 (da) | 2017-03-20 |
Family
ID=27396105
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK01948214.0T DK1313508T5 (da) | 2000-06-30 | 2001-06-15 | Kombination indeholdende et antifolat og methylmalonsyresænkende middel |
Country Status (11)
| Country | Link |
|---|---|
| US (4) | US7053065B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1313508B1 (cg-RX-API-DMAC7.html) |
| JP (7) | JP5102928B2 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE359823T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2001269688A1 (cg-RX-API-DMAC7.html) |
| CY (1) | CY1107649T1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE60127970T2 (cg-RX-API-DMAC7.html) |
| DK (1) | DK1313508T5 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2284660T3 (cg-RX-API-DMAC7.html) |
| PT (1) | PT1313508E (cg-RX-API-DMAC7.html) |
| WO (1) | WO2002002093A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1313508B1 (en) * | 2000-06-30 | 2007-04-18 | Eli Lilly And Company | Combination containing an antifolate and methylmalonic acid lowering agent |
| DK1874821T3 (da) | 2005-04-26 | 2013-07-08 | Trion Pharma Gmbh | Kombination af antistoffer med glykokortikoider til behandling af kræft |
| AU2007204410A1 (en) * | 2006-01-12 | 2007-07-19 | Novartis Ag | Combination of mTOR inhibitor and antipolate compound |
| WO2010021843A1 (en) * | 2008-08-20 | 2010-02-25 | Eli Lilly And Company | Use of antifolates in patients with detectable levels of tff-1 for the cancer treatment |
| WO2010138955A2 (en) | 2009-05-29 | 2010-12-02 | University Of Florida Research Foundation, Inc. | Methods and compositions for treating neoplasia |
| US10736969B2 (en) | 2010-12-21 | 2020-08-11 | Nektar Therapeutics | Multi-arm polymeric prodrug conjugates of pemetrexed-based compounds |
| LT2854768T (lt) | 2012-05-30 | 2017-06-12 | Fresenius Kabi Oncology Limited | Pemetreksedo farmacinės kompozicijos |
| US10064869B2 (en) | 2014-06-04 | 2018-09-04 | Thomas Helledays Stiftelse For Medicinsk Forskning | MTH1 inhibitors for treatment of inflammatory and autoimmune conditions |
| US10531957B2 (en) | 2015-05-21 | 2020-01-14 | Musculoskeletal Transplant Foundation | Modified demineralized cortical bone fibers |
| AU2016298439B2 (en) * | 2015-07-30 | 2018-11-08 | Expression Pathology, Inc. | Quantifying FR-alpha and GART proteins for optimal cancer therapy |
| DK3386546T3 (en) * | 2015-12-07 | 2024-11-25 | General Oncology Inc | Combination for the effective treatment of metastatic cancer in patients |
| WO2018031968A1 (en) | 2016-08-12 | 2018-02-15 | L.E.A.F. Holdings Group Llc | Alpha and gamma-d polyglutamated antifolates and uses thereof |
| CA3177187A1 (en) | 2016-08-12 | 2018-02-15 | L.E.A.F Holdings Group Llc | Alpha and gamma-d polyglutamated antifolates and uses thereof |
| EP3565549B1 (en) | 2017-01-09 | 2022-03-09 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
| US11584733B2 (en) | 2017-01-09 | 2023-02-21 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
| US11407723B2 (en) | 2018-01-09 | 2022-08-09 | Shuttle Pharmaceuticals, Inc. | Selective histone deacetylase inhibitors for the treatment of human disease |
| WO2019157133A1 (en) | 2018-02-07 | 2019-08-15 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated raltitrexed and uses thereof |
| CA3090381A1 (en) | 2018-02-07 | 2019-08-15 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated lometrexol and uses thereof |
| JP7491573B2 (ja) | 2018-02-07 | 2024-05-28 | エル．イー．エー．エフ． ホールディングス グループ エルエルシー | アルファポリグルタミン酸化メトトレキセートおよびその使用 |
| EP3749318A4 (en) | 2018-02-07 | 2022-07-06 | L.E.A.F Holdings Group LLC | GAMMA-POLYGLUTAMATED RALTITREXED AND ITS USES |
| CN111954531A (zh) | 2018-02-07 | 2020-11-17 | L.E.A.F.控股集团公司 | α聚谷氨酸化培美曲塞及其用途 |
| CN111954530A (zh) | 2018-02-07 | 2020-11-17 | L.E.A.F.控股集团公司 | γ聚谷氨酸化培美曲塞及其用途 |
| US12076402B2 (en) | 2018-02-07 | 2024-09-03 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated antifolates and uses thereof |
| US12220431B2 (en) | 2018-02-07 | 2025-02-11 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated antifolates and uses thereof |
| CA3090384A1 (en) | 2018-02-07 | 2019-08-15 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated aminopterin and uses thereof |
| US11730738B2 (en) | 2018-02-07 | 2023-08-22 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated pralatrexate and uses thereof |
| CA3090506A1 (en) | 2018-02-07 | 2019-08-15 | L.E.A.F. Holdings Group Llc | Alpha polyglutamated tetrahydrofolates and uses thereof |
| US12048766B2 (en) | 2018-02-14 | 2024-07-30 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated tetrahydrofolates and uses thereof |
| WO2019160734A1 (en) | 2018-02-14 | 2019-08-22 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated lometrexol and uses thereof |
| CA3090943A1 (en) | 2018-02-14 | 2019-08-22 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated aminopterin and uses thereof |
| US12048767B2 (en) | 2018-02-14 | 2024-07-30 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated pralatrexate and uses thereof |
| WO2019160733A1 (en) | 2018-02-14 | 2019-08-22 | L.E.A.F. Holdings Group Llc | Gamma polyglutamated methotrexate and uses thereof |
| WO2023177894A1 (en) | 2022-03-18 | 2023-09-21 | Ideaya Biosciences, Inc. | Combination therapy comprising a mat2a inhibitor and an antimetabolite agent |
| WO2025247952A1 (en) * | 2024-05-30 | 2025-12-04 | Université De Fribourg | Inhibition of cyanide overproduction for the therapy of down syndrome and nonketotic hyperglycinemia |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US225030A (en) * | 1880-03-02 | Rotary engine | ||
| US216350A (en) * | 1879-06-10 | Improvement in car-replacers | ||
| US2920015A (en) * | 1957-08-27 | 1960-01-05 | Armour & Co | Long-acting vitamin b12 |
| CH605550A5 (cg-RX-API-DMAC7.html) * | 1972-06-08 | 1978-09-29 | Research Corp | |
| US5563126A (en) * | 1986-11-20 | 1996-10-08 | Metabolite Laboratories | Method for treatment and prevention of deficiencies of vitamins B12, folic acid, and B6 |
| US5405839A (en) * | 1989-02-28 | 1995-04-11 | Teijin Limited | Vitamin B12 derivative, preparation process thereof, and use thereof |
| JP2962755B2 (ja) * | 1989-02-28 | 1999-10-12 | 帝人株式会社 | 新規ビタミンｂ▲下１▼▲下２▼誘導体、その製造方法並びにその用途 |
| KR0162654B1 (ko) * | 1989-12-11 | 1998-11-16 | 알렌 제이. 시니스갤리 | N-(피롤로[2,3-d]피리미딘-3-일아크릴)-글루타민산 유도체 |
| DK0505640T4 (da) * | 1991-03-29 | 2002-12-16 | Lilly Co Eli | Forbedret terapeutisk metode |
| JPH05163160A (ja) * | 1991-12-13 | 1993-06-29 | Snow Brand Milk Prod Co Ltd | 免疫低下に伴う感染症の予防及び治療用栄養剤 |
| US6207651B1 (en) * | 1996-08-02 | 2001-03-27 | Metabolite Laboratories | Method for treatment and prevention of deficiencies of vitamins B12, folic acid, and B6 |
| KR100361075B1 (ko) | 1994-04-08 | 2003-04-10 | 리셉타겐 코포레이션 | 리셉터조절제및그와관련된방법 |
| AU3972195A (en) * | 1994-10-12 | 1996-05-06 | Research & Diagnostics Systems, Inc. | Reticulocyte assay control |
| EP1313508B1 (en) * | 2000-06-30 | 2007-04-18 | Eli Lilly And Company | Combination containing an antifolate and methylmalonic acid lowering agent |
| US20040005311A1 (en) * | 2001-07-20 | 2004-01-08 | Pitman Bradford D. | Dietary supplement compositions |
-
2001
- 2001-06-15 EP EP01948214A patent/EP1313508B1/en not_active Expired - Lifetime
- 2001-06-15 WO PCT/US2001/014860 patent/WO2002002093A2/en not_active Ceased
- 2001-06-15 US US10/297,821 patent/US7053065B2/en not_active Expired - Lifetime
- 2001-06-15 PT PT01948214T patent/PT1313508E/pt unknown
- 2001-06-15 JP JP2002506715A patent/JP5102928B2/ja not_active Expired - Lifetime
- 2001-06-15 DE DE60127970T patent/DE60127970T2/de not_active Expired - Lifetime
- 2001-06-15 AT AT01948214T patent/ATE359823T1/de active
- 2001-06-15 ES ES01948214T patent/ES2284660T3/es not_active Expired - Lifetime
- 2001-06-15 DK DK01948214.0T patent/DK1313508T5/da active
- 2001-06-15 AU AU2001269688A patent/AU2001269688A1/en not_active Abandoned
-
2005
- 2005-11-29 US US11/288,807 patent/US20060079480A1/en not_active Abandoned
-
2007
- 2007-06-07 CY CY20071100756T patent/CY1107649T1/el unknown
- 2007-07-11 US US11/776,329 patent/US7772209B2/en not_active Expired - Fee Related
-
2010
- 2010-04-28 US US12/768,920 patent/US20100210583A1/en not_active Abandoned
-
2012
- 2012-06-27 JP JP2012144570A patent/JP5469706B2/ja not_active Expired - Lifetime
-
2013
- 2013-10-11 JP JP2013213276A patent/JP2014005304A/ja not_active Withdrawn
-
2015
- 2015-04-21 JP JP2015087012A patent/JP2015178501A/ja not_active Withdrawn
-
2016
- 2016-09-29 JP JP2016192173A patent/JP2017019852A/ja not_active Withdrawn
-
2018
- 2018-08-23 JP JP2018156677A patent/JP2018197265A/ja not_active Withdrawn
-
2020
- 2020-04-14 JP JP2020072098A patent/JP2020117536A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE60127970T2 (de) | 2007-12-20 |
| JP2018197265A (ja) | 2018-12-13 |
| JP5469706B2 (ja) | 2014-04-16 |
| JP2015178501A (ja) | 2015-10-08 |
| US7772209B2 (en) | 2010-08-10 |
| WO2002002093A2 (en) | 2002-01-10 |
| JP2014005304A (ja) | 2014-01-16 |
| US20030212038A1 (en) | 2003-11-13 |
| WO2002002093A3 (en) | 2003-02-06 |
| DK1313508T3 (da) | 2007-08-06 |
| EP1313508B1 (en) | 2007-04-18 |
| DE60127970D1 (de) | 2007-05-31 |
| JP2020117536A (ja) | 2020-08-06 |
| US7053065B2 (en) | 2006-05-30 |
| US20080032948A1 (en) | 2008-02-07 |
| AU2001269688A1 (en) | 2002-01-14 |
| ES2284660T3 (es) | 2007-11-16 |
| US20100210583A1 (en) | 2010-08-19 |
| ATE359823T1 (de) | 2007-05-15 |
| JP2017019852A (ja) | 2017-01-26 |
| US20060079480A1 (en) | 2006-04-13 |
| PT1313508E (pt) | 2007-06-21 |
| CY1107649T1 (el) | 2013-04-18 |
| JP5102928B2 (ja) | 2012-12-19 |
| EP1313508A2 (en) | 2003-05-28 |
| JP2004501964A (ja) | 2004-01-22 |
| JP2012180381A (ja) | 2012-09-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DK1313508T5 (da) | Kombination indeholdende et antifolat og methylmalonsyresænkende middel | |
| Bibbiani et al. | A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease | |
| CA2450777C (en) | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia | |
| US20090298791A1 (en) | Combinations comprising epothilones and antimetabolites | |
| Martin et al. | Phase II study of pemetrexed in breast cancer patients pretreated with anthracyclines | |
| Roberts et al. | Weekly lometrexol with daily oral folic acid is appropriate for phase II evaluation | |
| Conti et al. | Trial of sequential trimetrexate, fluorouracil, and high-dose leucovorin in previously treated patients with gastrointestinal carcinoma. | |
| Kimura et al. | Severe neutropenia: a prognosticator in patients with advanced/recurrent colorectal cancer under oral trifluridine-tipiracil (TAS-102) chemotherapy | |
| JP2011507880A (ja) | 慢性リンパ性白血病の処置のためのニロチニブとナイトロジェンマスタードの組み合わせ剤 | |
| Llombart-Cussac et al. | Pemetrexed in patients with locally advanced or metastatic breast cancer who had received previous anthracycline and taxane treatment: phase II study | |
| US12220405B2 (en) | Compositions for the treatment of hepatic steatosis | |
| CN1330308C (zh) | 含有4－吡啶基甲基酞嗪的联合产品及其应用 | |
| DE DK et al. | ZUSAMMENSETZUNG, WELCHE EIN ANTIFOLATE UND EIN METHYLMALONSÄURESENKENDES MITTEL ENTHÄLT COMPOSITION COMPRENANT UN ANTIFOLATE ET UN AGENT REDUCTEUR D’ACIDE METHYLMALONIQUE | |
| Takiguchi et al. | Long-term administration of second-line chemotherapy with S-1 and gemcitabine for platinum-resistant non-small cell lung cancer: a phase II study | |
| AU2007200677B2 (en) | Combinations comprising epothilones and anti-metabolites | |
| JP7414230B2 (ja) | 抗血液悪性腫瘍薬 | |
| KR20250156708A (ko) | 췌장암의 치료 | |
| US20210401812A1 (en) | Compositions for the prevention and treatment of metabolic syndrome | |
| HK1146804A (en) | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |