WO2006131649A2 - Utilisation de la fumagilline et de ses derives pour augmenter la biodisponibilite des lactones macrocycliques - Google Patents
Utilisation de la fumagilline et de ses derives pour augmenter la biodisponibilite des lactones macrocycliques Download PDFInfo
- Publication number
- WO2006131649A2 WO2006131649A2 PCT/FR2006/001297 FR2006001297W WO2006131649A2 WO 2006131649 A2 WO2006131649 A2 WO 2006131649A2 FR 2006001297 W FR2006001297 W FR 2006001297W WO 2006131649 A2 WO2006131649 A2 WO 2006131649A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- formula
- compound
- alkoxy
- amino
- Prior art date
Links
- NGGMYCMLYOUNGM-UHFFFAOYSA-N (-)-fumagillin Natural products O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)C=CC=CC=CC=CC(O)=O)CCC21CO2 NGGMYCMLYOUNGM-UHFFFAOYSA-N 0.000 title claims abstract description 73
- 229960000936 fumagillin Drugs 0.000 title claims abstract description 72
- NGGMYCMLYOUNGM-CSDLUJIJSA-N fumagillin Chemical compound C([C@H]([C@H]([C@@H]1[C@]2(C)[C@H](O2)CC=C(C)C)OC)OC(=O)\C=C\C=C\C=C\C=C\C(O)=O)C[C@@]21CO2 NGGMYCMLYOUNGM-CSDLUJIJSA-N 0.000 title claims abstract description 72
- 150000002596 lactones Chemical class 0.000 title claims abstract description 15
- 239000004480 active ingredient Substances 0.000 claims abstract description 51
- 238000011282 treatment Methods 0.000 claims abstract description 43
- 108010078791 Carrier Proteins Proteins 0.000 claims abstract description 32
- 230000001413 cellular effect Effects 0.000 claims abstract description 21
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 18
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 claims abstract description 10
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 claims abstract description 10
- 208000030852 Parasitic disease Diseases 0.000 claims abstract description 9
- 239000003112 inhibitor Substances 0.000 claims abstract description 9
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 claims abstract description 8
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 claims abstract description 7
- 230000007170 pathology Effects 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 115
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 229960004816 moxidectin Drugs 0.000 claims description 38
- YZBLFMPOMVTDJY-CBYMMZEQSA-N moxidectin Chemical compound O1[C@H](C(\C)=C\C(C)C)[C@@H](C)C(=N/OC)\C[C@@]11O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 YZBLFMPOMVTDJY-CBYMMZEQSA-N 0.000 claims description 37
- -1 cyano, carbamyl Chemical group 0.000 claims description 35
- 230000002141 anti-parasite Effects 0.000 claims description 31
- 239000003096 antiparasitic agent Substances 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 28
- 230000000694 effects Effects 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 230000001093 anti-cancer Effects 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 239000005660 Abamectin Substances 0.000 claims description 16
- 241001465754 Metazoa Species 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 claims description 12
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 claims description 12
- 229960002418 ivermectin Drugs 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 239000000969 carrier Substances 0.000 claims description 11
- 239000000758 substrate Substances 0.000 claims description 11
- 230000003834 intracellular effect Effects 0.000 claims description 10
- 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 claims description 8
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
- 244000045947 parasite Species 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 230000003993 interaction Effects 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 238000002512 chemotherapy Methods 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 230000003071 parasitic effect Effects 0.000 claims description 6
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 claims description 5
- 229950008167 abamectin Drugs 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- QLFZZSKTJWDQOS-YDBLARSUSA-N doramectin Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C3CCCCC3)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C QLFZZSKTJWDQOS-YDBLARSUSA-N 0.000 claims description 5
- 229960003997 doramectin Drugs 0.000 claims description 5
- YNFMRVVYUVPIAN-AQUURSMBSA-N nemadectin Chemical compound C1[C@H](O)[C@H](C)[C@@H](C(/C)=C/C(C)C)O[C@]11O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 YNFMRVVYUVPIAN-AQUURSMBSA-N 0.000 claims description 5
- 229950009729 nemadectin Drugs 0.000 claims description 5
- YNFMRVVYUVPIAN-UHFFFAOYSA-N nemadectin alpha Natural products C1C(O)C(C)C(C(C)=CC(C)C)OC11OC(CC=C(C)CC(C)C=CC=C2C3(C(C(=O)O4)C=C(C)C(O)C3OC2)O)CC4C1 YNFMRVVYUVPIAN-UHFFFAOYSA-N 0.000 claims description 5
- AFJYYKSVHJGXSN-KAJWKRCWSA-N selamectin Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1C(/C)=C/C[C@@H](O[C@]2(O[C@@H]([C@@H](C)CC2)C2CCCCC2)C2)C[C@@H]2OC(=O)[C@@H]([C@]23O)C=C(C)C(=N\O)/[C@H]3OC\C2=C/C=C/[C@@H]1C AFJYYKSVHJGXSN-KAJWKRCWSA-N 0.000 claims description 5
- 229960002245 selamectin Drugs 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 4
- 229940123237 Taxane Drugs 0.000 claims description 4
- 241000607479 Yersinia pestis Species 0.000 claims description 4
- 229930013930 alkaloid Natural products 0.000 claims description 4
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229960001156 mitoxantrone Drugs 0.000 claims description 4
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 4
- 230000003389 potentiating effect Effects 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 3
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 230000000259 anti-tumor effect Effects 0.000 claims description 3
- 229940088710 antibiotic agent Drugs 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 2
- 102100021339 Multidrug resistance-associated protein 1 Human genes 0.000 claims description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
- 229930012538 Paclitaxel Natural products 0.000 claims description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 238000011319 anticancer therapy Methods 0.000 claims description 2
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- 229960003668 docetaxel Drugs 0.000 claims description 2
- 229960004679 doxorubicin Drugs 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 229960004857 mitomycin Drugs 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 229960001592 paclitaxel Drugs 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 2
- 229960001278 teniposide Drugs 0.000 claims description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 2
- 229960000303 topotecan Drugs 0.000 claims description 2
- 229960003048 vinblastine Drugs 0.000 claims description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 2
- 229960004528 vincristine Drugs 0.000 claims description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 2
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 1
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims 1
- 101000969812 Homo sapiens Multidrug resistance-associated protein 1 Proteins 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 34
- 210000003494 hepatocyte Anatomy 0.000 description 25
- YJDYDFNKCBANTM-QCWCSKBGSA-N SDZ PSC 833 Chemical compound C\C=C\C[C@@H](C)C(=O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](C(C)C)NC1=O YJDYDFNKCBANTM-QCWCSKBGSA-N 0.000 description 17
- 108010082372 valspodar Proteins 0.000 description 16
- 229950010938 valspodar Drugs 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- 230000035508 accumulation Effects 0.000 description 12
- 238000009825 accumulation Methods 0.000 description 12
- 201000011510 cancer Diseases 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 230000007154 intracellular accumulation Effects 0.000 description 7
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 6
- 229940126601 medicinal product Drugs 0.000 description 6
- AZSNMRSAGSSBNP-XPNPUAGNSA-N 22,23-dihydroavermectin B1a Chemical compound C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 AZSNMRSAGSSBNP-XPNPUAGNSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 4
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 229960001285 quercetin Drugs 0.000 description 4
- 235000005875 quercetin Nutrition 0.000 description 4
- TUFFYSFVSYUHPA-UHFFFAOYSA-M rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C(C=CC(N)=C2)C2=[O+]C2=C1C=CC(N)=C2 TUFFYSFVSYUHPA-UHFFFAOYSA-M 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000032258 transport Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 238000011260 co-administration Methods 0.000 description 3
- WPNHOHPRXXCPRA-TVXIRPTOSA-N eprinomectin Chemical compound O1[C@@H](C)[C@@H](NC(C)=O)[C@H](OC)C[C@@H]1O[C@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C\C=C/[C@@H]2C)\C)O[C@H]1C WPNHOHPRXXCPRA-TVXIRPTOSA-N 0.000 description 3
- 229960002346 eprinomectin Drugs 0.000 description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 3
- 229960005420 etoposide Drugs 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- FXWHFKOXMBTCMP-WMEDONTMSA-N milbemycin Natural products COC1C2OCC3=C/C=C/C(C)CC(=CCC4CC(CC5(O4)OC(C)C(C)C(OC(=O)C(C)CC(C)C)C5O)OC(=O)C(C=C1C)C23O)C FXWHFKOXMBTCMP-WMEDONTMSA-N 0.000 description 3
- ZLBGSRMUSVULIE-GSMJGMFJSA-N milbemycin A3 Chemical class O1[C@H](C)[C@@H](C)CC[C@@]11O[C@H](C\C=C(C)\C[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 ZLBGSRMUSVULIE-GSMJGMFJSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 241000894007 species Species 0.000 description 3
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- 206010000830 Acute leukaemia Diseases 0.000 description 2
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- 241001643084 Cyrtanthus elatus virus A Species 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 229960001722 verapamil Drugs 0.000 description 2
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- NGGMYCMLYOUNGM-DEHUIYDQSA-N (2z,4e,6e,8e)-10-[[5-methoxy-4-[2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl]oxy]-10-oxodeca-2,4,6,8-tetraenoic acid Chemical compound O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)\C=C\C=C\C=C\C=C/C(O)=O)CCC21CO2 NGGMYCMLYOUNGM-DEHUIYDQSA-N 0.000 description 1
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 206010001986 Amoebic dysentery Diseases 0.000 description 1
- 241001225321 Aspergillus fumigatus Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101150091140 CDPK1 gene Proteins 0.000 description 1
- 101150108143 CPK1 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241001126268 Cooperia Species 0.000 description 1
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 1
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 241001147669 Dictyocaulus viviparus Species 0.000 description 1
- 208000029639 Ectoparasitic disease Diseases 0.000 description 1
- 241001442406 Enterocytozoon bieneusi Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 201000006353 Filariasis Diseases 0.000 description 1
- 241000243976 Haemonchus Species 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- 241000543830 Hypoderma bovis Species 0.000 description 1
- 241000257174 Hypoderma lineatum Species 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 201000000090 Microsporidiosis Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 241001137882 Nematodirus Species 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 241000243985 Onchocerca volvulus Species 0.000 description 1
- 241000243795 Ostertagia Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 101150053185 P450 gene Proteins 0.000 description 1
- 229940049937 Pgp inhibitor Drugs 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 241000826860 Trapezium Species 0.000 description 1
- 241000243797 Trichostrongylus Species 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 229940125687 antiparasitic agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004320 controlled atmosphere Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 244000078703 ectoparasite Species 0.000 description 1
- 244000079386 endoparasite Species 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 235000021050 feed intake Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 201000010666 keratoconjunctivitis Diseases 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 230000001418 larval effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 210000004914 menses Anatomy 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 108010066052 multidrug resistance-associated protein 1 Proteins 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- 208000002042 onchocerciasis Diseases 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
-
- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2006256616A AU2006256616A1 (en) | 2005-06-08 | 2006-06-08 | Use of fumagillin and the derivatives thereof to increase the bioavailability of the macrocyclic lactones |
CA002611201A CA2611201A1 (fr) | 2005-06-08 | 2006-06-08 | Utilisation de la fumagilline et de ses derives pour augmenter la biodisponibilite des lactones macrocycliques |
EP06764749A EP1888116A2 (fr) | 2005-06-08 | 2006-06-08 | Utilisation de la fumagilline et de ses derives pour augmenter la biodisponibilite des lactones macrocycliques |
US11/917,031 US20080200402A1 (en) | 2005-06-08 | 2006-06-08 | Use Of Fumagillin And The Derivatives Thereof To Increase The Bioavilability Of The Macrocyclic Lactones |
BRPI0611642-6A BRPI0611642A2 (pt) | 2005-06-08 | 2006-06-08 | utilização da fumagilina e de seus derivados para aumentar a biodisponibilidade das lactonas macrocìclicas |
MX2007015504A MX2007015504A (es) | 2005-06-08 | 2006-06-08 | Uso de fumagilina y sus derivados para aumentar la biodisponibilidad de lactonas macrociclicas. |
US12/975,410 US20110144045A1 (en) | 2005-06-08 | 2010-12-22 | Use of fumagillin and the derivatives thereof to increase the bioavailability of the macrocyclic lactones |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0505829A FR2886855B1 (fr) | 2005-06-08 | 2005-06-08 | Utilisation de la fumagilline et de ses derives pour augmenter la biodisponibilite des lactones macrocyliques |
FR0505829 | 2005-06-08 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/975,410 Division US20110144045A1 (en) | 2005-06-08 | 2010-12-22 | Use of fumagillin and the derivatives thereof to increase the bioavailability of the macrocyclic lactones |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2006131649A2 true WO2006131649A2 (fr) | 2006-12-14 |
WO2006131649A3 WO2006131649A3 (fr) | 2007-06-21 |
Family
ID=35064492
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR2006/001297 WO2006131649A2 (fr) | 2005-06-08 | 2006-06-08 | Utilisation de la fumagilline et de ses derives pour augmenter la biodisponibilite des lactones macrocycliques |
Country Status (9)
Country | Link |
---|---|
US (2) | US20080200402A1 (fr) |
EP (1) | EP1888116A2 (fr) |
AU (1) | AU2006256616A1 (fr) |
BR (1) | BRPI0611642A2 (fr) |
CA (1) | CA2611201A1 (fr) |
FR (1) | FR2886855B1 (fr) |
MX (1) | MX2007015504A (fr) |
WO (1) | WO2006131649A2 (fr) |
ZA (1) | ZA200710600B (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9604922B2 (en) | 2014-02-24 | 2017-03-28 | Alkermes Pharma Ireland Limited | Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases |
US10406133B2 (en) | 2013-03-14 | 2019-09-10 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11230548B2 (en) | 2013-03-14 | 2022-01-25 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2009270799B2 (en) * | 2008-07-18 | 2016-05-19 | Zafgen, Inc. | Methods of treating an overweight or obese subject |
US8642650B2 (en) | 2008-12-04 | 2014-02-04 | Zafgen, Inc. | Methods of treating an overweight or obese subject |
US20120004162A1 (en) | 2008-12-04 | 2012-01-05 | Vath James E | Methods of Treating an Overweight or Obese Subject |
AU2010303270A1 (en) | 2009-10-09 | 2012-05-03 | Zafgen Corporation | Sulphone compounds for use in the treatment of obesity |
US8815309B2 (en) | 2010-01-08 | 2014-08-26 | Zafgen, Inc. | Methods of treating a subject with benign prostate hyperplasia |
AU2011204267B2 (en) | 2010-01-08 | 2015-12-03 | Zafgen Corporation | Fumagillol type compounds and methods of making and using same |
US20130266578A1 (en) | 2010-04-07 | 2013-10-10 | Thomas E. Hughes | Methods of treating an overweight subject |
KR20130043207A (ko) | 2010-07-22 | 2013-04-29 | 자프겐 인크. | 트리시클릭 화합물 및 이의 제조 및 사용 방법 |
NZ610569A (en) | 2010-11-09 | 2015-06-26 | Zafgen Inc | Crystalline solids of a metap-2 inhibitor and methods of making and using same |
BR112013013411A2 (pt) | 2010-11-29 | 2016-09-13 | Zafgen Inc | tratamento de obesidade usando administração não diária de 6-0-(4-dimetilaminoetxi) cinamoil fumagilol |
JP6058557B2 (ja) | 2011-01-26 | 2017-01-11 | ザフゲン,インコーポレイテッド | テトラゾール化合物ならびにその作製方法および使用方法 |
WO2012122264A1 (fr) | 2011-03-08 | 2012-09-13 | Zafgen Corporation | Dérivés d'oxaspiro[2.5]octane et analogues |
US9351988B2 (en) | 2011-05-02 | 2016-05-31 | Universite De Geneve | Macrocyclic lactones and use thereof |
BR112013028665A2 (pt) | 2011-05-06 | 2016-09-06 | Zafgen Inc | compostos de sulfonamida tricíclicos e métodos para fazer e usar os mesmos |
BR112013028534A2 (pt) | 2011-05-06 | 2016-09-06 | Zafgen Inc | compostos tricíclicos parcialmente saturados e métodos para produção e utilização dos mesmos |
BR112013028666A2 (pt) | 2011-05-06 | 2017-08-08 | Zafgen Inc | compostos de pirazolo sulfonamida tricícilos e métodos para fazer e usar o mesmo |
EP2763671A2 (fr) | 2011-10-03 | 2014-08-13 | Zafgen, Inc. | Méthodes de traitement de troubles liés à l âge |
EP2804856B1 (fr) | 2012-01-18 | 2017-03-15 | Zafgen, Inc. | Composés sulfones tricycliques et leurs procédés de fabrication et d'utilisation |
JP6035347B2 (ja) | 2012-01-18 | 2016-11-30 | ザフゲン,インコーポレイテッド | 三環式スルホンアミド化合物ならびにその作製および使用方法 |
KR20150016303A (ko) | 2012-05-07 | 2015-02-11 | 자프겐 인크. | 6-o-(4-디메틸아미노에톡시) 신나모일 푸마지롤의 옥살레이트 염의 다형체 염 및 이의 제조 및 사용 방법 |
CA2872876A1 (fr) | 2012-05-08 | 2013-11-14 | Zafgen, Inc. | Traitement de l'obesite hypothalamique au moyen d'inhibiteurs de metap2 |
EP2850079B1 (fr) | 2012-05-09 | 2018-05-02 | Zafgen, Inc. | Dérivés de fumigillol, procédés pour leurs préparation et leurs utilisation |
CN104918615B (zh) | 2012-11-05 | 2018-10-12 | 扎夫根股份有限公司 | 治疗肝病的方法 |
EP2925737B1 (fr) | 2012-11-05 | 2017-06-14 | Zafgen, Inc. | Composés tricycliques à utiliser dans le traitement et/ou la lutte contre l'obésité |
CA2890342A1 (fr) | 2012-11-05 | 2014-05-08 | Zafgen, Inc. | Composes tricycliques et procedes de fabrication et d'utilisation associes |
EP2968250B1 (fr) | 2013-03-14 | 2019-06-19 | Zafgen, Inc. | Méthodes de traitement de maladie rénale et d'autres troubles |
TW201636342A (zh) | 2014-12-19 | 2016-10-16 | 武田藥品工業有限公司 | 煙黴醇衍生物 |
AR105671A1 (es) | 2015-08-11 | 2017-10-25 | Zafgen Inc | Compuestos heterocíclicos de fumagillol y sus métodos de elaboración y uso |
CN106432255A (zh) | 2015-08-11 | 2017-02-22 | 扎夫根公司 | 烟曲霉素醇螺环化合物和制备和使用其的方法 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5135919A (en) * | 1988-01-19 | 1992-08-04 | Children's Medical Center Corporation | Method and a pharmaceutical composition for the inhibition of angiogenesis |
WO1994019946A1 (fr) * | 1993-03-01 | 1994-09-15 | Emory University | Traitement de la keratoconjonctivite de microsporidia et d'acanthamoeba par application locale de fumagilline |
EP0658342A1 (fr) * | 1993-09-24 | 1995-06-21 | Takeda Chemical Industries, Ltd. | Composition pharmaceutique antineoplastique contenant des dérivées de fumagillol |
WO1996030010A2 (fr) * | 1995-03-27 | 1996-10-03 | Sanofi | Utilisation du fumagillol et ses derives pour preparer les medicaments destines a combattre les infections intestinales |
EP0819430A1 (fr) * | 1996-07-17 | 1998-01-21 | Takeda Chemical Industries, Ltd. | Inhibiteur de métastase ou réapparition des tumeurs |
EP1258248A2 (fr) * | 2001-05-18 | 2002-11-20 | TAP Pharmaceutical Products, Inc. | Traitement de tumeurs avec un dérivé de fumagillol et un autre agent antinéoplastique |
WO2004039172A1 (fr) * | 2002-10-31 | 2004-05-13 | Szoke Annamaria | Systeme d'administration par voie orale d'un medicament veterinaire et/ou systeme d'administration d'un additif alimentaire, procede de preparation et d'utilisation de ceux-ci |
-
2005
- 2005-06-08 FR FR0505829A patent/FR2886855B1/fr not_active Expired - Fee Related
-
2006
- 2006-06-08 US US11/917,031 patent/US20080200402A1/en not_active Abandoned
- 2006-06-08 ZA ZA200710600A patent/ZA200710600B/xx unknown
- 2006-06-08 MX MX2007015504A patent/MX2007015504A/es not_active Application Discontinuation
- 2006-06-08 EP EP06764749A patent/EP1888116A2/fr not_active Withdrawn
- 2006-06-08 CA CA002611201A patent/CA2611201A1/fr not_active Abandoned
- 2006-06-08 BR BRPI0611642-6A patent/BRPI0611642A2/pt not_active IP Right Cessation
- 2006-06-08 AU AU2006256616A patent/AU2006256616A1/en not_active Abandoned
- 2006-06-08 WO PCT/FR2006/001297 patent/WO2006131649A2/fr active Application Filing
-
2010
- 2010-12-22 US US12/975,410 patent/US20110144045A1/en not_active Abandoned
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5135919A (en) * | 1988-01-19 | 1992-08-04 | Children's Medical Center Corporation | Method and a pharmaceutical composition for the inhibition of angiogenesis |
WO1994019946A1 (fr) * | 1993-03-01 | 1994-09-15 | Emory University | Traitement de la keratoconjonctivite de microsporidia et d'acanthamoeba par application locale de fumagilline |
EP0658342A1 (fr) * | 1993-09-24 | 1995-06-21 | Takeda Chemical Industries, Ltd. | Composition pharmaceutique antineoplastique contenant des dérivées de fumagillol |
WO1996030010A2 (fr) * | 1995-03-27 | 1996-10-03 | Sanofi | Utilisation du fumagillol et ses derives pour preparer les medicaments destines a combattre les infections intestinales |
EP0819430A1 (fr) * | 1996-07-17 | 1998-01-21 | Takeda Chemical Industries, Ltd. | Inhibiteur de métastase ou réapparition des tumeurs |
EP1258248A2 (fr) * | 2001-05-18 | 2002-11-20 | TAP Pharmaceutical Products, Inc. | Traitement de tumeurs avec un dérivé de fumagillol et un autre agent antinéoplastique |
WO2004039172A1 (fr) * | 2002-10-31 | 2004-05-13 | Szoke Annamaria | Systeme d'administration par voie orale d'un medicament veterinaire et/ou systeme d'administration d'un additif alimentaire, procede de preparation et d'utilisation de ceux-ci |
Non-Patent Citations (3)
Title |
---|
DRINYAEV V A ET AL: "Antitumor effect of avermectins" EUROPEAN JOURNAL OF PHARMACOLOGY, AMSTERDAM, NL, vol. 501, no. 1-3, 6 octobre 2004 (2004-10-06), pages 19-23, XP004587589 ISSN: 0014-2999 * |
LESPINE A ET AL: "Role of the p-glycoprotein in the cellular efflux of macrocyclic lactones: Influence of interfering agents." JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, vol. 26, no. Supplement 1, août 2003 (2003-08), pages 161-162, XP008077611 & PROCEEDINGS OF THE 9TH INTERNATIONAL CONGRESS OF THE EUROPEAN ASSOCIATION FOR VETERINARY PHARMACOLOG; LISBON, PORTUGAL; JULY 13-18, 2003 ISSN: 0140-7783 * |
WILHELMUS K R: "Antiparasitic drugs in ophthalmology" INTERNATIONAL OPHTHALMOLOGY CLINICS 1996 UNITED STATES, vol. 36, no. 2, 1996, pages 117-152, XP008077587 ISSN: 0020-8167 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10406133B2 (en) | 2013-03-14 | 2019-09-10 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US10596140B2 (en) | 2013-03-14 | 2020-03-24 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11083703B2 (en) | 2013-03-14 | 2021-08-10 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11230548B2 (en) | 2013-03-14 | 2022-01-25 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11679092B2 (en) | 2013-03-14 | 2023-06-20 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11905298B2 (en) | 2013-03-14 | 2024-02-20 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US9604922B2 (en) | 2014-02-24 | 2017-03-28 | Alkermes Pharma Ireland Limited | Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases |
Also Published As
Publication number | Publication date |
---|---|
BRPI0611642A2 (pt) | 2010-09-28 |
US20080200402A1 (en) | 2008-08-21 |
FR2886855B1 (fr) | 2009-07-17 |
EP1888116A2 (fr) | 2008-02-20 |
FR2886855A1 (fr) | 2006-12-15 |
MX2007015504A (es) | 2008-03-18 |
CA2611201A1 (fr) | 2006-12-14 |
ZA200710600B (en) | 2009-05-27 |
AU2006256616A1 (en) | 2006-12-14 |
US20110144045A1 (en) | 2011-06-16 |
WO2006131649A3 (fr) | 2007-06-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1888116A2 (fr) | Utilisation de la fumagilline et de ses derives pour augmenter la biodisponibilite des lactones macrocycliques | |
US11286274B2 (en) | Nicotinamide riboside derivatives and their uses | |
US20200397807A1 (en) | Nicotinyl riboside compounds and their uses | |
US11833167B2 (en) | Nicotinyl riboside compounds and their uses | |
CA2606887C (fr) | Composition pharmaceutique | |
JP2008520746A (ja) | アデノシンa3受容体アンタゴニストを用いる癌及びhif−1が介在する疾患の促進的治療 | |
Lundström-Stadelmann et al. | Drug repurposing applied: Activity of the anti-malarial mefloquine against Echinococcus multilocularis | |
JP2020520995A (ja) | 皮膚障害の処置用のピロロピリジン−アニリン化合物 | |
WO2018127748A1 (fr) | Composition pharmaceutique utilisée pour traiter les troubles du syndrome métabolique, les maladies infectieuses, et leurs complications. | |
FR3058059A1 (fr) | Composition pharmaceutique comprenant le beta-elemene, le lupeol et le 2-hydroxycinnamaldehyde et/ou le 2'-benzoyloxycinnalmaldehyde et/ou le beta-sitosterol et/ou la curcumine. | |
US11583509B2 (en) | Compound for treating cancer and diabetes | |
Albérich et al. | Ivermectin exposure leads to up-regulation of detoxification genes in vitro and in vivo in mice | |
WO2016142508A1 (fr) | Composition pour le traitement des tumeurs neuroendocrines pancréatiques | |
US20070010477A1 (en) | Acyl homoserine lactones for inhibition of cell growth | |
Stern | The Role of Car and Nrf2 Dual Activation in Doxorubicin/Cyclophosphamide-Based Treatment of Triple Negative Breast Cancer | |
WO2011157936A1 (fr) | Compositions à base de flavones et d'anthelminthiques | |
US10231958B2 (en) | Methods and compositions for enhancing chemotherapy | |
FR3121038A1 (fr) | Composition pharmaceutique destinée à inhiber l’infectiosité des virus à bicouche lipidique, à traiter les maladies associées et leurs complications. | |
CA3216227A1 (fr) | Cardioprotection par induction d'autophagie et reprogrammation metabolique | |
Labrie | Développement de modèles 3D-QSAR et synthèse de nouveaux inhibiteurs de la glycoprotéine-P de type anthranilamide et leur évaluation in vitro et in vivo | |
FR3058060A1 (fr) | Composition pharmaceutique comprenant le beta-elemene, le lupeol, le cinnamaldehyde et/ou le 2-hydroxycinnamaldehyde et/ou le 2'-benzoyloxycinnalmaldehyde et/ou le beta-sitosterol et/ou la curcumine. | |
WO2012095804A1 (fr) | Moyens pour reduire ou eradiquer le pouvoir tumoral de cellules souches cancereuses et/ou metastasiques. | |
NZ619377B2 (en) | Compositions, methods and kits for treating leukemia | |
NZ619377A (en) | Compositions, methods and kits for treating leukemia |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2006764749 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/a/2007/015504 Country of ref document: MX Ref document number: 2611201 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 564101 Country of ref document: NZ |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006256616 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006256616 Country of ref document: AU |
|
WWP | Wipo information: published in national office |
Ref document number: 2006256616 Country of ref document: AU |
|
WWP | Wipo information: published in national office |
Ref document number: 2006764749 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 11917031 Country of ref document: US |
|
ENP | Entry into the national phase |
Ref document number: PI0611642 Country of ref document: BR Kind code of ref document: A2 |