JP2008539273A - １７−ａａｇ又は１７−ａｇ又はどちらかのプロドラッグをプロテアソーム阻害剤と組み合わせて使用する多発性骨髄腫の治療方法 - Google Patents
１７−ａａｇ又は１７−ａｇ又はどちらかのプロドラッグをプロテアソーム阻害剤と組み合わせて使用する多発性骨髄腫の治療方法 Download PDFInfo
- Publication number
- JP2008539273A JP2008539273A JP2008509175A JP2008509175A JP2008539273A JP 2008539273 A JP2008539273 A JP 2008539273A JP 2008509175 A JP2008509175 A JP 2008509175A JP 2008509175 A JP2008509175 A JP 2008509175A JP 2008539273 A JP2008539273 A JP 2008539273A
- Authority
- JP
- Japan
- Prior art keywords
- aag
- dose
- patient
- administered
- prodrug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 title claims abstract description 303
- 206010035226 Plasma cell myeloma Diseases 0.000 title claims abstract description 88
- 239000000651 prodrug Substances 0.000 title claims abstract description 81
- 229940002612 prodrug Drugs 0.000 title claims abstract description 81
- 229940079156 Proteasome inhibitor Drugs 0.000 title claims abstract description 37
- 239000003207 proteasome inhibitor Substances 0.000 title claims abstract description 37
- 208000034578 Multiple myelomas Diseases 0.000 title claims abstract description 15
- 239000003795 chemical substances by application Substances 0.000 title claims description 110
- 238000000034 method Methods 0.000 title claims description 90
- 229950007866 tanespimycin Drugs 0.000 title description 231
- XYFFWTYOFPSZRM-NBTLBREFSA-N [(3r,5r,6s,7r,8e,10r,11r,12z,14e)-21-amino-6-hydroxy-5,11-dimethoxy-3,7,9,15-tetramethyl-16,20,22-trioxo-17-azabicyclo[16.3.1]docosa-1(21),8,12,14,18-pentaen-10-yl] carbamate Chemical compound N1C(=O)\C(C)=C\C=C/[C@@H](OC)[C@H](OC(N)=O)\C(C)=C\[C@@H](C)[C@H](O)[C@H](OC)C[C@H](C)CC2=C(N)C(=O)C=C1C2=O XYFFWTYOFPSZRM-NBTLBREFSA-N 0.000 claims abstract description 42
- 238000011282 treatment Methods 0.000 claims description 115
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 88
- 229960001467 bortezomib Drugs 0.000 claims description 79
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 72
- 239000003814 drug Substances 0.000 claims description 39
- 229940079593 drug Drugs 0.000 claims description 38
- 210000004027 cell Anatomy 0.000 claims description 35
- 210000001185 bone marrow Anatomy 0.000 claims description 18
- 230000001225 therapeutic effect Effects 0.000 claims description 18
- 230000003442 weekly effect Effects 0.000 claims description 14
- 230000001965 increasing effect Effects 0.000 claims description 12
- 238000009826 distribution Methods 0.000 claims description 9
- 230000006907 apoptotic process Effects 0.000 claims description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
- 108010016626 Dipeptides Proteins 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 230000006698 induction Effects 0.000 claims description 3
- 101710163595 Chaperone protein DnaK Proteins 0.000 claims 2
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 claims 2
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 description 38
- 210000002966 serum Anatomy 0.000 description 33
- 238000001802 infusion Methods 0.000 description 30
- 201000011510 cancer Diseases 0.000 description 23
- 230000004044 response Effects 0.000 description 20
- 230000009467 reduction Effects 0.000 description 19
- 238000001990 intravenous administration Methods 0.000 description 18
- 230000000694 effects Effects 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 238000002512 chemotherapy Methods 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 230000036470 plasma concentration Effects 0.000 description 14
- 231100000419 toxicity Toxicity 0.000 description 14
- 230000001988 toxicity Effects 0.000 description 14
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 13
- 101710085938 Matrix protein Proteins 0.000 description 13
- 101710127721 Membrane protein Proteins 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 description 12
- 229960003957 dexamethasone Drugs 0.000 description 12
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 12
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 239000008194 pharmaceutical composition Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 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 10
- 108091008611 Protein Kinase B Proteins 0.000 description 10
- 239000002246 antineoplastic agent Substances 0.000 description 10
- 229940126534 drug product Drugs 0.000 description 10
- 239000000825 pharmaceutical preparation Substances 0.000 description 10
- 230000003285 pharmacodynamic effect Effects 0.000 description 10
- 210000004180 plasmocyte Anatomy 0.000 description 10
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 9
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 8
- 231100000226 haematotoxicity Toxicity 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 239000002207 metabolite Substances 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 229960003433 thalidomide Drugs 0.000 description 8
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 7
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 7
- 239000008186 active pharmaceutical agent Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 208000007502 anemia Diseases 0.000 description 7
- 238000009093 first-line therapy Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 210000002700 urine Anatomy 0.000 description 7
- 239000008215 water for injection Substances 0.000 description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 6
- 102000004506 Blood Proteins Human genes 0.000 description 6
- 108010017384 Blood Proteins Proteins 0.000 description 6
- 206010061728 Bone lesion Diseases 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 102100032965 Myomesin-2 Human genes 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000001093 anti-cancer Effects 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000011476 stem cell transplantation Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 5
- 208000037147 Hypercalcaemia Diseases 0.000 description 5
- 206010028813 Nausea Diseases 0.000 description 5
- 208000007452 Plasmacytoma Diseases 0.000 description 5
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 5
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 5
- 239000003246 corticosteroid Substances 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000000148 hypercalcaemia Effects 0.000 description 5
- 208000030915 hypercalcemia disease Diseases 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000002101 lytic effect Effects 0.000 description 5
- 230000008693 nausea Effects 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 239000008389 polyethoxylated castor oil Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 206010012735 Diarrhoea Diseases 0.000 description 4
- 206010061818 Disease progression Diseases 0.000 description 4
- 101710113864 Heat shock protein 90 Proteins 0.000 description 4
- 102000001554 Hemoglobins Human genes 0.000 description 4
- 108010054147 Hemoglobins Proteins 0.000 description 4
- 108010064255 Paraproteins Proteins 0.000 description 4
- 102000015094 Paraproteins Human genes 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 238000011394 anticancer treatment Methods 0.000 description 4
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 4
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000011254 conventional chemotherapy Methods 0.000 description 4
- 229960001334 corticosteroids Drugs 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 230000005750 disease progression Effects 0.000 description 4
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 4
- 230000002489 hematologic effect Effects 0.000 description 4
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 4
- 229960001924 melphalan Drugs 0.000 description 4
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical group OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 208000037821 progressive disease Diseases 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229940099039 velcade Drugs 0.000 description 4
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical group O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 3
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 3
- 201000004384 Alopecia Diseases 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 206010010214 Compression fracture Diseases 0.000 description 3
- 239000004803 Di-2ethylhexylphthalate Substances 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010019851 Hepatotoxicity Diseases 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 208000001647 Renal Insufficiency Diseases 0.000 description 3
- 108010085012 Steroid Receptors Proteins 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 108010002974 benzyloxycarbonylleucyl-leucyl-leucine aldehyde Proteins 0.000 description 3
- 230000036765 blood level Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 229940115080 doxil Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- -1 erbB2 Proteins 0.000 description 3
- 229960005420 etoposide 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
- 238000011156 evaluation Methods 0.000 description 3
- 206010016256 fatigue Diseases 0.000 description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 231100000304 hepatotoxicity Toxicity 0.000 description 3
- 230000007686 hepatotoxicity Effects 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000006882 induction of apoptosis Effects 0.000 description 3
- 201000006370 kidney failure Diseases 0.000 description 3
- 238000009533 lab test Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 3
- 206010035485 plasmacytosis Diseases 0.000 description 3
- 229960004618 prednisone Drugs 0.000 description 3
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 210000004872 soft tissue Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 102000005969 steroid hormone receptors Human genes 0.000 description 3
- 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 description 3
- 229940034915 thalomid Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 206010043554 thrombocytopenia Diseases 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000002485 urinary effect Effects 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 230000008673 vomiting Effects 0.000 description 3
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 3
- VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 description 2
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 108700004676 Bence Jones Proteins 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 2
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 2
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010022095 Injection Site reaction Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 108010006519 Molecular Chaperones Proteins 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- FMYKJLXRRQTBOR-BZSNNMDCSA-N acetylleucyl-leucyl-norleucinal Chemical compound CCCC[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(C)=O FMYKJLXRRQTBOR-BZSNNMDCSA-N 0.000 description 2
- 108010091545 acetylleucyl-leucyl-norleucinal Proteins 0.000 description 2
- 208000037844 advanced solid tumor Diseases 0.000 description 2
- 231100000360 alopecia Toxicity 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 230000001446 anti-myeloma Effects 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037012 chymotrypsin-like activity Effects 0.000 description 2
- 231100000313 clinical toxicology Toxicity 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 230000001687 destabilization Effects 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 229960000520 diphenhydramine Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N epoxyketone group Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229940083646 famotidine 20 mg Drugs 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229960004942 lenalidomide Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 2
- 229960003088 loratadine Drugs 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 229950002736 marizomib Drugs 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 208000004235 neutropenia Diseases 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 238000009101 premedication Methods 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229930010796 primary metabolite Natural products 0.000 description 2
- 239000013037 reversible inhibitor Substances 0.000 description 2
- 229940120975 revlimid Drugs 0.000 description 2
- NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- TYFTWYMXUWCOOB-YICLCXKGSA-N tert-butyl (4s)-5-[[(2s)-1-[[(2s)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2s,3s)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)OCC1=CC=CC=C1 TYFTWYMXUWCOOB-YICLCXKGSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 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 description 2
- 229960004528 vincristine Drugs 0.000 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 description 2
- 229940002005 zometa Drugs 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010007509 Cardiac amyloidosis Diseases 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- 102000003909 Cyclin E Human genes 0.000 description 1
- 108090000257 Cyclin E Proteins 0.000 description 1
- 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000003849 Cytochrome P450 Human genes 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- ZPLVYYNMRMBNGE-UHFFFAOYSA-N Eponemycin Natural products CC(C)CCCCC(=O)NC(CO)C(=O)NC(CC(C)=C)C(=O)C1(CO)CO1 ZPLVYYNMRMBNGE-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 208000002633 Febrile Neutropenia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 230000037057 G1 phase arrest Effects 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 description 1
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102100037792 Interleukin-6 receptor subunit alpha Human genes 0.000 description 1
- DAQAKHDKYAWHCG-UHFFFAOYSA-N Lactacystin Natural products CC(=O)NC(C(O)=O)CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O DAQAKHDKYAWHCG-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 101150018665 MAPK3 gene Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 108010045717 Proto-Oncogene Proteins c-akt Proteins 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 1
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 1
- 102000015176 Proton-Translocating ATPases Human genes 0.000 description 1
- 108010039518 Proton-Translocating ATPases Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010070308 Refractory cancer Diseases 0.000 description 1
- 102000004584 Somatomedin Receptors Human genes 0.000 description 1
- 108010017622 Somatomedin Receptors Proteins 0.000 description 1
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- 229930195246 TMC-95 Natural products 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000012550 audit Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000007470 bone biopsy Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000035572 chemosensitivity Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940124558 contraceptive agent Drugs 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 108010020059 efrapeptin Proteins 0.000 description 1
- 239000008344 egg yolk phospholipid Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- ZPLVYYNMRMBNGE-TWOQFEAHSA-N eponemycin Chemical compound CC(C)CCCCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)=C)C(=O)[C@@]1(CO)CO1 ZPLVYYNMRMBNGE-TWOQFEAHSA-N 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 108700002672 epoxomicin Proteins 0.000 description 1
- DOGIDQKFVLKMLQ-JTHVHQAWSA-N epoxomicin Chemical compound CC[C@H](C)[C@H](N(C)C(C)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1 DOGIDQKFVLKMLQ-JTHVHQAWSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 125000000687 hydroquinonyl group Chemical group C1(O)=C(C=C(O)C=C1)* 0.000 description 1
- 230000002727 hyperosmolar Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 108040006858 interleukin-6 receptor activity proteins Proteins 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- DAQAKHDKYAWHCG-RWTHQLGUSA-N lactacystin Chemical compound CC(=O)N[C@H](C(O)=O)CSC(=O)[C@]1([C@@H](O)C(C)C)NC(=O)[C@H](C)[C@@H]1O DAQAKHDKYAWHCG-RWTHQLGUSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 208000013469 light sensitivity Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229960001810 meprednisone Drugs 0.000 description 1
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000006070 nanosuspension Substances 0.000 description 1
- 230000011234 negative regulation of signal transduction Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940045681 other alkylating agent in atc Drugs 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 229940046231 pamidronate Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940046159 pegylated liposomal doxorubicin Drugs 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960000885 rifabutin Drugs 0.000 description 1
- ATEBXHFBFRCZMA-VXTBVIBXSA-N rifabutin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC(=C2N3)C(=O)C=4C(O)=C5C)C)OC)C5=C1C=4C2=NC13CCN(CC(C)C)CC1 ATEBXHFBFRCZMA-VXTBVIBXSA-N 0.000 description 1
- 238000009118 salvage therapy Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 238000009528 vital sign measurement Methods 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D225/06—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67655605P | 2005-04-29 | 2005-04-29 | |
| US68623205P | 2005-05-31 | 2005-05-31 | |
| US74919005P | 2005-12-09 | 2005-12-09 | |
| PCT/US2006/016283 WO2006119032A1 (en) | 2005-04-29 | 2006-04-26 | Method of treating multiple myeloma using 17-aag or 17-ag or a prodrug of either in combination with a proteasome inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008539273A true JP2008539273A (ja) | 2008-11-13 |
| JP2008539273A5 JP2008539273A5 (https=) | 2009-06-18 |
Family
ID=37308288
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008509175A Abandoned JP2008539273A (ja) | 2005-04-29 | 2006-04-26 | １７−ａａｇ又は１７−ａｇ又はどちらかのプロドラッグをプロテアソーム阻害剤と組み合わせて使用する多発性骨髄腫の治療方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20060252740A1 (https=) |
| EP (1) | EP1874297A4 (https=) |
| JP (1) | JP2008539273A (https=) |
| KR (1) | KR20080007642A (https=) |
| AU (1) | AU2006242446A1 (https=) |
| BR (1) | BRPI0609861A2 (https=) |
| CA (1) | CA2604424A1 (https=) |
| IL (1) | IL186293A0 (https=) |
| MX (1) | MX2007013499A (https=) |
| WO (1) | WO2006119032A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009538881A (ja) * | 2006-06-01 | 2009-11-12 | ヴィロローギク ゲゼルシャフト ミット ベシュレンクテル ハフツング | タンパク質フォールディング及びタンパク質分解の阻害による、ウィルス感染及び／又は腫瘍疾患の治療のための医薬組成物 |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090197852A9 (en) * | 2001-08-06 | 2009-08-06 | Johnson Robert G Jr | Method of treating breast cancer using 17-AAG or 17-AG or a prodrug of either in combination with a HER2 inhibitor |
| US6872715B2 (en) * | 2001-08-06 | 2005-03-29 | Kosan Biosciences, Inc. | Benzoquinone ansamycins |
| US20050026893A1 (en) * | 2003-05-30 | 2005-02-03 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with immunosuppressants |
| US20050020556A1 (en) * | 2003-05-30 | 2005-01-27 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with platinum coordination complexes |
| US20050020534A1 (en) * | 2003-05-30 | 2005-01-27 | Kosan Biosciences, Inc. | Method for treating diseases using HSP90-inhibiting agents in combination with antimetabolites |
| MX2007013494A (es) * | 2005-04-29 | 2008-01-24 | Kosan Biosciences Inc | Metodo para tratar mieloma multiple utilizando 17-aag o 17-ag o un profarmaco de ya sea 17-aag o 17-ag. |
| PE20081506A1 (es) * | 2006-12-12 | 2008-12-09 | Infinity Discovery Inc | Formulaciones de ansamicina |
| JPWO2008108386A1 (ja) * | 2007-03-05 | 2010-06-17 | 協和発酵キリン株式会社 | 医薬組成物 |
| US7442830B1 (en) | 2007-08-06 | 2008-10-28 | Millenium Pharmaceuticals, Inc. | Proteasome inhibitors |
| WO2009023846A2 (en) * | 2007-08-15 | 2009-02-19 | The Research Foundation Of State University Of New York | Methods for heat shock protein dependent cancer treatment |
| US20110118274A1 (en) * | 2007-08-23 | 2011-05-19 | Cornell Research Foundation, Inc. | Proteasome inhibitors and their use in treating pathogen infection and cancer |
| US8672869B2 (en) * | 2007-10-30 | 2014-03-18 | Bellco S.R.L. | Kit, system and method of treating myeloma patients |
| EP2294186B1 (en) * | 2008-05-20 | 2019-10-09 | Incuron, Inc. | Inducing cell death by inhibiting adaptive heat shock response |
| EP2730579A1 (en) | 2008-06-17 | 2014-05-14 | Millennium Pharmaceuticals, Inc. | Boronate ester compounds and pharmaceutical compositions thereof |
| US20120142634A1 (en) * | 2008-11-10 | 2012-06-07 | Mount Sinai School Of Medicine Of New York University | Method of Treating Cancer with a Combination of a Proteasome Inhibitor and Salubrinal |
| CA2763471A1 (en) * | 2009-05-27 | 2010-12-02 | Cephalon, Inc. | Combination therapy for the treatment of multiple myeloma |
| MA39964A (fr) | 2014-05-20 | 2015-11-26 | Millennium Pharm Inc | Inhibiteurs du protéasome contenant du bore destinés à être utilisés après une thérapie contre le cancer primaire |
| US20180172712A1 (en) * | 2015-06-16 | 2018-06-21 | Mayo Foundation For Medical Education And Research | Methods and materials for assessing hydrogen peroxide accumulation in cells |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4261989A (en) * | 1979-02-19 | 1981-04-14 | Kaken Chemical Co. Ltd. | Geldanamycin derivatives and antitumor drug |
| ATE194767T1 (de) * | 1992-03-23 | 2000-08-15 | Univ Georgetown | In liposomen verkapseltes taxol und verwendungsverfahren |
| US5387584A (en) * | 1993-04-07 | 1995-02-07 | Pfizer Inc. | Bicyclic ansamycins |
| WO1994026254A1 (en) * | 1993-05-17 | 1994-11-24 | The Liposome Company, Inc. | Incorporation of taxol into liposomes and gels |
| US5415869A (en) * | 1993-11-12 | 1995-05-16 | The Research Foundation Of State University Of New York | Taxol formulation |
| US5932566A (en) * | 1994-06-16 | 1999-08-03 | Pfizer Inc. | Ansamycin derivatives as antioncogene and anticancer agents |
| US6083903A (en) * | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
| US5662883A (en) * | 1995-01-10 | 1997-09-02 | Nanosystems L.L.C. | Microprecipitation of micro-nanoparticulate pharmaceutical agents |
| US5534270A (en) * | 1995-02-09 | 1996-07-09 | Nanosystems Llc | Method of preparing stable drug nanoparticles |
| US5510118A (en) * | 1995-02-14 | 1996-04-23 | Nanosystems Llc | Process for preparing therapeutic compositions containing nanoparticles |
| US6682758B1 (en) * | 1998-12-22 | 2004-01-27 | The United States Of America As Represented By The Department Of Health And Human Services | Water-insoluble drug delivery system |
| ES2571219T3 (es) * | 2001-01-25 | 2024-09-23 | The United States Of America Represented By The Sec Dep Of Health And Human Services | Formulación de compuestos de ácido borónico |
| DK1373215T3 (da) * | 2001-03-30 | 2006-11-13 | Us Health | Gelanamycinderivater egnet til behandling af cancer |
| US20050043233A1 (en) * | 2003-04-29 | 2005-02-24 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis |
| US6887993B1 (en) * | 2003-11-12 | 2005-05-03 | Kosan Biosciences, Inc. | 11-O-methylgeldanamycin compounds |
| US20050256097A1 (en) * | 2004-05-11 | 2005-11-17 | Kosan Biosciences, Inc. | Pharmaceutical solution formulations containing 17-AAG |
| US20060067953A1 (en) * | 2004-09-29 | 2006-03-30 | Conforma Therapeutics Corporation | Oral pharmaceutical formulations and methods for producing and using same |
| US8999289B2 (en) * | 2005-03-22 | 2015-04-07 | President And Fellows Of Harvard College | Treatment of protein degradation disorders |
-
2006
- 2006-04-26 KR KR1020077027765A patent/KR20080007642A/ko not_active Withdrawn
- 2006-04-26 EP EP06758739A patent/EP1874297A4/en not_active Withdrawn
- 2006-04-26 MX MX2007013499A patent/MX2007013499A/es not_active Application Discontinuation
- 2006-04-26 AU AU2006242446A patent/AU2006242446A1/en not_active Abandoned
- 2006-04-26 BR BRPI0609861-4A patent/BRPI0609861A2/pt not_active IP Right Cessation
- 2006-04-26 US US11/412,299 patent/US20060252740A1/en not_active Abandoned
- 2006-04-26 WO PCT/US2006/016283 patent/WO2006119032A1/en not_active Ceased
- 2006-04-26 CA CA002604424A patent/CA2604424A1/en not_active Abandoned
- 2006-04-26 JP JP2008509175A patent/JP2008539273A/ja not_active Abandoned
-
2007
- 2007-09-25 IL IL186293A patent/IL186293A0/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009538881A (ja) * | 2006-06-01 | 2009-11-12 | ヴィロローギク ゲゼルシャフト ミット ベシュレンクテル ハフツング | タンパク質フォールディング及びタンパク質分解の阻害による、ウィルス感染及び／又は腫瘍疾患の治療のための医薬組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2604424A1 (en) | 2006-11-09 |
| AU2006242446A1 (en) | 2006-11-09 |
| BRPI0609861A2 (pt) | 2010-05-11 |
| WO2006119032A1 (en) | 2006-11-09 |
| EP1874297A1 (en) | 2008-01-09 |
| IL186293A0 (en) | 2008-01-20 |
| US20060252740A1 (en) | 2006-11-09 |
| MX2007013499A (es) | 2008-01-24 |
| EP1874297A4 (en) | 2009-04-22 |
| KR20080007642A (ko) | 2008-01-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008539273A (ja) | １７−ａａｇ又は１７−ａｇ又はどちらかのプロドラッグをプロテアソーム阻害剤と組み合わせて使用する多発性骨髄腫の治療方法 | |
| US11827706B2 (en) | Anti-B7-H1 antibodies for treating tumors | |
| US8003105B2 (en) | Method of treating cancer by co-administration of anticancer agents | |
| EP2632954B1 (en) | Means and methods for treating dlbcl | |
| US12240903B2 (en) | Biomarkers for determining the effectiveness of immune checkpoint inhibitors | |
| JP2022504468A (ja) | 転移性膵臓腺癌の処置 | |
| US20090197852A9 (en) | Method of treating breast cancer using 17-AAG or 17-AG or a prodrug of either in combination with a HER2 inhibitor | |
| KR20070050918A (ko) | 암의 치료 | |
| US7691392B2 (en) | Method of treating multiple myeloma using 17-AAG or 17-AG or a prodrug of either | |
| EP4353265A1 (en) | Method for treating cancer through combination of cd47 inhibitor, immune checkpoint inhibitor, and standard therapy | |
| CN101166526A (zh) | 用17-aag或17-ag或其前药与蛋白酶体抑制剂联合治疗多发性骨髓瘤的方法 | |
| MX2008005467A (en) | Method of treating breast cancer using 17-aag or 17-ag or a prodrug of either in combination with a her2 inhibitor | |
| CN101528705A (zh) | 17-aag或17-ag或两者之一的前药与her2抑制剂联用治疗乳腺癌的方法 | |
| WO2026086908A1 (zh) | Ast-3424治疗免疫检查点抑制剂耐药的癌症患者 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090423 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090423 |
|
| A762 | Written abandonment of application |
Free format text: JAPANESE INTERMEDIATE CODE: A762 Effective date: 20110304 |