JP2008539265A - １７−ａａｇ又は１７−ａｇ又はどちらかのプロドラッグを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使用する多発性骨髄腫の治療方法 Download PDFInfo
- Publication number
- JP2008539265A JP2008539265A JP2008509123A JP2008509123A JP2008539265A JP 2008539265 A JP2008539265 A JP 2008539265A JP 2008509123 A JP2008509123 A JP 2008509123A JP 2008509123 A JP2008509123 A JP 2008509123A JP 2008539265 A JP2008539265 A JP 2008539265A
- Authority
- JP
- Japan
- Prior art keywords
- aag
- dose
- patient
- administered
- max
- 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 276
- 238000000034 method Methods 0.000 title claims abstract description 80
- 229940002612 prodrug Drugs 0.000 title claims abstract description 58
- 239000000651 prodrug Substances 0.000 title claims abstract description 58
- 206010035226 Plasma cell myeloma Diseases 0.000 title claims abstract description 29
- 208000034578 Multiple myelomas Diseases 0.000 title claims abstract description 10
- 229950007866 tanespimycin Drugs 0.000 title description 220
- 239000003795 chemical substances by application Substances 0.000 title description 3
- 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 114
- 238000011282 treatment Methods 0.000 claims description 91
- 210000004027 cell Anatomy 0.000 claims description 40
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 17
- 230000001225 therapeutic effect Effects 0.000 claims description 17
- 230000001965 increasing effect Effects 0.000 claims description 15
- 230000003442 weekly effect Effects 0.000 claims description 13
- 238000009826 distribution Methods 0.000 claims description 11
- 230000006907 apoptotic process Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 210000001185 bone marrow Anatomy 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000006698 induction Effects 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 claims description 2
- 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
- 206010028980 Neoplasm Diseases 0.000 description 37
- 239000003814 drug Substances 0.000 description 31
- 210000002966 serum Anatomy 0.000 description 31
- 229940079593 drug Drugs 0.000 description 30
- 238000009472 formulation Methods 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- 230000004044 response Effects 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 201000011510 cancer Diseases 0.000 description 22
- 201000010099 disease Diseases 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- 238000001802 infusion Methods 0.000 description 20
- 230000036470 plasma concentration Effects 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 230000009467 reduction Effects 0.000 description 15
- 231100000419 toxicity Toxicity 0.000 description 15
- 230000001988 toxicity Effects 0.000 description 15
- 101710085938 Matrix protein Proteins 0.000 description 14
- 101710127721 Membrane protein Proteins 0.000 description 14
- 229960003957 dexamethasone Drugs 0.000 description 14
- 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 14
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 13
- 108091008611 Protein Kinase B Proteins 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 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 11
- 238000002512 chemotherapy Methods 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- 239000002207 metabolite Substances 0.000 description 11
- 230000003285 pharmacodynamic effect Effects 0.000 description 11
- 210000004180 plasmocyte Anatomy 0.000 description 11
- 239000008389 polyethoxylated castor oil Substances 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 229940126534 drug product Drugs 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 239000000825 pharmaceutical preparation Substances 0.000 description 10
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000008859 change Effects 0.000 description 9
- 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
- 238000001990 intravenous administration Methods 0.000 description 9
- 208000037821 progressive disease Diseases 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 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 8
- 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
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 231100000226 haematotoxicity Toxicity 0.000 description 8
- 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 7
- 102100032965 Myomesin-2 Human genes 0.000 description 7
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 7
- 239000008186 active pharmaceutical agent Substances 0.000 description 7
- 208000007502 anemia Diseases 0.000 description 7
- 238000009093 first-line therapy Methods 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 238000012360 testing method Methods 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
- 241000282472 Canis lupus familiaris Species 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
- 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 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000002438 mitochondrial effect Effects 0.000 description 6
- 150000003904 phospholipids Chemical class 0.000 description 6
- 238000011476 stem cell transplantation Methods 0.000 description 6
- 101710113864 Heat shock protein 90 Proteins 0.000 description 5
- 208000037147 Hypercalcaemia Diseases 0.000 description 5
- 206010028813 Nausea Diseases 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 229960001467 bortezomib Drugs 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 230000000148 hypercalcaemia Effects 0.000 description 5
- 208000030915 hypercalcemia disease Diseases 0.000 description 5
- 230000002101 lytic effect Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000008693 nausea Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 230000002485 urinary effect Effects 0.000 description 5
- 239000008215 water for injection Substances 0.000 description 5
- 206010012735 Diarrhoea Diseases 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
- 208000007452 Plasmacytoma Diseases 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 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 4
- 239000003246 corticosteroid Substances 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 4
- 206010016256 fatigue Diseases 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
- 238000005259 measurement Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 229960003433 thalidomide Drugs 0.000 description 4
- 210000002700 urine Anatomy 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101001047681 Homo sapiens Tyrosine-protein kinase Lck Proteins 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 108010006519 Molecular Chaperones Proteins 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
- 238000011394 anticancer treatment Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 102000015736 beta 2-Microglobulin Human genes 0.000 description 3
- 108010081355 beta 2-Microglobulin Proteins 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000011254 conventional chemotherapy Methods 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 238000011161 development Methods 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
- 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
- 238000003119 immunoblot Methods 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
- 239000003112 inhibitor Substances 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
- 210000000265 leukocyte Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 229960001924 melphalan Drugs 0.000 description 3
- 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 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
- 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
- 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
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 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
- 239000004803 Di-2ethylhexylphthalate Substances 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- 206010059024 Gastrointestinal toxicity Diseases 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
- 102000005431 Molecular Chaperones Human genes 0.000 description 2
- 208000001132 Osteoporosis Diseases 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
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 231100000313 clinical toxicology Toxicity 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000002354 daily effect 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
- 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
- 230000005750 disease progression Effects 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
- -1 erbB2 Proteins 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 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 2
- 201000005884 exanthem Diseases 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
- 239000011521 glass Substances 0.000 description 2
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 229960004942 lenalidomide Drugs 0.000 description 2
- 239000002502 liposome Substances 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
- 231100000682 maximum tolerated dose Toxicity 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
- 230000002265 prevention Effects 0.000 description 2
- 229930010796 primary metabolite Natural products 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 229940120975 revlimid Drugs 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 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
- 230000007730 Akt signaling Effects 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000004121 Annexin A5 Human genes 0.000 description 1
- 108090000672 Annexin A5 Proteins 0.000 description 1
- 102000010565 Apoptosis Regulatory Proteins Human genes 0.000 description 1
- 108010063104 Apoptosis Regulatory Proteins Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091007914 CDKs Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 206010009944 Colon cancer Diseases 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
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000283086 Equidae Species 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
- 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
- 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 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 101000967216 Homo sapiens Eosinophil cationic protein Proteins 0.000 description 1
- 101000712530 Homo sapiens RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- 206010020631 Hypergammaglobulinaemia benign monoclonal Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 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
- 206010027480 Metastatic malignant melanoma Diseases 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
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010033645 Pancreatitis 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
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 1
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010070308 Refractory cancer Diseases 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 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
- 206010047924 Wheezing Diseases 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 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
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 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
- 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
- 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
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 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
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death 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
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940115080 doxil Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000008406 drug-drug interaction Effects 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
- 229930013356 epothilone Natural products 0.000 description 1
- 150000003883 epothilone derivatives Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000010195 expression analysis Methods 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
- 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
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 238000011223 gene expression profiling Methods 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
- 230000008642 heat stress Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 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
- 230000007686 hepatotoxicity Effects 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
- 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
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 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
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000006662 intracellular pathway Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011005 laboratory method Methods 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
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000007056 liver toxicity Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 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
- 238000002493 microarray Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 201000005328 monoclonal gammopathy of uncertain significance Diseases 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
- 230000000737 periodic effect Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 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
- 229920000573 polyethylene Polymers 0.000 description 1
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000002601 radiography Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
- 230000001105 regulatory effect 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
- 238000012216 screening 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
- 231100000046 skin rash Toxicity 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
- 210000000130 stem cell Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 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
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 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
- 229940099039 velcade Drugs 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
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67644905P | 2005-04-29 | 2005-04-29 | |
| US68094405P | 2005-05-12 | 2005-05-12 | |
| US72170705P | 2005-09-28 | 2005-09-28 | |
| US74920005P | 2005-12-09 | 2005-12-09 | |
| PCT/US2006/016043 WO2006118953A2 (en) | 2005-04-29 | 2006-04-26 | Method of treating multiple myeloma using 17-aag of 17-ag of a prodrug of either |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008539265A true JP2008539265A (ja) | 2008-11-13 |
| JP2008539265A5 JP2008539265A5 (enExample) | 2009-06-18 |
Family
ID=37308498
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008509123A Abandoned JP2008539265A (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使用する多発性骨髄腫の治療方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7691392B2 (enExample) |
| EP (1) | EP1874296A4 (enExample) |
| JP (1) | JP2008539265A (enExample) |
| KR (1) | KR20080000682A (enExample) |
| CN (1) | CN101175489A (enExample) |
| AU (1) | AU2006242540A1 (enExample) |
| BR (1) | BRPI0610411A2 (enExample) |
| CA (1) | CA2604473A1 (enExample) |
| IL (1) | IL186292A0 (enExample) |
| MX (1) | MX2007013494A (enExample) |
| RU (1) | RU2007144195A (enExample) |
| WO (1) | WO2006118953A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016505018A (ja) * | 2013-01-11 | 2016-02-18 | アブラクシス バイオサイエンス， エルエルシー | 膵臓がんの処置方法 |
Families Citing this family (3)
| 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 |
| PE20081506A1 (es) * | 2006-12-12 | 2008-12-09 | Infinity Discovery Inc | Formulaciones de ansamicina |
| CN110917190B (zh) * | 2019-11-29 | 2022-12-23 | 中国人民解放军军事科学院军事医学研究院 | 一种抑制阿片类镇痛药物不良反应的制剂及其应用 |
Family Cites Families (27)
| 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 |
| AU3415295A (en) * | 1994-09-22 | 1996-04-09 | Glenayre Electronics, Inc | Synchronized paging system |
| 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 |
| US6458373B1 (en) | 1997-01-07 | 2002-10-01 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| 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 |
| WO2000071163A1 (en) | 1999-05-24 | 2000-11-30 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
| GB9918429D0 (en) | 1999-08-04 | 1999-10-06 | Novartis Ag | Organic compounds |
| TW200408407A (en) * | 2001-11-30 | 2004-06-01 | Dana Farber Cancer Inst Inc | Methods and compositions for modulating the immune system and uses thereof |
| CA2481683A1 (en) | 2002-04-10 | 2003-10-23 | Conforma Therapeutics Corporation | Ansamycin formulations and methods for producing and using same |
| WO2004000229A2 (en) * | 2002-06-24 | 2003-12-31 | Research Development Foundation | Treatment of human multiple myeloma by curcumin |
| JP2006514994A (ja) | 2003-03-13 | 2006-05-18 | コンフォーマ・セラピューティクス・コーポレイション | 長鎖および中鎖トリグリセリドを有する医薬製剤 |
| 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 |
| US7282493B2 (en) * | 2003-12-23 | 2007-10-16 | Infinity Pharmaceuticals, Inc. | Analogs of benzoquinone-containing ansamycins and methods of use thereof |
| US20050256097A1 (en) * | 2004-05-11 | 2005-11-17 | Kosan Biosciences, Inc. | Pharmaceutical solution formulations containing 17-AAG |
| WO2005115431A2 (en) | 2004-05-24 | 2005-12-08 | Adonia Papathanassiu | Methods for inhibiting proteasome and heat shock protein 90 |
| WO2006034147A2 (en) | 2004-09-16 | 2006-03-30 | Abraxis Bioscience, Inc. | Compositions and methods for the preparation and administration of poorly water soluble drugs |
| US20060067953A1 (en) * | 2004-09-29 | 2006-03-30 | Conforma Therapeutics Corporation | Oral pharmaceutical formulations and methods for producing and using same |
| JP2008531708A (ja) | 2005-02-28 | 2008-08-14 | コーザン バイオサイエンシス インコーポレイテッド | １７−アリルアミノ−１７−デメトキシゲルダナマイシンを含有する医薬製剤 |
| CA2601706C (en) * | 2005-03-22 | 2016-09-20 | Dana-Farber Cancer Institute, Inc. | Treatment of protein degradation disorders |
| EP1874297A4 (en) * | 2005-04-29 | 2009-04-22 | Kosan Biosciences Inc | METHOD OF TREATING MULTIPLE MYELOMES USING 17AGENE OR 17-AG OR A PRODRUG OR ALL IN COMBINATION WITH A PROTEASOMIC INHIBITOR |
-
2006
- 2006-04-26 CN CNA2006800140087A patent/CN101175489A/zh active Pending
- 2006-04-26 JP JP2008509123A patent/JP2008539265A/ja not_active Abandoned
- 2006-04-26 RU RU2007144195/14A patent/RU2007144195A/ru not_active Application Discontinuation
- 2006-04-26 WO PCT/US2006/016043 patent/WO2006118953A2/en not_active Ceased
- 2006-04-26 US US11/412,298 patent/US7691392B2/en not_active Expired - Fee Related
- 2006-04-26 AU AU2006242540A patent/AU2006242540A1/en not_active Abandoned
- 2006-04-26 MX MX2007013494A patent/MX2007013494A/es not_active Application Discontinuation
- 2006-04-26 EP EP06751653A patent/EP1874296A4/en not_active Withdrawn
- 2006-04-26 KR KR1020077027686A patent/KR20080000682A/ko not_active Withdrawn
- 2006-04-26 CA CA002604473A patent/CA2604473A1/en not_active Abandoned
- 2006-04-26 BR BRPI0610411-8A patent/BRPI0610411A2/pt not_active IP Right Cessation
-
2007
- 2007-09-25 IL IL186292A patent/IL186292A0/en unknown
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016505018A (ja) * | 2013-01-11 | 2016-02-18 | アブラクシス バイオサイエンス， エルエルシー | 膵臓がんの処置方法 |
| US9855220B2 (en) | 2013-01-11 | 2018-01-02 | Abraxis Bioscience, Llc | Methods of treating pancreatic cancer |
| JP2018087235A (ja) * | 2013-01-11 | 2018-06-07 | アブラクシス バイオサイエンス， エルエルシー | 膵臓がんの処置方法 |
| JP2019081790A (ja) * | 2013-01-11 | 2019-05-30 | アブラクシス バイオサイエンス， エルエルシー | 膵臓がんの処置方法 |
| US10328031B2 (en) | 2013-01-11 | 2019-06-25 | Abraxis Bioscience, Llc | Methods of treating pancreatic cancer |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2007144195A (ru) | 2009-06-10 |
| EP1874296A2 (en) | 2008-01-09 |
| IL186292A0 (en) | 2008-08-07 |
| MX2007013494A (es) | 2008-01-24 |
| WO2006118953A2 (en) | 2006-11-09 |
| WO2006118953A3 (en) | 2007-12-06 |
| US7691392B2 (en) | 2010-04-06 |
| CN101175489A (zh) | 2008-05-07 |
| KR20080000682A (ko) | 2008-01-02 |
| BRPI0610411A2 (pt) | 2010-06-22 |
| EP1874296A4 (en) | 2010-06-30 |
| AU2006242540A1 (en) | 2006-11-09 |
| US20060252739A1 (en) | 2006-11-09 |
| CA2604473A1 (en) | 2006-11-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2702332C2 (ru) | Антитела к в7-н1 и к ctla-4 для лечения немелкоклеточного рака легкого | |
| AU2014320343B2 (en) | Anti-B7-H1 antibodies for treating tumors | |
| 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 | |
| US8003105B2 (en) | Method of treating cancer by co-administration of anticancer agents | |
| CN112263677A (zh) | 用于治疗癌症的pd-1/pd-l1抑制剂 | |
| JP6695003B2 (ja) | 癌のための併用療法 | |
| US20200155599A1 (en) | Anti-egfr/high affinity nk-cells compositions and methods for chordoma treatment | |
| JP2022504468A (ja) | 転移性膵臓腺癌の処置 | |
| KR20070050918A (ko) | 암의 치료 | |
| US20090197852A9 (en) | Method of treating breast cancer using 17-AAG or 17-AG or a prodrug of either in combination with a HER2 inhibitor | |
| Reardon et al. | Ridaforolimus for patients with progressive or recurrent malignant glioma: a perisurgical, sequential, ascending-dose trial | |
| JP2008539265A (ja) | １７−ａａｇ又は１７−ａｇ又はどちらかのプロドラッグを使用する多発性骨髄腫の治療方法 | |
| KR20200003811A (ko) | 백금-내성 암 치료제 | |
| 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 | |
| HK40040793A (en) | Pd-1 / pd-l1 inhibitors for the treatment of cancer | |
| CN120957724A (zh) | 索托拉西布/卡铂/培美曲塞在癌症治疗中的剂量方案 | |
| HK1242210A1 (en) | Pd-1 / pd-l1 inhibitors for the treatment of cancer | |
| BR112016026197B1 (pt) | Uso de medi4736 e tremelimumab |
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 |