JP2015519339A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2015519339A5 JP2015519339A5 JP2015511804A JP2015511804A JP2015519339A5 JP 2015519339 A5 JP2015519339 A5 JP 2015519339A5 JP 2015511804 A JP2015511804 A JP 2015511804A JP 2015511804 A JP2015511804 A JP 2015511804A JP 2015519339 A5 JP2015519339 A5 JP 2015519339A5
- Authority
- JP
- Japan
- Prior art keywords
- protein
- pharmaceutical composition
- composition according
- group
- cancer
- 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.)
- Granted
Links
- 102000004169 proteins and genes Human genes 0.000 claims description 107
- 108090000623 proteins and genes Proteins 0.000 claims description 107
- 239000008194 pharmaceutical composition Substances 0.000 claims description 89
- 102000000412 Annexin Human genes 0.000 claims description 57
- 108050008874 Annexin Proteins 0.000 claims description 57
- 150000001875 compounds Chemical class 0.000 claims description 56
- 238000000034 method Methods 0.000 claims description 46
- 125000005647 linker group Chemical group 0.000 claims description 25
- 230000001225 therapeutic effect Effects 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 21
- 150000003573 thiols Chemical class 0.000 claims description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
- 239000003446 ligand Substances 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 11
- 125000000729 N-terminal amino-acid group Chemical group 0.000 claims description 10
- 108010043958 Peptoids Proteins 0.000 claims description 10
- 239000000090 biomarker Substances 0.000 claims description 10
- 210000004027 cell Anatomy 0.000 claims description 10
- 150000001540 azides Chemical class 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical group NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 101710177166 Phosphoprotein Proteins 0.000 claims description 6
- 150000001299 aldehydes Chemical class 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 102100023635 Alpha-fetoprotein Human genes 0.000 claims description 5
- 102000014914 Carrier Proteins Human genes 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 5
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 150000001345 alkine derivatives Chemical class 0.000 claims description 5
- 108010026331 alpha-Fetoproteins Proteins 0.000 claims description 5
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 239000000178 monomer Substances 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 229940002612 prodrug Drugs 0.000 claims description 5
- 239000000651 prodrug Substances 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 5
- 239000011782 vitamin Substances 0.000 claims description 5
- 235000013343 vitamin Nutrition 0.000 claims description 5
- 229940088594 vitamin Drugs 0.000 claims description 5
- 229930003231 vitamin Natural products 0.000 claims description 5
- 101710191666 Lactadherin Proteins 0.000 claims description 4
- 102100039648 Lactadherin Human genes 0.000 claims description 4
- 108090000901 Transferrin Proteins 0.000 claims description 4
- 102000004338 Transferrin Human genes 0.000 claims description 4
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims description 4
- 150000002576 ketones Chemical class 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
- 150000008055 alkyl aryl sulfonates Chemical class 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 3
- 150000004982 aromatic amines Chemical class 0.000 claims description 3
- 108091008324 binding proteins Proteins 0.000 claims description 3
- 238000006352 cycloaddition reaction Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- 102000003137 synaptotagmin Human genes 0.000 claims description 3
- 108060008004 synaptotagmin Proteins 0.000 claims description 3
- 108010078791 Carrier Proteins Proteins 0.000 claims description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 claims description 2
- SSURCGGGQUWIHH-UHFFFAOYSA-N NNON Chemical compound NNON SSURCGGGQUWIHH-UHFFFAOYSA-N 0.000 claims description 2
- PBODTAIVRFQKHW-UHFFFAOYSA-N O=[C]c1nc[nH]c1[C]=O Chemical group O=[C]c1nc[nH]c1[C]=O PBODTAIVRFQKHW-UHFFFAOYSA-N 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 2
- 230000000269 nucleophilic effect Effects 0.000 claims description 2
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 2
- 239000012474 protein marker Substances 0.000 claims description 2
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 2
- 102000006495 integrins Human genes 0.000 claims 2
- 108010044426 integrins Proteins 0.000 claims 2
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 claims 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 108010024976 Asparaginase Proteins 0.000 claims 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 102100032231 Caveolae-associated protein 2 Human genes 0.000 claims 1
- 108050005259 Caveolae-associated protein 2 Proteins 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 208000006332 Choriocarcinoma Diseases 0.000 claims 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 208000032320 Germ cell tumor of testis Diseases 0.000 claims 1
- 101000780122 Homo sapiens Annexin A5 Proteins 0.000 claims 1
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 229940121849 Mitotic inhibitor Drugs 0.000 claims 1
- 208000034578 Multiple myelomas Diseases 0.000 claims 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010055006 Pancreatic sarcoma Diseases 0.000 claims 1
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000006265 Renal cell carcinoma Diseases 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 1
- 206010057644 Testis cancer Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 208000008383 Wilms tumor Diseases 0.000 claims 1
- 208000009956 adenocarcinoma Diseases 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 230000000340 anti-metabolite Effects 0.000 claims 1
- 229940100197 antimetabolite Drugs 0.000 claims 1
- 239000002256 antimetabolite Substances 0.000 claims 1
- 239000003972 antineoplastic antibiotic Substances 0.000 claims 1
- 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 1
- 229960001467 bortezomib Drugs 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 238000007385 chemical modification Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 1
- 239000003246 corticosteroid Substances 0.000 claims 1
- 230000004069 differentiation Effects 0.000 claims 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims 1
- 229940088598 enzyme Drugs 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims 1
- 229960002584 gefitinib Drugs 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 208000006359 hepatoblastoma Diseases 0.000 claims 1
- 230000003054 hormonal effect Effects 0.000 claims 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims 1
- 229960002411 imatinib Drugs 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 239000000411 inducer Substances 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 201000008026 nephroblastoma Diseases 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 201000004228 ovarian endometrial cancer Diseases 0.000 claims 1
- 201000002526 pancreas sarcoma Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 230000035935 pregnancy Effects 0.000 claims 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 claims 1
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims 1
- 229960001796 sunitinib Drugs 0.000 claims 1
- 201000003120 testicular cancer Diseases 0.000 claims 1
- 208000002918 testicular germ cell tumor Diseases 0.000 claims 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 94
- 108090000672 Annexin A5 Proteins 0.000 description 17
- 102000004121 Annexin A5 Human genes 0.000 description 17
- 229930012538 Paclitaxel Natural products 0.000 description 10
- 239000000539 dimer Substances 0.000 description 10
- 229960001592 paclitaxel Drugs 0.000 description 10
- 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 10
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 8
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 7
- 125000003275 alpha amino acid group Chemical group 0.000 description 7
- 229940045799 anthracyclines and related substance Drugs 0.000 description 7
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 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 6
- 230000000975 bioactive effect Effects 0.000 description 6
- 229940014144 folate Drugs 0.000 description 6
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 6
- 235000019152 folic acid Nutrition 0.000 description 6
- 239000011724 folic acid Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 5
- 239000000470 constituent Substances 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- FWVCSXWHVOOTFJ-UHFFFAOYSA-N 1-(2-chloroethylsulfanyl)-2-[2-(2-chloroethylsulfanyl)ethoxy]ethane Chemical compound ClCCSCCOCCSCCCl FWVCSXWHVOOTFJ-UHFFFAOYSA-N 0.000 description 4
- 108010006654 Bleomycin Proteins 0.000 description 4
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 description 4
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 4
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- 102000016267 Leptin Human genes 0.000 description 4
- 108010092277 Leptin Proteins 0.000 description 4
- 229930126263 Maytansine Natural products 0.000 description 4
- -1 antibodies Substances 0.000 description 4
- 108010044540 auristatin Proteins 0.000 description 4
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 description 4
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 4
- 229960001561 bleomycin Drugs 0.000 description 4
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 4
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 4
- 229930195731 calicheamicin Natural products 0.000 description 4
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 4
- 229940127093 camptothecin Drugs 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 235000018417 cysteine Nutrition 0.000 description 4
- 229960000684 cytarabine Drugs 0.000 description 4
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229960005420 etoposide Drugs 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 4
- 229940039781 leptin Drugs 0.000 description 4
- WKPWGQKGSOKKOO-RSFHAFMBSA-N maytansine Chemical compound CO[C@@H]([C@@]1(O)C[C@](OC(=O)N1)([C@H]([C@@H]1O[C@@]1(C)[C@@H](OC(=O)[C@H](C)N(C)C(C)=O)CC(=O)N1C)C)[H])\C=C\C=C(C)\CC2=CC(OC)=C(Cl)C1=C2 WKPWGQKGSOKKOO-RSFHAFMBSA-N 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 229960001603 tamoxifen Drugs 0.000 description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 3
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 3
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 3
- 150000001371 alpha-amino acids Chemical class 0.000 description 3
- 235000008206 alpha-amino acids Nutrition 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 239000000833 heterodimer Substances 0.000 description 3
- 239000000710 homodimer Substances 0.000 description 3
- 125000001151 peptidyl group Chemical group 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 229960003048 vinblastine Drugs 0.000 description 3
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 3
- 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 3
- 229960004528 vincristine Drugs 0.000 description 3
- 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 3
- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 description 2
- 125000005865 C2-C10alkynyl group Chemical group 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102100034256 Mucin-1 Human genes 0.000 description 2
- 108010008707 Mucin-1 Proteins 0.000 description 2
- 108010055170 Synaptotagmin I Proteins 0.000 description 2
- 102000001317 Synaptotagmin I Human genes 0.000 description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 230000005809 anti-tumor immunity Effects 0.000 description 2
- 239000012867 bioactive agent Substances 0.000 description 2
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 239000000696 magnetic material Substances 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000013638 trimer Substances 0.000 description 2
- DLKUYSQUHXBYPB-NSSHGSRYSA-N (2s,4r)-4-[[2-[(1r,3r)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(C)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C DLKUYSQUHXBYPB-NSSHGSRYSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- XQUPVDVFXZDTLT-UHFFFAOYSA-N 1-[4-[[4-(2,5-dioxopyrrol-1-yl)phenyl]methyl]phenyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(C=C1)=CC=C1CC1=CC=C(N2C(C=CC2=O)=O)C=C1 XQUPVDVFXZDTLT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 1
- FZRKAZHKEDOPNN-UHFFFAOYSA-N Nitric oxide anion Chemical compound O=[N-] FZRKAZHKEDOPNN-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 102000006815 folate receptor Human genes 0.000 description 1
- 108020005243 folate receptor Proteins 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 239000013636 protein dimer Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000710 thiopropargyl group Chemical group [H]SC#CC([H])([H])* 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229930184737 tubulysin Natural products 0.000 description 1
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261688308P | 2012-05-11 | 2012-05-11 | |
| US61/688,308 | 2012-05-11 | ||
| US201261741984P | 2012-08-01 | 2012-08-01 | |
| US61/741,984 | 2012-08-01 | ||
| US201361848601P | 2013-01-07 | 2013-01-07 | |
| US61/848,601 | 2013-01-07 | ||
| US201361849034P | 2013-01-17 | 2013-01-17 | |
| US61/849,034 | 2013-01-17 | ||
| PCT/US2013/040823 WO2013170272A2 (en) | 2012-05-11 | 2013-05-13 | Site-specific labeling and targeted delivery of proteins for the treatment of cancer |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015519339A JP2015519339A (ja) | 2015-07-09 |
| JP2015519339A5 true JP2015519339A5 (enExample) | 2016-07-07 |
| JP6290187B2 JP6290187B2 (ja) | 2018-03-07 |
Family
ID=49551481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015511804A Expired - Fee Related JP6290187B2 (ja) | 2012-05-11 | 2013-05-13 | 癌の処置のためのタンパク質の部位特異的標識及び標的送達 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US9545449B2 (enExample) |
| EP (1) | EP2850201A4 (enExample) |
| JP (1) | JP6290187B2 (enExample) |
| CA (1) | CA2873112A1 (enExample) |
| WO (1) | WO2013170272A2 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8288557B2 (en) | 2004-07-23 | 2012-10-16 | Endocyte, Inc. | Bivalent linkers and conjugates thereof |
| CN101678124A (zh) | 2007-03-14 | 2010-03-24 | 恩多塞特公司 | 结合配体连接的微管溶素递药缀合物 |
| CN104383553A (zh) | 2007-06-25 | 2015-03-04 | 恩多塞特公司 | 含有亲水性间隔区接头的共轭物 |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| US10080805B2 (en) | 2012-02-24 | 2018-09-25 | Purdue Research Foundation | Cholecystokinin B receptor targeting for imaging and therapy |
| US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
| US9662402B2 (en) | 2012-10-16 | 2017-05-30 | Endocyte, Inc. | Drug delivery conjugates containing unnatural amino acids and methods for using |
| PL2991683T3 (pl) | 2013-05-02 | 2020-03-31 | Glykos Finland Oy | Koniugaty glikoproteiny lub glikanu z toksycznym ładunkiem |
| NZ758050A (en) | 2013-10-15 | 2024-03-22 | Seagen Inc | Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics |
| CN106573956A (zh) | 2014-06-13 | 2017-04-19 | 诺华股份有限公司 | 澳瑞他汀衍生物及其缀合物 |
| CN107743494B (zh) | 2015-06-02 | 2022-04-29 | 诺和诺德股份有限公司 | 具有极性重组延伸体的胰岛素 |
| CN108135881B (zh) * | 2015-08-11 | 2020-11-13 | 同宜医药（苏州）有限公司 | 多配体药物偶联体及其用途 |
| GB2542391A (en) * | 2015-09-17 | 2017-03-22 | Annexin Pharmaceuticals Ab | Process of manufacture |
| MA43348A (fr) | 2015-10-01 | 2018-08-08 | Novo Nordisk As | Conjugués de protéines |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| ES2919323T3 (es) | 2015-12-04 | 2022-07-26 | Seagen Inc | Conjugados de compuestos de tubulisina cuaternizados |
| JP7073266B2 (ja) | 2016-03-25 | 2022-05-23 | シージェン インコーポレイテッド | Ｐｅｇ化薬物リンカー及びその中間体を調製するためのプロセス |
| EP3570894A4 (en) * | 2017-01-17 | 2021-04-07 | The Texas A&M University System | ENDOLYSOSOMAL TARGETING CONJUGATES FOR BETTER LOAD MOLECULES DISTRIBUTION TO ENDOLYSOSOMAL COMPARTMENT OF TARGET CELLS |
| KR102648564B1 (ko) | 2017-03-24 | 2024-03-19 | 씨젠 인크. | 글루쿠로니드 약물-링커의 제조 공정 및 그 중간물 |
| JP2020513019A (ja) | 2017-04-05 | 2020-04-30 | ノヴォ ノルディスク アー／エス | オリゴマー伸長インスリン−Ｆｃコンジュゲート |
| CN113454097B (zh) | 2018-12-21 | 2024-08-30 | 里珍纳龙药品有限公司 | 微管溶素及蛋白质-微管溶素偶联物 |
| EP3980076A1 (en) * | 2019-06-05 | 2022-04-13 | Boston Scientific Scimed, Inc. | Click chemistry capturable platinum-based antineoplastic agents |
| AU2022307460A1 (en) * | 2021-07-09 | 2024-01-04 | Bright Peak Therapeutics Ag | Checkpoint inhibitors conjugated to il-2, and uses thereof |
| US20230201365A1 (en) * | 2021-07-09 | 2023-06-29 | Bright Peak Therapeutics Ag | Modified cd20 antibodies and uses thereof |
| CN116407640B (zh) * | 2023-03-03 | 2025-10-31 | 河南真实生物科技有限公司 | 包含阿兹夫定和化疗试剂的抗肿瘤药物组合物 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5066490A (en) * | 1988-06-01 | 1991-11-19 | The United States Of America As Represented By The Secretary Of The Department Of Health & Human Services | Protein crosslinking reagents cleavable within acidified intracellular vesicles |
| ES2235336T3 (es) | 1997-06-13 | 2005-07-01 | Gryphon Therapeutics, Inc. | Ligacion quimica nativa en fase solida de peptidos desprotegidos o protegidos en la cisteina n-terminal en solucion acuosa. |
| US6017876A (en) | 1997-08-15 | 2000-01-25 | Amgen Inc. | Chemical modification of granulocyte-colony stimulating factor (G-CSF) bioactivity |
| US5900404A (en) | 1997-08-15 | 1999-05-04 | Amgen Inc. | Chemical modification of proteins to improve biocompatibility and bioactivity |
| US6787154B2 (en) | 1998-10-20 | 2004-09-07 | Salvatore Albani | Artificial antigen presenting cells |
| US20020164649A1 (en) | 2000-10-25 | 2002-11-07 | Rajendra Singh | Mass tags for quantitative analysis |
| WO2002087497A2 (en) * | 2001-04-26 | 2002-11-07 | Board Of Regents, The University Of Texas System | Therapeutic agent/ligand conjugate compositions, their methods of synthesis and use |
| AU2003228449A1 (en) | 2002-04-04 | 2003-10-27 | California Institute Of Technology | Directed protein docking algorithm |
| GB0209896D0 (en) * | 2002-04-30 | 2002-06-05 | Molmed Spa | Conjugate |
| JP4800614B2 (ja) * | 2002-07-19 | 2011-10-26 | ザ ジェネラル ホスピタル コーポレイション | オキシム結合体、およびそれらの形成および使用のための方法 |
| US20110002978A1 (en) * | 2003-06-17 | 2011-01-06 | Harrison Roger G | Enzyme prodrug cancer therapy selectively targeted to tumor cells or tumor vasculature and methods of production and use thereof |
| AP2081A (en) | 2004-06-18 | 2010-01-04 | Ipf Pharmaceuticals Gmbh | Oligomeric peptides and their use for the treatment of HIV infections |
| US8946391B2 (en) | 2006-03-24 | 2015-02-03 | The Regents Of The University Of California | Construction of a multivalent scFv through alkyne-azide 1,3-dipolar cycloaddition |
| WO2009158668A1 (en) * | 2008-06-26 | 2009-12-30 | Prolynx Llc | Prodrugs and drug-macromolecule conjugates having controlled drug release rates |
| CA2739445A1 (en) * | 2008-10-03 | 2010-04-08 | Advanced Proteome Therapeutics, Inc. | Site specific n-terminal modifications of proteins and conjugate formation |
| CA2764029C (en) * | 2009-06-03 | 2019-10-29 | Mosamedix B.V. | Method for enhancing phagocytosis of phosphatidylserine-exposing cells |
| US8927485B2 (en) | 2010-02-18 | 2015-01-06 | Advanced Proteome Therapeutics Inc. | Site-specific modification of proteins through chemical modification enabling protein conjugates, protein dimer formation, and stapled peptides |
| US8946405B2 (en) * | 2010-05-05 | 2015-02-03 | Prolynx Llc | Controlled release from solid supports |
| CA2801064A1 (en) | 2010-06-01 | 2011-12-08 | Advanced Proteome Therapeutics Inc. | Crosslinking of proteins and other entities via conjugates of alpha-haloacetophenones, benzyl halides, quinones, and their derivatives |
-
2013
- 2013-05-13 US US14/400,190 patent/US9545449B2/en active Active
- 2013-05-13 EP EP13787738.7A patent/EP2850201A4/en not_active Withdrawn
- 2013-05-13 JP JP2015511804A patent/JP6290187B2/ja not_active Expired - Fee Related
- 2013-05-13 WO PCT/US2013/040823 patent/WO2013170272A2/en not_active Ceased
- 2013-05-13 CA CA2873112A patent/CA2873112A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2015519339A5 (enExample) | ||
| EP3912641B1 (en) | Hydrophilic drug-linker compounds | |
| US20230248842A1 (en) | Site-specific antibody conjugation and antibody-drug conjugate as specific embodiment thereof | |
| Shah et al. | Targeted nanomedicine for suppression of CD44 and simultaneous cell death induction in ovarian cancer: an optimal delivery of siRNA and anticancer drug | |
| JP2018138588A (ja) | 新規リンカー、その製造方法およびその応用 | |
| CN108779127A (zh) | 美登素类化合物衍生物、其偶联物和使用方法 | |
| TWI838358B (zh) | 疏水性奧瑞他汀(auristatin)f化合物及其結合物 | |
| JP2002543111A (ja) | ポリマーを使用する葉酸で仲介された腫瘍細胞へのターゲッティングの増幅 | |
| US20090069220A1 (en) | Dna-binding polyamide drug conjugates | |
| CN112080467A (zh) | 用于过继细胞疗法的肿瘤浸润淋巴细胞 | |
| CN113631539B (zh) | 用于制备抗体-载荷部分偶联物的化合物及其用途 | |
| WO2015165413A1 (zh) | 一种新型的稳定型抗体药物耦联物及其制备方法和用途 | |
| JP7780253B2 (ja) | ステープルペプチドの細胞内送達のためのポリペプチド接合体 | |
| TW201004647A (en) | Novel dual targeting antitumoural conjugates | |
| JPH10502334A (ja) | 受容体調節剤およびこれに関連した方法 | |
| TWI618697B (zh) | 化合物、連接子－藥物、及配體－藥物耦合體 | |
| RU2007116973A (ru) | Терапевтические средства с пониженной токсичностью | |
| WO2021167107A1 (ja) | ヒトトランスフェリンレセプター結合ペプチド | |
| JPWO2020027100A5 (enExample) | ||
| US7311892B2 (en) | Multidrug multiligand conjugates for targeted drug delivery | |
| JP2018507689A5 (enExample) | ||
| JP7356677B2 (ja) | 複合体 | |
| JP2024543016A (ja) | トランス－シクロオクテンコンジュゲート | |
| JP2024542021A (ja) | ペイロードのｉｎ ｖｉｖｏ標的化送達用のテトラジンコンジュゲート | |
| Krauss et al. | Novel daunorubicin‐carrier peptide conjugates derived from human calcitonin segments |