ZA200307682B - Combination methods of inhibiting tumor growth with a vascular endothelial growth factor receptor antagonist. - Google Patents

Info

Publication number

ZA200307682B

ZA200307682B ZA200307682A ZA200307682A ZA200307682B ZA 200307682 B ZA200307682 B ZA 200307682B ZA 200307682 A ZA200307682 A ZA 200307682A ZA 200307682 A ZA200307682 A ZA 200307682A ZA 200307682 B ZA200307682 B ZA 200307682B

Authority

ZA

South Africa

Prior art keywords

vegf

vegfr

antibody

substance

composition

Prior art date

2001-03-02

Links

• Espacenet
• Global Dossier
• Discuss

• 108091008605 VEGF receptors Proteins 0.000 title claims description 180
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 title claims description 163
• 238000000034 method Methods 0.000 title claims description 110
• 239000002464 receptor antagonist Substances 0.000 title claims description 53
• 230000004614 tumor growth Effects 0.000 title claims description 44
• 230000002401 inhibitory effect Effects 0.000 title claims description 35
• 229940124676 vascular endothelial growth factor receptor Drugs 0.000 title description 65
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 208
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 208
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 208
• 102000005962 receptors Human genes 0.000 claims description 168
• 108020003175 receptors Proteins 0.000 claims description 168
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 153
• 206010028980 Neoplasm Diseases 0.000 claims description 110
• 230000027455 binding Effects 0.000 claims description 98
• 102000001301 EGF receptor Human genes 0.000 claims description 94
• 108060006698 EGF receptor Proteins 0.000 claims description 92
• 239000005557 antagonist Substances 0.000 claims description 76
• 239000000203 mixture Substances 0.000 claims description 58
• 239000000126 substance Substances 0.000 claims description 55
• 238000011282 treatment Methods 0.000 claims description 54
• 229940044551 receptor antagonist Drugs 0.000 claims description 52
• 239000003446 ligand Substances 0.000 claims description 51
• 229940122558 EGFR antagonist Drugs 0.000 claims description 43
• 239000002246 antineoplastic agent Substances 0.000 claims description 42
• 150000003384 small molecules Chemical class 0.000 claims description 36
• 230000005855 radiation Effects 0.000 claims description 35
• 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 claims description 31
• 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 claims description 30
• 229940127089 cytotoxic agent Drugs 0.000 claims description 30
• 230000012010 growth Effects 0.000 claims description 17
• 238000004519 manufacturing process Methods 0.000 claims description 17
• 229940123777 Vascular endothelial growth factor (VEGF)receptor antagonist Drugs 0.000 claims description 13
• 229940034982 antineoplastic agent Drugs 0.000 claims description 13
• 108010047041 Complementarity Determining Regions Proteins 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 10
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 8
• 239000002671 adjuvant Substances 0.000 claims description 7
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 7
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 7
• 229930012538 Paclitaxel Natural products 0.000 claims description 6
• 210000004185 liver Anatomy 0.000 claims description 6
• 229960001592 paclitaxel Drugs 0.000 claims description 6
• 210000003491 skin Anatomy 0.000 claims description 6
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 5
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims description 5
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 claims description 5
• 210000004556 brain Anatomy 0.000 claims description 5
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 5
• 229960004316 cisplatin Drugs 0.000 claims description 5
• 210000003734 kidney Anatomy 0.000 claims description 5
• 210000004072 lung Anatomy 0.000 claims description 5
• 210000002307 prostate Anatomy 0.000 claims description 5
• 210000000952 spleen Anatomy 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 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 claims description 4
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 4
• 210000001072 colon Anatomy 0.000 claims description 4
• 208000029742 colonic neoplasm Diseases 0.000 claims description 4
• 229960004679 doxorubicin Drugs 0.000 claims description 4
• 210000003128 head Anatomy 0.000 claims description 4
• 210000002216 heart Anatomy 0.000 claims description 4
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 claims description 4
• 210000003739 neck Anatomy 0.000 claims description 4
• 210000001672 ovary Anatomy 0.000 claims description 4
• 229960003171 plicamycin Drugs 0.000 claims description 4
• 210000000813 small intestine Anatomy 0.000 claims description 4
• 229960001052 streptozocin Drugs 0.000 claims description 4
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims description 4
• 210000001541 thymus gland Anatomy 0.000 claims description 4
• 210000003932 urinary bladder Anatomy 0.000 claims description 4
• 210000004291 uterus Anatomy 0.000 claims description 4
• 208000026310 Breast neoplasm Diseases 0.000 claims description 3
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 3
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 3
• 210000004369 blood Anatomy 0.000 claims description 3
• 239000008280 blood Substances 0.000 claims description 3
• 210000000988 bone and bone Anatomy 0.000 claims description 3
• 210000001185 bone marrow Anatomy 0.000 claims description 3
• 210000003679 cervix uteri Anatomy 0.000 claims description 3
• 229960003901 dacarbazine Drugs 0.000 claims description 3
• 229960004961 mechlorethamine Drugs 0.000 claims description 3
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 3
• 210000000496 pancreas Anatomy 0.000 claims description 3
• FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 claims description 2
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 2
• QXLQZLBNPTZMRK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-(2,4-dimethylphenyl)prop-2-en-1-one Chemical compound CN(C)CC(=C)C(=O)C1=CC=C(C)C=C1C QXLQZLBNPTZMRK-UHFFFAOYSA-N 0.000 claims description 2
• IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims description 2
• WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 2
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 2
• 108010024976 Asparaginase Proteins 0.000 claims description 2
• 102000015790 Asparaginase Human genes 0.000 claims description 2
• 108010006654 Bleomycin Proteins 0.000 claims description 2
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
• JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 claims description 2
• PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• 108010092160 Dactinomycin Proteins 0.000 claims description 2
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
• 102000006992 Interferon-alpha Human genes 0.000 claims description 2
• 108010047761 Interferon-alpha Proteins 0.000 claims description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
• 108010000817 Leuprolide Proteins 0.000 claims description 2
• 229930192392 Mitomycin Natural products 0.000 claims description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 2
• FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 claims description 2
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 2
• 229960005310 aldesleukin Drugs 0.000 claims description 2
• 108700025316 aldesleukin Proteins 0.000 claims description 2
• 229960003272 asparaginase Drugs 0.000 claims description 2
• DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 claims description 2
• 229960001561 bleomycin Drugs 0.000 claims description 2
• 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 claims description 2
• 229960002092 busulfan Drugs 0.000 claims description 2
• 229960004562 carboplatin Drugs 0.000 claims description 2
• 229960005243 carmustine Drugs 0.000 claims description 2
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 2
• 229960004630 chlorambucil Drugs 0.000 claims description 2
• 229960002436 cladribine Drugs 0.000 claims description 2
• 229960004397 cyclophosphamide Drugs 0.000 claims description 2
• 229960000684 cytarabine Drugs 0.000 claims description 2
• 229960000640 dactinomycin Drugs 0.000 claims description 2
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 2
• 229960000975 daunorubicin Drugs 0.000 claims description 2
• 229960005420 etoposide Drugs 0.000 claims 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 claims description 2
• ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 2
• 229960000961 floxuridine Drugs 0.000 claims description 2
• 229960000390 fludarabine Drugs 0.000 claims description 2
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 2
• 229960002949 fluorouracil Drugs 0.000 claims description 2
• 229960001101 ifosfamide Drugs 0.000 claims description 2
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 2
• GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims description 2
• 229960004338 leuprorelin Drugs 0.000 claims description 2
• 229960002247 lomustine Drugs 0.000 claims description 2
• 229960001786 megestrol Drugs 0.000 claims description 2
• RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 claims description 2
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 2
• 229960001924 melphalan Drugs 0.000 claims description 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 2
• 229960001428 mercaptopurine Drugs 0.000 claims description 2
• 229960000485 methotrexate Drugs 0.000 claims description 2
• 229960004857 mitomycin Drugs 0.000 claims description 2
• 229960000350 mitotane Drugs 0.000 claims description 2
• 229960001744 pegaspargase Drugs 0.000 claims description 2
• 108010001564 pegaspargase Proteins 0.000 claims description 2
• 229960002340 pentostatin Drugs 0.000 claims description 2
• FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 claims description 2
• NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 claims description 2
• 229960000952 pipobroman Drugs 0.000 claims description 2
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 2
• 229960000624 procarbazine Drugs 0.000 claims description 2
• 229960001603 tamoxifen Drugs 0.000 claims description 2
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 2
• 229960001278 teniposide Drugs 0.000 claims description 2
• 210000001550 testis Anatomy 0.000 claims description 2
• BPEWUONYVDABNZ-DZBHQSCQSA-N testolactone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(OC(=O)CC4)[C@@H]4[C@@H]3CCC2=C1 BPEWUONYVDABNZ-DZBHQSCQSA-N 0.000 claims description 2
• 229960005353 testolactone Drugs 0.000 claims description 2
• 229960001196 thiotepa Drugs 0.000 claims description 2
• 229960003087 tioguanine Drugs 0.000 claims description 2
• MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims description 2
• 229960001055 uracil mustard Drugs 0.000 claims description 2
• 229960003048 vinblastine Drugs 0.000 claims description 2
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
• 229960004528 vincristine Drugs 0.000 claims description 2
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 2
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 2
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 2
• 229960002066 vinorelbine Drugs 0.000 claims description 2
• 230000001419 dependent effect Effects 0.000 claims 20
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims 1
• 190000008236 carboplatin Chemical compound 0.000 claims 1
• 229960003668 docetaxel Drugs 0.000 claims 1
• 210000004027 cell Anatomy 0.000 description 250
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 230
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 95
• 108090000623 proteins and genes Proteins 0.000 description 72
• 230000004913 activation Effects 0.000 description 49
• 102000004169 proteins and genes Human genes 0.000 description 49
• 238000003556 assay Methods 0.000 description 48
• 230000005764 inhibitory process Effects 0.000 description 45
• 108020004414 DNA Proteins 0.000 description 44
• 230000000694 effects Effects 0.000 description 41
• 230000026731 phosphorylation Effects 0.000 description 39
• 210000002889 endothelial cell Anatomy 0.000 description 38
• 238000006366 phosphorylation reaction Methods 0.000 description 38
• 230000014509 gene expression Effects 0.000 description 37
• 239000013598 vector Substances 0.000 description 37
• 241000700159 Rattus Species 0.000 description 36
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 34
• 239000002953 phosphate buffered saline Substances 0.000 description 34
• 239000002609 medium Substances 0.000 description 32
• 210000004881 tumor cell Anatomy 0.000 description 28
• 241000699666 Mus <mouse, genus> Species 0.000 description 27
• 230000033115 angiogenesis Effects 0.000 description 27
• 241000699670 Mus sp. Species 0.000 description 26
• 150000001413 amino acids Chemical group 0.000 description 26
• 208000005017 glioblastoma Diseases 0.000 description 26
• 210000004408 hybridoma Anatomy 0.000 description 26
• 230000003993 interaction Effects 0.000 description 25
• 230000000903 blocking effect Effects 0.000 description 24
• 241000124008 Mammalia Species 0.000 description 23
• 241001465754 Metazoa Species 0.000 description 22
• 238000002965 ELISA Methods 0.000 description 21
• 150000001875 compounds Chemical class 0.000 description 21
• 108090000765 processed proteins & peptides Proteins 0.000 description 21
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
• 239000012634 fragment Substances 0.000 description 20
• 239000002773 nucleotide Substances 0.000 description 19
• 125000003729 nucleotide group Chemical group 0.000 description 19
• 238000004458 analytical method Methods 0.000 description 18
• 238000001514 detection method Methods 0.000 description 18
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 17
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 17
• -1 5: 519-524 (1990) Proteins 0.000 description 16
• 241001529936 Murinae Species 0.000 description 16
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 16
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 16
• 238000002474 experimental method Methods 0.000 description 16
• 238000001114 immunoprecipitation Methods 0.000 description 16
• 239000007924 injection Substances 0.000 description 16
• 238000002347 injection Methods 0.000 description 16
• 238000001262 western blot Methods 0.000 description 16
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
• 241000283973 Oryctolagus cuniculus Species 0.000 description 15
• 230000001965 increasing effect Effects 0.000 description 15
• 238000011534 incubation Methods 0.000 description 15
• 230000000638 stimulation Effects 0.000 description 15
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 15
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 14
• 239000013615 primer Substances 0.000 description 14
• 102400001368 Epidermal growth factor Human genes 0.000 description 13
• 101800003838 Epidermal growth factor Proteins 0.000 description 13
• 201000011510 cancer Diseases 0.000 description 13
• 229940116977 epidermal growth factor Drugs 0.000 description 13
• 238000003566 phosphorylation assay Methods 0.000 description 13
• 239000013612 plasmid Substances 0.000 description 13
• 210000001519 tissue Anatomy 0.000 description 13
• 241000283707 Capra Species 0.000 description 12
• 241000588724 Escherichia coli Species 0.000 description 12
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 12
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 12
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 12
• 238000001042 affinity chromatography Methods 0.000 description 12
• 239000011324 bead Substances 0.000 description 12
• 239000002299 complementary DNA Substances 0.000 description 12
• 102000004196 processed proteins & peptides Human genes 0.000 description 12
• 101710151245 Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 11
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 11
• 239000000872 buffer Substances 0.000 description 11
• 239000013604 expression vector Substances 0.000 description 11
• 210000002966 serum Anatomy 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• 206010003445 Ascites Diseases 0.000 description 10
• 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 10
• 239000013592 cell lysate Substances 0.000 description 10
• 230000002860 competitive effect Effects 0.000 description 10
• 238000001727 in vivo Methods 0.000 description 10
• 238000006386 neutralization reaction Methods 0.000 description 10
• 238000003752 polymerase chain reaction Methods 0.000 description 10
• 230000009467 reduction Effects 0.000 description 10
• 210000003556 vascular endothelial cell Anatomy 0.000 description 10
• 102000043136 MAP kinase family Human genes 0.000 description 9
• 108091054455 MAP kinase family Proteins 0.000 description 9
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 9
• 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 9
• 102000003992 Peroxidases Human genes 0.000 description 9
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 9
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 9
• 238000002725 brachytherapy Methods 0.000 description 9
• 210000004899 c-terminal region Anatomy 0.000 description 9
• 238000007912 intraperitoneal administration Methods 0.000 description 9
• 238000002823 phage display Methods 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 108091028043 Nucleic acid sequence Proteins 0.000 description 8
• 102100035194 Placenta growth factor Human genes 0.000 description 8
• 229920002684 Sepharose Polymers 0.000 description 8
• 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 8
• 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 8
• 230000004663 cell proliferation Effects 0.000 description 8
• 108020001507 fusion proteins Proteins 0.000 description 8
• 102000037865 fusion proteins Human genes 0.000 description 8
• 239000003102 growth factor Substances 0.000 description 8
• 229920000669 heparin Polymers 0.000 description 8
• 229960002897 heparin Drugs 0.000 description 8
• 230000003211 malignant effect Effects 0.000 description 8
• 108040007629 peroxidase activity proteins Proteins 0.000 description 8
• 230000035755 proliferation Effects 0.000 description 8
• 230000009257 reactivity Effects 0.000 description 8
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 8
• 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 7
• 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 description 7
• 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 7
• 206010027476 Metastases Diseases 0.000 description 7
• 241000699660 Mus musculus Species 0.000 description 7
• 108091000080 Phosphotransferase Proteins 0.000 description 7
• 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 7
• 101710120037 Toxin CcdB Proteins 0.000 description 7
• 239000011230 binding agent Substances 0.000 description 7
• 238000002512 chemotherapy Methods 0.000 description 7
• 231100000673 dose–response relationship Toxicity 0.000 description 7
• 238000011580 nude mouse model Methods 0.000 description 7
• 102000020233 phosphotransferase Human genes 0.000 description 7
• 229920001184 polypeptide Polymers 0.000 description 7
• 238000000159 protein binding assay Methods 0.000 description 7
• 230000019491 signal transduction Effects 0.000 description 7
• 239000007787 solid Substances 0.000 description 7
• 239000000758 substrate Substances 0.000 description 7
• 239000006228 supernatant Substances 0.000 description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• 102000018233 Fibroblast Growth Factor Human genes 0.000 description 6
• 108050007372 Fibroblast Growth Factor Proteins 0.000 description 6
• 108091034117 Oligonucleotide Proteins 0.000 description 6
• 108700020796 Oncogene Proteins 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 230000001640 apoptogenic effect Effects 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 238000010367 cloning Methods 0.000 description 6
• UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 6
• 238000002710 external beam radiation therapy Methods 0.000 description 6
• 229940126864 fibroblast growth factor Drugs 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 230000003834 intracellular effect Effects 0.000 description 6
• 239000006166 lysate Substances 0.000 description 6
• 230000007246 mechanism Effects 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 108020004999 messenger RNA Proteins 0.000 description 6
• 230000002297 mitogenic effect Effects 0.000 description 6
• 230000035772 mutation Effects 0.000 description 6
• 230000003472 neutralizing effect Effects 0.000 description 6
• 238000004091 panning Methods 0.000 description 6
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
• 230000002285 radioactive effect Effects 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• 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 5
• 206010035226 Plasma cell myeloma Diseases 0.000 description 5
• 229920001213 Polysorbate 20 Polymers 0.000 description 5
• 108020004511 Recombinant DNA Proteins 0.000 description 5
• 239000007983 Tris buffer Substances 0.000 description 5
• 238000002835 absorbance Methods 0.000 description 5
• 239000000427 antigen Substances 0.000 description 5
• 108091007433 antigens Proteins 0.000 description 5
• 102000036639 antigens Human genes 0.000 description 5
• 230000035578 autophosphorylation Effects 0.000 description 5
• 244000309466 calf Species 0.000 description 5
• 238000001516 cell proliferation assay Methods 0.000 description 5
• 238000012512 characterization method Methods 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 230000006957 competitive inhibition Effects 0.000 description 5
• 239000003636 conditioned culture medium Substances 0.000 description 5
• 230000007423 decrease Effects 0.000 description 5
• 238000012217 deletion Methods 0.000 description 5
• 230000001605 fetal effect Effects 0.000 description 5
• 239000001963 growth medium Substances 0.000 description 5
• 239000012133 immunoprecipitate Substances 0.000 description 5
• 239000003112 inhibitor Substances 0.000 description 5
• 210000002510 keratinocyte Anatomy 0.000 description 5
• 208000032839 leukemia Diseases 0.000 description 5
• 230000005012 migration Effects 0.000 description 5
• 238000013508 migration Methods 0.000 description 5
• 201000000050 myeloid neoplasm Diseases 0.000 description 5
• 230000009871 nonspecific binding Effects 0.000 description 5
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 238000012163 sequencing technique Methods 0.000 description 5
• 238000010561 standard procedure Methods 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 5
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
• 108050006400 Cyclin Proteins 0.000 description 4
• 230000004544 DNA amplification Effects 0.000 description 4
• 206010018338 Glioma Diseases 0.000 description 4
• 102000009465 Growth Factor Receptors Human genes 0.000 description 4
• 108010009202 Growth Factor Receptors Proteins 0.000 description 4
• 229940123011 Growth factor receptor antagonist Drugs 0.000 description 4
• 108060003951 Immunoglobulin Proteins 0.000 description 4
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
• 206010025323 Lymphomas Diseases 0.000 description 4
• 102100036691 Proliferating cell nuclear antigen Human genes 0.000 description 4
• 108010076504 Protein Sorting Signals Proteins 0.000 description 4
• 108020005038 Terminator Codon Proteins 0.000 description 4
• 206010064390 Tumour invasion Diseases 0.000 description 4
• 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 4
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
• 238000011717 athymic nude mouse Methods 0.000 description 4
• 230000009400 cancer invasion Effects 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 108700010039 chimeric receptor Proteins 0.000 description 4
• 238000010276 construction Methods 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 230000001086 cytosolic effect Effects 0.000 description 4
• 230000029087 digestion Effects 0.000 description 4
• 238000001962 electrophoresis Methods 0.000 description 4
• 230000003511 endothelial effect Effects 0.000 description 4
• 239000002158 endotoxin Substances 0.000 description 4
• 210000003527 eukaryotic cell Anatomy 0.000 description 4
• 238000011156 evaluation Methods 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 102000018358 immunoglobulin Human genes 0.000 description 4
• 108020001756 ligand binding domains Proteins 0.000 description 4
• 150000002632 lipids Chemical class 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• 235000013336 milk Nutrition 0.000 description 4
• 239000008267 milk Substances 0.000 description 4
• 210000004080 milk Anatomy 0.000 description 4
• 230000010807 negative regulation of binding Effects 0.000 description 4
• 108020004707 nucleic acids Proteins 0.000 description 4
• 102000039446 nucleic acids Human genes 0.000 description 4
• 150000007523 nucleic acids Chemical class 0.000 description 4
• 230000001575 pathological effect Effects 0.000 description 4
• 238000001959 radiotherapy Methods 0.000 description 4
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 230000035945 sensitivity Effects 0.000 description 4
• 239000012679 serum free medium Substances 0.000 description 4
• 230000011664 signaling Effects 0.000 description 4
• 210000004988 splenocyte Anatomy 0.000 description 4
• 230000004936 stimulating effect Effects 0.000 description 4
• 238000004448 titration Methods 0.000 description 4
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 4
• 241000701161 unidentified adenovirus Species 0.000 description 4
• 241000701447 unidentified baculovirus Species 0.000 description 4
• 238000005406 washing Methods 0.000 description 4
• 230000003442 weekly effect Effects 0.000 description 4
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 3
• 208000030507 AIDS Diseases 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 102100034278 Annexin A6 Human genes 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 102000053602 DNA Human genes 0.000 description 3
• 230000006820 DNA synthesis Effects 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 3
• 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 3
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 3
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 3
• 108010029485 Protein Isoforms Proteins 0.000 description 3
• 102000001708 Protein Isoforms Human genes 0.000 description 3
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 3
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 3
• 239000013504 Triton X-100 Substances 0.000 description 3
• 229920004890 Triton X-100 Polymers 0.000 description 3
• 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 3
• 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 3
• 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 3
• 241000700605 Viruses Species 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 230000003321 amplification Effects 0.000 description 3
• 230000001621 anti-mitogenic effect Effects 0.000 description 3
• 230000003305 autocrine Effects 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 210000004204 blood vessel Anatomy 0.000 description 3
• 229940098773 bovine serum albumin Drugs 0.000 description 3
• 238000010804 cDNA synthesis Methods 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 230000010261 cell growth Effects 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 238000002648 combination therapy Methods 0.000 description 3
• 230000000295 complement effect Effects 0.000 description 3
• 239000012228 culture supernatant Substances 0.000 description 3
• 230000037430 deletion Effects 0.000 description 3
• 238000000326 densiometry Methods 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 238000006471 dimerization reaction Methods 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
• 238000010494 dissociation reaction Methods 0.000 description 3
• 230000005593 dissociations Effects 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 238000001976 enzyme digestion Methods 0.000 description 3
• 238000000684 flow cytometry Methods 0.000 description 3
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
• 230000004927 fusion Effects 0.000 description 3
• 102000055590 human KDR Human genes 0.000 description 3
• 102000058223 human VEGFA Human genes 0.000 description 3
• 229910052739 hydrogen Inorganic materials 0.000 description 3
• 230000003053 immunization Effects 0.000 description 3
• 230000002163 immunogen Effects 0.000 description 3
• 238000002991 immunohistochemical analysis Methods 0.000 description 3
• 239000007928 intraperitoneal injection Substances 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 238000012423 maintenance Methods 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• 239000003226 mitogen Substances 0.000 description 3
• 239000013642 negative control Substances 0.000 description 3
• 229910052757 nitrogen Inorganic materials 0.000 description 3
• 238000003199 nucleic acid amplification method Methods 0.000 description 3
• 150000002894 organic compounds Chemical class 0.000 description 3
• 230000003076 paracrine Effects 0.000 description 3
• 230000037361 pathway Effects 0.000 description 3
• 235000020030 perry Nutrition 0.000 description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 238000011533 pre-incubation Methods 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
• 108091008146 restriction endonucleases Proteins 0.000 description 3
• 230000003248 secreting effect Effects 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 239000000725 suspension Substances 0.000 description 3
• 238000013518 transcription Methods 0.000 description 3
• 230000035897 transcription Effects 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• 230000005740 tumor formation Effects 0.000 description 3
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
• 241001430294 unidentified retrovirus Species 0.000 description 3
• 238000011144 upstream manufacturing Methods 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
• IFPPYSWJNWHOLQ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpyrido[2,3-d]pyrimidin-7-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1NC1=NC=C(C=C(C=2C(=CC=CC=2Cl)Cl)C(=O)N2C)C2=N1 IFPPYSWJNWHOLQ-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• 108090000656 Annexin A6 Proteins 0.000 description 2
• 108010039627 Aprotinin Proteins 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 102100023995 Beta-nerve growth factor Human genes 0.000 description 2
• 208000005623 Carcinogenesis Diseases 0.000 description 2
• 102000014914 Carrier Proteins Human genes 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 108020004635 Complementary DNA Proteins 0.000 description 2
• 229920002307 Dextran Polymers 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 241000283073 Equus caballus Species 0.000 description 2
• 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 2
• 241000724791 Filamentous phage Species 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 239000012981 Hank's balanced salt solution Substances 0.000 description 2
• 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
• 208000017604 Hodgkin disease Diseases 0.000 description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
• 208000007766 Kaposi sarcoma Diseases 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
• 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 2
• 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 2
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
• 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• 238000011887 Necropsy Methods 0.000 description 2
• 108010025020 Nerve Growth Factor Proteins 0.000 description 2
• 108010038807 Oligopeptides Proteins 0.000 description 2
• 102000015636 Oligopeptides Human genes 0.000 description 2
• 206010033128 Ovarian cancer Diseases 0.000 description 2
• 238000012408 PCR amplification Methods 0.000 description 2
• 108091008606 PDGF receptors Proteins 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 206010054827 Peritoneal lesion Diseases 0.000 description 2
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
• 241000276498 Pollachius virens Species 0.000 description 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 241000589516 Pseudomonas Species 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
• 108010073443 Ribi adjuvant Proteins 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• 208000000453 Skin Neoplasms Diseases 0.000 description 2
• 102000013275 Somatomedins Human genes 0.000 description 2
• 108091081024 Start codon Proteins 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 241000011102 Thera Species 0.000 description 2
• 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• 238000011167 VEGF-binding assay Methods 0.000 description 2
• 229960000723 ampicillin Drugs 0.000 description 2
• AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
• 230000002491 angiogenic effect Effects 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 230000001772 anti-angiogenic effect Effects 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 229960004405 aprotinin Drugs 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 238000013357 binding ELISA Methods 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 239000012472 biological sample Substances 0.000 description 2
• 229960002685 biotin Drugs 0.000 description 2
• 239000011616 biotin Substances 0.000 description 2
• 239000012888 bovine serum Substances 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 230000036952 cancer formation Effects 0.000 description 2
• 150000001720 carbohydrates Chemical class 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 231100000504 carcinogenesis Toxicity 0.000 description 2
• 208000025997 central nervous system neoplasm Diseases 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 230000002759 chromosomal effect Effects 0.000 description 2
• 238000012875 competitive assay Methods 0.000 description 2
• 230000021615 conjugation Effects 0.000 description 2
• 230000009260 cross reactivity Effects 0.000 description 2
• 238000012258 culturing Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000009089 cytolysis Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000002950 deficient Effects 0.000 description 2
• 239000005546 dideoxynucleotide Substances 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 239000006167 equilibration buffer Substances 0.000 description 2
• GTTBEUCJPZQMDZ-UHFFFAOYSA-N erlotinib hydrochloride Chemical compound [H+].[Cl-].C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 GTTBEUCJPZQMDZ-UHFFFAOYSA-N 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 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 2
• 238000011404 fractionated radiotherapy Methods 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 150000004676 glycans Chemical class 0.000 description 2
• 201000002222 hemangioblastoma Diseases 0.000 description 2
• 125000001072 heteroaryl group Chemical group 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 230000001900 immune effect Effects 0.000 description 2
• 238000002649 immunization Methods 0.000 description 2
• 238000003119 immunoblot Methods 0.000 description 2
• 238000010166 immunofluorescence Methods 0.000 description 2
• 238000003364 immunohistochemistry Methods 0.000 description 2
• 239000007943 implant Substances 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000007901 in situ hybridization Methods 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 239000000411 inducer Substances 0.000 description 2
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 229960000318 kanamycin Drugs 0.000 description 2
• 229930027917 kanamycin Natural products 0.000 description 2
• SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
• 229930182823 kanamycin A Natural products 0.000 description 2
• 238000003674 kinase activity assay Methods 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• 238000011005 laboratory method Methods 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
• 108010052968 leupeptin Proteins 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 239000012160 loading buffer Substances 0.000 description 2
• 208000037841 lung tumor Diseases 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 208000002780 macular degeneration Diseases 0.000 description 2
• 238000007885 magnetic separation Methods 0.000 description 2
• 238000013507 mapping Methods 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
• 229940053128 nerve growth factor Drugs 0.000 description 2
• 229920001542 oligosaccharide Polymers 0.000 description 2
• 150000002482 oligosaccharides Chemical class 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 150000002902 organometallic compounds Chemical class 0.000 description 2
• 229960001972 panitumumab Drugs 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 229920002401 polyacrylamide Polymers 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 108091033319 polynucleotide Proteins 0.000 description 2
• 102000040430 polynucleotide Human genes 0.000 description 2
• 239000002157 polynucleotide Substances 0.000 description 2
• 229920001282 polysaccharide Polymers 0.000 description 2
• 239000005017 polysaccharide Substances 0.000 description 2
• 239000011148 porous material Substances 0.000 description 2
• 210000001236 prokaryotic cell Anatomy 0.000 description 2
• 230000001737 promoting effect Effects 0.000 description 2
• 150000003246 quinazolines Chemical class 0.000 description 2
• 230000022910 regulation of vasculogenesis Effects 0.000 description 2
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 150000003839 salts Chemical class 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 235000020183 skimmed milk Nutrition 0.000 description 2
• 210000004989 spleen cell Anatomy 0.000 description 2
• 206010041823 squamous cell carcinoma Diseases 0.000 description 2
• 238000010186 staining Methods 0.000 description 2
• 238000012289 standard assay Methods 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 239000003053 toxin Substances 0.000 description 2
• 230000001131 transforming effect Effects 0.000 description 2
• 238000002054 transplantation Methods 0.000 description 2
• 210000002993 trophoblast Anatomy 0.000 description 2
• 230000005747 tumor angiogenesis Effects 0.000 description 2
• 230000003827 upregulation Effects 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 230000008728 vascular permeability Effects 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• WZUVPPKBWHMQCE-XJKSGUPXSA-N (+)-haematoxylin Chemical compound C12=CC(O)=C(O)C=C2C[C@]2(O)[C@H]1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-XJKSGUPXSA-N 0.000 description 1
• MWWSFMDVAYGXBV-MYPASOLCSA-N (7r,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-MYPASOLCSA-N 0.000 description 1
• WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
• GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
• NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
• ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
• RLFXJQPKMZNLMP-UHFFFAOYSA-N 2-phenylprop-2-enenitrile Chemical class N#CC(=C)C1=CC=CC=C1 RLFXJQPKMZNLMP-UHFFFAOYSA-N 0.000 description 1
• OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
• XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 description 1
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
• KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
• WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 1
• 102000013563 Acid Phosphatase Human genes 0.000 description 1
• 108010051457 Acid Phosphatase Proteins 0.000 description 1
• NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical class C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
• 102000007299 Amphiregulin Human genes 0.000 description 1
• 108010033760 Amphiregulin Proteins 0.000 description 1
• 208000003120 Angiofibroma Diseases 0.000 description 1
• 108010037870 Anthranilate Synthase Proteins 0.000 description 1
• 101100067974 Arabidopsis thaliana POP2 gene Proteins 0.000 description 1
• 108010031480 Artificial Receptors Proteins 0.000 description 1
• 101100136076 Aspergillus oryzae (strain ATCC 42149 / RIB 40) pel1 gene Proteins 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• 244000063299 Bacillus subtilis Species 0.000 description 1
• 235000014469 Bacillus subtilis Nutrition 0.000 description 1
• 206010004146 Basal cell carcinoma Diseases 0.000 description 1
• 102100026189 Beta-galactosidase Human genes 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 101000908384 Bos taurus Dipeptidyl peptidase 4 Proteins 0.000 description 1
• 210000003771 C cell Anatomy 0.000 description 1
• 101100275473 Caenorhabditis elegans ctc-3 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 101710132601 Capsid protein Proteins 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 108010078791 Carrier Proteins Proteins 0.000 description 1
• 102000053642 Catalytic RNA Human genes 0.000 description 1
• 108090000994 Catalytic RNA Proteins 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 101710094648 Coat protein Proteins 0.000 description 1
• 108091026890 Coding region Proteins 0.000 description 1
• 108020004705 Codon Proteins 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 239000003155 DNA primer Substances 0.000 description 1
• 238000001712 DNA sequencing Methods 0.000 description 1
• AHCYMLUZIRLXAA-SHYZEUOFSA-N Deoxyuridine 5'-triphosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C=C1 AHCYMLUZIRLXAA-SHYZEUOFSA-N 0.000 description 1
• 241000702421 Dependoparvovirus Species 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• 101150039808 Egfr gene Proteins 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 241001131785 Escherichia coli HB101 Species 0.000 description 1
• 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 1
• 241000701959 Escherichia virus Lambda Species 0.000 description 1
• 206010015548 Euthanasia Diseases 0.000 description 1
• 108700024394 Exon Proteins 0.000 description 1
• 108091008794 FGF receptors Proteins 0.000 description 1
• 108091006020 Fc-tagged proteins Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 1
• 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• 108010070675 Glutathione transferase Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
• 208000012766 Growth delay Diseases 0.000 description 1
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Natural products C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 1
• 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
• 206010019695 Hepatic neoplasm Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 241001272567 Hominoidea Species 0.000 description 1
• 101100118549 Homo sapiens EGFR gene Proteins 0.000 description 1
• 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
• 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 1
• 101000926206 Homo sapiens Putative glutathione hydrolase 3 proenzyme Proteins 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 101150088608 Kdr gene Proteins 0.000 description 1
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
• 239000012480 LAL reagent Substances 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 208000018142 Leiomyosarcoma Diseases 0.000 description 1
• 241000713666 Lentivirus Species 0.000 description 1
• 206010024305 Leukaemia monocytic Diseases 0.000 description 1
• 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 101710125418 Major capsid protein Proteins 0.000 description 1
• 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
• 206010051676 Metastases to peritoneum Diseases 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 101000932477 Mus musculus Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
• OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 206010061309 Neoplasm progression Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• 238000000636 Northern blotting Methods 0.000 description 1
• 102000019040 Nuclear Antigens Human genes 0.000 description 1
• 108010051791 Nuclear Antigens Proteins 0.000 description 1
• 101710141454 Nucleoprotein Proteins 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 108700026244 Open Reading Frames Proteins 0.000 description 1
• 102000016979 Other receptors Human genes 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 102400001093 PAK-2p27 Human genes 0.000 description 1
• 101150012394 PHO5 gene Proteins 0.000 description 1
• 241000609499 Palicourea Species 0.000 description 1
• 241000282579 Pan Species 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 239000001888 Peptone Substances 0.000 description 1
• 108010080698 Peptones Proteins 0.000 description 1
• 208000012896 Peritoneal disease Diseases 0.000 description 1
• 108700020962 Peroxidase Proteins 0.000 description 1
• 108010064785 Phospholipases Proteins 0.000 description 1
• 102000015439 Phospholipases Human genes 0.000 description 1
• 108010089430 Phosphoproteins Proteins 0.000 description 1
• 102000007982 Phosphoproteins Human genes 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 108010082093 Placenta Growth Factor Proteins 0.000 description 1
• 108010069381 Platelet Endothelial Cell Adhesion Molecule-1 Proteins 0.000 description 1
• 102100040681 Platelet-derived growth factor C Human genes 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 101710083689 Probable capsid protein Proteins 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 102100034060 Putative glutathione hydrolase 3 proenzyme Human genes 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 238000010240 RT-PCR analysis Methods 0.000 description 1
• 244000088415 Raphanus sativus Species 0.000 description 1
• 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
• 101000852966 Rattus norvegicus Interleukin-1 receptor-like 1 Proteins 0.000 description 1
• 230000010799 Receptor Interactions Effects 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 206010038934 Retinopathy proliferative Diseases 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• 208000036822 Small cell carcinoma of the ovary Diseases 0.000 description 1
• 238000002105 Southern blotting Methods 0.000 description 1
• 241000187747 Streptomyces Species 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 1
• 108010022394 Threonine synthase Proteins 0.000 description 1
• 102000002262 Thromboplastin Human genes 0.000 description 1
• 108010000499 Thromboplastin Proteins 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 1
• 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
• 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 1
• 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• IUHFWCGCSVTMPG-UHFFFAOYSA-N [C].[C] Chemical group [C].[C] IUHFWCGCSVTMPG-UHFFFAOYSA-N 0.000 description 1
• 210000001015 abdomen Anatomy 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000009824 affinity maturation Effects 0.000 description 1
• 238000001261 affinity purification Methods 0.000 description 1
• 239000011543 agarose gel Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• LXQXZNRPTYVCNG-YPZZEJLDSA-N americium-241 Chemical compound [241Am] LXQXZNRPTYVCNG-YPZZEJLDSA-N 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 210000000648 angioblast Anatomy 0.000 description 1
• 230000006427 angiogenic response Effects 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 238000011122 anti-angiogenic therapy Methods 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 230000009833 antibody interaction Effects 0.000 description 1
• 238000009175 antibody therapy Methods 0.000 description 1
• 210000000628 antibody-producing cell Anatomy 0.000 description 1
• 102000025171 antigen binding proteins Human genes 0.000 description 1
• 108091000831 antigen binding proteins Proteins 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003972 antineoplastic antibiotic Substances 0.000 description 1
• 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000003190 augmentative effect Effects 0.000 description 1
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 239000012148 binding buffer Substances 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 230000008512 biological response Effects 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 201000000053 blastoma Diseases 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000002798 bone marrow cell Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 230000025084 cell cycle arrest Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 239000013553 cell monolayer Substances 0.000 description 1
• 230000015861 cell surface binding Effects 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000004700 cellular uptake Effects 0.000 description 1
• 201000007455 central nervous system cancer Diseases 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• TVFDJXOCXUVLDH-RNFDNDRNSA-N cesium-137 Chemical compound [137Cs] TVFDJXOCXUVLDH-RNFDNDRNSA-N 0.000 description 1
• 229960003677 chloroquine Drugs 0.000 description 1
• WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
• 150000001854 cinnolines Chemical class 0.000 description 1
• 229940030792 clinac Drugs 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000000512 collagen gel Substances 0.000 description 1
• 230000003750 conditioning effect Effects 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000006341 curative response Effects 0.000 description 1
• 238000005520 cutting process Methods 0.000 description 1
• 239000002254 cytotoxic agent Substances 0.000 description 1
• 231100000599 cytotoxic agent Toxicity 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 239000007857 degradation product Substances 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 229960003964 deoxycholic acid Drugs 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 230000009699 differential effect Effects 0.000 description 1
• 208000018554 digestive system carcinoma Diseases 0.000 description 1
• 102000004419 dihydrofolate reductase Human genes 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 229940121647 egfr inhibitor Drugs 0.000 description 1
• 230000013020 embryo development Effects 0.000 description 1
• 201000008184 embryoma Diseases 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000006274 endogenous ligand Substances 0.000 description 1
• 230000010595 endothelial cell migration Effects 0.000 description 1
• 230000029578 entry into host Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
• 108700021358 erbB-1 Genes Proteins 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• 210000003722 extracellular fluid Anatomy 0.000 description 1
• 235000013861 fat-free Nutrition 0.000 description 1
• 238000000855 fermentation Methods 0.000 description 1
• 230000004151 fermentation Effects 0.000 description 1
• 210000004700 fetal blood Anatomy 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
• 229960000304 folic acid Drugs 0.000 description 1
• 235000019152 folic acid Nutrition 0.000 description 1
• 239000004052 folic acid antagonist Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 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 description 1
• 239000000499 gel Substances 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 230000002414 glycolytic effect Effects 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• PCHJSUWPFVWCPO-OUBTZVSYSA-N gold-198 Chemical compound [198Au] PCHJSUWPFVWCPO-OUBTZVSYSA-N 0.000 description 1
• 239000011544 gradient gel Substances 0.000 description 1
• 230000009036 growth inhibition Effects 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 102000045108 human EGFR Human genes 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 210000004201 immune sera Anatomy 0.000 description 1
• 229940042743 immune sera Drugs 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 238000003018 immunoassay Methods 0.000 description 1
• 230000000984 immunochemical effect Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000000415 inactivating effect Effects 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 150000002484 inorganic compounds Chemical class 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• XMBWDFGMSWQBCA-YPZZEJLDSA-N iodane Chemical compound [125IH] XMBWDFGMSWQBCA-YPZZEJLDSA-N 0.000 description 1
• 229940044173 iodine-125 Drugs 0.000 description 1
• 229940084651 iressa Drugs 0.000 description 1
• 229960004768 irinotecan Drugs 0.000 description 1
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
• 150000002545 isoxazoles Chemical class 0.000 description 1
• 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
• 230000002147 killing effect Effects 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 238000011694 lewis rat Methods 0.000 description 1
• 230000029226 lipidation Effects 0.000 description 1
• 229920006008 lipopolysaccharide Chemical class 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 239000008297 liquid dosage form Substances 0.000 description 1
• 239000011344 liquid material Substances 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 210000003141 lower extremity Anatomy 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 238000000504 luminescence detection Methods 0.000 description 1
• 210000001365 lymphatic vessel Anatomy 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 206010027191 meningioma Diseases 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 238000010232 migration assay Methods 0.000 description 1
• 230000008747 mitogenic response Effects 0.000 description 1
• 230000000394 mitotic effect Effects 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• ZDZOTLJHXYCWBA-BSEPLHNVSA-N molport-006-823-826 Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-BSEPLHNVSA-N 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 201000006894 monocytic leukemia Diseases 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 238000002703 mutagenesis Methods 0.000 description 1
• 231100000350 mutagenesis Toxicity 0.000 description 1
• 239000003471 mutagenic agent Substances 0.000 description 1
• 210000004897 n-terminal region Anatomy 0.000 description 1
• 230000027405 negative regulation of phosphorylation Effects 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 201000003142 neovascular glaucoma Diseases 0.000 description 1
• GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• 239000002777 nucleoside Chemical class 0.000 description 1
• 125000003835 nucleoside group Chemical class 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 238000006384 oligomerization reaction Methods 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 201000005292 ovarian small cell carcinoma Diseases 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 238000006213 oxygenation reaction Methods 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 101150040383 pel2 gene Proteins 0.000 description 1
• 101150050446 pelB gene Proteins 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• 229950000964 pepstatin Drugs 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 235000019319 peptone Nutrition 0.000 description 1
• 229940066779 peptones Drugs 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 108700010839 phage proteins Proteins 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000003905 phosphatidylinositols Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 108091005981 phosphorylated proteins Proteins 0.000 description 1
• DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 210000002826 placenta Anatomy 0.000 description 1
• 230000003169 placental effect Effects 0.000 description 1
• 108010017992 platelet-derived growth factor C Proteins 0.000 description 1
• YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 238000010837 poor prognosis Methods 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 235000008476 powdered milk Nutrition 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
• 230000009696 proliferative response Effects 0.000 description 1
• 230000000644 propagated effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 201000001514 prostate carcinoma Diseases 0.000 description 1
• 208000023958 prostate neoplasm Diseases 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 239000000649 purine antagonist Substances 0.000 description 1
• 239000003790 pyrimidine antagonist Substances 0.000 description 1
• 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 150000003248 quinolines Chemical class 0.000 description 1
• 238000003127 radioimmunoassay Methods 0.000 description 1
• 238000003653 radioligand binding assay Methods 0.000 description 1
• 230000000637 radiosensitizating effect Effects 0.000 description 1
• 229910052705 radium Inorganic materials 0.000 description 1
• HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 1
• 229910052704 radon Inorganic materials 0.000 description 1
• SYUHGPGVQRZVTB-UHFFFAOYSA-N radon atom Chemical compound [Rn] SYUHGPGVQRZVTB-UHFFFAOYSA-N 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 102000027240 receptors by ligand Human genes 0.000 description 1
• 108091008562 receptors by ligand Proteins 0.000 description 1
• 238000005215 recombination Methods 0.000 description 1
• 230000006798 recombination Effects 0.000 description 1
• 230000034932 regulation of DNA biosynthetic process Effects 0.000 description 1
• 230000006884 regulation of angiogenesis Effects 0.000 description 1
• 230000031539 regulation of cell division Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
• 108091092562 ribozyme Proteins 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 239000012056 semi-solid material Substances 0.000 description 1
• 239000008299 semisolid dosage form Substances 0.000 description 1
• 239000013605 shuttle vector Substances 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
• FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
• 229940048086 sodium pyrophosphate Drugs 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 238000003153 stable transfection Methods 0.000 description 1
• 238000007619 statistical method Methods 0.000 description 1
• 239000012058 sterile packaged powder Substances 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 125000005504 styryl group Chemical group 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
• 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229960002784 thioridazine Drugs 0.000 description 1
• 208000013076 thyroid tumor Diseases 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• 231100000167 toxic agent Toxicity 0.000 description 1
• 239000003440 toxic substance Substances 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 239000011573 trace mineral Substances 0.000 description 1
• 235000013619 trace mineral Nutrition 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 101150108727 trpl gene Proteins 0.000 description 1
• 230000005751 tumor progression Effects 0.000 description 1
• 238000013042 tunel staining Methods 0.000 description 1
• 210000003954 umbilical cord Anatomy 0.000 description 1
• 210000003606 umbilical vein Anatomy 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 201000011531 vascular cancer Diseases 0.000 description 1
• 210000005167 vascular cell Anatomy 0.000 description 1
• 206010055031 vascular neoplasm Diseases 0.000 description 1
• 230000004862 vasculogenesis Effects 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1