JP5704722B2 - 細胞接着阻害剤およびその用途 - Google Patents
細胞接着阻害剤およびその用途 Download PDFInfo
- Publication number
- JP5704722B2 JP5704722B2 JP2011501535A JP2011501535A JP5704722B2 JP 5704722 B2 JP5704722 B2 JP 5704722B2 JP 2011501535 A JP2011501535 A JP 2011501535A JP 2011501535 A JP2011501535 A JP 2011501535A JP 5704722 B2 JP5704722 B2 JP 5704722B2
- Authority
- JP
- Japan
- Prior art keywords
- protein
- present
- cells
- dna
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000021164 cell adhesion Effects 0.000 title claims description 42
- 239000003112 inhibitor Substances 0.000 title claims description 33
- 108090000623 proteins and genes Proteins 0.000 claims description 428
- 102000004169 proteins and genes Human genes 0.000 claims description 339
- 206010028980 Neoplasm Diseases 0.000 claims description 98
- 201000011510 cancer Diseases 0.000 claims description 96
- 102000040430 polynucleotide Human genes 0.000 claims description 90
- 108091033319 polynucleotide Proteins 0.000 claims description 90
- 239000002157 polynucleotide Substances 0.000 claims description 90
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 78
- 230000000692 anti-sense effect Effects 0.000 claims description 59
- 239000003814 drug Substances 0.000 claims description 59
- 230000000694 effects Effects 0.000 claims description 59
- 150000001413 amino acids Chemical class 0.000 claims description 47
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 41
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 34
- 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 claims description 31
- 230000000295 complement effect Effects 0.000 claims description 30
- 229940124597 therapeutic agent Drugs 0.000 claims description 29
- 230000000069 prophylactic effect Effects 0.000 claims description 19
- 230000035945 sensitivity Effects 0.000 claims description 16
- 230000003449 preventive effect Effects 0.000 claims description 15
- 230000017455 cell-cell adhesion Effects 0.000 claims description 3
- 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 4
- 230000002708 enhancing effect Effects 0.000 claims 4
- 235000018102 proteins Nutrition 0.000 description 318
- 210000004027 cell Anatomy 0.000 description 277
- 238000000034 method Methods 0.000 description 255
- 108020004414 DNA Proteins 0.000 description 242
- 241000282414 Homo sapiens Species 0.000 description 132
- 241001465754 Metazoa Species 0.000 description 116
- 108090000765 processed proteins & peptides Proteins 0.000 description 91
- 230000014509 gene expression Effects 0.000 description 90
- 239000000427 antigen Substances 0.000 description 77
- 108091007433 antigens Proteins 0.000 description 76
- 102000036639 antigens Human genes 0.000 description 76
- 241000699666 Mus <mouse, genus> Species 0.000 description 72
- 239000002585 base Substances 0.000 description 59
- 150000001875 compounds Chemical class 0.000 description 57
- 230000036961 partial effect Effects 0.000 description 57
- 235000001014 amino acid Nutrition 0.000 description 51
- 239000000126 substance Substances 0.000 description 51
- 238000012216 screening Methods 0.000 description 49
- 150000003839 salts Chemical class 0.000 description 41
- -1 aromatic amino acids Chemical class 0.000 description 40
- 238000012360 testing method Methods 0.000 description 39
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 38
- 201000010099 disease Diseases 0.000 description 37
- 239000013598 vector Substances 0.000 description 37
- 108020004999 messenger RNA Proteins 0.000 description 36
- 241000124008 Mammalia Species 0.000 description 35
- 239000002609 medium Substances 0.000 description 34
- 210000001519 tissue Anatomy 0.000 description 34
- 210000004408 hybridoma Anatomy 0.000 description 33
- 238000004519 manufacturing process Methods 0.000 description 33
- 230000014616 translation Effects 0.000 description 31
- 241000699670 Mus sp. Species 0.000 description 28
- 238000002347 injection Methods 0.000 description 28
- 239000007924 injection Substances 0.000 description 28
- 241000700159 Rattus Species 0.000 description 26
- 238000011282 treatment Methods 0.000 description 26
- 101001015006 Homo sapiens Integrin beta-4 Proteins 0.000 description 25
- 229940079593 drug Drugs 0.000 description 25
- 125000003729 nucleotide group Chemical group 0.000 description 25
- 210000004102 animal cell Anatomy 0.000 description 24
- 239000002773 nucleotide Substances 0.000 description 24
- 238000013519 translation Methods 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 22
- 241000588724 Escherichia coli Species 0.000 description 21
- 241000283973 Oryctolagus cuniculus Species 0.000 description 21
- 241000700605 Viruses Species 0.000 description 21
- 210000000349 chromosome Anatomy 0.000 description 21
- 241000282412 Homo Species 0.000 description 20
- 150000002148 esters Chemical class 0.000 description 20
- 208000032839 leukemia Diseases 0.000 description 20
- 102000039446 nucleic acids Human genes 0.000 description 20
- 108020004707 nucleic acids Proteins 0.000 description 20
- 238000000746 purification Methods 0.000 description 20
- 206010006187 Breast cancer Diseases 0.000 description 19
- 208000026310 Breast neoplasm Diseases 0.000 description 19
- 239000003795 chemical substances by application Substances 0.000 description 19
- 239000012634 fragment Substances 0.000 description 19
- 230000006870 function Effects 0.000 description 19
- 150000007523 nucleic acids Chemical class 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- 230000002950 deficient Effects 0.000 description 18
- 235000013601 eggs Nutrition 0.000 description 17
- 125000006239 protecting group Chemical group 0.000 description 17
- 229920005989 resin Polymers 0.000 description 17
- 239000011347 resin Substances 0.000 description 17
- 241000283690 Bos taurus Species 0.000 description 16
- 101710132601 Capsid protein Proteins 0.000 description 16
- 101710094648 Coat protein Proteins 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 101710125418 Major capsid protein Proteins 0.000 description 16
- 101710141454 Nucleoprotein Proteins 0.000 description 16
- 241001494479 Pecora Species 0.000 description 16
- 101710083689 Probable capsid protein Proteins 0.000 description 16
- 230000002159 abnormal effect Effects 0.000 description 16
- 238000012258 culturing Methods 0.000 description 16
- 210000004602 germ cell Anatomy 0.000 description 16
- 238000012546 transfer Methods 0.000 description 16
- 108091029865 Exogenous DNA Proteins 0.000 description 15
- 239000002246 antineoplastic agent Substances 0.000 description 15
- 239000012228 culture supernatant Substances 0.000 description 15
- 239000013604 expression vector Substances 0.000 description 15
- 241000282472 Canis lupus familiaris Species 0.000 description 14
- 241000282693 Cercopithecidae Species 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 241000282326 Felis catus Species 0.000 description 14
- 101150112982 Itga6 gene Proteins 0.000 description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 14
- 210000001671 embryonic stem cell Anatomy 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 230000002265 prevention Effects 0.000 description 14
- 238000013518 transcription Methods 0.000 description 14
- 230000035897 transcription Effects 0.000 description 14
- 238000010367 cloning Methods 0.000 description 13
- 229920001223 polyethylene glycol Polymers 0.000 description 13
- 239000012488 sample solution Substances 0.000 description 13
- 230000008685 targeting Effects 0.000 description 13
- 108090000994 Catalytic RNA Proteins 0.000 description 12
- 102000053642 Catalytic RNA Human genes 0.000 description 12
- 101000994365 Homo sapiens Integrin alpha-6 Proteins 0.000 description 12
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 239000002202 Polyethylene glycol Substances 0.000 description 12
- 108010076504 Protein Sorting Signals Proteins 0.000 description 12
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 12
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 12
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 12
- 125000003277 amino group Chemical group 0.000 description 12
- 210000003719 b-lymphocyte Anatomy 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 230000003053 immunization Effects 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 108091092562 ribozyme Proteins 0.000 description 12
- 206010005003 Bladder cancer Diseases 0.000 description 11
- 208000003174 Brain Neoplasms Diseases 0.000 description 11
- 206010009944 Colon cancer Diseases 0.000 description 11
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 11
- 102100032816 Integrin alpha-6 Human genes 0.000 description 11
- 102100033000 Integrin beta-4 Human genes 0.000 description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 11
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 11
- 206010033128 Ovarian cancer Diseases 0.000 description 11
- 206010061535 Ovarian neoplasm Diseases 0.000 description 11
- 206010060862 Prostate cancer Diseases 0.000 description 11
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 11
- 208000000277 Splenic Neoplasms Diseases 0.000 description 11
- 208000005718 Stomach Neoplasms Diseases 0.000 description 11
- 208000024770 Thyroid neoplasm Diseases 0.000 description 11
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 11
- 208000002495 Uterine Neoplasms Diseases 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 150000001408 amides Chemical class 0.000 description 11
- 201000009036 biliary tract cancer Diseases 0.000 description 11
- 208000020790 biliary tract neoplasm Diseases 0.000 description 11
- 230000027455 binding Effects 0.000 description 11
- 238000004422 calculation algorithm Methods 0.000 description 11
- 239000002299 complementary DNA Substances 0.000 description 11
- 238000007796 conventional method Methods 0.000 description 11
- 239000002552 dosage form Substances 0.000 description 11
- 201000004101 esophageal cancer Diseases 0.000 description 11
- 206010017758 gastric cancer Diseases 0.000 description 11
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 description 11
- 238000009396 hybridization Methods 0.000 description 11
- 238000002649 immunization Methods 0.000 description 11
- 230000016784 immunoglobulin production Effects 0.000 description 11
- 238000002372 labelling Methods 0.000 description 11
- 201000007270 liver cancer Diseases 0.000 description 11
- 208000014018 liver neoplasm Diseases 0.000 description 11
- 201000005202 lung cancer Diseases 0.000 description 11
- 208000020816 lung neoplasm Diseases 0.000 description 11
- 238000002823 phage display Methods 0.000 description 11
- 201000002471 spleen cancer Diseases 0.000 description 11
- 201000011549 stomach cancer Diseases 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 201000002510 thyroid cancer Diseases 0.000 description 11
- 201000005112 urinary bladder cancer Diseases 0.000 description 11
- 206010046766 uterine cancer Diseases 0.000 description 11
- 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 10
- 208000008839 Kidney Neoplasms Diseases 0.000 description 10
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 10
- 206010035226 Plasma cell myeloma Diseases 0.000 description 10
- 206010038389 Renal cancer Diseases 0.000 description 10
- 241000282887 Suidae Species 0.000 description 10
- 208000024313 Testicular Neoplasms Diseases 0.000 description 10
- 206010057644 Testis cancer Diseases 0.000 description 10
- 238000007792 addition Methods 0.000 description 10
- 210000001185 bone marrow Anatomy 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 10
- 238000003018 immunoassay Methods 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 201000010982 kidney cancer Diseases 0.000 description 10
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 10
- 230000035772 mutation Effects 0.000 description 10
- 201000000050 myeloid neoplasm Diseases 0.000 description 10
- 201000002528 pancreatic cancer Diseases 0.000 description 10
- 208000008443 pancreatic carcinoma Diseases 0.000 description 10
- 238000000926 separation method Methods 0.000 description 10
- 239000007790 solid phase Substances 0.000 description 10
- 210000001082 somatic cell Anatomy 0.000 description 10
- 201000003120 testicular cancer Diseases 0.000 description 10
- 241000238631 Hexapoda Species 0.000 description 9
- 239000002671 adjuvant Substances 0.000 description 9
- 238000000246 agarose gel electrophoresis Methods 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 208000029742 colonic neoplasm Diseases 0.000 description 9
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 235000000346 sugar Nutrition 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 230000009261 transgenic effect Effects 0.000 description 9
- 229960005486 vaccine Drugs 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 8
- 241000699800 Cricetinae Species 0.000 description 8
- 241000588722 Escherichia Species 0.000 description 8
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 210000000628 antibody-producing cell Anatomy 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 238000009833 condensation Methods 0.000 description 8
- 230000005494 condensation Effects 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 210000004698 lymphocyte Anatomy 0.000 description 8
- 230000013011 mating Effects 0.000 description 8
- 239000013615 primer Substances 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 241000283707 Capra Species 0.000 description 7
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
- 241000701022 Cytomegalovirus Species 0.000 description 7
- 241000287828 Gallus gallus Species 0.000 description 7
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 7
- 239000012980 RPMI-1640 medium Substances 0.000 description 7
- 241000283984 Rodentia Species 0.000 description 7
- 230000009471 action Effects 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 210000002798 bone marrow cell Anatomy 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 235000013330 chicken meat Nutrition 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 239000012894 fetal calf serum Substances 0.000 description 7
- 230000004927 fusion Effects 0.000 description 7
- 102000006495 integrins Human genes 0.000 description 7
- 108010044426 integrins Proteins 0.000 description 7
- 238000010253 intravenous injection Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 238000003757 reverse transcription PCR Methods 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000193830 Bacillus <bacterium> Species 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 6
- 102000014914 Carrier Proteins Human genes 0.000 description 6
- 108010078791 Carrier Proteins Proteins 0.000 description 6
- 241000700198 Cavia Species 0.000 description 6
- 206010059866 Drug resistance Diseases 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 108091005804 Peptidases Proteins 0.000 description 6
- 102000035195 Peptidases Human genes 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 108091081021 Sense strand Proteins 0.000 description 6
- 229960003896 aminopterin Drugs 0.000 description 6
- 230000000890 antigenic effect Effects 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 6
- 238000009395 breeding Methods 0.000 description 6
- 230000001488 breeding effect Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 210000004899 c-terminal region Anatomy 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 230000015556 catabolic process Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000006731 degradation reaction Methods 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 201000005787 hematologic cancer Diseases 0.000 description 6
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 6
- 238000002744 homologous recombination Methods 0.000 description 6
- 230000006801 homologous recombination Effects 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 230000000984 immunochemical effect Effects 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 125000005647 linker group Chemical group 0.000 description 6
- 231100000053 low toxicity Toxicity 0.000 description 6
- 239000006166 lysate Substances 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 230000003472 neutralizing effect Effects 0.000 description 6
- 238000004091 panning Methods 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- 238000010647 peptide synthesis reaction Methods 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 229940104230 thymidine Drugs 0.000 description 6
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 5
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 5
- 101150074155 DHFR gene Proteins 0.000 description 5
- 102000053602 DNA Human genes 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 5
- 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 5
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 5
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 5
- 108700008625 Reporter Genes Proteins 0.000 description 5
- 108020004459 Small interfering RNA Proteins 0.000 description 5
- 108020005038 Terminator Codon Proteins 0.000 description 5
- 241000209140 Triticum Species 0.000 description 5
- 235000021307 Triticum Nutrition 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 238000005273 aeration Methods 0.000 description 5
- 238000013019 agitation Methods 0.000 description 5
- 108010005774 beta-Galactosidase Proteins 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 238000003352 cell adhesion assay Methods 0.000 description 5
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 230000032050 esterification Effects 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 238000010353 genetic engineering Methods 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 210000003917 human chromosome Anatomy 0.000 description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
- 230000002163 immunogen Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 210000001161 mammalian embryo Anatomy 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 238000000691 measurement method Methods 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 210000004989 spleen cell Anatomy 0.000 description 5
- 238000010254 subcutaneous injection Methods 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 4
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 4
- 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 4
- 244000063299 Bacillus subtilis Species 0.000 description 4
- 235000014469 Bacillus subtilis Nutrition 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 102100034343 Integrase Human genes 0.000 description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 4
- 101710163270 Nuclease Proteins 0.000 description 4
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 4
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 4
- 108091081024 Start codon Proteins 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 101001057161 Xenopus laevis MDS1 and EVI1 complex locus protein EVI1-A Proteins 0.000 description 4
- 238000010306 acid treatment Methods 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 238000001042 affinity chromatography Methods 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
- 210000002459 blastocyst Anatomy 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 239000000032 diagnostic agent Substances 0.000 description 4
- 229940039227 diagnostic agent Drugs 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 238000010828 elution Methods 0.000 description 4
- 210000002257 embryonic structure Anatomy 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical group N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 235000005985 organic acids Nutrition 0.000 description 4
- 210000000963 osteoblast Anatomy 0.000 description 4
- 210000005259 peripheral blood Anatomy 0.000 description 4
- 239000011886 peripheral blood Substances 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 229920002401 polyacrylamide Polymers 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 238000001243 protein synthesis Methods 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000001995 reticulocyte Anatomy 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 125000003396 thiol group Chemical group [H]S* 0.000 description 4
- 210000001685 thyroid gland Anatomy 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 230000001131 transforming effect Effects 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- 241001515965 unidentified phage Species 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 206010003445 Ascites Diseases 0.000 description 3
- 235000019750 Crude protein Nutrition 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 241000283086 Equidae Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 3
- 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 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 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 3
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229930193140 Neomycin Natural products 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000251131 Sphyrna Species 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 210000004748 cultured cell Anatomy 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 238000002523 gelfiltration Methods 0.000 description 3
- 230000009368 gene silencing by RNA Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000003100 immobilizing effect Effects 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000010255 intramuscular injection Methods 0.000 description 3
- 239000007927 intramuscular injection Substances 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 210000002429 large intestine Anatomy 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000000520 microinjection Methods 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 229920005615 natural polymer Polymers 0.000 description 3
- 229960004927 neomycin Drugs 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 210000000496 pancreas Anatomy 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 244000144977 poultry Species 0.000 description 3
- 235000013594 poultry meat Nutrition 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000005185 salting out Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000012679 serum free medium Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229920001059 synthetic polymer Polymers 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 210000001550 testis Anatomy 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 230000014621 translational initiation Effects 0.000 description 3
- 210000004291 uterus Anatomy 0.000 description 3
- NPWMTBZSRRLQNJ-VKHMYHEASA-N (3s)-3-aminopiperidine-2,6-dione Chemical compound N[C@H]1CCC(=O)NC1=O NPWMTBZSRRLQNJ-VKHMYHEASA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
- VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 2
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 2
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 206010000830 Acute leukaemia Diseases 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 241000255789 Bombyx mori Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108091033380 Coding strand Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
- 108020001019 DNA Primers Proteins 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 2
- 239000003155 DNA primer Substances 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 241000701959 Escherichia virus Lambda Species 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 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 2
- 108010058683 Immobilized Proteins Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 101710203526 Integrase Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010036012 Iodide peroxidase Proteins 0.000 description 2
- 101150091824 Itgb4 gene Proteins 0.000 description 2
- 238000012449 Kunming mouse Methods 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
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 102000013460 Malate Dehydrogenase Human genes 0.000 description 2
- 108010026217 Malate Dehydrogenase Proteins 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 2
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 2
- 241000282579 Pan Species 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 208000007660 Residual Neoplasm Diseases 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 244000166550 Strophanthus gratus Species 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
- 108010034949 Thyroglobulin Proteins 0.000 description 2
- 102000009843 Thyroglobulin Human genes 0.000 description 2
- 102000014267 Thyroid peroxidases Human genes 0.000 description 2
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 2
- 241000255993 Trichoplusia ni Species 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 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
- 101150117115 V gene Proteins 0.000 description 2
- 241000700618 Vaccinia virus Species 0.000 description 2
- 108010051583 Ventricular Myosins Proteins 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 210000003486 adipose tissue brown Anatomy 0.000 description 2
- 210000000593 adipose tissue white Anatomy 0.000 description 2
- 210000004100 adrenal gland Anatomy 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 238000000137 annealing Methods 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 210000003651 basophil Anatomy 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 229960002903 benzyl benzoate Drugs 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 102000006995 beta-Glucosidase Human genes 0.000 description 2
- 108010047754 beta-Glucosidase Proteins 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 238000006664 bond formation reaction Methods 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000002449 bone cell Anatomy 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 230000009702 cancer cell proliferation Effects 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 230000007910 cell fusion Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 239000003398 denaturant Substances 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000003113 dilution method Methods 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 210000001339 epidermal cell Anatomy 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000007941 film coated tablet Substances 0.000 description 2
- ZFKJVJIDPQDDFY-UHFFFAOYSA-N fluorescamine Chemical compound C12=CC=CC=C2C(=O)OC1(C1=O)OC=C1C1=CC=CC=C1 ZFKJVJIDPQDDFY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 210000002175 goblet cell Anatomy 0.000 description 2
- 210000002149 gonad Anatomy 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229960000789 guanidine hydrochloride Drugs 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 210000000688 human artificial chromosome Anatomy 0.000 description 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 239000000644 isotonic solution Substances 0.000 description 2
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 2
- 210000001821 langerhans cell Anatomy 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- KNJDBYZZKAZQNG-UHFFFAOYSA-N lucigenin Chemical compound [O-][N+]([O-])=O.[O-][N+]([O-])=O.C12=CC=CC=C2[N+](C)=C(C=CC=C2)C2=C1C1=C(C=CC=C2)C2=[N+](C)C2=CC=CC=C12 KNJDBYZZKAZQNG-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 210000003593 megakaryocyte Anatomy 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000003584 mesangial cell Anatomy 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000011242 molecular targeted therapy Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 210000000956 olfactory bulb Anatomy 0.000 description 2
- 210000002997 osteoclast Anatomy 0.000 description 2
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 2
- 229960003343 ouabain Drugs 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 210000004976 peripheral blood cell Anatomy 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000013034 phenoxy resin Substances 0.000 description 2
- 229920006287 phenoxy resin Polymers 0.000 description 2
- 210000002826 placenta Anatomy 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002987 primer (paints) Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000010517 secondary reaction Methods 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 210000002536 stromal cell Anatomy 0.000 description 2
- 210000001913 submandibular gland Anatomy 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000002511 suppository base Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 210000002437 synoviocyte Anatomy 0.000 description 2
- 239000000057 synthetic resin Substances 0.000 description 2
- 229920003002 synthetic resin Polymers 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 210000001103 thalamus Anatomy 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 229960002175 thyroglobulin Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- NNJPGOLRFBJNIW-HNNXBMFYSA-N (-)-demecolcine Chemical compound C1=C(OC)C(=O)C=C2[C@@H](NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-HNNXBMFYSA-N 0.000 description 1
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 1
- XNRRDBJRLNJVMF-GKAPJAKFSA-N (2s)-3-(dimethylamino)-n-(ethyliminomethylidene)pyrrolidine-2-carboxamide Chemical compound CCN=C=NC(=O)[C@H]1NCCC1N(C)C XNRRDBJRLNJVMF-GKAPJAKFSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- UHPQFNXOFFPHJW-UHFFFAOYSA-N (4-methylphenyl)-phenylmethanamine Chemical compound C1=CC(C)=CC=C1C(N)C1=CC=CC=C1 UHPQFNXOFFPHJW-UHFFFAOYSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- UFFVWIGGYXLXPC-UHFFFAOYSA-N 1-[2-(2,5-dioxopyrrol-1-yl)phenyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C1=CC=CC=C1N1C(=O)C=CC1=O UFFVWIGGYXLXPC-UHFFFAOYSA-N 0.000 description 1
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-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
- LHJGJYXLEPZJPM-UHFFFAOYSA-N 2,4,5-trichlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C=C1Cl LHJGJYXLEPZJPM-UHFFFAOYSA-N 0.000 description 1
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- HJBUBXIDMQBSQW-UHFFFAOYSA-N 4-(4-diazoniophenyl)benzenediazonium Chemical compound C1=CC([N+]#N)=CC=C1C1=CC=C([N+]#N)C=C1 HJBUBXIDMQBSQW-UHFFFAOYSA-N 0.000 description 1
- OEBIVOHKFYSBPE-UHFFFAOYSA-N 4-Benzyloxybenzyl alcohol Chemical compound C1=CC(CO)=CC=C1OCC1=CC=CC=C1 OEBIVOHKFYSBPE-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- 108010042708 Acetylmuramyl-Alanyl-Isoglutamine Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000031504 Asymptomatic Infections Diseases 0.000 description 1
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241001037822 Bacillus bacterium Species 0.000 description 1
- 241000409811 Bombyx mori nucleopolyhedrovirus Species 0.000 description 1
- 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 101000800130 Bos taurus Thyroglobulin Proteins 0.000 description 1
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
- NNJPGOLRFBJNIW-UHFFFAOYSA-N Demecolcine Natural products C1=C(OC)C(=O)C=C2C(NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical class N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 description 1
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 241000724791 Filamentous phage Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 101710082961 GATA-binding factor 2 Proteins 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- 101000609762 Gallus gallus Ovalbumin Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 102100036242 HLA class II histocompatibility antigen, DQ alpha 2 chain Human genes 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000756632 Homo sapiens Actin, cytoplasmic 1 Proteins 0.000 description 1
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 1
- 101000930801 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 2 chain Proteins 0.000 description 1
- 101001033728 Homo sapiens Histone-lysine N-methyltransferase MECOM Proteins 0.000 description 1
- 101000979333 Homo sapiens Neurofilament light polypeptide Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 108010041012 Integrin alpha4 Proteins 0.000 description 1
- 108010041100 Integrin alpha6 Proteins 0.000 description 1
- 102000000426 Integrin alpha6 Human genes 0.000 description 1
- 102000012355 Integrin beta1 Human genes 0.000 description 1
- 108010022222 Integrin beta1 Proteins 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241000701460 JC polyomavirus Species 0.000 description 1
- 102100023970 Keratin, type I cytoskeletal 10 Human genes 0.000 description 1
- 101710183404 Keratin, type I cytoskeletal 10 Proteins 0.000 description 1
- 102100040445 Keratin, type I cytoskeletal 14 Human genes 0.000 description 1
- 101710183391 Keratin, type I cytoskeletal 14 Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 238000012218 Kunkel's method Methods 0.000 description 1
- 208000032420 Latent Infection Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 description 1
- 108010059343 MM Form Creatine Kinase Proteins 0.000 description 1
- 241000555303 Mamestra brassicae Species 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 102000036675 Myoglobin Human genes 0.000 description 1
- 108010062374 Myoglobin Proteins 0.000 description 1
- 102000005604 Myosin Heavy Chains Human genes 0.000 description 1
- 108010084498 Myosin Heavy Chains Proteins 0.000 description 1
- 102100030740 Myosin light chain 1/3, skeletal muscle isoform Human genes 0.000 description 1
- 102100026925 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform Human genes 0.000 description 1
- 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 description 1
- 210000004460 N cell Anatomy 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- VIHYIVKEECZGOU-UHFFFAOYSA-N N-acetylimidazole Chemical compound CC(=O)N1C=CN=C1 VIHYIVKEECZGOU-UHFFFAOYSA-N 0.000 description 1
- 229930182474 N-glycoside Natural products 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 102100023057 Neurofilament light polypeptide Human genes 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108010079246 OMPA outer membrane proteins Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 101150012394 PHO5 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010033546 Pallor Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 101710182846 Polyhedrin Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108090000944 RNA Helicases Proteins 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 229910003797 SPO1 Inorganic materials 0.000 description 1
- 229910003798 SPO2 Inorganic materials 0.000 description 1
- 101150014136 SUC2 gene Proteins 0.000 description 1
- 101100150136 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SPO1 gene Proteins 0.000 description 1
- 241000235347 Schizosaccharomyces pombe Species 0.000 description 1
- 101100478210 Schizosaccharomyces pombe (strain 972 / ATCC 24843) spo2 gene Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010045517 Serum Amyloid P-Component Proteins 0.000 description 1
- 102100036202 Serum amyloid P-component Human genes 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 235000019764 Soybean Meal Nutrition 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 101150052863 THY1 gene Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000005353 Tissue Inhibitor of Metalloproteinase-1 Human genes 0.000 description 1
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 102000013534 Troponin C Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 102000013532 Uroplakin II Human genes 0.000 description 1
- 108010065940 Uroplakin II Proteins 0.000 description 1
- 108700029233 VDJ Exons Proteins 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000012452 Xenomouse strains Methods 0.000 description 1
- 210000002593 Y chromosome Anatomy 0.000 description 1
- QNEPTKZEXBPDLF-JDTILAPWSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] carbonochloridate Chemical compound C1C=C2C[C@@H](OC(Cl)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 QNEPTKZEXBPDLF-JDTILAPWSA-N 0.000 description 1
- 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 Chemical class 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 1
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 108020002494 acetyltransferase Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 description 1
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 238000007844 allele-specific PCR Methods 0.000 description 1
- 102000004139 alpha-Amylases Human genes 0.000 description 1
- 108090000637 alpha-Amylases Proteins 0.000 description 1
- 229940024171 alpha-amylase Drugs 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 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 1
- 210000004727 amygdala Anatomy 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 108010030518 arginine endopeptidase Proteins 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 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
- 150000001540 azides Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- RXUBZLMIGSAPEJ-UHFFFAOYSA-N benzyl n-aminocarbamate Chemical compound NNC(=O)OCC1=CC=CC=C1 RXUBZLMIGSAPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 201000006491 bone marrow cancer Diseases 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000004712 cancer cell adhesion Effects 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000003163 cell fusion method Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[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 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229940096422 collagen type i Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000003935 denaturing gradient gel electrophoresis Methods 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 208000037771 disease arising from reactivation of latent virus Diseases 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000004662 dithiols Chemical class 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 125000005414 dithiopyridyl group Chemical group 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 108091007231 endothelial receptors Proteins 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000003619 fibrillary effect Effects 0.000 description 1
- 210000000630 fibrocyte Anatomy 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000005861 gene abnormality Effects 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000006451 grace's insect medium Substances 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000000442 hair follicle cell Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 208000021760 high fever Diseases 0.000 description 1
- 102000048399 human ITGA6 Human genes 0.000 description 1
- 102000048611 human ITGB4 Human genes 0.000 description 1
- 102000057134 human MECOM Human genes 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 201000006747 infectious mononucleosis Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000001155 isoelectric focusing Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 210000001767 medulla oblongata Anatomy 0.000 description 1
- 210000001809 melena Anatomy 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 238000004264 monolayer culture Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- BSOQXXWZTUDTEL-ZUYCGGNHSA-N muramyl dipeptide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@@H](O)[C@@H]1NC(C)=O BSOQXXWZTUDTEL-ZUYCGGNHSA-N 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 108010065781 myosin light chain 2 Proteins 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 230000023578 negative regulation of cell adhesion Effects 0.000 description 1
- 210000000441 neoplastic stem cell Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 210000000633 nuclear envelope Anatomy 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000005868 ontogenesis Effects 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 101150019841 penP gene Proteins 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000008298 phosphoramidates Chemical class 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical compound NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- VIBUIHYCIPNHIL-IDIVVRGQSA-L potassium;sodium;[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] phosphono phosphate Chemical compound [Na+].[K+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O VIBUIHYCIPNHIL-IDIVVRGQSA-L 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108010074732 preproenkephalin Proteins 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011403 purification operation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 101150079601 recA gene Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 208000037922 refractory disease Diseases 0.000 description 1
- 239000011819 refractory material Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 238000012090 tissue culture technique Methods 0.000 description 1
- DVKJHBMWWAPEIU-UHFFFAOYSA-N toluene 2,4-diisocyanate Chemical compound CC1=CC=C(N=C=O)C=C1N=C=O DVKJHBMWWAPEIU-UHFFFAOYSA-N 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 210000003501 vero cell Anatomy 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010451 viral insertion Methods 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
(i)M.BodanszkyおよびM.A.Ondetti、ペプチド・シンセシス(Peptide Synthesis),Interscience Publishers,New York(1966年)
(ii)SchroederおよびLuebke、ザ・ペプチド(The Peptide),Academic Press,New York(1965年)
(iii)泉屋信夫他、ペプチド合成の基礎と実験、丸善(株)(1975年)
(iv)矢島治明および榊原俊平、生化学実験講座1、タンパク質の化学IV、205、(1977年)
(v)矢島治明監修、続医薬品の開発、第14巻、ペプチド合成、広川書店
このようにして得られたタンパク質(ペプチド)は、公知の精製法により精製単離することができる。ここで、精製法としては、例えば、溶媒抽出・蒸留・カラムクロマトグラフィー・液体クロマトグラフィー・再結晶などが挙げられる。
本発明の抗体を調製するために使用される抗原としては、上記した本発明のタンパク質またはその部分ペプチド、あるいはそれと同一の抗原決定基を1種あるいは2種以上有する(合成)ペプチドなど、いずれのものも使用されうる(以下、これらを単に「本発明の抗原」とも称する)。
(a)モノクローナル抗体産生細胞の作製
本発明の抗原は、温血動物に対して、例えば腹腔内注入、静脈注入、皮下注射、皮内注射などの投与方法によって、抗体産生が可能な部位にそれ自体単独で、あるいは担体、希釈剤とともに投与される。投与に際して抗体産生能を高めるため、完全フロイントアジュバントや不完全フロイントアジュバントを投与してもよい。投与は通常1〜6週毎に1回ずつ、計2〜10回程度行なわれる。用いられる温血動物としては、例えば、サル、ウサギ、イヌ、モルモット、マウス、ラット、ハムスター、ヒツジ、ヤギ、ロバ、ニワトリが挙げられる。抗Ig抗体産生の問題を回避するためには、投与対象と同一種の哺乳動物を用いることが好ましいが、モノクローナル抗体作製には一般にマウスおよびラットが好ましく用いられる。
モノクローナル抗体の分離精製は、それ自体公知の方法、例えば、免疫グロブリンの分離精製法[例:塩析法、アルコール沈殿法、等電点沈殿法、電気泳動法、イオン交換体(例えば、DEAE、QEAE)による吸脱着法、超遠心法、ゲルろ過法、抗原結合固相あるいはプロテインAあるいはプロテインGなどの活性吸着剤により抗体のみを採取し、結合を解離させて抗体を得る特異的精製法など]に従って行なうことができる。
本明細書において「キメラ抗体」とは、H鎖およびL鎖の可変領域(VHおよびVL)の配列がある哺乳動物種に由来し、定常領域(CHおよびCL)の配列が他の哺乳動物種に由来する抗体を意味する。可変領域の配列は、例えばマウス等の容易にハイブリドーマを作製することができる動物種由来であることが好ましく、定常領域の配列は投与対象となる哺乳動物種由来であることが好ましい。
本明細書において「ヒト化抗体」とは、可変領域に存在する相補性決定領域(CDR)以外のすべての領域(すなわち、定常領域および可変領域中のフレームワーク領域(FR))の配列がヒト由来であり、CDRの配列のみが他の哺乳動物種由来である抗体を意味する。他の哺乳動物種としては、例えばマウス等の容易にハイブリドーマを作製することができる動物種が好ましい。
内因性免疫グロブリン(Ig)遺伝子をノックアウト(KO)した非ヒト温血動物に機能的なヒトIg遺伝子を導入し、これを抗原で免疫すれば、該動物由来の抗体の代わりにヒト抗体が産生される。従って、マウス等のようにハイブリドーマ作製技術が確立している動物を用いれば、従来のマウスモノクローナル抗体の作製と同様の方法によって完全ヒトモノクローナル抗体を取得することが可能となる。まず、ヒトIgのH鎖およびL鎖のミニ遺伝子を通常のトランスジェニック(Tg)技術を用いて導入したマウスと、内因性マウスIg遺伝子を通常のKO技術を用いて不活性化したマウスとを交配して得られたヒト抗体産生マウス(Immunol.Today,17,391−397(1996)を参照)を用いて作製されたヒトモノクローナル抗体のいくつかは既に臨床段階にあり、現在までのところ抗ヒトIgヒト抗体(HAHA)の産生は報告されていない。
完全ヒト抗体を作製するもう1つのアプローチは、ファージディスプレイを用いる方法である。この方法はPCRによる変異がCDR以外に導入される場合があり、そのため臨床段階で少数のHAHA産生の報告例があるが、その一方で宿主動物に由来する異種間ウイルス感染の危険性がない点や抗体の特異性が無限である(禁止クローンや糖鎖などに対する抗体も容易に作製可能)等の利点を有している。
ヒト抗体産生動物およびファージディスプレイヒト抗体ライブラリーを用いた完全ヒト抗体作製技術は、他の動物種のモノクローナル抗体を作製するのにも応用することができる。例えば、ウシ、ブタ、ヒツジ、ヤギ、ニワトリなどの家畜(家禽)として広く繁殖されている動物やイヌやネコなどのペット動物などが対象として挙げられる。非ヒト動物においては標的抗原の人為的免疫に対する倫理的問題が少ないので、免疫ライブラリーの利用がより有効である。
本発明のポリクローナル抗体は、それ自体公知の方法あるいはそれに準じる方法に従って製造することができる。例えば、免疫抗原(タンパク質もしくはペプチド抗原)自体、あるいはそれとキャリアータンパク質との複合体をつくり、上記のモノクローナル抗体の製造法と同様に温血動物に免疫を行い、該免疫動物から本発明のタンパク質に対する抗体含有物を採取して、抗体の分離精製を行なうことにより製造することができる。
本発明の遺伝子の転写産物に相補的に結合し、該遺伝子の発現を抑制することができる本発明のアンチセンスポリヌクレオチドは低毒性であり、生体内における本発明のタンパク質または本発明の遺伝子の機能や作用を抑制し、癌細胞の細胞接着を阻害することができる。このため、本発明のアンチセンスポリヌクレオチドは、癌細胞の細胞接着阻害剤、癌(例えば、大腸癌、乳癌、肺癌、前立腺癌、食道癌、胃癌、肝臓癌、胆道癌、脾臓癌、腎癌、膀胱癌、子宮癌、卵巣癌、精巣癌、甲状腺癌、膵臓癌、脳腫瘍、造血器腫瘍(例えば、急性骨髄性白血病、急性前骨髄性白血病、急性リンパ性白血病、慢性骨髄性白血病、慢性リンパ性白血病等)など)の予防・治療剤(好ましくは、造血器腫瘍の予防・治療剤、より好ましくは、急性骨髄性白血病(AML)の予防・治療剤)として使用することができる。また、他の実施形態として、本発明のアンチセンスポリヌクレオチドは、当該アンチセンスポリヌクレオチド以外の抗癌剤と併用された際に、癌細胞の前記抗癌剤に対する感受性を向上させるための剤(薬剤感受性向上剤)としても用いられうる。
本発明のタンパク質は、癌組織で発現が亢進しており、さらに、EVI1、ITGA6、またはITGB4タンパク質の発現および/または活性を阻害すると、癌細胞の細胞接着が阻害されうる。従って、EVI1、ITGA6、またはITGB4タンパク質の発現および/または活性を阻害する化合物またはその塩は、癌細胞の細胞接着阻害剤、癌(例えば、大腸癌、乳癌、肺癌、前立腺癌、食道癌、胃癌、肝臓癌、胆道癌、脾臓癌、腎癌、膀胱癌、子宮癌、卵巣癌、精巣癌、甲状腺癌、膵臓癌、脳腫瘍、造血器腫瘍(例えば、急性骨髄性白血病、急性前骨髄性白血病、急性リンパ性白血病、慢性骨髄性白血病、慢性リンパ性白血病等)など)の予防・治療剤(好ましくは、造血器腫瘍の予防・治療剤、より好ましくは、急性骨髄性白血病(AML)の予防・治療剤)として用いられうる。
(a−1)単離された本発明のタンパク質の活性を、被験物質の存在下と非存在下とで比較する方法と、
(a−2)本発明のタンパク質を産生する能力を有する細胞を被験物質の存在下および非存在下で培養し、両条件下における本発明のタンパク質の活性を比較する方法とに大別される。
(b)本発明のタンパク質を産生する能力を有する細胞を被験物質の存在下および非存在下で培養し、両条件下における本発明のタンパク質をコードするmRNAの量を、本発明のセンスもしくはアンチセンスポリヌクレオチドを用いて測定・比較する、癌細胞の細胞接着阻害物質、癌の予防・治療物質のスクリーニング方法、および
(c)本発明のタンパク質を産生する能力を有する細胞を被験物質の存在下および非存在下で培養し、両条件下における本発明のタンパク質の量を、本発明の抗体を用いて測定・比較する、癌細胞の細胞接着阻害物質、癌の予防・治療物質のスクリーニング方法が提供される。
(i)正常あるいは疾患モデル非ヒト温血動物に対して、薬剤あるいは物理化学的ストレスなどを与える一定時間前(30分前〜24時間前、好ましくは30分前〜12時間前、より好ましくは1時間前〜6時間前)もしくは一定時間後(30分後〜3日後、好ましくは1時間後〜2日後、より好ましくは1時間後〜24時間後)、または薬剤あるいは物理化学的ストレスと同時に被験物質を投与し、投与から一定時間が経過した後(30分後〜3日後、好ましくは1時間後〜2日後、より好ましくは1時間後〜24時間後)、該動物から単離した細胞に含まれる本発明のタンパク質をコードするmRNA量、または本発明のタンパク質の量を定量、解析することにより、あるいは
(ii)形質転換体を常法に従って培養する際に被験物質を培地中に添加し、一定時間培養後(1日後〜7日後、好ましくは1日後〜3日後、より好ましくは2日後〜3日後)、該形質転換体に含まれる本発明のタンパク質のmRNA量または本発明のタンパク質の量を定量、解析することにより行なうことができる。
(i)本発明の抗体と、試料液および標識化された本発明のタンパク質とを競合的に反応させ、該抗体に結合した標識化された本発明のタンパク質を検出することにより試料液中の本発明のタンパク質を定量する方法や、
(ii)試料液と、担体上に不溶化した本発明の抗体および標識化された別の本発明の抗体とを、同時あるいは連続的に反応させた後、不溶化担体上の標識剤の量(活性)を測定することにより、試料液中の本発明のタンパク質を定量する方法等が挙げられる。
本発明の抗体は、本発明のタンパク質を特異的に認識することができる。このため、当該抗体は、被験液中の本発明のタンパク質の定量などに使用されうる。従って、上述の本発明の抗体を用いる本発明のタンパク質の発現阻害物質のスクリーニング方法において、本発明のタンパク質を産生する能力を有する細胞の代わりに、被験温血動物から採取した生体試料(例、血液、血漿、尿、生検など)を用いてイムノアッセイを実施することにより、該動物体内における本発明のタンパク質の発現の程度を調べることができ、ひいては癌の診断に用いることができる。イムノアッセイの結果、該試料中の本発明のタンパク質の増加が検出された場合は、癌(例えば、大腸癌、乳癌、肺癌、前立腺癌、食道癌、胃癌、肝臓癌、胆道癌、脾臓癌、腎癌、膀胱癌、子宮癌、卵巣癌、精巣癌、甲状腺癌、膵臓癌、脳腫瘍、造血器腫瘍(特に、AML)など)を発症しているか、あるいは将来発症する可能性が高いと診断することができる。
本発明のタンパク質は癌細胞において過剰に発現していることから、癌患者の免疫系を活性化するために本発明のタンパク質を癌ワクチンとして用いることもできる。
本発明は、外来性の本発明のタンパク質をコードするDNA(以下、「本発明の外来性DNA」とも称する)またはその変異DNA(「本発明の外来性変異DNA」とも称する)を有する非ヒト哺乳動物を提供する。
(1)本発明の外来性DNAまたはその変異DNAを有する非ヒト哺乳動物、
(2)非ヒト哺乳動物がゲッ歯動物である第(1)記載の動物、
(3)ゲッ歯動物がマウスまたはラットである第(2)記載の動物、および
(4)本発明の外来性DNAまたはその変異DNAを含有し、哺乳動物において発現しうる組換えベクターが提供される。
(i)組織培養のための細胞源としての使用、
(ii)本発明のDNA転移動物の組織中DNAもしくはRNAを直接分析するか、またはDNAにより発現されたペプチド組織を分析することによる、本発明のタンパク質により特異的に発現あるいは活性化するペプチドとの関連性についての解析、
(iii)DNAを有する組織の細胞を標準組織培養技術により培養し、これらを使用して、一般に培養困難な組織からの細胞の機能の研究、
(iv)上記(iii)記載の細胞を用いることによる細胞の機能を高めるような薬剤のスクリーニング、および
(v)本発明の変異タンパク質の単離精製およびその抗体作製などが考えられる。
本発明は、本発明のDNAが不活性化された非ヒト哺乳動物胚幹細胞および本発明のDNA発現不全非ヒト哺乳動物を提供する。
(1)本発明のDNAが不活性化された非ヒト哺乳動物胚幹細胞、
(2)該DNAがレポーター遺伝子(例、大腸菌由来のβ−ガラクトシダーゼ遺伝子)を導入することにより不活性化された第(1)項記載の胚幹細胞、
(3)ネオマイシン耐性である第(1)項記載の胚幹細胞、
(4)非ヒト哺乳動物がゲッ歯動物である第(1)項記載の胚幹細胞、
(5)ゲッ歯動物がマウスである第(4)項記載の胚幹細胞、
(6)本発明のDNAが不活性化された該DNA発現不全非ヒト哺乳動物、
(7)該DNAがレポーター遺伝子(例、大腸菌由来のβ−ガラクトシダーゼ遺伝子)を導入することにより不活性化され、該レポーター遺伝子が本発明のDNAに対するプロモーターの制御下で発現しうる第(6)項記載の非ヒト哺乳動物、
(8)非ヒト哺乳動物がゲッ歯動物である第(6)項記載の非ヒト哺乳動物、
(9)ゲッ歯動物がマウスである第(8)項記載の非ヒト哺乳動物、および
(10)第(7)項記載の動物に、試験化合物を投与し、レポーター遺伝子の発現を検出する、本発明のDNAに対するプロモーター活性を促進または阻害する化合物またはその塩のスクリーニング方法が提供される。
本発明のDNA発現不全非ヒト哺乳動物は、本発明のDNAの欠損や損傷などに起因する疾病に対して治療・予防効果を有する化合物のスクリーニングに用いることができる。
本発明によれば、本発明のDNA発現不全非ヒト哺乳動物に、試験化合物を投与し、レポーター遺伝子の発現を検出する、本発明のDNAに対するプロモーターの活性を促進または阻害する化合物またはその塩のスクリーニング方法が提供される。
上記スクリーニング方法を用いて得られる化合物またはその塩は、上記した試験化合物から選ばれた化合物であり、本発明のDNAに対するプロモーター活性を促進または阻害する化合物である。
〔配列番号:1〕
EVI1をコードするDNA(CDS)の塩基配列を示す。
〔配列番号:2〕
EVI1のアミノ酸配列を示す。
〔配列番号:3〕
ITGA6をコードするDNA(CDS)の塩基配列を示す。
〔配列番号:4〕
ITGA6のアミノ酸配列を示す。
〔配列番号:5〕
ITGB4をコードするDNA(CDS)の塩基配列を示す。
〔配列番号:6〕
ITGB4のアミノ酸配列を示す。
〔配列番号:7〕
配列番号8とともにshEVI1を形成するRNA配列を示す。
〔配列番号:8〕
配列番号7とともにshEVI1を形成するRNA配列を示す。
〔配列番号:9〕
ヒトEVI1遺伝子の増幅に用いたフォワードプライマーの塩基配列を示す。
〔配列番号:10〕
ヒトEVI1遺伝子の増幅に用いたリバースプライマーの塩基配列を示す。
〔配列番号:11〕
ヒトβ−アクチン遺伝子の増幅に用いたフォワードプライマーの塩基配列を示す。
〔配列番号:12〕
ヒトβ−アクチン遺伝子の増幅に用いたリバースプライマーの塩基配列を示す。
〔配列番号:13〕
配列番号14とともにshEVI1を形成するRNA配列を示す。
〔配列番号:14〕
配列番号13とともにshEVI1を形成するRNA配列を示す。
(EVI1発現抑制AML1細胞の樹立)
ヒト急性骨髄性白血病(AML)由来であるAML1細胞株に対して、EVI1遺伝子のmRNAを切断する活性を有するショートヘアピンRNA(shRNA)であるshEVI1をトランスフェクションすることにより、EVI1発現抑制AML1細胞株(以下、「AML1(shEVI1)」とも称する)を樹立した。
上記で樹立したAML1(shEVI1)およびAML1(shLuc)を安定に培養したものを、遠心分離によりそれぞれ回収し、培地を除去した後、TRIZOL(登録商標)(インビトロジェン社製)1mLを添加した。次いで、クロロホルム500μLを添加し、15000rpmにて15分間遠心分離した後、上層を別のチューブに移し、2−プロパノール500μLを添加して、15000rpmにて10分間遠心分離し、80%エタノールを用いて洗浄した。得られたRNAをRNaseフリーの水に溶解させ、分光光度計にて波長260nmでRNA量を測定した後、このRNA1μgを逆転写酵素(superscript3(インビトロジェン社製))を用いてcDNAに変換した。
(ヒトEVI1)
フォワード:CGAAAGCGAGAATGATCTCC(配列番号:9)
リバース:GGAAGACGTAGTGCTGAACA(配列番号:10)
(ヒトβ−アクチン)
フォワード:AAGAGATGGCCACGGCTGCT(配列番号:11)
リバース:TCCTTCTGCATCCTGTCGGC(配列番号:12)
(インテグリンファミリー)
Journal of Biomedical Science(2005)12:803−813に開示のもの。
上記で樹立したAML1(shEVI1)(トリプリケート)およびAML1(shLuc)について、その細胞接着能を評価した。
EVI1遺伝子を発現していない細胞株として、ヒト由来のHL60細胞株、ヒト由来のU937細胞株、およびヒト由来のK562細胞株を安定に培養したものを準備した。一方、EVI1遺伝子を発現している細胞株として、ヒト急性骨髄性白血病由来のAML1細胞株(上述)、ヒト由来のMOLM1細胞株、およびヒト由来のHNT34細胞株を安定に培養したものを準備した。これらの細胞株について、上述した実施例1−1と同様の手法により、EVI1遺伝子および各種インテグリンファミリー遺伝子の発現を確認した。
ヒト由来であるHNT34細胞株に対し、遺伝子導入システムであるNucleofector(アマクサバイオシステムズ社製)を用いて、上述した実施例1−1で用いたshEVI1を導入して、EVI1発現抑制HNT34細胞株(以下、「HNT34(shEVI1)」とも称する)を樹立した。同様に、コントロール細胞として、shLucを導入した細胞株(以下、「HNT34(shLuc)」とも称する)も樹立した。これらの細胞株について、上述した実施例1と同様の手法により、EVI1遺伝子および各種インテグリンファミリー遺伝子の発現を確認した。
上記で樹立したHNT34(shEVI1)およびHNT34(shLuc)について、上述した実施例1−2と同様の手法により、その細胞接着能を評価した。
上記で樹立したHNT34(shEVI1)およびHNT34(shLuc)について、その細胞増殖能を評価した。
上述した実施例2−1と同様の手法により、AML1細胞株に対して、ITGB4遺伝子のmRNAを切断する活性を有するshRNA(以下、「shITGB4」とも称する)をトランスフェクションすることにより、ITGB4発現抑制AML1細胞株(以下、「AML1(shITGB4)」とも称する)を樹立した。なお、用いたshITGB4の塩基配列は以下の通りである。
アンチセンス鎖:AAUUCAAAAAGAGCUGCACGGAGUGUGUCUCUCUUGAAGACACACCCCACGCAACUCGGA(配列番号:14)
コントロール細胞としては、上述した実施例1−1において樹立したAML1(shLuc)を用いた。
ヒト由来であるAML1細胞株に対して、β4インテグリン中和抗体を投与することにより、当該細胞株の細胞接着能に対する影響を評価した。
EVI1遺伝子を発現していないU937細胞株に対して、EVI1遺伝子を導入することにより、各種インテグリンファミリー遺伝子の発現が増加するかどうかを調べた。
U937細胞株、並びに、上記で樹立したコントロールであるU937(GFP)およびEVI1導入細胞株であるU937(FLAG−EVI1)について、上述した実施例2−1と同様の手法により、EVI1遺伝子の導入による細胞接着能への影響を評価した。
U937細胞株、並びに、上記で樹立したコントロールであるU937(GFP)およびEVI1導入細胞株であるU937(FLAG−EVI1)について、上述した参考例2と同様の手法により、EVI1遺伝子の導入による細胞増殖能への影響を評価した。
EVI1遺伝子をまったくまたはほとんど発現していない細胞株として、U937、K562、KG1、HEL、HL−60、K052、THP−1、FKH−1、K051、NH、およびOIH−1を準備した。一方、EVI1遺伝子を高度に発現している細胞株として、AML−1、HNT−34、Kasumi3、およびMOLM−1を準備した。
臨床検体として、EVI1遺伝子を発現していない急性骨髄性白血病(AML)細胞を3サンプル、EVI1遺伝子を高度に発現しているAMLの1種であるt(3;7)のAML細胞を4サンプル、同様にEVI1遺伝子を高度に発現しているAMLの1種である3q21q26症候群のAML細胞を3サンプル準備した。なお、細胞株コントロールとして、EVI1遺伝子を発現していないBone Marrow(BM)細胞、およびEVI1遺伝子を高度に発現しているCD34陽性細胞を併せて準備した。
EVI1遺伝子を発現していない細胞株として、HEL、HL60、K052、THP−1、FKH−1、K051、NH、OIH−1を準備した。一方、EVI1遺伝子を高度に発現している細胞株として、AML1、HNT34、MOLM1、Kasumi3を準備した。これらの細胞株について、ITGA6遺伝子およびITGB4遺伝子の発現を、アフィメトリクス社製のジーンチップ(Gene−chip)のマニュアルに従ってDNAマイクロアレイにより検出した。
臨床検体として、EVI1遺伝子を発現していない急性骨髄性白血病(AML)細胞を10サンプル、EVI1遺伝子を高度に発現しているAML細胞を12サンプル準備した。
上記で準備したサンプルおよび細胞株コントロールについて、ITGA6遺伝子およびITGB4遺伝子の発現を、上述した参考例4−3と同様の手法により、DNAマイクロアレイにより確認した。
骨芽細胞の存在が、ヒト急性骨髄性白血病(AML)由来であるAML1細胞株の薬剤耐性に及ぼす影響を調べた。
上述した参考例5(Ara−C存在下)において、AML1細胞株に代えて上記で樹立したAML1(shEVI1)細胞およびAML1(shLuc)細胞をそれぞれ用い、同様の手法によりWST法による薬剤耐性アッセイを行なった。
アメリカ合衆国国立生物工学情報センター(NCBI;National Center for Biotechnology Information)の遺伝子発現バンク(GEO;Gene Expression Omnibus)から、ヒトAML患者の骨髄細胞における遺伝子発現データを55例収集した。そして、これらのデータをAML完治群(30例)とAML再発群(25例)とに分け、それぞれの群の間で、ITGA6遺伝子およびITGB4遺伝子の発現量に有意差があるか否かを、対応のないt検定により統計的に評価した。
NCBIの遺伝子発現バンク(GEO)から、ヒトにおける各種の骨髄/末梢血細胞における遺伝子発現データを30例(15種×2)収集した。そして、これらのデータにおけるITGA6遺伝子およびITGB4遺伝子のそれぞれの発現量を比較した。
上述した参考例7に示す結果を受けて、ヒト臍帯血由来のCD34陽性細胞(造血幹細胞)およびAML1細胞におけるインテグリンファミリー遺伝子の発現を比較した。ここで、CD34陽性細胞(「CD34+」とも称する)については、ヒト臍帯血より分離し、Methoculture(ステムセル社製)を培地として用いて培養した。なお、インテグリン遺伝子の発現量の比較については、上述した実施例1−1と同様のPCR法により行なった。
上記で樹立したAML1(shEVI1)細胞をNOGマウス(登録商標)へ移植し、移植後におけるマウス大腿骨へのAML1(shEVI1)細胞の集積を調べた。ここで、NOGマウスとは、ヒト化モデルマウスの作製に適した重度免疫不全マウスであり、実験動物中央研究所より入手可能である。
Claims (2)
- 以下の(a)〜(c)のいずれかに記載のタンパク質に対する抗体を含有し、急性骨髄性白血病の予防剤または治療剤として用いられてAra−Cと併用された際に、癌細胞の前記Ara−Cに対する感受性を向上させるのに用いられる、癌細胞の細胞接着阻害剤:
(a)配列番号:2で表されるアミノ酸配列からなるタンパク質;
(b)配列番号:2で表されるアミノ酸配列において1個または2個以上のアミノ酸が欠失、付加、挿入または置換されたアミノ酸配列からなり、急性骨髄性白血病における細胞接着能の亢進活性を有するタンパク質;
(c)配列番号2に示すアミノ酸配列に対して90%以上の同一性を有するアミノ酸配列からなり、急性骨髄性白血病における細胞接着能の亢進活性を有するタンパク質。 - 以下の(a)〜(c)のいずれかに記載のタンパク質をコードするポリヌクレオチドの塩基配列に、相補的もしくは実質的に相補的な塩基配列またはその一部を含むアンチセンスポリヌクレオチドを含有し、急性骨髄性白血病の予防剤または治療剤として用いられてAra−Cと併用された際に、癌細胞の前記Ara−Cに対する感受性を向上させるのに用いられる、癌細胞の細胞接着阻害剤:
(a)配列番号:2で表されるアミノ酸配列からなるタンパク質;
(b)配列番号:2で表されるアミノ酸配列において1個または2個以上のアミノ酸が欠失、付加、挿入または置換されたアミノ酸配列からなり、急性骨髄性白血病における細胞接着能の亢進活性を有するタンパク質;
(c)配列番号2に示すアミノ酸配列に対して90%以上の同一性を有するアミノ酸配列からなり、急性骨髄性白血病における細胞接着能の亢進活性を有するタンパク質。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011501535A JP5704722B2 (ja) | 2009-02-24 | 2010-01-28 | 細胞接着阻害剤およびその用途 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009041204 | 2009-02-24 | ||
JP2009041204 | 2009-02-24 | ||
PCT/JP2010/051109 WO2010098166A1 (ja) | 2009-02-24 | 2010-01-28 | 細胞接着阻害剤およびその用途 |
JP2011501535A JP5704722B2 (ja) | 2009-02-24 | 2010-01-28 | 細胞接着阻害剤およびその用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2010098166A1 JPWO2010098166A1 (ja) | 2012-08-30 |
JP5704722B2 true JP5704722B2 (ja) | 2015-04-22 |
Family
ID=42665376
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011501535A Active JP5704722B2 (ja) | 2009-02-24 | 2010-01-28 | 細胞接着阻害剤およびその用途 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20120045773A1 (ja) |
EP (1) | EP2402033B1 (ja) |
JP (1) | JP5704722B2 (ja) |
CN (1) | CN102333543B (ja) |
WO (1) | WO2010098166A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130330761A1 (en) | 2012-06-12 | 2013-12-12 | Celcuity, LLC | Whole cell assays and methods |
US10030071B2 (en) * | 2013-09-05 | 2018-07-24 | University Of Miyazaki | Antibody which specifically reacts with human integrin A6B4 |
WO2015089380A2 (en) | 2013-12-12 | 2015-06-18 | Celcuity Llc | Assays and methods for determining the responsiveness of an individual subject to a therapeutic agent |
TWI639699B (zh) * | 2015-03-06 | 2018-11-01 | 中山醫學大學 | Method for screening fused cells |
KR20190126070A (ko) | 2017-03-20 | 2019-11-08 | 셀퀴티 인크. | 치료제의 선택을 위한 신호전달 경로 활성을 측정하는 방법 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
JPH05227970A (ja) | 1992-02-19 | 1993-09-07 | Chugai Pharmaceut Co Ltd | ヒトインターロイキン−6受容体に対する再構成ヒト抗体 |
CA2078817A1 (en) * | 1991-10-18 | 1993-04-19 | Beat A. Imhof | Anti-.alpha.6-integrin-antibodies |
JP2000333673A (ja) | 1999-05-31 | 2000-12-05 | Wakenyaku Kk | 連続無細胞タンパク質合成手段 |
US6869795B1 (en) * | 1999-10-07 | 2005-03-22 | Avi Biopharma, Inc. | Antisense compositions and cancer-treatment methods |
US6436703B1 (en) * | 2000-03-31 | 2002-08-20 | Hyseq, Inc. | Nucleic acids and polypeptides |
WO2008127655A1 (en) * | 2007-04-13 | 2008-10-23 | Biogen Idec Ma Inc. | Anti-alpha 6 beta 4 integrin antibodies and uses therof |
JP2009041204A (ja) | 2007-08-07 | 2009-02-26 | Hayashi Bussan Hatsumei Kenkyusho:Kk | 災害用トイレ |
US8211646B1 (en) * | 2008-11-14 | 2012-07-03 | University Of South Florida | Methods of treating ovarian cancer by modulating SnoN |
-
2010
- 2010-01-28 US US13/203,073 patent/US20120045773A1/en not_active Abandoned
- 2010-01-28 JP JP2011501535A patent/JP5704722B2/ja active Active
- 2010-01-28 WO PCT/JP2010/051109 patent/WO2010098166A1/ja active Application Filing
- 2010-01-28 CN CN201080009144.3A patent/CN102333543B/zh not_active Expired - Fee Related
- 2010-01-28 EP EP10746047.9A patent/EP2402033B1/en active Active
Non-Patent Citations (3)
Title |
---|
JPN6014010092; Oncogene Vol.25, 2006, p.3565-3575 * |
JPN6014010094; The Journal of Biological Chemistry Vol.280, 2005, p.30712-30722 * |
JPN6014010097; Cell Stem Cell Vol.3, 2008, p.207-220 * |
Also Published As
Publication number | Publication date |
---|---|
JPWO2010098166A1 (ja) | 2012-08-30 |
EP2402033A4 (en) | 2013-01-23 |
CN102333543A (zh) | 2012-01-25 |
US20120045773A1 (en) | 2012-02-23 |
EP2402033A1 (en) | 2012-01-04 |
EP2402033B1 (en) | 2019-02-27 |
WO2010098166A1 (ja) | 2010-09-02 |
CN102333543B (zh) | 2014-05-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5704722B2 (ja) | 細胞接着阻害剤およびその用途 | |
JPWO2006093337A1 (ja) | 癌の予防・治療剤 | |
JPWO2005097204A1 (ja) | 癌の予防・治療剤 | |
JPWO2007018316A1 (ja) | 癌の予防・治療剤 | |
JP5167539B2 (ja) | 遺伝子多型およびその用途 | |
JP2010046057A (ja) | 癌細胞の治療感受性増強剤、癌細胞の治療感受性の判定方法、および癌細胞の治療感受性判定キット | |
JP6029019B2 (ja) | 細胞接着阻害剤、細胞増殖阻害剤、並びに癌の検査方法および検査用キット | |
EP2623119B1 (en) | Drug used in glioma treatment method, glioma examination method, method of delivering a desired material to a glioma | |
EP2016949A1 (en) | Novel use of g-protein-conjugated receptor and ligand thereof | |
JPWO2008111520A1 (ja) | 寿命延長関連遺伝子およびその用途 | |
JP4530631B2 (ja) | 新規タンパク質および癌の予防・治療剤 | |
US20100086911A1 (en) | Preventive/therapeutic agent for cancer | |
JPWO2005061704A1 (ja) | 癌の予防・治療剤 | |
JP4353697B2 (ja) | がんの予防・治療剤 | |
JP2004217634A (ja) | がんの予防・治療剤 | |
WO2004058817A1 (ja) | 新規タンパク質およびその用途 | |
JP4300008B2 (ja) | 新規タンパク質およびそのdna | |
JP2005015460A (ja) | Sgltホモログ用途 | |
JPWO2006101273A1 (ja) | 癌の予防・治療剤 | |
JP2004261172A (ja) | 疾患関連遺伝子の用途 | |
WO2008004406A1 (fr) | Agent pour moduler une dégranulation des mastocytes | |
JP2004173677A (ja) | 新規タンパク質およびそのdna | |
WO2004039407A1 (ja) | アポトーシス誘導剤 | |
JP2004290177A (ja) | 新規タンパク質およびその用途 | |
JP2004290170A (ja) | 疾患関連遺伝子の用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130123 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130123 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140311 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140512 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140610 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140811 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141125 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141211 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150210 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150220 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5704722 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |