CA2796306A1 - Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (alk) kinase inhibitors - Google Patents
Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (alk) kinase inhibitors Download PDFInfo
- Publication number
- CA2796306A1 CA2796306A1 CA2796306A CA2796306A CA2796306A1 CA 2796306 A1 CA2796306 A1 CA 2796306A1 CA 2796306 A CA2796306 A CA 2796306A CA 2796306 A CA2796306 A CA 2796306A CA 2796306 A1 CA2796306 A1 CA 2796306A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- amino acid
- alk
- polypeptide
- residue
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 title claims abstract description 612
- 101710168331 ALK tyrosine kinase receptor Proteins 0.000 title claims abstract description 611
- 229940043355 kinase inhibitor Drugs 0.000 title claims abstract description 211
- 239000003757 phosphotransferase inhibitor Substances 0.000 title claims abstract description 211
- 238000000034 method Methods 0.000 title claims abstract description 148
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 73
- 201000011510 cancer Diseases 0.000 title claims abstract description 61
- 239000000203 mixture Substances 0.000 title abstract description 12
- 238000011282 treatment Methods 0.000 title abstract description 6
- 238000003745 diagnosis Methods 0.000 title abstract description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 534
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 529
- 229920001184 polypeptide Polymers 0.000 claims abstract description 527
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 336
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 336
- 239000002157 polynucleotide Substances 0.000 claims abstract description 336
- 230000000694 effects Effects 0.000 claims abstract description 226
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 206
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 206
- 230000035772 mutation Effects 0.000 claims abstract description 104
- 229940122531 Anaplastic lymphoma kinase inhibitor Drugs 0.000 claims abstract description 72
- 230000014509 gene expression Effects 0.000 claims abstract description 49
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 48
- 229940126069 ALK kinase inhibitor Drugs 0.000 claims abstract description 21
- 230000001594 aberrant effect Effects 0.000 claims abstract description 21
- 125000000539 amino acid group Chemical group 0.000 claims description 340
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 230
- 150000003384 small molecules Chemical class 0.000 claims description 197
- 239000002773 nucleotide Substances 0.000 claims description 178
- 125000003729 nucleotide group Chemical group 0.000 claims description 178
- 231100000590 oncogenic Toxicity 0.000 claims description 79
- 230000002246 oncogenic effect Effects 0.000 claims description 79
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 76
- 210000004027 cell Anatomy 0.000 claims description 74
- 102000037865 fusion proteins Human genes 0.000 claims description 73
- 108020001507 fusion proteins Proteins 0.000 claims description 73
- 239000012472 biological sample Substances 0.000 claims description 53
- 108090000623 proteins and genes Proteins 0.000 claims description 50
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 38
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 38
- 230000027455 binding Effects 0.000 claims description 37
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 34
- 102100027418 E3 ubiquitin-protein ligase RNF213 Human genes 0.000 claims description 27
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims description 25
- 230000030279 gene silencing Effects 0.000 claims description 24
- 102100027100 Echinoderm microtubule-associated protein-like 4 Human genes 0.000 claims description 23
- 101710203446 Echinoderm microtubule-associated protein-like 4 Proteins 0.000 claims description 23
- 239000003112 inhibitor Substances 0.000 claims description 21
- 210000003205 muscle Anatomy 0.000 claims description 21
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 19
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 claims description 19
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 19
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 19
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 19
- 102000039446 nucleic acids Human genes 0.000 claims description 19
- 108020004707 nucleic acids Proteins 0.000 claims description 19
- 150000007523 nucleic acids Chemical class 0.000 claims description 19
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 19
- 102100022678 Nucleophosmin Human genes 0.000 claims description 17
- 108010025568 Nucleophosmin Proteins 0.000 claims description 17
- 102100024944 Tropomyosin alpha-4 chain Human genes 0.000 claims description 16
- 101710193115 Tropomyosin alpha-4 chain Proteins 0.000 claims description 16
- 239000003153 chemical reaction reagent Substances 0.000 claims description 16
- 101000800847 Homo sapiens Protein TFG Proteins 0.000 claims description 15
- 102100038938 Myosin-9 Human genes 0.000 claims description 15
- 101710204108 Myosin-9 Proteins 0.000 claims description 15
- 102100033661 Protein TFG Human genes 0.000 claims description 15
- 102100033080 Tropomyosin alpha-3 chain Human genes 0.000 claims description 15
- 101710091952 Tropomyosin alpha-3 chain Proteins 0.000 claims description 15
- 230000001413 cellular effect Effects 0.000 claims description 15
- 101710157159 E3 ubiquitin-protein ligase RNF213 Proteins 0.000 claims description 14
- 102100020796 Inosine 5'-monophosphate cyclohydrolase Human genes 0.000 claims description 14
- 102100027869 Moesin Human genes 0.000 claims description 14
- 102000014907 clathrin heavy chain Human genes 0.000 claims description 14
- 108060001643 clathrin heavy chain Proteins 0.000 claims description 14
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 14
- 108010071525 moesin Proteins 0.000 claims description 14
- 101000650316 Homo sapiens E3 ubiquitin-protein ligase RNF213 Proteins 0.000 claims description 13
- 101001138523 Homo sapiens Inosine 5'-monophosphate cyclohydrolase Proteins 0.000 claims description 13
- 102100038912 E3 SUMO-protein ligase RanBP2 Human genes 0.000 claims description 12
- 108010062219 ran-binding protein 2 Proteins 0.000 claims description 12
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 claims description 11
- 101001050559 Homo sapiens Kinesin-1 heavy chain Proteins 0.000 claims description 10
- 102100023422 Kinesin-1 heavy chain Human genes 0.000 claims description 10
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 claims description 9
- LAJAFFLJAJMYLK-CVOKMOJFSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[[(7s)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5h-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound N1([C@H]2CCC3=CC=C(C(=C3CC2)OC)NC=2N=C(C(=CN=2)Cl)N[C@H]2[C@H]([C@@]3([H])C[C@@]2(C=C3)[H])C(N)=O)CCOCC1 LAJAFFLJAJMYLK-CVOKMOJFSA-N 0.000 claims description 7
- QQWUGDVOUVUTOY-UHFFFAOYSA-N 5-chloro-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine Chemical compound COC1=CC(N2CCC(CC2)N2CCN(C)CC2)=CC=C1NC(N=1)=NC=C(Cl)C=1NC1=CC=CC=C1S(=O)(=O)C(C)C QQWUGDVOUVUTOY-UHFFFAOYSA-N 0.000 claims description 7
- PBCZSGKMGDDXIJ-XMCQDBRXSA-N 7-hydroxystaurosporine Chemical compound N([C@@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@@H]1C[C@@H](NC)[C@@H](OC)[C@@]3(C)O1 PBCZSGKMGDDXIJ-XMCQDBRXSA-N 0.000 claims description 7
- PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 claims description 7
- 101100256382 Candida albicans (strain SC5314 / ATCC MYA-2876) PGA63 gene Proteins 0.000 claims description 7
- 102000004403 Cysteine-tRNA ligases Human genes 0.000 claims description 7
- 108090000918 Cysteine-tRNA ligases Proteins 0.000 claims description 7
- 201000003803 Inflammatory myofibroblastic tumor Diseases 0.000 claims description 7
- 206010067917 Inflammatory myofibroblastic tumour Diseases 0.000 claims description 7
- 101150092584 SEC31 gene Proteins 0.000 claims description 7
- ZFKJDNACAGAYFJ-UHFFFAOYSA-N [19-methyl-3-(2-methylpropyl)-14-oxo-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-7-yl] N-[[4-(dimethylamino)phenyl]methyl]carbamate Chemical compound CN(C1=CC=C(CNC(OC=2C=C3C=4C5=C(C6=C(C=4N(C3=CC=2)CC(C)C)CCC2=NN(C=C26)C)C(NC5)=O)=O)C=C1)C ZFKJDNACAGAYFJ-UHFFFAOYSA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 claims description 7
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 7
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 claims description 7
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 claims description 7
- 206010029260 Neuroblastoma Diseases 0.000 claims description 6
- 206010039491 Sarcoma Diseases 0.000 claims description 6
- 230000008859 change Effects 0.000 claims description 6
- 208000005017 glioblastoma Diseases 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 208000002291 Histiocytic Sarcoma Diseases 0.000 claims description 5
- 206010061534 Oesophageal squamous cell carcinoma Diseases 0.000 claims description 5
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 claims description 5
- 230000004709 cell invasion Effects 0.000 claims description 5
- 238000001514 detection method Methods 0.000 claims description 5
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 claims description 5
- 201000008825 fibrosarcoma of bone Diseases 0.000 claims description 5
- 230000012010 growth Effects 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 201000006812 malignant histiocytosis Diseases 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 4
- 230000030833 cell death Effects 0.000 claims description 4
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 230000017095 negative regulation of cell growth Effects 0.000 claims description 4
- 230000013152 negative regulation of cell migration Effects 0.000 claims description 4
- 230000000638 stimulation Effects 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 4
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 108091093088 Amplicon Proteins 0.000 claims description 2
- 108010084795 Fusion Oncogene Proteins Proteins 0.000 claims description 2
- 102000005668 Fusion Oncogene Proteins Human genes 0.000 claims description 2
- 238000007899 nucleic acid hybridization Methods 0.000 claims description 2
- 239000000523 sample Substances 0.000 claims description 2
- 238000012163 sequencing technique Methods 0.000 claims description 2
- 210000005260 human cell Anatomy 0.000 claims 1
- 238000004393 prognosis Methods 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 49
- 239000012634 fragment Substances 0.000 description 44
- 238000006467 substitution reaction Methods 0.000 description 35
- 235000018102 proteins Nutrition 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 28
- 230000009261 transgenic effect Effects 0.000 description 21
- 239000000427 antigen Substances 0.000 description 18
- 102000036639 antigens Human genes 0.000 description 18
- 108091007433 antigens Proteins 0.000 description 18
- 108020004414 DNA Proteins 0.000 description 17
- 230000004927 fusion Effects 0.000 description 17
- 230000001105 regulatory effect Effects 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 16
- 239000013598 vector Substances 0.000 description 16
- 108060003951 Immunoglobulin Proteins 0.000 description 15
- 108700019146 Transgenes Proteins 0.000 description 15
- 235000001014 amino acid Nutrition 0.000 description 15
- 102000018358 immunoglobulin Human genes 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 108091026890 Coding region Proteins 0.000 description 12
- 150000001413 amino acids Chemical class 0.000 description 11
- 239000003550 marker Substances 0.000 description 11
- 238000003556 assay Methods 0.000 description 10
- 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 9
- 238000001994 activation Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 102000051965 human ALK Human genes 0.000 description 8
- 230000003053 immunization Effects 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 101150023956 ALK gene Proteins 0.000 description 7
- 230000001093 anti-cancer Effects 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 238000002744 homologous recombination Methods 0.000 description 6
- 230000006801 homologous recombination Effects 0.000 description 6
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 6
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 108010091086 Recombinases Proteins 0.000 description 5
- 102000018120 Recombinases Human genes 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 210000004408 hybridoma Anatomy 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000011159 matrix material Substances 0.000 description 5
- 239000002644 phorbol ester Substances 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 4
- 108700020796 Oncogene Proteins 0.000 description 4
- 108091030071 RNAI Proteins 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 230000035578 autophosphorylation Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 210000001671 embryonic stem cell Anatomy 0.000 description 4
- 230000009368 gene silencing by RNA Effects 0.000 description 4
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound 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
- 210000001161 mammalian embryo Anatomy 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 238000006384 oligomerization reaction Methods 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 229940072221 immunoglobulins Drugs 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000000287 oocyte Anatomy 0.000 description 3
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 238000002864 sequence alignment Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 235000002374 tyrosine Nutrition 0.000 description 3
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108091029865 Exogenous DNA Proteins 0.000 description 2
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 2
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102000003746 Insulin Receptor Human genes 0.000 description 2
- 108010001127 Insulin Receptor Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 102100030335 Midkine Human genes 0.000 description 2
- 108010092801 Midkine Proteins 0.000 description 2
- 241000713333 Mouse mammary tumor virus Species 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 241000276498 Pollachius virens Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 102000003923 Protein Kinase C Human genes 0.000 description 2
- 108090000315 Protein Kinase C Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 108020001778 catalytic domains Proteins 0.000 description 2
- 239000012707 chemical precursor Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 229960001433 erlotinib Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 229940080856 gleevec Drugs 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 108700009251 p80(NPM-ALK) Proteins 0.000 description 2
- 102000005162 pleiotrophin Human genes 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 238000003259 recombinant expression Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 239000004055 small Interfering RNA Substances 0.000 description 2
- 210000004989 spleen cell Anatomy 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- -1 tripeptides Proteins 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
- FPYJSJDOHRDAMT-KQWNVCNZSA-N 1h-indole-5-sulfonamide, n-(3-chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1h-pyrrol-2-yl]methylene]-2,3-dihydro-n-methyl-2-oxo-, (3z)- Chemical compound C=1C=C2NC(=O)\C(=C/C3=C(C(C(=O)N4CCN(C)CC4)=C(C)N3)C)C2=CC=1S(=O)(=O)N(C)C1=CC=CC(Cl)=C1 FPYJSJDOHRDAMT-KQWNVCNZSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- NOTGFIUVDGNKRI-UUOKFMHZSA-N AICA ribonucleotide Chemical compound NC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 NOTGFIUVDGNKRI-UUOKFMHZSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 241000132092 Aster Species 0.000 description 1
- 241000711404 Avian avulavirus 1 Species 0.000 description 1
- 102000019260 B-Cell Antigen Receptors Human genes 0.000 description 1
- 108010012919 B-Cell Antigen Receptors Proteins 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
- 241000223782 Ciliophora Species 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 108091035710 E-box Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000258955 Echinodermata Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 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
- 241000702191 Escherichia virus P1 Species 0.000 description 1
- 108010046276 FLP recombinase Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- 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 1
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 241001135569 Human adenovirus 5 Species 0.000 description 1
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
- 108010072462 Hydroxymethyl and Formyl Transferases Proteins 0.000 description 1
- 102000006933 Hydroxymethyl and Formyl Transferases Human genes 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 102100029098 Hypoxanthine-guanine phosphoribosyltransferase Human genes 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 108010007666 IMP cyclohydrolase Proteins 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102000012745 Immunoglobulin Subunits Human genes 0.000 description 1
- 108010079585 Immunoglobulin Subunits Proteins 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- ZQISRDCJNBUVMM-UHFFFAOYSA-N L-Histidinol Natural products OCC(N)CC1=CN=CN1 ZQISRDCJNBUVMM-UHFFFAOYSA-N 0.000 description 1
- ZQISRDCJNBUVMM-YFKPBYRVSA-N L-histidinol Chemical compound OC[C@@H](N)CC1=CNC=N1 ZQISRDCJNBUVMM-YFKPBYRVSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 108091054437 MHC class I family Proteins 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- 101710201349 Metallothionein B Proteins 0.000 description 1
- 101710094505 Metallothionein-2 Proteins 0.000 description 1
- 102100031347 Metallothionein-2 Human genes 0.000 description 1
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100323015 Mus musculus Alk gene Proteins 0.000 description 1
- 241000204025 Mycoplasma capricolum Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 101100124346 Photorhabdus laumondii subsp. laumondii (strain DSM 15139 / CIP 105565 / TT01) hisCD gene Proteins 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 241000255588 Tephritidae Species 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 102100035071 Vimentin Human genes 0.000 description 1
- 108010065472 Vimentin Proteins 0.000 description 1
- VRGWBRLULZUWAJ-XFFXIZSCSA-N [(2s)-2-[(1r,3z,5s,8z,12z,15s)-5,17-dihydroxy-4,8,12,15-tetramethyl-16-oxo-18-bicyclo[13.3.0]octadeca-3,8,12,17-tetraenyl]propyl] acetate Chemical compound C1\C=C(C)/CC\C=C(C)/CC[C@H](O)\C(C)=C/C[C@@H]2C([C@@H](COC(C)=O)C)=C(O)C(=O)[C@]21C VRGWBRLULZUWAJ-XFFXIZSCSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 210000002459 blastocyst Anatomy 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- VRGWBRLULZUWAJ-UHFFFAOYSA-N fusaproliferin Natural products C1C=C(C)CCC=C(C)CCC(O)C(C)=CCC2C(C(COC(C)=O)C)=C(O)C(=O)C21C VRGWBRLULZUWAJ-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 101150028578 grp78 gene Proteins 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 101150113423 hisD gene Proteins 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 229960003685 imatinib mesylate Drugs 0.000 description 1
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000002231 macronucleus Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 101150008049 mx gene Proteins 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229930185346 proliferin Natural products 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 102220197960 rs1057519783 Human genes 0.000 description 1
- 102220197961 rs1057519784 Human genes 0.000 description 1
- 102220272179 rs1555615051 Human genes 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000005048 vimentin Anatomy 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
- C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5308—Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Tropical Medicine & Parasitology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/761,050 | 2010-04-15 | ||
| US12/761,050 US8383793B2 (en) | 2010-04-15 | 2010-04-15 | Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors |
| PCT/US2011/032204 WO2011130340A1 (en) | 2010-04-15 | 2011-04-13 | Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (alk) kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2796306A1 true CA2796306A1 (en) | 2011-10-20 |
Family
ID=44314994
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2796306A Abandoned CA2796306A1 (en) | 2010-04-15 | 2011-04-13 | Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (alk) kinase inhibitors |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US8383793B2 (enExample) |
| EP (1) | EP2558490B1 (enExample) |
| JP (2) | JP6223822B2 (enExample) |
| KR (1) | KR20130064067A (enExample) |
| CN (1) | CN103201286B (enExample) |
| AU (1) | AU2011240636B2 (enExample) |
| BR (1) | BR112012026239A2 (enExample) |
| CA (1) | CA2796306A1 (enExample) |
| RU (1) | RU2012148450A (enExample) |
| WO (1) | WO2011130340A1 (enExample) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110206691A1 (en) * | 2008-02-15 | 2011-08-25 | Mosse Yael P | Methods and Compositions for Treating Neuroblastoma |
| WO2009103061A2 (en) * | 2008-02-15 | 2009-08-20 | The Children's Hospital Of Philadelphia | Methods and compositions for identifying, diagnosing, and treating neuroblastoma |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| PT2300013T (pt) | 2008-05-21 | 2017-10-31 | Ariad Pharma Inc | Derivados de fósforo como inibidores de cinases |
| SI2350075T1 (sl) | 2008-09-22 | 2014-06-30 | Array Biopharma, Inc. | Substituirane imidazo (1,2b)piridazinske spojine kot Trk kinazni inhibitorji |
| SG10201914059WA (en) | 2008-10-22 | 2020-03-30 | Array Biopharma Inc | Substituted pyrazolo[1,5-a]pyrimidine compounds as trk kinase inhibitors |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| EP2464954B1 (en) | 2009-08-13 | 2019-06-05 | Teleflex Life Sciences Unlimited Company | Pressure indicator |
| EP2918588B1 (en) | 2010-05-20 | 2017-05-03 | Array Biopharma, Inc. | Macrocyclic compounds as TRK kinase inhibitors |
| US20130288240A1 (en) * | 2010-05-21 | 2013-10-31 | Cell Signaling Technology, Inc. | Alk and ros kinase in cancer |
| US10549054B2 (en) | 2011-02-02 | 2020-02-04 | Teleflex Life Sciences Unlimited Company | Artificial airway |
| EP2704572B1 (en) | 2011-05-04 | 2015-12-30 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| EP2822953B9 (en) | 2012-03-06 | 2017-06-21 | Pfizer Inc | Macrocyclic derivatives for the treatment of proliferative diseases |
| AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| JP6205216B2 (ja) * | 2012-09-24 | 2017-09-27 | アークレイ株式会社 | 変異検出用プローブ、変異検出方法、薬効判定方法及び変異検出用キット |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN104513253A (zh) | 2013-10-01 | 2015-04-15 | 南京波尔泰药业科技有限公司 | 用于治疗增殖性疾病的大环化合物 |
| ES2811927T3 (es) * | 2014-04-10 | 2021-03-15 | Memorial Sloan Kettering Cancer Center | Isoforma novedosa de cinasa de linfoma anaplásico y sus usos |
| US9428812B2 (en) * | 2014-04-28 | 2016-08-30 | Insight Genetics, Inc. | Kit comprising primers for amplifying ALK kinase domain nucleic acids |
| US10799505B2 (en) | 2014-11-16 | 2020-10-13 | Array Biopharma, Inc. | Crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-A]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate |
| EP3244927A1 (en) * | 2015-01-16 | 2017-11-22 | Vedantra Pharmaceuticals Inc. | Multilamellar lipid vesicle compositions including a conjugated anaplastic lymphoma kinase (alk) variant and uses thereof |
| EP3303382A4 (en) * | 2015-05-29 | 2018-12-19 | Ignyta, Inc. | Compositions and methods for treating patients with rtk mutant cells |
| JP2018534296A (ja) | 2015-10-26 | 2018-11-22 | ロクソ オンコロジー， インコーポレイテッドＬｏｘｏ Ｏｎｃｏｌｏｇｙ， Ｉｎｃ． | Ｔｒｋ阻害薬耐性がんにおける点変異およびそれに関連する方法 |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| MX386416B (es) | 2016-04-04 | 2025-03-18 | Loxo Oncology Inc | Formulaciones liquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida. |
| HUE063877T2 (hu) | 2016-05-18 | 2024-02-28 | Loxo Oncology Inc | (S)-N-(5-((R)-2-(2,5-dlfluorofenil)pirolidin-1-il)plrazolo[1,5-A]pirimidin-3-il) -3-hidroxipirolidin-1-karboxamid elõállítása |
| CN107885972B (zh) * | 2016-09-30 | 2021-07-27 | 广州华大基因医学检验所有限公司 | 一种基于单端测序的融合基因检测方法及其应用 |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CN110716042A (zh) * | 2019-10-23 | 2020-01-21 | 郑州大学 | 一种用于卵巢癌早期筛查和诊断的血清蛋白标志物、试剂盒及检测方法 |
| CN111235272B (zh) * | 2020-01-10 | 2023-07-07 | 厦门艾德生物医药科技股份有限公司 | 一次性检测肺癌多重基因突变的组合物及其应用 |
| IL297442A (en) | 2020-04-22 | 2022-12-01 | Iovance Biotherapeutics Inc | Systems and methods for coordinating production of cells for patient-specific immunotherapy |
| CN112391390A (zh) * | 2020-11-19 | 2021-02-23 | 山西大学 | 飞蝗网格蛋白重链基因及其靶向dsRNA的合成与应用 |
Family Cites Families (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| NZ201918A (en) | 1981-09-18 | 1987-04-30 | Genentech Inc | N-terminal methionyl analogues of bovine growth hormone |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4870009A (en) | 1982-11-22 | 1989-09-26 | The Salk Institute For Biological Studies | Method of obtaining gene product through the generation of transgenic animals |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4736866B1 (en) | 1984-06-22 | 1988-04-12 | Transgenic non-human mammals | |
| US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
| EP0232967B1 (en) | 1986-01-10 | 1993-04-28 | Amoco Corporation | Competitive homogeneous assay |
| US4800159A (en) | 1986-02-07 | 1989-01-24 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US5107065A (en) | 1986-03-28 | 1992-04-21 | Calgene, Inc. | Anti-sense regulation of gene expression in plant cells |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| US4873192A (en) | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| US5225326A (en) | 1988-08-31 | 1993-07-06 | Research Development Foundation | One step in situ hybridization assay |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| FR2646438B1 (fr) | 1989-03-20 | 2007-11-02 | Pasteur Institut | Procede de remplacement specifique d'une copie d'un gene present dans le genome receveur par l'integration d'un gene different de celui ou se fait l'integration |
| US5800992A (en) | 1989-06-07 | 1998-09-01 | Fodor; Stephen P.A. | Method of detecting nucleic acids |
| US6040138A (en) | 1995-09-15 | 2000-03-21 | Affymetrix, Inc. | Expression monitoring by hybridization to high density oligonucleotide arrays |
| DE69033493D1 (de) | 1989-07-25 | 2004-08-12 | Cell Genesys Inc | Homologe rekombination für universelle donorzellen und chimerische säugetierzellen |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
| IL98764A0 (en) | 1990-07-10 | 1992-07-15 | Smithkline Beecham Corp | Oxamides |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| GB9022543D0 (en) | 1990-10-17 | 1990-11-28 | Wellcome Found | Antibody production |
| KR100236506B1 (ko) | 1990-11-29 | 2000-01-15 | 퍼킨-엘머시터스인스트루먼츠 | 폴리머라제 연쇄 반응 수행 장치 |
| US5455166A (en) | 1991-01-31 | 1995-10-03 | Becton, Dickinson And Company | Strand displacement amplification |
| CA2218875C (en) | 1991-07-23 | 2000-11-07 | The Research Foundation Of State University Of New York | Improvements in the in situ pcr |
| US5756096A (en) | 1991-07-25 | 1998-05-26 | Idec Pharmaceuticals Corporation | Recombinant antibodies for human therapy |
| MX9204374A (es) | 1991-07-25 | 1993-03-01 | Idec Pharma Corp | Anticuerpo recombinante y metodo para su produccion. |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| US5270184A (en) | 1991-11-19 | 1993-12-14 | Becton, Dickinson And Company | Nucleic acid target generation |
| US5545524A (en) | 1991-12-04 | 1996-08-13 | The Regents Of The University Of Michigan | Compositions and methods for chromosome region-specific probes |
| US5397703A (en) | 1992-07-09 | 1995-03-14 | Cetus Oncology Corporation | Method for generation of antibodies to cell surface molecules |
| DE69333366T2 (de) | 1992-10-30 | 2004-09-16 | The General Hospital Corp., Boston | Ein neues zellzyklus kontrollprotein |
| WO1994012520A1 (en) | 1992-11-20 | 1994-06-09 | Enzon, Inc. | Linker for linked fusion polypeptides |
| DE614989T1 (de) | 1993-02-17 | 1995-09-28 | Morphosys Proteinoptimierung | Verfahren für in vivo Selektion von Ligandenbindende Proteine. |
| US5925517A (en) | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
| US6696548B2 (en) * | 1993-12-03 | 2004-02-24 | St. Jude Children's Research Hospital | Antibodies for recognition of alk protein tyrosine/kinase receptor |
| US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
| US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
| JP3189000B2 (ja) | 1994-12-01 | 2001-07-16 | 東ソー株式会社 | 特定核酸配列の検出方法 |
| US6091001A (en) | 1995-03-29 | 2000-07-18 | Abgenix, Inc. | Production of antibodies using Cre-mediated site-specific recombination |
| US5710029A (en) | 1995-06-07 | 1998-01-20 | Gen-Probe Incorporated | Methods for determining pre-amplification levels of a nucleic acid target sequence from post-amplification levels of product |
| GB9517780D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| GB9517779D0 (en) | 1995-08-31 | 1995-11-01 | Roslin Inst Edinburgh | Biological manipulation |
| US5612473A (en) | 1996-01-16 | 1997-03-18 | Gull Laboratories | Methods, kits and solutions for preparing sample material for nucleic acid amplification |
| EP0880598A4 (en) | 1996-01-23 | 2005-02-23 | Affymetrix Inc | RAPID EVALUATION OF NUCLEIC ACID ABUNDANCE DIFFERENCE, WITH A HIGH-DENSITY OLIGONUCLEOTIDE SYSTEM |
| US6121489A (en) | 1996-03-05 | 2000-09-19 | Trega Biosciences, Inc. | Selectively N-alkylated peptidomimetic combinatorial libraries and compounds therein |
| DE69738687D1 (de) | 1996-04-12 | 2008-06-26 | Phri Properties Inc | Sonden, kits und assays |
| US5830698A (en) | 1997-03-14 | 1998-11-03 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| DE69829402T2 (de) | 1997-10-31 | 2006-04-13 | Affymetrix, Inc. (a Delaware Corp.), Santa Clara | Expressionsprofile in adulten und fötalen organen |
| US6020135A (en) | 1998-03-27 | 2000-02-01 | Affymetrix, Inc. | P53-regulated genes |
| WO2000001850A2 (en) | 1998-07-02 | 2000-01-13 | Gen-Probe Incorporated | Molecular torches |
| US6573043B1 (en) | 1998-10-07 | 2003-06-03 | Genentech, Inc. | Tissue analysis and kits therefor |
| US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
| US6303305B1 (en) | 1999-03-30 | 2001-10-16 | Roche Diagnostics, Gmbh | Method for quantification of an analyte |
| US6541205B1 (en) | 1999-05-24 | 2003-04-01 | Tosoh Corporation | Method for assaying nucleic acid |
| US20030198627A1 (en) | 2001-09-01 | 2003-10-23 | Gert-Jan Arts | siRNA knockout assay method and constructs |
| CA2524572C (en) | 2003-05-01 | 2018-07-10 | Gen-Probe Incorporated | Oligonucleotides comprising a molecular switch having enhanced sensitivity to the presence of a mismatch |
| US20080051419A1 (en) | 2006-07-26 | 2008-02-28 | Pfizer Inc. | Amine derivatives useful as anticancer agents |
| US8063225B2 (en) | 2006-08-14 | 2011-11-22 | Chembridge Corporation | Tricyclic compound derivatives useful in the treatment of neoplastic diseases, inflammatory disorders and immunomodulatory disorders |
| CA2598893C (en) | 2006-10-11 | 2012-04-10 | Astellas Pharma Inc. | Eml4-alk fusion gene |
| EP2042191B1 (en) * | 2007-09-28 | 2013-01-02 | Roberto Chiarle | Anaplastic Lymphoma Kinase (ALK) as oncoantigen for lymphoma vaccination |
| WO2009103061A2 (en) * | 2008-02-15 | 2009-08-20 | The Children's Hospital Of Philadelphia | Methods and compositions for identifying, diagnosing, and treating neuroblastoma |
| TWI518325B (zh) * | 2010-02-04 | 2016-01-21 | 自治醫科大學 | 對ａｌｋ抑制劑具有先抗性或後抗性癌症的識別、判斷和治療 |
-
2010
- 2010-04-15 US US12/761,050 patent/US8383793B2/en not_active Expired - Fee Related
-
2011
- 2011-04-13 KR KR1020127029988A patent/KR20130064067A/ko not_active Withdrawn
- 2011-04-13 BR BR112012026239A patent/BR112012026239A2/pt not_active IP Right Cessation
- 2011-04-13 EP EP11721840.4A patent/EP2558490B1/en not_active Not-in-force
- 2011-04-13 AU AU2011240636A patent/AU2011240636B2/en not_active Ceased
- 2011-04-13 CN CN201180023776.XA patent/CN103201286B/zh not_active Expired - Fee Related
- 2011-04-13 CA CA2796306A patent/CA2796306A1/en not_active Abandoned
- 2011-04-13 RU RU2012148450/10A patent/RU2012148450A/ru not_active Application Discontinuation
- 2011-04-13 JP JP2013505074A patent/JP6223822B2/ja not_active Expired - Fee Related
- 2011-04-13 WO PCT/US2011/032204 patent/WO2011130340A1/en not_active Ceased
-
2013
- 2013-02-20 US US13/771,948 patent/US9458508B2/en not_active Expired - Fee Related
-
2016
- 2016-10-03 JP JP2016195911A patent/JP2017018141A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011130340A1 (en) | 2011-10-20 |
| BR112012026239A2 (pt) | 2018-06-26 |
| US20110256546A1 (en) | 2011-10-20 |
| AU2011240636B2 (en) | 2014-10-02 |
| KR20130064067A (ko) | 2013-06-17 |
| AU2011240636A1 (en) | 2012-11-15 |
| CN103201286B (zh) | 2017-05-03 |
| JP2013534804A (ja) | 2013-09-09 |
| EP2558490A1 (en) | 2013-02-20 |
| RU2012148450A (ru) | 2014-05-20 |
| EP2558490B1 (en) | 2016-12-14 |
| CN103201286A (zh) | 2013-07-10 |
| JP6223822B2 (ja) | 2017-11-01 |
| US8383793B2 (en) | 2013-02-26 |
| JP2017018141A (ja) | 2017-01-26 |
| US20130244893A1 (en) | 2013-09-19 |
| US9458508B2 (en) | 2016-10-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9458508B2 (en) | Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors | |
| WO2014152777A2 (en) | Methods and compositions for the diagnosis and treatment of cancers resistant to ros1 inhibitors | |
| JP5290884B2 (ja) | 真性赤血球増加症に関与するｊａｋ２の変異の識別方法 | |
| DK2881402T3 (en) | Mutant ROS expression in human liver cancer | |
| CN101528921B (zh) | 人非小细胞肺癌中的易位和突变的ros激酶 | |
| DK2838998T3 (en) | EGFR AND ROS1 IN CANCER | |
| US20210171631A1 (en) | Novel Immune Checkpoint Inhibitors | |
| CN106148525B (zh) | 肺癌中的ros激酶 | |
| DK2688907T3 (en) | DOMINANT NEGATIVE HSP110 MUTANT AND ITS APPLICATION TO FORECAST AND treatment of cancers | |
| CA2814598A1 (en) | Recurrent gene fusions in prostate cancer | |
| US20050106150A1 (en) | Compositions and methods for restoring sensitivity to treatment with HER2 antagonists | |
| AU2006206343A1 (en) | GITR antibodies for the diagnosis of NSCLC | |
| US7214374B2 (en) | 12832, a novel human kinase-like molecule and uses thereof | |
| JP4705469B2 (ja) | 抗ｂａｍｂｉ抗体、及びそれを含有する大腸癌及び肝臓癌の診断剤又は治療剤 | |
| WO2006112401A1 (ja) | 癌治療用組成物 | |
| US20110047634A1 (en) | Methods and compositions for the diagnosis and treatment of acute lymphoblastic leukemia | |
| JP2004135618A (ja) | 癌遺伝子及びその用途 | |
| MX2007008691A (en) | Gitr antibodies for the diagnosis of nsclc |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20190628 |