ES2489475T3 - Inhibidores MET para potenciar la eficacia de la radioterapia - Google Patents
Inhibidores MET para potenciar la eficacia de la radioterapia Download PDFInfo
- Publication number
- ES2489475T3 ES2489475T3 ES11158861.2T ES11158861T ES2489475T3 ES 2489475 T3 ES2489475 T3 ES 2489475T3 ES 11158861 T ES11158861 T ES 11158861T ES 2489475 T3 ES2489475 T3 ES 2489475T3
- Authority
- ES
- Spain
- Prior art keywords
- met
- met inhibitor
- cdr
- nucleotide sequence
- sequence encoding
- 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
- 239000003112 inhibitor Substances 0.000 title claims abstract description 60
- 238000001959 radiotherapy Methods 0.000 title claims abstract description 29
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 43
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims abstract description 38
- 230000033228 biological regulation Effects 0.000 claims abstract description 16
- 239000012634 fragment Substances 0.000 claims abstract description 15
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 101150105382 MET gene Proteins 0.000 claims abstract description 8
- 230000002708 enhancing effect Effects 0.000 claims abstract description 6
- 210000004408 hybridoma Anatomy 0.000 claims abstract description 6
- 230000005855 radiation Effects 0.000 claims abstract description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 6
- 230000001939 inductive effect Effects 0.000 claims abstract 2
- 210000004027 cell Anatomy 0.000 claims description 85
- 108090000623 proteins and genes Proteins 0.000 claims description 33
- 239000002773 nucleotide Substances 0.000 claims description 24
- 125000003729 nucleotide group Chemical group 0.000 claims description 24
- 102000004169 proteins and genes Human genes 0.000 claims description 23
- 201000011510 cancer Diseases 0.000 claims description 18
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims description 13
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims description 13
- 239000013598 vector Substances 0.000 claims description 7
- 102000009027 Albumins Human genes 0.000 claims description 6
- 108010088751 Albumins Proteins 0.000 claims description 6
- 108020003175 receptors Proteins 0.000 claims description 6
- 230000000087 stabilizing effect Effects 0.000 claims description 6
- 206010039491 Sarcoma Diseases 0.000 claims description 5
- 238000002347 injection Methods 0.000 claims description 5
- 239000007924 injection Substances 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 230000003247 decreasing effect Effects 0.000 claims description 3
- 238000001802 infusion Methods 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 230000008685 targeting Effects 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 206010027406 Mesothelioma Diseases 0.000 claims description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 2
- 208000008383 Wilms tumor Diseases 0.000 claims description 2
- 230000003394 haemopoietic effect Effects 0.000 claims description 2
- 230000002601 intratumoral effect Effects 0.000 claims description 2
- 230000009885 systemic effect Effects 0.000 claims description 2
- 201000008026 nephroblastoma Diseases 0.000 claims 1
- 230000005865 ionizing radiation Effects 0.000 description 28
- 108010057466 NF-kappa B Proteins 0.000 description 24
- 102000003945 NF-kappa B Human genes 0.000 description 24
- 102100035100 Transcription factor p65 Human genes 0.000 description 21
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 20
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 20
- 230000014509 gene expression Effects 0.000 description 20
- 108020004414 DNA Proteins 0.000 description 19
- 238000002474 experimental method Methods 0.000 description 13
- 150000001413 amino acids Chemical group 0.000 description 12
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 108020004459 Small interfering RNA Proteins 0.000 description 9
- 230000002018 overexpression Effects 0.000 description 9
- 230000026731 phosphorylation Effects 0.000 description 9
- 238000006366 phosphorylation reaction Methods 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 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 8
- 241000282414 Homo sapiens Species 0.000 description 8
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 description 8
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 description 8
- 101100160997 Mus musculus Rchy1 gene Proteins 0.000 description 8
- 238000002487 chromatin immunoprecipitation Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 230000002103 transcriptional effect Effects 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- XRKYMMUGXMWDAO-UHFFFAOYSA-N 2-(4-morpholinyl)-6-(1-thianthrenyl)-4-pyranone Chemical compound O1C(C=2C=3SC4=CC=CC=C4SC=3C=CC=2)=CC(=O)C=C1N1CCOCC1 XRKYMMUGXMWDAO-UHFFFAOYSA-N 0.000 description 6
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 206010021143 Hypoxia Diseases 0.000 description 6
- 230000007954 hypoxia Effects 0.000 description 6
- 230000024799 morphogenesis of a branching structure Effects 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 5
- 230000035508 accumulation Effects 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 230000029578 entry into host Effects 0.000 description 5
- 108010066733 mRNA (guanine(N7))-methyltransferase Proteins 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- HLCDNLNLQNYZTK-UHFFFAOYSA-N 2,2-diphenyl-N-[2,2,2-trichloro-1-[[(4-fluoro-3-nitroanilino)-sulfanylidenemethyl]amino]ethyl]acetamide Chemical compound C1=C(F)C([N+](=O)[O-])=CC(NC(=S)NC(NC(=O)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(Cl)(Cl)Cl)=C1 HLCDNLNLQNYZTK-UHFFFAOYSA-N 0.000 description 4
- 101000961071 Homo sapiens NF-kappa-B inhibitor alpha Proteins 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 108700020796 Oncogene Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 230000001594 aberrant effect Effects 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 210000002469 basement membrane Anatomy 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 102000057421 human MET Human genes 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 230000005937 nuclear translocation Effects 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 238000011069 regeneration method Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 102000002804 Ataxia Telangiectasia Mutated Proteins Human genes 0.000 description 3
- 108010004586 Ataxia Telangiectasia Mutated Proteins Proteins 0.000 description 3
- 108010077544 Chromatin Proteins 0.000 description 3
- 230000005778 DNA damage Effects 0.000 description 3
- 231100000277 DNA damage Toxicity 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 3
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 3
- 101000596769 Homo sapiens Transcription factor p65 Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- 230000003044 adaptive effect Effects 0.000 description 3
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 3
- 230000002424 anti-apoptotic effect Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000004709 cell invasion Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 210000003483 chromatin Anatomy 0.000 description 3
- 230000002074 deregulated effect Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 102000052648 human RELA Human genes 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 238000012353 t test Methods 0.000 description 3
- 238000011287 therapeutic dose Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 101100291013 Mus musculus Met gene Proteins 0.000 description 2
- 102000007999 Nuclear Proteins Human genes 0.000 description 2
- 108010089610 Nuclear Proteins Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 230000008649 adaptation response Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 230000002051 biphasic effect Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 230000004942 nuclear accumulation Effects 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000006320 pegylation Effects 0.000 description 2
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000002384 proinvasive effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 235000013599 spices Nutrition 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 210000005239 tubule Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 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
- 229940122485 ATM kinase inhibitor Drugs 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 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
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 239000012721 SDS lysis buffer Substances 0.000 description 1
- 238000010818 SYBR green PCR Master Mix Methods 0.000 description 1
- 206010039509 Scab Diseases 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
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000005747 Transcription Factor RelA Human genes 0.000 description 1
- 108010031154 Transcription Factor RelA Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 238000013043 cell viability test Methods 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940030792 clinac Drugs 0.000 description 1
- 230000003021 clonogenic effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 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
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 101150042537 dld1 gene Proteins 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000006832 extrinsic signaling Effects 0.000 description 1
- 230000003328 fibroblastic effect Effects 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000009454 functional inhibition Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000012405 in silico analysis Methods 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000006623 intrinsic pathway Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 102000049853 macrophage stimulating protein Human genes 0.000 description 1
- 108010053292 macrophage stimulating protein Proteins 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000008883 metastatic behaviour Effects 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000010232 migration assay Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000007491 morphometric analysis Methods 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000030147 nuclear export Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 230000003076 paracrine Effects 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000001686 pro-survival effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 238000000730 protein immunoprecipitation Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000009396 radiation induced apoptosis Effects 0.000 description 1
- 230000006950 reactive oxygen species formation Effects 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 230000006335 response to radiation Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 108091006108 transcriptional coactivators Proteins 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000013520 translational research Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11158861.2A EP2500036B1 (en) | 2011-03-18 | 2011-03-18 | MET inhibitors for enhancing radiotherapy efficacy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2489475T3 true ES2489475T3 (es) | 2014-09-02 |
Family
ID=44260211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11158861.2T Active ES2489475T3 (es) | 2011-03-18 | 2011-03-18 | Inhibidores MET para potenciar la eficacia de la radioterapia |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US20120237524A1 (enExample) |
| EP (1) | EP2500036B1 (enExample) |
| JP (1) | JP5671487B2 (enExample) |
| KR (1) | KR101540838B1 (enExample) |
| CN (1) | CN102688491A (enExample) |
| AU (1) | AU2012201303B2 (enExample) |
| BR (1) | BR102012006063B1 (enExample) |
| CA (1) | CA2769991C (enExample) |
| CY (1) | CY1115374T1 (enExample) |
| DK (1) | DK2500036T3 (enExample) |
| EA (1) | EA028590B1 (enExample) |
| ES (1) | ES2489475T3 (enExample) |
| HR (1) | HRP20140729T1 (enExample) |
| IL (1) | IL218293A (enExample) |
| MX (1) | MX2012003084A (enExample) |
| PL (1) | PL2500036T3 (enExample) |
| PT (1) | PT2500036E (enExample) |
| RS (1) | RS53468B (enExample) |
| SG (1) | SG184637A1 (enExample) |
| SI (1) | SI2500036T1 (enExample) |
| SM (1) | SMT201400106B (enExample) |
| ZA (1) | ZA201201992B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9168300B2 (en) | 2013-03-14 | 2015-10-27 | Oncomed Pharmaceuticals, Inc. | MET-binding agents and uses thereof |
| TWI782930B (zh) | 2016-11-16 | 2022-11-11 | 美商再生元醫藥公司 | 抗ｍｅｔ抗體，結合ｍｅｔ之雙特異性抗原結合分子及其使用方法 |
| IT201800009282A1 (it) * | 2018-10-09 | 2020-04-09 | Metis Prec Medicine Sb Srl | Nuovo agente terapeutico per il trattamento di un tumore e/o metastasi |
| CN110320365B (zh) * | 2019-07-06 | 2022-07-22 | 湖南莱拓福生物科技有限公司 | NF-κB RelA/p65蛋白位点特异性磷酸化诊断试剂盒 |
| MX2022002886A (es) | 2019-09-16 | 2022-04-06 | Regeneron Pharma | Proteinas de union met radiomarcadas para la obtencion de imagenes por inmuno-pet. |
| AU2024241633A1 (en) | 2023-03-30 | 2025-11-06 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI310684B (en) * | 2000-03-27 | 2009-06-11 | Bristol Myers Squibb Co | Synergistic pharmaceutical kits for treating cancer |
| CA2516236A1 (en) * | 2003-02-13 | 2004-08-26 | Pharmacia Corporation | Antibodies to c-met for the treatment of cancers |
| US8609090B2 (en) * | 2003-07-18 | 2013-12-17 | Amgen Inc. | Specific binding agents to hepatocyte growth factor |
| HN2004000285A (es) * | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
| US8388958B2 (en) * | 2006-02-06 | 2013-03-05 | Metheresis Translational Research Sa | Anti-MET monoclonal antibody, fragments and vectors thereof, for the treatment of tumors and corresponding products |
| EP2019116A1 (en) * | 2007-07-26 | 2009-01-28 | Helmholtz-Zentrum für Infektionsforschung GmbH | Inhibitor of the met-receptor and its use |
-
2011
- 2011-03-18 PL PL11158861T patent/PL2500036T3/pl unknown
- 2011-03-18 DK DK11158861.2T patent/DK2500036T3/da active
- 2011-03-18 ES ES11158861.2T patent/ES2489475T3/es active Active
- 2011-03-18 SI SI201130217T patent/SI2500036T1/sl unknown
- 2011-03-18 PT PT111588612T patent/PT2500036E/pt unknown
- 2011-03-18 RS RS20140404A patent/RS53468B/sr unknown
- 2011-03-18 EP EP11158861.2A patent/EP2500036B1/en active Active
-
2012
- 2012-02-22 SG SG2012012514A patent/SG184637A1/en unknown
- 2012-02-23 IL IL218293A patent/IL218293A/en active IP Right Grant
- 2012-02-24 JP JP2012039193A patent/JP5671487B2/ja active Active
- 2012-03-01 CA CA2769991A patent/CA2769991C/en active Active
- 2012-03-02 AU AU2012201303A patent/AU2012201303B2/en active Active
- 2012-03-13 KR KR1020120025311A patent/KR101540838B1/ko active Active
- 2012-03-13 MX MX2012003084A patent/MX2012003084A/es active IP Right Grant
- 2012-03-16 ZA ZA2012/01992A patent/ZA201201992B/en unknown
- 2012-03-16 CN CN2012100803665A patent/CN102688491A/zh active Pending
- 2012-03-16 BR BR102012006063-9A patent/BR102012006063B1/pt active IP Right Grant
- 2012-03-16 EA EA201200329A patent/EA028590B1/ru not_active IP Right Cessation
- 2012-03-19 US US13/423,830 patent/US20120237524A1/en not_active Abandoned
-
2014
- 2014-07-24 CY CY20141100561T patent/CY1115374T1/el unknown
- 2014-07-29 HR HRP20140729AT patent/HRP20140729T1/hr unknown
- 2014-07-31 SM SM201400106T patent/SMT201400106B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HRP20140729T1 (hr) | 2014-08-29 |
| EA201200329A3 (ru) | 2013-01-30 |
| JP2012196206A (ja) | 2012-10-18 |
| JP5671487B2 (ja) | 2015-02-18 |
| PT2500036E (pt) | 2014-08-25 |
| KR20120106582A (ko) | 2012-09-26 |
| CA2769991A1 (en) | 2012-09-18 |
| EP2500036B1 (en) | 2014-05-07 |
| PL2500036T3 (pl) | 2014-10-31 |
| CN102688491A (zh) | 2012-09-26 |
| SI2500036T1 (sl) | 2014-09-30 |
| KR101540838B1 (ko) | 2015-08-06 |
| AU2012201303B2 (en) | 2013-11-07 |
| IL218293A0 (en) | 2012-07-31 |
| IL218293A (en) | 2016-06-30 |
| US20120237524A1 (en) | 2012-09-20 |
| DK2500036T3 (da) | 2014-08-04 |
| SMT201400106B (it) | 2014-11-10 |
| ZA201201992B (en) | 2015-05-27 |
| SG184637A1 (en) | 2012-10-30 |
| EA028590B1 (ru) | 2017-12-29 |
| EP2500036A1 (en) | 2012-09-19 |
| EA201200329A2 (ru) | 2012-09-28 |
| MX2012003084A (es) | 2012-09-17 |
| BR102012006063A2 (pt) | 2021-11-16 |
| HK1174539A1 (en) | 2013-06-14 |
| CA2769991C (en) | 2018-05-15 |
| RS53468B (sr) | 2014-12-31 |
| BR102012006063A8 (pt) | 2022-11-08 |
| AU2012201303A1 (en) | 2012-10-04 |
| BR102012006063B1 (pt) | 2023-03-07 |
| CY1115374T1 (el) | 2017-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2489475T3 (es) | Inhibidores MET para potenciar la eficacia de la radioterapia | |
| Tang et al. | An artificial lncRNA targeting multiple miRNAs overcomes sorafenib resistance in hepatocellular carcinoma cells | |
| Dooley et al. | Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats | |
| Li et al. | MicroRNA-143 promotes apoptosis of osteosarcoma cells by caspase-3 activation via targeting Bcl-2 | |
| Yu et al. | Potential approaches to the treatment of Ewing's sarcoma | |
| Peyre et al. | PDGF activation in PGDS-positive arachnoid cells induces meningioma formation in mice promoting tumor progression in combination with Nf2 and Cdkn2ab loss | |
| US10703820B2 (en) | Methods and compositions for reducing cardiac damage and other conditions | |
| Pei et al. | Angiotensin-(1-7) decreases cell growth and angiogenesis of human nasopharyngeal carcinoma xenografts | |
| CN107709359A (zh) | Ror1‑ror2结合的调节剂 | |
| CN107249636B (zh) | 以ckap4作为靶分子的抗肿瘤剂 | |
| Zhang et al. | Transgelin as a therapeutic target to prevent hypoxic pulmonary hypertension | |
| Royet et al. | Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4 | |
| CN115873110A (zh) | 抑制scube2，一种新颖vegfr2辅助受体，抑制肿瘤血管发生 | |
| EP2723350B1 (en) | New uses of nanog inhibitors and related methods | |
| Crose et al. | Receptor tyrosine kinases as therapeutic targets in rhabdomyosarcoma | |
| US20210212997A1 (en) | Methods of enhancing immunity | |
| CA2756851A1 (en) | Therapeutic agent for cancer having reduced sensitivity to molecular target drug and pharmaceutical composition for enhancing sensitivity to molecular target drug | |
| Kawakami et al. | Extracellular-regulated-kinase 5-mediated renal protection against ischemia–reperfusion injury | |
| CN107715103B (zh) | Clusterin在制备杀伤肿瘤干细胞的癌症治疗药物中的应用 | |
| CA2656577A1 (en) | Method for evaluation of a cancer | |
| CN104138593A (zh) | Chip蛋白在胰腺癌治疗中的用途 | |
| HK1174539B (en) | Met inhibitors for enhancing radiotherapy efficacy | |
| Jaunecker | The role of FGFR4 activity on proliferation, differentiation and downstream signaling in glioma | |
| Factor | A Potential Oncogenic Activity of Platelet-Derived Growth | |
| CN105194671A (zh) | CABYR-a/b在促进肿瘤细胞对VP16和TRAIL的敏感性中的应用 |