CA2919690C - Methods and molecular pharmacodynamic biomarkers for multiple signaling pathways in response to carboxyamidotriazole orotate - Google Patents
Methods and molecular pharmacodynamic biomarkers for multiple signaling pathways in response to carboxyamidotriazole orotate Download PDFInfo
- Publication number
- CA2919690C CA2919690C CA2919690A CA2919690A CA2919690C CA 2919690 C CA2919690 C CA 2919690C CA 2919690 A CA2919690 A CA 2919690A CA 2919690 A CA2919690 A CA 2919690A CA 2919690 C CA2919690 C CA 2919690C
- Authority
- CA
- Canada
- Prior art keywords
- signature
- pathways
- cto
- response
- pharmacodynamic biomarkers
- 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
- 230000004044 response Effects 0.000 title claims abstract description 142
- 238000000034 method Methods 0.000 title claims abstract description 106
- 239000000090 biomarker Substances 0.000 title claims abstract description 92
- 230000003285 pharmacodynamic effect Effects 0.000 title claims abstract description 76
- MNWOBDDXRRBONM-UHFFFAOYSA-N 5-amino-1-[[3,5-dichloro-4-(4-chlorobenzoyl)phenyl]methyl]triazole-4-carboxamide;2,4-dioxo-1h-pyrimidine-6-carboxylic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1.NC1=C(C(=O)N)N=NN1CC(C=C1Cl)=CC(Cl)=C1C(=O)C1=CC=C(Cl)C=C1 MNWOBDDXRRBONM-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 230000019491 signal transduction Effects 0.000 title abstract description 29
- 230000028956 calcium-mediated signaling Effects 0.000 claims abstract description 52
- 230000001419 dependent effect Effects 0.000 claims abstract description 29
- 230000014509 gene expression Effects 0.000 claims abstract description 28
- 102000003964 Histone deacetylase Human genes 0.000 claims abstract description 22
- 108090000353 Histone deacetylase Proteins 0.000 claims abstract description 22
- 101710113864 Heat shock protein 90 Proteins 0.000 claims abstract description 17
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims abstract description 17
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims abstract description 12
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims abstract description 12
- -1 GFS Proteins 0.000 claims abstract description 11
- 230000002103 transcriptional effect Effects 0.000 claims abstract description 8
- 102100023226 Early growth response protein 1 Human genes 0.000 claims abstract 4
- 101001049697 Homo sapiens Early growth response protein 1 Proteins 0.000 claims abstract 4
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims abstract 4
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims abstract 4
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims abstract 4
- 230000037361 pathway Effects 0.000 claims description 183
- 108090000623 proteins and genes Proteins 0.000 claims description 117
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 claims description 30
- 101100243447 Arabidopsis thaliana PER53 gene Proteins 0.000 claims description 21
- 101150080074 TP53 gene Proteins 0.000 claims description 21
- WNRZHQBJSXRYJK-UHFFFAOYSA-N carboxyamidotriazole Chemical compound NC1=C(C(=O)N)N=NN1CC(C=C1Cl)=CC(Cl)=C1C(=O)C1=CC=C(Cl)C=C1 WNRZHQBJSXRYJK-UHFFFAOYSA-N 0.000 claims description 14
- 102100032249 Dystonin Human genes 0.000 claims description 13
- 108010013976 Dystonin Proteins 0.000 claims description 12
- 238000001727 in vivo Methods 0.000 claims description 9
- 238000013518 transcription Methods 0.000 claims description 9
- 230000035897 transcription Effects 0.000 claims description 9
- 239000002299 complementary DNA Substances 0.000 claims description 8
- 230000004075 alteration Effects 0.000 claims description 6
- 108020004999 messenger RNA Proteins 0.000 claims description 6
- 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 claims description 5
- 238000003068 pathway analysis Methods 0.000 claims description 5
- 108010062802 CD66 antigens Proteins 0.000 claims description 4
- 230000005723 MEK inhibition Effects 0.000 claims description 4
- 108700005081 Overlapping Genes Proteins 0.000 claims description 4
- 229940125374 mitogen-activated extracellular signal-regulated kinase inhibitor Drugs 0.000 claims description 3
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 79
- 210000004209 hair Anatomy 0.000 abstract description 56
- 230000003698 anagen phase Effects 0.000 abstract description 27
- 230000005764 inhibitory process Effects 0.000 abstract description 19
- 102000016914 ras Proteins Human genes 0.000 abstract description 18
- 101150040459 RAS gene Proteins 0.000 abstract description 17
- 101150076031 RAS1 gene Proteins 0.000 abstract description 17
- 238000012544 monitoring process Methods 0.000 abstract description 10
- 230000001939 inductive effect Effects 0.000 abstract description 9
- 238000003556 assay Methods 0.000 abstract description 8
- 230000008826 genomic mutation Effects 0.000 abstract description 3
- 238000011282 treatment Methods 0.000 description 57
- 210000004027 cell Anatomy 0.000 description 41
- 230000011664 signaling Effects 0.000 description 40
- 201000011510 cancer Diseases 0.000 description 39
- 102000004169 proteins and genes Human genes 0.000 description 37
- 239000003814 drug Substances 0.000 description 29
- 229940079593 drug Drugs 0.000 description 25
- JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 description 21
- 229950006418 dactolisib Drugs 0.000 description 21
- 238000011161 development Methods 0.000 description 20
- 230000018109 developmental process Effects 0.000 description 20
- 230000002401 inhibitory effect Effects 0.000 description 19
- 230000001629 suppression Effects 0.000 description 19
- 239000003112 inhibitor Substances 0.000 description 18
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 17
- 108091000080 Phosphotransferase Proteins 0.000 description 17
- 239000011575 calcium Substances 0.000 description 17
- 229910052791 calcium Inorganic materials 0.000 description 17
- 201000010099 disease Diseases 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 102000020233 phosphotransferase Human genes 0.000 description 17
- 102000001301 EGF receptor Human genes 0.000 description 16
- 108060006698 EGF receptor Proteins 0.000 description 16
- 230000033228 biological regulation Effects 0.000 description 14
- 230000001105 regulatory effect Effects 0.000 description 14
- 238000013459 approach Methods 0.000 description 13
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 102000013814 Wnt Human genes 0.000 description 11
- 108050003627 Wnt Proteins 0.000 description 11
- 206010059866 Drug resistance Diseases 0.000 description 10
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 10
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 230000004913 activation Effects 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 8
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- 101710132081 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Proteins 0.000 description 8
- 102100032543 Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN Human genes 0.000 description 8
- 238000000540 analysis of variance Methods 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 239000003102 growth factor Substances 0.000 description 8
- 210000004761 scalp Anatomy 0.000 description 8
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 7
- 102000038030 PI3Ks Human genes 0.000 description 7
- 108091007960 PI3Ks Proteins 0.000 description 7
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 7
- 230000005856 abnormality Effects 0.000 description 7
- 230000006907 apoptotic process Effects 0.000 description 7
- 231100000590 oncogenic Toxicity 0.000 description 7
- 230000002246 oncogenic effect Effects 0.000 description 7
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 6
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 6
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 6
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 6
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 230000002222 downregulating effect Effects 0.000 description 6
- 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 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 239000011701 zinc Substances 0.000 description 6
- 229910052725 zinc Inorganic materials 0.000 description 6
- 108091006146 Channels Proteins 0.000 description 5
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 5
- 102000014736 Notch Human genes 0.000 description 5
- 108010070047 Notch Receptors Proteins 0.000 description 5
- 230000009460 calcium influx Effects 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 229940121647 egfr inhibitor Drugs 0.000 description 5
- 230000004547 gene signature Effects 0.000 description 5
- 208000005017 glioblastoma Diseases 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000004650 oncogenic pathway Effects 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 229940120982 tarceva Drugs 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 240000005020 Acaciella glauca Species 0.000 description 4
- 102100032912 CD44 antigen Human genes 0.000 description 4
- 102000014914 Carrier Proteins Human genes 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 4
- 101000611251 Homo sapiens Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform Proteins 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 102100040320 Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform Human genes 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 108091008324 binding proteins Proteins 0.000 description 4
- 238000007622 bioinformatic analysis Methods 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 231100000640 hair analysis Toxicity 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 238000002626 targeted therapy Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 101150082072 14 gene Proteins 0.000 description 3
- 102000003922 Calcium Channels Human genes 0.000 description 3
- 108090000312 Calcium Channels Proteins 0.000 description 3
- 102100025176 Cyclin-A1 Human genes 0.000 description 3
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 3
- 206010018338 Glioma Diseases 0.000 description 3
- 108010033040 Histones Proteins 0.000 description 3
- 101000934314 Homo sapiens Cyclin-A1 Proteins 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 3
- 108700025695 Suppressor Genes Proteins 0.000 description 3
- 241000906446 Theraps Species 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 238000011284 combination treatment Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 3
- 210000003780 hair follicle Anatomy 0.000 description 3
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000010208 microarray analysis Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 210000002307 prostate Anatomy 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 235000003499 redwood Nutrition 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001685 thyroid gland Anatomy 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 239000000225 tumor suppressor protein Substances 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 2
- 102100035623 ATP-citrate synthase Human genes 0.000 description 2
- 101710145634 Antigen 1 Proteins 0.000 description 2
- 102100030356 Arginase-2, mitochondrial Human genes 0.000 description 2
- 102100039341 Atrial natriuretic peptide receptor 2 Human genes 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- OWNRRUFOJXFKCU-UHFFFAOYSA-N Bromadiolone Chemical compound C=1C=C(C=2C=CC(Br)=CC=2)C=CC=1C(O)CC(C=1C(OC2=CC=CC=C2C=1O)=O)C1=CC=CC=C1 OWNRRUFOJXFKCU-UHFFFAOYSA-N 0.000 description 2
- 102100034808 CCAAT/enhancer-binding protein alpha Human genes 0.000 description 2
- 102100033086 Calcium/calmodulin-dependent protein kinase type 1 Human genes 0.000 description 2
- 102100025227 Calcium/calmodulin-dependent protein kinase type II subunit gamma Human genes 0.000 description 2
- 102100025926 Calmodulin-3 Human genes 0.000 description 2
- 102100029968 Calreticulin Human genes 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102100029855 Caspase-3 Human genes 0.000 description 2
- 102000016362 Catenins Human genes 0.000 description 2
- 108010067316 Catenins Proteins 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 101150118364 Crkl gene Proteins 0.000 description 2
- 241000270311 Crocodylus niloticus Species 0.000 description 2
- 230000004544 DNA amplification Effects 0.000 description 2
- 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 description 2
- 102100037858 G1/S-specific cyclin-E1 Human genes 0.000 description 2
- 102100030669 Glutamate receptor 3 Human genes 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 2
- 102100021454 Histone deacetylase 4 Human genes 0.000 description 2
- 101000782969 Homo sapiens ATP-citrate synthase Proteins 0.000 description 2
- 101000792835 Homo sapiens Arginase-2, mitochondrial Proteins 0.000 description 2
- 101000961040 Homo sapiens Atrial natriuretic peptide receptor 2 Proteins 0.000 description 2
- 101000945515 Homo sapiens CCAAT/enhancer-binding protein alpha Proteins 0.000 description 2
- 101000944250 Homo sapiens Calcium/calmodulin-dependent protein kinase type 1 Proteins 0.000 description 2
- 101001077334 Homo sapiens Calcium/calmodulin-dependent protein kinase type II subunit gamma Proteins 0.000 description 2
- 101000933777 Homo sapiens Calmodulin-3 Proteins 0.000 description 2
- 101000793651 Homo sapiens Calreticulin Proteins 0.000 description 2
- 101000980741 Homo sapiens G1/S-specific cyclin-D2 Proteins 0.000 description 2
- 101000738568 Homo sapiens G1/S-specific cyclin-E1 Proteins 0.000 description 2
- 101001010434 Homo sapiens Glutamate receptor 3 Proteins 0.000 description 2
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 description 2
- 101001001478 Homo sapiens Importin subunit alpha-3 Proteins 0.000 description 2
- 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 description 2
- 101000950687 Homo sapiens Mitogen-activated protein kinase 7 Proteins 0.000 description 2
- 101001064169 Homo sapiens Protein EOLA2 Proteins 0.000 description 2
- 101000798015 Homo sapiens RAC-beta serine/threonine-protein kinase Proteins 0.000 description 2
- 102100036188 Importin subunit alpha-3 Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 2
- 102100034724 Lipocalin-1 Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 102100037805 Mitogen-activated protein kinase 7 Human genes 0.000 description 2
- 108010006519 Molecular Chaperones Proteins 0.000 description 2
- 102000005431 Molecular Chaperones Human genes 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- 108060008487 Myosin Proteins 0.000 description 2
- 102000003505 Myosin Human genes 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102100030750 Protein EOLA2 Human genes 0.000 description 2
- 102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 2
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 2
- 108010030731 Stromal Interaction Molecule 2 Proteins 0.000 description 2
- 102100035562 Stromal interaction molecule 2 Human genes 0.000 description 2
- 102100037219 Syntenin-1 Human genes 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 229940124650 anti-cancer therapies Drugs 0.000 description 2
- 230000001740 anti-invasion Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 238000011319 anticancer therapy Methods 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000008777 canonical pathway Effects 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 230000025084 cell cycle arrest Effects 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 229940000425 combination drug Drugs 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 239000003596 drug target Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 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 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229960000367 inositol Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000003595 mist Substances 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 229960001972 panitumumab Drugs 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 2
- 210000003705 ribosome Anatomy 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 2
- 230000009758 senescence Effects 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- UBWXUGDQUBIEIZ-UHFFFAOYSA-N (13-methyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl) 3-phenylpropanoate Chemical compound CC12CCC(C3CCC(=O)C=C3CC3)C3C1CCC2OC(=O)CCC1=CC=CC=C1 UBWXUGDQUBIEIZ-UHFFFAOYSA-N 0.000 description 1
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
- PJOHVEQSYPOERL-SHEAVXILSA-N (e)-n-[(4r,4as,7ar,12br)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-4a-yl]-3-(4-methylphenyl)prop-2-enamide Chemical compound C1=CC(C)=CC=C1\C=C\C(=O)N[C@]1(CCC(=O)[C@@H]2O3)[C@H]4CC5=CC=C(O)C3=C5[C@]12CCN4CC1CC1 PJOHVEQSYPOERL-SHEAVXILSA-N 0.000 description 1
- 108091064702 1 family Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- 101150072531 10 gene Proteins 0.000 description 1
- 101150029062 15 gene Proteins 0.000 description 1
- NJNFCDQQEIAOIF-UHFFFAOYSA-N 2-(3,4-dimethoxy-2-methylsulfanylphenyl)ethanamine Chemical compound COC1=CC=C(CCN)C(SC)=C1OC NJNFCDQQEIAOIF-UHFFFAOYSA-N 0.000 description 1
- 102100029511 26S proteasome regulatory subunit 6B Human genes 0.000 description 1
- XDLMVUHYZWKMMD-UHFFFAOYSA-N 3-trimethoxysilylpropyl 2-methylprop-2-enoate Chemical compound CO[Si](OC)(OC)CCCOC(=O)C(C)=C XDLMVUHYZWKMMD-UHFFFAOYSA-N 0.000 description 1
- ATXGTUVMXAHMLW-PJQLUOCWSA-N 8-[4-(4-fluorophenyl)-4-oxobutyl]-3-[(e)-3-iodoprop-2-enyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(N(C\C=C\I)CN2C=2C=CC=CC=2)=O)CC1 ATXGTUVMXAHMLW-PJQLUOCWSA-N 0.000 description 1
- 108050003506 ABL interactor 2 Proteins 0.000 description 1
- 102100028162 ATP-binding cassette sub-family C member 3 Human genes 0.000 description 1
- 102100025514 ATP-dependent 6-phosphofructokinase, platelet type Human genes 0.000 description 1
- 102100028221 Abl interactor 2 Human genes 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 102000005606 Activins Human genes 0.000 description 1
- 108010059616 Activins Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000001270 Allium sibiricum Nutrition 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 108010049777 Ankyrins Proteins 0.000 description 1
- 102000008102 Ankyrins Human genes 0.000 description 1
- 241000284466 Antarctothoa delta Species 0.000 description 1
- 101100168934 Arabidopsis thaliana C/VIF1 gene Proteins 0.000 description 1
- 102100033653 Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 101150044281 Arr2 gene Proteins 0.000 description 1
- 102000007371 Ataxin-3 Human genes 0.000 description 1
- 108010032947 Ataxin-3 Proteins 0.000 description 1
- 102100024507 BMP-2-inducible protein kinase Human genes 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- IRIAEXORFWYRCZ-UHFFFAOYSA-N Butylbenzyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCC1=CC=CC=C1 IRIAEXORFWYRCZ-UHFFFAOYSA-N 0.000 description 1
- 102100021287 CUE domain-containing protein 2 Human genes 0.000 description 1
- 101100335054 Caenorhabditis elegans flp-1 gene Proteins 0.000 description 1
- 101100309447 Caenorhabditis elegans sad-1 gene Proteins 0.000 description 1
- 108010028326 Calbindin 2 Proteins 0.000 description 1
- 102100036431 Calcineurin subunit B type 1 Human genes 0.000 description 1
- 102100029801 Calcium-transporting ATPase type 2C member 1 Human genes 0.000 description 1
- 102100033093 Calcium/calmodulin-dependent protein kinase type II subunit alpha Human genes 0.000 description 1
- 102100025228 Calcium/calmodulin-dependent protein kinase type II subunit delta Human genes 0.000 description 1
- 102100022789 Calcium/calmodulin-dependent protein kinase type IV Human genes 0.000 description 1
- 102100025579 Calmodulin-2 Human genes 0.000 description 1
- 102100021849 Calretinin Human genes 0.000 description 1
- 101100441838 Candida maltosa CYHR gene Proteins 0.000 description 1
- 102100029949 Caprin-1 Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 1
- 102100027848 Cartilage-associated protein Human genes 0.000 description 1
- 102100025634 Caspase recruitment domain-containing protein 16 Human genes 0.000 description 1
- 102100035904 Caspase-1 Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 102100023126 Cell surface glycoprotein MUC18 Human genes 0.000 description 1
- 241001155433 Centrarchus macropterus Species 0.000 description 1
- 208000013641 Cerebrofacial arteriovenous metameric syndrome Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 235000010205 Cola acuminata Nutrition 0.000 description 1
- 244000228088 Cola acuminata Species 0.000 description 1
- 235000015438 Cola nitida Nutrition 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 101000932768 Conus catus Alpha-conotoxin CIC Proteins 0.000 description 1
- 102100031673 Corneodesmosin Human genes 0.000 description 1
- 108010037663 Cortactin Proteins 0.000 description 1
- 102000010958 Cortactin Human genes 0.000 description 1
- 102100025191 Cyclin-A2 Human genes 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 102100029021 DBIRD complex subunit ZNF326 Human genes 0.000 description 1
- 102100029816 DEP domain-containing mTOR-interacting protein Human genes 0.000 description 1
- 108091028710 DLEU2 Proteins 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
- 101500011077 Diploptera punctata Allatostatin-9 Proteins 0.000 description 1
- 101100432802 Drosophila melanogaster Ypel gene Proteins 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102100029982 Dynein axonemal light chain 4 Human genes 0.000 description 1
- 101150039808 Egfr gene Proteins 0.000 description 1
- 102100022462 Eukaryotic initiation factor 4A-II Human genes 0.000 description 1
- 241000975394 Evechinus chloroticus Species 0.000 description 1
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
- 101710205374 Extracellular elastase Proteins 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 241000272186 Falco columbarius Species 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102100022148 G protein pathway suppressor 2 Human genes 0.000 description 1
- 102100037854 G1/S-specific cyclin-E2 Human genes 0.000 description 1
- 102100024418 GTPase IMAP family member 8 Human genes 0.000 description 1
- 102100022631 Glutamate receptor ionotropic, NMDA 2C Human genes 0.000 description 1
- 102100022626 Glutamate receptor ionotropic, NMDA 2D Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000017679 HTR3A Human genes 0.000 description 1
- 102100027421 Heat shock cognate 71 kDa protein Human genes 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 102100021455 Histone deacetylase 3 Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001125524 Homo sapiens 26S proteasome regulatory subunit 6B Proteins 0.000 description 1
- 101000761343 Homo sapiens 5-hydroxytryptamine receptor 3A Proteins 0.000 description 1
- 101000986633 Homo sapiens ATP-binding cassette sub-family C member 3 Proteins 0.000 description 1
- 101000693765 Homo sapiens ATP-dependent 6-phosphofructokinase, platelet type Proteins 0.000 description 1
- 101000733557 Homo sapiens Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 Proteins 0.000 description 1
- 101000762370 Homo sapiens BMP-2-inducible protein kinase Proteins 0.000 description 1
- 101000762366 Homo sapiens Bone morphogenetic protein 2 Proteins 0.000 description 1
- 101000899390 Homo sapiens Bone morphogenetic protein 6 Proteins 0.000 description 1
- 101000894806 Homo sapiens CUE domain-containing protein 2 Proteins 0.000 description 1
- 101000714321 Homo sapiens Calcineurin subunit B type 1 Proteins 0.000 description 1
- 101000728145 Homo sapiens Calcium-transporting ATPase type 2C member 1 Proteins 0.000 description 1
- 101000944249 Homo sapiens Calcium/calmodulin-dependent protein kinase type II subunit alpha Proteins 0.000 description 1
- 101001077338 Homo sapiens Calcium/calmodulin-dependent protein kinase type II subunit delta Proteins 0.000 description 1
- 101000974816 Homo sapiens Calcium/calmodulin-dependent protein kinase type IV Proteins 0.000 description 1
- 101000984150 Homo sapiens Calmodulin-2 Proteins 0.000 description 1
- 101000793727 Homo sapiens Caprin-1 Proteins 0.000 description 1
- 101000981093 Homo sapiens Carcinoembryonic antigen-related cell adhesion molecule 1 Proteins 0.000 description 1
- 101000859758 Homo sapiens Cartilage-associated protein Proteins 0.000 description 1
- 101000933103 Homo sapiens Caspase recruitment domain-containing protein 16 Proteins 0.000 description 1
- 101000715398 Homo sapiens Caspase-1 Proteins 0.000 description 1
- 101000623903 Homo sapiens Cell surface glycoprotein MUC18 Proteins 0.000 description 1
- 101000777796 Homo sapiens Corneodesmosin Proteins 0.000 description 1
- 101000934320 Homo sapiens Cyclin-A2 Proteins 0.000 description 1
- 101000915665 Homo sapiens DBIRD complex subunit ZNF326 Proteins 0.000 description 1
- 101000865183 Homo sapiens DEP domain-containing mTOR-interacting protein Proteins 0.000 description 1
- 101000864172 Homo sapiens Dolichol-phosphate mannosyltransferase subunit 3 Proteins 0.000 description 1
- 101000863731 Homo sapiens Dynein axonemal light chain 4 Proteins 0.000 description 1
- 101001044475 Homo sapiens Eukaryotic initiation factor 4A-II Proteins 0.000 description 1
- 101000900320 Homo sapiens G protein pathway suppressor 2 Proteins 0.000 description 1
- 101000738575 Homo sapiens G1/S-specific cyclin-E2 Proteins 0.000 description 1
- 101100014658 Homo sapiens GIMAP8 gene Proteins 0.000 description 1
- 101000972846 Homo sapiens Glutamate receptor ionotropic, NMDA 2C Proteins 0.000 description 1
- 101000972840 Homo sapiens Glutamate receptor ionotropic, NMDA 2D Proteins 0.000 description 1
- 101001080568 Homo sapiens Heat shock cognate 71 kDa protein Proteins 0.000 description 1
- 101000899282 Homo sapiens Histone deacetylase 3 Proteins 0.000 description 1
- 101001001418 Homo sapiens Inhibitor of growth protein 4 Proteins 0.000 description 1
- 101001026236 Homo sapiens Intermediate conductance calcium-activated potassium channel protein 4 Proteins 0.000 description 1
- 101000605522 Homo sapiens Kallikrein-1 Proteins 0.000 description 1
- 101001091385 Homo sapiens Kallikrein-6 Proteins 0.000 description 1
- 101001091266 Homo sapiens Kinesin-like protein KIF13A Proteins 0.000 description 1
- 101001077840 Homo sapiens Lipid-phosphate phosphatase Proteins 0.000 description 1
- 101000957335 Homo sapiens Lysophospholipid acyltransferase 1 Proteins 0.000 description 1
- 101001055346 Homo sapiens Mediator of RNA polymerase II transcription subunit 30 Proteins 0.000 description 1
- 101000589407 Homo sapiens Membrane progestin receptor gamma Proteins 0.000 description 1
- 101001052490 Homo sapiens Mitogen-activated protein kinase 3 Proteins 0.000 description 1
- 101001052477 Homo sapiens Mitogen-activated protein kinase 4 Proteins 0.000 description 1
- 101000958041 Homo sapiens Musculin Proteins 0.000 description 1
- 101000634537 Homo sapiens Neuronal PAS domain-containing protein 2 Proteins 0.000 description 1
- 101000745163 Homo sapiens Neuronal acetylcholine receptor subunit alpha-3 Proteins 0.000 description 1
- 101000745175 Homo sapiens Neuronal acetylcholine receptor subunit alpha-5 Proteins 0.000 description 1
- 101000822072 Homo sapiens Neuronal acetylcholine receptor subunit alpha-6 Proteins 0.000 description 1
- 101000822103 Homo sapiens Neuronal acetylcholine receptor subunit alpha-7 Proteins 0.000 description 1
- 101000979347 Homo sapiens Nuclear factor 1 X-type Proteins 0.000 description 1
- 101001109698 Homo sapiens Nuclear receptor subfamily 4 group A member 2 Proteins 0.000 description 1
- 101001137535 Homo sapiens Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 Proteins 0.000 description 1
- 101000586302 Homo sapiens Oncostatin-M-specific receptor subunit beta Proteins 0.000 description 1
- 101000651906 Homo sapiens Paired amphipathic helix protein Sin3a Proteins 0.000 description 1
- 101000579484 Homo sapiens Period circadian protein homolog 1 Proteins 0.000 description 1
- 101001074954 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A Proteins 0.000 description 1
- 101001097889 Homo sapiens Platelet-activating factor acetylhydrolase Proteins 0.000 description 1
- 101001064282 Homo sapiens Platelet-activating factor acetylhydrolase IB subunit beta Proteins 0.000 description 1
- 101000583178 Homo sapiens Pleckstrin homology domain-containing family M member 1 Proteins 0.000 description 1
- 101001126591 Homo sapiens Post-GPI attachment to proteins factor 2 Proteins 0.000 description 1
- 101001126582 Homo sapiens Post-GPI attachment to proteins factor 3 Proteins 0.000 description 1
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 1
- 101000920644 Homo sapiens Protein EOLA1 Proteins 0.000 description 1
- 101000994307 Homo sapiens Protein ITPRID2 Proteins 0.000 description 1
- 101001065830 Homo sapiens Protein LRATD1 Proteins 0.000 description 1
- 101000652433 Homo sapiens Protein SON Proteins 0.000 description 1
- 101000620365 Homo sapiens Protein TMEPAI Proteins 0.000 description 1
- 101000830691 Homo sapiens Protein tyrosine phosphatase type IVA 2 Proteins 0.000 description 1
- 101001134896 Homo sapiens Protein-L-isoaspartate O-methyltransferase domain-containing protein 1 Proteins 0.000 description 1
- 101001134890 Homo sapiens Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 Proteins 0.000 description 1
- 101000798007 Homo sapiens RAC-gamma serine/threonine-protein kinase Proteins 0.000 description 1
- 101001130505 Homo sapiens Ras GTPase-activating protein 2 Proteins 0.000 description 1
- 101000831949 Homo sapiens Receptor for retinol uptake STRA6 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000574648 Homo sapiens Retinoid-inducible serine carboxypeptidase Proteins 0.000 description 1
- 101000733752 Homo sapiens Retroviral-like aspartic protease 1 Proteins 0.000 description 1
- 101001106406 Homo sapiens Rho GTPase-activating protein 1 Proteins 0.000 description 1
- 101000945090 Homo sapiens Ribosomal protein S6 kinase alpha-3 Proteins 0.000 description 1
- 101000654484 Homo sapiens SID1 transmembrane family member 2 Proteins 0.000 description 1
- 101000706557 Homo sapiens SUN domain-containing protein 1 Proteins 0.000 description 1
- 101000650808 Homo sapiens Semaphorin-3G Proteins 0.000 description 1
- 101001123859 Homo sapiens Sialidase-1 Proteins 0.000 description 1
- 101000952234 Homo sapiens Sphingolipid delta(4)-desaturase DES1 Proteins 0.000 description 1
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 1
- 101001131204 Homo sapiens Sulfhydryl oxidase 1 Proteins 0.000 description 1
- 101000704557 Homo sapiens Sulfiredoxin-1 Proteins 0.000 description 1
- 101000706175 Homo sapiens Syntaxin-17 Proteins 0.000 description 1
- 101000740523 Homo sapiens Syntenin-1 Proteins 0.000 description 1
- 101000740516 Homo sapiens Syntenin-2 Proteins 0.000 description 1
- 101000801891 Homo sapiens Thioredoxin, mitochondrial Proteins 0.000 description 1
- 101000837626 Homo sapiens Thyroid hormone receptor alpha Proteins 0.000 description 1
- 101000801260 Homo sapiens Troponin C, slow skeletal and cardiac muscles Proteins 0.000 description 1
- 101000851334 Homo sapiens Troponin I, cardiac muscle Proteins 0.000 description 1
- 101000954798 Homo sapiens WD repeat domain phosphoinositide-interacting protein 2 Proteins 0.000 description 1
- 101000871498 Homo sapiens m7GpppX diphosphatase Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 101150017040 I gene Proteins 0.000 description 1
- 241000976924 Inca Species 0.000 description 1
- 102000002746 Inhibins Human genes 0.000 description 1
- 108010004250 Inhibins Proteins 0.000 description 1
- 102100035677 Inhibitor of growth protein 4 Human genes 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 102100037441 Intermediate conductance calcium-activated potassium channel protein 4 Human genes 0.000 description 1
- 241001585244 Itame Species 0.000 description 1
- 206010069755 K-ras gene mutation Diseases 0.000 description 1
- 102100034866 Kallikrein-6 Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 108010063296 Kinesin Proteins 0.000 description 1
- 102000010638 Kinesin Human genes 0.000 description 1
- 102100034865 Kinesin-like protein KIF13A Human genes 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
- 102100025357 Lipid-phosphate phosphatase Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 102100038754 Lysophospholipid acyltransferase 1 Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 241000211181 Manta Species 0.000 description 1
- 102100026176 Mediator of RNA polymerase II transcription subunit 30 Human genes 0.000 description 1
- 102100032334 Membrane progestin receptor gamma Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 1
- 102100024189 Mitogen-activated protein kinase 4 Human genes 0.000 description 1
- 102100025744 Mothers against decapentaplegic homolog 1 Human genes 0.000 description 1
- 101100179469 Mus musculus Ighg2b gene Proteins 0.000 description 1
- 101100087528 Mus musculus Rhoj gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 102100029045 Neuronal PAS domain-containing protein 2 Human genes 0.000 description 1
- 102100039908 Neuronal acetylcholine receptor subunit alpha-3 Human genes 0.000 description 1
- 102100039907 Neuronal acetylcholine receptor subunit alpha-5 Human genes 0.000 description 1
- 102100021518 Neuronal acetylcholine receptor subunit alpha-6 Human genes 0.000 description 1
- 102100021511 Neuronal acetylcholine receptor subunit alpha-7 Human genes 0.000 description 1
- 101100182136 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) loc-1 gene Proteins 0.000 description 1
- 101100426589 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) trp-3 gene Proteins 0.000 description 1
- 102000015532 Nicotinamide phosphoribosyltransferase Human genes 0.000 description 1
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 description 1
- 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 1
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 1
- 102100023049 Nuclear factor 1 X-type Human genes 0.000 description 1
- 102100022676 Nuclear receptor subfamily 4 group A member 2 Human genes 0.000 description 1
- 102100021007 Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 Human genes 0.000 description 1
- 102100032604 Occludin Human genes 0.000 description 1
- 108090000304 Occludin Proteins 0.000 description 1
- 102100030098 Oncostatin-M-specific receptor subunit beta Human genes 0.000 description 1
- 102000002131 PAS domains Human genes 0.000 description 1
- 108050009469 PAS domains Proteins 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- MIQYPPGTNIFAPO-CABCVRRESA-N PS(6:0/6:0) Chemical compound CCCCCC(=O)OC[C@@H](OC(=O)CCCCC)COP(O)(=O)OC[C@H](N)C(O)=O MIQYPPGTNIFAPO-CABCVRRESA-N 0.000 description 1
- 102100027334 Paired amphipathic helix protein Sin3a Human genes 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 240000002834 Paulownia tomentosa Species 0.000 description 1
- 235000010678 Paulownia tomentosa Nutrition 0.000 description 1
- 102000005877 Peptide Initiation Factors Human genes 0.000 description 1
- 108010044843 Peptide Initiation Factors Proteins 0.000 description 1
- 102100028293 Period circadian protein homolog 1 Human genes 0.000 description 1
- 102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 description 1
- 102100035985 Phosphatidylinositol 4,5-bisphosphate 5-phosphatase A Human genes 0.000 description 1
- 102100038374 Pinin Human genes 0.000 description 1
- 101710173952 Pinin Proteins 0.000 description 1
- 241000404883 Pisa Species 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 102100030655 Platelet-activating factor acetylhydrolase IB subunit beta Human genes 0.000 description 1
- 102100030349 Pleckstrin homology domain-containing family M member 1 Human genes 0.000 description 1
- 102000010995 Pleckstrin homology domains Human genes 0.000 description 1
- 108050001185 Pleckstrin homology domains Proteins 0.000 description 1
- 102100030422 Post-GPI attachment to proteins factor 2 Human genes 0.000 description 1
- 102100031946 Protein EOLA1 Human genes 0.000 description 1
- 102100032831 Protein ITPRID2 Human genes 0.000 description 1
- 102100032095 Protein LRATD1 Human genes 0.000 description 1
- 102100030232 Protein SON Human genes 0.000 description 1
- 102100022429 Protein TMEPAI Human genes 0.000 description 1
- 102100024602 Protein tyrosine phosphatase type IVA 2 Human genes 0.000 description 1
- 102100033431 Protein-L-isoaspartate O-methyltransferase domain-containing protein 1 Human genes 0.000 description 1
- 102100033430 Protein-L-isoaspartate O-methyltransferase domain-containing protein 2 Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 241000287531 Psittacidae Species 0.000 description 1
- 102100032314 RAC-gamma serine/threonine-protein kinase Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 102100031427 Ras GTPase-activating protein 2 Human genes 0.000 description 1
- 102100028191 Ras-related protein Rab-1A Human genes 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 102100024235 Receptor for retinol uptake STRA6 Human genes 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 102100021289 Regulator of G-protein signaling 20 Human genes 0.000 description 1
- 101710148117 Regulator of G-protein signaling 20 Proteins 0.000 description 1
- 102100025483 Retinoid-inducible serine carboxypeptidase Human genes 0.000 description 1
- 102100033717 Retroviral-like aspartic protease 1 Human genes 0.000 description 1
- 102100021433 Rho GTPase-activating protein 1 Human genes 0.000 description 1
- 102100040312 Ribonuclease 7 Human genes 0.000 description 1
- 108010085025 Ribonuclease 7 Proteins 0.000 description 1
- 102100033643 Ribosomal protein S6 kinase alpha-3 Human genes 0.000 description 1
- UEJYSALTSUZXFV-SRVKXCTJSA-N Rigin Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O UEJYSALTSUZXFV-SRVKXCTJSA-N 0.000 description 1
- 108091005487 SCARB1 Proteins 0.000 description 1
- 102000051614 SET domains Human genes 0.000 description 1
- 108700039010 SET domains Proteins 0.000 description 1
- 102100031453 SID1 transmembrane family member 2 Human genes 0.000 description 1
- 101700032040 SMAD1 Proteins 0.000 description 1
- 102100031130 SUN domain-containing protein 1 Human genes 0.000 description 1
- 101001092180 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) RHO GTPase-activating protein RGD1 Proteins 0.000 description 1
- 101100314406 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) TPS1 gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241001274197 Scatophagus argus Species 0.000 description 1
- 102100037118 Scavenger receptor class B member 1 Human genes 0.000 description 1
- 101100137261 Schizosaccharomyces pombe (strain 972 / ATCC 24843) poz1 gene Proteins 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- 102000040739 Secretory proteins Human genes 0.000 description 1
- 102100023843 Selenoprotein P Human genes 0.000 description 1
- 102100027750 Semaphorin-3G Human genes 0.000 description 1
- 206010040037 Sensory neuropathy hereditary Diseases 0.000 description 1
- 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 description 1
- 101710128612 Sialidase-1 Proteins 0.000 description 1
- 102100028760 Sialidase-1 Human genes 0.000 description 1
- 102100037416 Sphingolipid delta(4)-desaturase DES1 Human genes 0.000 description 1
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 1
- 102100034371 Sulfhydryl oxidase 1 Human genes 0.000 description 1
- 102100031797 Sulfiredoxin-1 Human genes 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- DRVWTOSBCBKXOR-ZLDLUXBVSA-N Supinine Chemical compound C1CC[C@H]2C(COC(=O)[C@@](O)([C@@H](C)O)C(C)C)=CCN21 DRVWTOSBCBKXOR-ZLDLUXBVSA-N 0.000 description 1
- 101100421179 Sus scrofa SELENOW gene Proteins 0.000 description 1
- 102100031101 Syntaxin-17 Human genes 0.000 description 1
- 102100037225 Syntenin-2 Human genes 0.000 description 1
- 108010083130 Syntenins Proteins 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 108090000925 TNF receptor-associated factor 2 Proteins 0.000 description 1
- 102100034779 TRAF family member-associated NF-kappa-B activator Human genes 0.000 description 1
- 101150066742 TRI1 gene Proteins 0.000 description 1
- 102000003629 TRPC3 Human genes 0.000 description 1
- 102000003623 TRPC6 Human genes 0.000 description 1
- 102000003564 TRPC7 Human genes 0.000 description 1
- 101150095096 TRPM2 gene Proteins 0.000 description 1
- 102100034795 Thioredoxin, mitochondrial Human genes 0.000 description 1
- 102100028702 Thyroid hormone receptor alpha Human genes 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
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 108050001421 Transient receptor potential channel, canonical 6 Proteins 0.000 description 1
- 102100036859 Troponin I, cardiac muscle Human genes 0.000 description 1
- 101150037542 Trpc3 gene Proteins 0.000 description 1
- 101150033973 Trpc7 gene Proteins 0.000 description 1
- 102100040653 Tryptophan 2,3-dioxygenase Human genes 0.000 description 1
- 101710136122 Tryptophan 2,3-dioxygenase Proteins 0.000 description 1
- 102100024537 Tyrosine-protein kinase Fer Human genes 0.000 description 1
- 241000218220 Ulmaceae Species 0.000 description 1
- 102100037050 WD repeat domain phosphoinositide-interacting protein 2 Human genes 0.000 description 1
- 230000004156 Wnt signaling pathway Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000488 activin Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 230000006364 cellular survival Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 101150100265 cif-1 gene Proteins 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 238000011962 continuous elektro deionisation Methods 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 230000037437 driver mutation Effects 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 229940096118 ella Drugs 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 208000023965 endometrium neoplasm Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 108700021358 erbB-1 Genes Proteins 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- 238000011124 ex vivo culture Methods 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 102000009543 guanyl-nucleotide exchange factor activity proteins Human genes 0.000 description 1
- 238000009957 hemming Methods 0.000 description 1
- 208000037584 hereditary sensory and autonomic neuropathy Diseases 0.000 description 1
- 201000006847 hereditary sensory neuropathy Diseases 0.000 description 1
- 230000006195 histone acetylation Effects 0.000 description 1
- 102000046949 human MSC Human genes 0.000 description 1
- 210000005260 human cell Anatomy 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
- 238000010874 in vitro model Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 244000145841 kine Species 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 102100033718 m7GpppX diphosphatase Human genes 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- NFGXHKASABOEEW-LDRANXPESA-N methoprene Chemical compound COC(C)(C)CCCC(C)C\C=C\C(\C)=C\C(=O)OC(C)C NFGXHKASABOEEW-LDRANXPESA-N 0.000 description 1
- 238000013470 microfluidic resistive pulse sensing Methods 0.000 description 1
- 238000005065 mining Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000000921 morphogenic effect Effects 0.000 description 1
- 238000000491 multivariate analysis Methods 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960001346 nilotinib Drugs 0.000 description 1
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 108010067366 proto-oncogene protein c-fes-fps Proteins 0.000 description 1
- 108010054067 rab1 GTP-Binding Proteins Proteins 0.000 description 1
- 108010014186 ras Proteins Proteins 0.000 description 1
- 239000002964 rayon Substances 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 231100000628 reference dose Toxicity 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 108010091078 rigin Proteins 0.000 description 1
- 210000004918 root sheath Anatomy 0.000 description 1
- 102200139497 rs2274268 Human genes 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940028231 symax Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- OOLLAFOLCSJHRE-ZHAKMVSLSA-N ulipristal acetate Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(OC(C)=O)C(C)=O)[C@]2(C)C1 OOLLAFOLCSJHRE-ZHAKMVSLSA-N 0.000 description 1
- 108700026220 vif Genes Proteins 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
- 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
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- 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
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physics & Mathematics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Evolutionary Biology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Medical Informatics (AREA)
- Theoretical Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/957,720 | 2013-08-02 | ||
| US13/957,720 US10378059B2 (en) | 2013-08-02 | 2013-08-02 | Methods and molecular pharmacodynamic biomarkers for multiple signaling pathways in response to carboxyamidotriazole orotate |
| PCT/US2014/048905 WO2015017545A1 (en) | 2013-08-02 | 2014-07-30 | Methods and molecular pharmacodynamic biomarkers for multiple signaling pathways in response to carboxyamidotriazole orotate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2919690A1 CA2919690A1 (en) | 2015-02-05 |
| CA2919690C true CA2919690C (en) | 2021-11-02 |
Family
ID=52428197
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2919690A Active CA2919690C (en) | 2013-08-02 | 2014-07-30 | Methods and molecular pharmacodynamic biomarkers for multiple signaling pathways in response to carboxyamidotriazole orotate |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10378059B2 (enExample) |
| EP (1) | EP3027776B1 (enExample) |
| JP (1) | JP6913459B2 (enExample) |
| KR (1) | KR102389934B1 (enExample) |
| CN (1) | CN105531380B (enExample) |
| AU (1) | AU2014296212B2 (enExample) |
| CA (1) | CA2919690C (enExample) |
| IL (1) | IL243894B (enExample) |
| WO (1) | WO2015017545A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3423452B1 (en) | 2016-03-01 | 2025-05-07 | University of Maryland, Baltimore | Wnt signaling pathway inhibitors for treatments of disease |
| JP6889009B2 (ja) * | 2017-04-13 | 2021-06-18 | 浜松ホトニクス株式会社 | 画像取得システム及び画像取得方法 |
| US20220168276A1 (en) * | 2020-08-05 | 2022-06-02 | Tactical Therapeotics Inc. | Mehods and Compositions for Treating SARS-CoV-2 Infection using Carboxyamidotriazole Orotate |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2227205C (en) * | 1995-07-21 | 2007-05-01 | Constantia Gruppe | Treatment and prevention of neoplasms with salts of aminoimidazole carboxamide and 5-amino or substituted amino 1,2,3-triazoles |
| US20030170720A1 (en) * | 2001-01-23 | 2003-09-11 | Van Der Kuyl Antoinette Cornelia | Means and methods for treatment evaluation |
| SI1504126T1 (sl) | 2002-05-03 | 2014-08-29 | Duke University Office Of Science And Technology | Postopek regulacije izraĹľanja genov |
| WO2008021115A2 (en) | 2006-08-14 | 2008-02-21 | The Brigham And Women's Hospital, Inc. | Diagnostic tests using gene expression ratios |
| US7750018B2 (en) * | 2006-12-06 | 2010-07-06 | Tactical Therapeutics, Inc | Use of carboxiamidotriazole (CAI) orotate in macular degeneration |
| AU2008232732A1 (en) | 2007-03-28 | 2008-10-09 | Medarex, Inc. | Methods of gene amplification and expression |
| JP2011515088A (ja) * | 2008-03-22 | 2011-05-19 | メルク・シャープ・エンド・ドーム・コーポレイション | 増殖因子シグナル伝達経路レギュレーション状態を評価するための方法及び遺伝子発現サイン |
| KR101597338B1 (ko) * | 2009-09-04 | 2016-02-24 | 탁티칼 떼라페우틱스 인크. | 5-아미노 또는 치환된 아미노 1,2,3-트리아졸 화합물 및 이의 오로트산염 제형들의 신규한 조성물들 및 이의 제조방법 |
| US8877785B2 (en) * | 2009-09-04 | 2014-11-04 | Tactical Therapeutics Inc | Methods and compositions for enhancing sensitivity of cytotoxic drugs with timely combinatorial therapy with carboxyamidotriazole orotate |
| JP6355555B2 (ja) * | 2011-04-01 | 2018-07-11 | キアゲン | Ｗｎｔ／ｂ−カテニンシグナル伝達経路に関する遺伝子発現シグネチャーおよびその使用 |
-
2013
- 2013-08-02 US US13/957,720 patent/US10378059B2/en active Active
-
2014
- 2014-07-30 CN CN201480050189.3A patent/CN105531380B/zh active Active
- 2014-07-30 CA CA2919690A patent/CA2919690C/en active Active
- 2014-07-30 AU AU2014296212A patent/AU2014296212B2/en active Active
- 2014-07-30 KR KR1020167002926A patent/KR102389934B1/ko active Active
- 2014-07-30 WO PCT/US2014/048905 patent/WO2015017545A1/en not_active Ceased
- 2014-07-30 EP EP14832909.7A patent/EP3027776B1/en active Active
- 2014-07-30 JP JP2016531859A patent/JP6913459B2/ja active Active
-
2016
- 2016-02-01 IL IL243894A patent/IL243894B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| KR20160030535A (ko) | 2016-03-18 |
| WO2015017545A1 (en) | 2015-02-05 |
| KR102389934B1 (ko) | 2022-04-21 |
| JP6913459B2 (ja) | 2021-08-04 |
| CN105531380A (zh) | 2016-04-27 |
| US20150038349A1 (en) | 2015-02-05 |
| US10378059B2 (en) | 2019-08-13 |
| AU2014296212A1 (en) | 2016-02-25 |
| EP3027776C0 (en) | 2024-02-07 |
| EP3027776B1 (en) | 2024-02-07 |
| IL243894B (en) | 2020-06-30 |
| CA2919690A1 (en) | 2015-02-05 |
| JP2016526908A (ja) | 2016-09-08 |
| IL243894A0 (en) | 2016-04-21 |
| AU2014296212B2 (en) | 2020-10-22 |
| EP3027776A4 (en) | 2017-03-08 |
| HK1220493A1 (en) | 2017-05-05 |
| EP3027776A1 (en) | 2016-06-08 |
| CN105531380B (zh) | 2021-07-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Shinde et al. | Spleen tyrosine kinase–mediated autophagy is required for epithelial–mesenchymal plasticity and metastasis in breast cancer | |
| Farren et al. | Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy | |
| Watson et al. | Transcriptomic definition of molecular subgroups of small round cell sarcomas | |
| Wagner et al. | CXCL12 and CXCR4 in adenocarcinoma of the lung: association with metastasis and survival | |
| Rubio et al. | Non-canonical integrin signaling activates EGFR and RAS-MAPK-ERK signaling in small cell lung cancer | |
| Schulze et al. | RELN signaling modulates glioblastoma growth and substrate‐dependent migration | |
| Chandrani et al. | Drug-sensitiveFGFR3 mutations in lung adenocarcinoma | |
| Lunghi et al. | The p53 family protein p73 provides new insights into cancer chemosensitivity and targeting | |
| CA2819399C (en) | Marker for determination of sensitivity to triplet combination anti-cancer agent | |
| Comert et al. | Changes in molecular biology of chronic myeloid leukemia in tyrosine kinase inhibitor era | |
| Piccaluga et al. | Molecular genetics of peripheral T-cell lymphomas | |
| Banerjee et al. | Loss of the PTCH1 tumor suppressor defines a new subset of plexiform fibromyxoma | |
| Garrido et al. | Multidisciplinary consensus on optimising the detection of NTRK gene alterations in tumours | |
| Harada et al. | TRK inhibitors in non-small cell lung cancer | |
| Thielhelm et al. | Understanding the radiobiology of vestibular schwannomas to overcome radiation resistance | |
| CA2919690C (en) | Methods and molecular pharmacodynamic biomarkers for multiple signaling pathways in response to carboxyamidotriazole orotate | |
| Johnson et al. | Genomic profiling of a Hepatocyte growth factor-dependent signature for MET-targeted therapy in glioblastoma | |
| Song et al. | Cyclin D1 expression in peripheral T-cell lymphomas | |
| Krulikas et al. | Application of integrated drug screening/kinome analysis to identify inhibitors of gemcitabine-resistant pancreatic cancer cell growth | |
| Kim et al. | Randomized, two‐arm, noncomparative phase 2 study of olaparib plus cediranib or durvalumab in HRR‐mutated, platinum‐resistant ovarian cancer: A substudy of KGOG 3045 | |
| Wu et al. | Single-cell intratumoral stemness analysis reveals the involvement of cell cycle and DNA damage repair in two different types of esophageal cancer | |
| Kiura et al. | Osimertinib in patients with epidermal growth factor receptor T790M advanced non‐small cell lung cancer selected using cytology samples | |
| Somers et al. | CCI-007, a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements | |
| Marchesini et al. | Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML | |
| Devi et al. | Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20190514 |