BR112016024672A2 - método para o tratamento de adenocarcinoma de pulmão - Google Patents

Info

Publication number

BR112016024672A2

BR112016024672A2 BR112016024672-1A BR112016024672A BR112016024672A2 BR 112016024672 A2 BR112016024672 A2 BR 112016024672A2 BR 112016024672 A BR112016024672 A BR 112016024672A BR 112016024672 A2 BR112016024672 A2 BR 112016024672A2

Authority

BR

Brazil

Prior art keywords

ros1

compound

fusion

slc34a2

leu

Prior art date

2014-04-25

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 146
• 238000011282 treatment Methods 0.000 title claims abstract description 121
• 201000005249 lung adenocarcinoma Diseases 0.000 title claims abstract description 36
• 208000010507 Adenocarcinoma of Lung Diseases 0.000 title claims abstract description 34
• 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 claims abstract description 370
• 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 claims abstract description 351
• 230000004927 fusion Effects 0.000 claims abstract description 304
• 150000001875 compounds Chemical class 0.000 claims abstract description 193
• 150000003839 salts Chemical class 0.000 claims abstract description 112
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 106
• 201000011510 cancer Diseases 0.000 claims abstract description 93
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims abstract description 92
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims abstract description 89
• -1 with a MET Proteins 0.000 claims abstract description 36
• 230000001404 mediated effect Effects 0.000 claims abstract description 12
• 229940125904 compound 1 Drugs 0.000 claims description 111
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 95
• 229920001184 polypeptide Polymers 0.000 claims description 93
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 93
• 239000012634 fragment Substances 0.000 claims description 71
• 239000000203 mixture Substances 0.000 claims description 59
• KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 claims description 51
• 239000002146 L01XE16 - Crizotinib Substances 0.000 claims description 47
• 229960005061 crizotinib Drugs 0.000 claims description 45
• 108091000080 Phosphotransferase Proteins 0.000 claims description 40
• 102000020233 phosphotransferase Human genes 0.000 claims description 40
• 238000001514 detection method Methods 0.000 claims description 39
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
• 239000002775 capsule Substances 0.000 claims description 28
• 239000012458 free base Substances 0.000 claims description 28
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 27
• 229960005277 gemcitabine Drugs 0.000 claims description 27
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 26
• 201000010099 disease Diseases 0.000 claims description 23
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 21
• 238000003556 assay Methods 0.000 claims description 21
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 21
• 229960004562 carboplatin Drugs 0.000 claims description 21
• 229960003668 docetaxel Drugs 0.000 claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims description 18
• 229960004316 cisplatin Drugs 0.000 claims description 14
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 14
• 238000002509 fluorescent in situ hybridization Methods 0.000 claims description 14
• ONIQOQHATWINJY-UHFFFAOYSA-N cabozantinib Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 ONIQOQHATWINJY-UHFFFAOYSA-N 0.000 claims description 12
• 238000012163 sequencing technique Methods 0.000 claims description 12
• 102000045479 human ROS1 Human genes 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• 230000005764 inhibitory process Effects 0.000 claims description 10
• 229940049920 malate Drugs 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 7
• 239000002176 L01XE26 - Cabozantinib Substances 0.000 claims description 6
• 230000002441 reversible effect Effects 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 5
• 238000003757 reverse transcription PCR Methods 0.000 claims description 5
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
• 229960001292 cabozantinib Drugs 0.000 claims description 4
• 230000004044 response Effects 0.000 claims description 4
• 230000001225 therapeutic effect Effects 0.000 claims description 4
• 230000036961 partial effect Effects 0.000 claims description 2
• 102100032218 Cytokine-inducible SH2-containing protein Human genes 0.000 claims 2
• 101000943420 Homo sapiens Cytokine-inducible SH2-containing protein Proteins 0.000 claims 2
• COEXAQSTZUWMRI-STQMWFEESA-N (2s)-1-[2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([C@H](N)C(=O)NCC(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=C(O)C=C1 COEXAQSTZUWMRI-STQMWFEESA-N 0.000 claims 1
• SITWEMZOJNKJCH-WDSKDSINSA-N Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N SITWEMZOJNKJCH-WDSKDSINSA-N 0.000 claims 1
• XZWXFWBHYRFLEF-FSPLSTOPSA-N Ala-His Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 XZWXFWBHYRFLEF-FSPLSTOPSA-N 0.000 claims 1
• OTCJMMRQBVDQRK-DCAQKATOSA-N Arg-Asp-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O OTCJMMRQBVDQRK-DCAQKATOSA-N 0.000 claims 1
• YVTHEZNOKSAWRW-DCAQKATOSA-N Arg-Lys-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O YVTHEZNOKSAWRW-DCAQKATOSA-N 0.000 claims 1
• AWMAZIIEFPFHCP-RCWTZXSCSA-N Arg-Pro-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O AWMAZIIEFPFHCP-RCWTZXSCSA-N 0.000 claims 1
• BXLDDWZOTGGNOJ-SZMVWBNQSA-N Arg-Trp-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCCN=C(N)N)N BXLDDWZOTGGNOJ-SZMVWBNQSA-N 0.000 claims 1
• BPAUXFVCSYQDQX-JRQIVUDYSA-N Asp-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(=O)O)N)O BPAUXFVCSYQDQX-JRQIVUDYSA-N 0.000 claims 1
• ALMIMUZAWTUNIO-BZSNNMDCSA-N Asp-Tyr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O ALMIMUZAWTUNIO-BZSNNMDCSA-N 0.000 claims 1
• OAGVHWYIBZMWLA-YFKPBYRVSA-N Glu-Gly-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)NCC(O)=O OAGVHWYIBZMWLA-YFKPBYRVSA-N 0.000 claims 1
• OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 claims 1
• RPLLQZBOVIVGMX-QWRGUYRKSA-N Gly-Asp-Phe Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O RPLLQZBOVIVGMX-QWRGUYRKSA-N 0.000 claims 1
• 101000595669 Homo sapiens Pituitary homeobox 2 Proteins 0.000 claims 1
• SITWEMZOJNKJCH-UHFFFAOYSA-N L-alanine-L-arginine Natural products CC(N)C(=O)NC(C(O)=O)CCCNC(N)=N SITWEMZOJNKJCH-UHFFFAOYSA-N 0.000 claims 1
• QCSFMCFHVGTLFF-NHCYSSNCSA-N Leu-Asp-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O QCSFMCFHVGTLFF-NHCYSSNCSA-N 0.000 claims 1
• LESXFEZIFXFIQR-LURJTMIESA-N Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)NCC(O)=O LESXFEZIFXFIQR-LURJTMIESA-N 0.000 claims 1
• IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 claims 1
• GCXGCIYIHXSKAY-ULQDDVLXSA-N Leu-Phe-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GCXGCIYIHXSKAY-ULQDDVLXSA-N 0.000 claims 1
• QWWPYKKLXWOITQ-VOAKCMCISA-N Leu-Thr-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QWWPYKKLXWOITQ-VOAKCMCISA-N 0.000 claims 1
• VKVDRTGWLVZJOM-DCAQKATOSA-N Leu-Val-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O VKVDRTGWLVZJOM-DCAQKATOSA-N 0.000 claims 1
• 241000234435 Lilium Species 0.000 claims 1
• NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 claims 1
• HUKLXYYPZWPXCC-KZVJFYERSA-N Met-Ala-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O HUKLXYYPZWPXCC-KZVJFYERSA-N 0.000 claims 1
• 206010027476 Metastases Diseases 0.000 claims 1
• BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 claims 1
• SWCOXQLDICUYOL-ULQDDVLXSA-N Phe-His-Arg Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SWCOXQLDICUYOL-ULQDDVLXSA-N 0.000 claims 1
• YFXXRYFWJFQAFW-JHYOHUSXSA-N Phe-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N)O YFXXRYFWJFQAFW-JHYOHUSXSA-N 0.000 claims 1
• 102100036090 Pituitary homeobox 2 Human genes 0.000 claims 1
• GLEOIKLQBZNKJZ-WDSKDSINSA-N Pro-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 GLEOIKLQBZNKJZ-WDSKDSINSA-N 0.000 claims 1
• ILMLVTGTUJPQFP-FXQIFTODSA-N Pro-Asp-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ILMLVTGTUJPQFP-FXQIFTODSA-N 0.000 claims 1
• JLMZKEQFMVORMA-SRVKXCTJSA-N Pro-Pro-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 JLMZKEQFMVORMA-SRVKXCTJSA-N 0.000 claims 1
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims 1
• SWSRFJZZMNLMLY-ZKWXMUAHSA-N Ser-Asp-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O SWSRFJZZMNLMLY-ZKWXMUAHSA-N 0.000 claims 1
• XXNYYSXNXCJYKX-DCAQKATOSA-N Ser-Leu-Met Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(O)=O XXNYYSXNXCJYKX-DCAQKATOSA-N 0.000 claims 1
• OWCVUSJMEBGMOK-YUMQZZPRSA-N Ser-Lys-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O OWCVUSJMEBGMOK-YUMQZZPRSA-N 0.000 claims 1
• XKFJENWJGHMDLI-QWRGUYRKSA-N Ser-Phe-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(O)=O XKFJENWJGHMDLI-QWRGUYRKSA-N 0.000 claims 1
• IOWJRKAVLALBQB-IWGUZYHVSA-N Thr-Asp Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC(O)=O IOWJRKAVLALBQB-IWGUZYHVSA-N 0.000 claims 1
• BQBCIBCLXBKYHW-CSMHCCOUSA-N Thr-Leu Chemical compound CC(C)C[C@@H](C([O-])=O)NC(=O)[C@@H]([NH3+])[C@@H](C)O BQBCIBCLXBKYHW-CSMHCCOUSA-N 0.000 claims 1
• JAWUQFCGNVEDRN-MEYUZBJRSA-N Thr-Tyr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CC(C)C)C(=O)O)N)O JAWUQFCGNVEDRN-MEYUZBJRSA-N 0.000 claims 1
• WFZYXGSAPWKTHR-XEGUGMAKSA-N Trp-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N WFZYXGSAPWKTHR-XEGUGMAKSA-N 0.000 claims 1
• AOLHUMAVONBBEZ-STQMWFEESA-N Tyr-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AOLHUMAVONBBEZ-STQMWFEESA-N 0.000 claims 1
• XLDYBRXERHITNH-QSFUFRPTSA-N Val-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)C(C)C XLDYBRXERHITNH-QSFUFRPTSA-N 0.000 claims 1
• IOUPEELXVYPCPG-UHFFFAOYSA-N Valylglycine Chemical compound CC(C)C(N)C(=O)NCC(O)=O IOUPEELXVYPCPG-UHFFFAOYSA-N 0.000 claims 1
• 108010070944 alanylhistidine Proteins 0.000 claims 1
• 108010047857 aspartylglycine Proteins 0.000 claims 1
• 108010006664 gamma-glutamyl-glycyl-glycine Proteins 0.000 claims 1
• 108010050848 glycylleucine Proteins 0.000 claims 1
• 108010083708 leucyl-aspartyl-valine Proteins 0.000 claims 1
• 230000009401 metastasis Effects 0.000 claims 1
• 230000001575 pathological effect Effects 0.000 claims 1
• 108010051110 tyrosyl-lysine Proteins 0.000 claims 1
• 108091006576 SLC34A2 Proteins 0.000 abstract description 75
• 102100038437 Sodium-dependent phosphate transport protein 2B Human genes 0.000 abstract description 74
• 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 abstract description 57
• 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 abstract description 49
• 208000020816 lung neoplasm Diseases 0.000 abstract description 40
• 206010058467 Lung neoplasm malignant Diseases 0.000 abstract description 38
• 201000005202 lung cancer Diseases 0.000 abstract description 38
• 239000003112 inhibitor Substances 0.000 abstract description 31
• 238000003745 diagnosis Methods 0.000 abstract description 12
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 abstract description 3
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 abstract description 3
• 239000002131 composite material Substances 0.000 abstract 1
• 108020001507 fusion proteins Proteins 0.000 description 189
• 102000037865 fusion proteins Human genes 0.000 description 189
• 239000000523 sample Substances 0.000 description 160
• 108091033319 polynucleotide Proteins 0.000 description 157
• 102000040430 polynucleotide Human genes 0.000 description 157
• 239000002157 polynucleotide Substances 0.000 description 157
• 108090000623 proteins and genes Proteins 0.000 description 143
• 150000007523 nucleic acids Chemical class 0.000 description 81
• 210000004027 cell Anatomy 0.000 description 78
• 102000039446 nucleic acids Human genes 0.000 description 71
• 108020004707 nucleic acids Proteins 0.000 description 71
• 239000013615 primer Substances 0.000 description 68
• 102000004169 proteins and genes Human genes 0.000 description 49
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 49
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
• 235000001014 amino acid Nutrition 0.000 description 45
• 235000018102 proteins Nutrition 0.000 description 44
• 229940024606 amino acid Drugs 0.000 description 43
• 239000000243 solution Substances 0.000 description 43
• 150000001413 amino acids Chemical class 0.000 description 42
• 150000004701 malic acid derivatives Chemical class 0.000 description 41
• 230000000694 effects Effects 0.000 description 39
• 108700024394 Exon Proteins 0.000 description 38
• 101150035397 Ros1 gene Proteins 0.000 description 38
• 239000002773 nucleotide Substances 0.000 description 37
• 125000003729 nucleotide group Chemical group 0.000 description 37
• 230000002759 chromosomal effect Effects 0.000 description 34
• 108020004414 DNA Proteins 0.000 description 33
• 239000002585 base Substances 0.000 description 33
• 239000003826 tablet Substances 0.000 description 30
• 238000009396 hybridization Methods 0.000 description 28
• 210000004899 c-terminal region Anatomy 0.000 description 26
• 230000000295 complement effect Effects 0.000 description 26
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 25
• 230000035772 mutation Effects 0.000 description 24
• 239000000047 product Substances 0.000 description 24
• 238000002360 preparation method Methods 0.000 description 22
• 210000000349 chromosome Anatomy 0.000 description 21
• 238000012360 testing method Methods 0.000 description 21
• 230000005945 translocation Effects 0.000 description 21
• 125000003275 alpha amino acid group Chemical group 0.000 description 20
• 238000007901 in situ hybridization Methods 0.000 description 20
• 101150046784 Slc34a2 gene Proteins 0.000 description 19
• 239000012472 biological sample Substances 0.000 description 19
• 239000000126 substance Substances 0.000 description 19
• 238000006243 chemical reaction Methods 0.000 description 18
• 108091026890 Coding region Proteins 0.000 description 17
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
• 230000014509 gene expression Effects 0.000 description 16
• 108020004999 messenger RNA Proteins 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 15
• 230000002401 inhibitory effect Effects 0.000 description 15
• 239000007787 solid Substances 0.000 description 15
• 208000037516 chromosome inversion disease Diseases 0.000 description 14
• 238000002844 melting Methods 0.000 description 14
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 14
• 210000001519 tissue Anatomy 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 13
• 210000003917 human chromosome Anatomy 0.000 description 13
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• 230000002159 abnormal effect Effects 0.000 description 12
• 208000009956 adenocarcinoma Diseases 0.000 description 12
• 230000010261 cell growth Effects 0.000 description 12
• 238000005516 engineering process Methods 0.000 description 12
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 11
• 241000124008 Mammalia Species 0.000 description 11
• 238000004458 analytical method Methods 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 10
• 239000002246 antineoplastic agent Substances 0.000 description 10
• 239000003153 chemical reaction reagent Substances 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
• 241000282412 Homo Species 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 230000000692 anti-sense effect Effects 0.000 description 9
• JJWKPURADFRFRB-UHFFFAOYSA-N carbonyl sulfide Chemical compound O=C=S JJWKPURADFRFRB-UHFFFAOYSA-N 0.000 description 9
• 239000002299 complementary DNA Substances 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 125000005843 halogen group Chemical group 0.000 description 9
• 239000004615 ingredient Substances 0.000 description 9
• 229940043355 kinase inhibitor Drugs 0.000 description 9
• 210000004072 lung Anatomy 0.000 description 9
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 9
• 239000007858 starting material Substances 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 208000011580 syndromic disease Diseases 0.000 description 9
• VXEQRXJATQUJSN-UHFFFAOYSA-N 4-(6,7-dimethoxyquinolin-4-yl)oxyaniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C(N)C=C1 VXEQRXJATQUJSN-UHFFFAOYSA-N 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• 108091034117 Oligonucleotide Proteins 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 230000004913 activation Effects 0.000 description 8
• 229940041181 antineoplastic drug Drugs 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 229910052739 hydrogen Inorganic materials 0.000 description 8
• 239000001257 hydrogen Substances 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 239000003550 marker Substances 0.000 description 8
• 230000008018 melting Effects 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 238000005292 vacuum distillation Methods 0.000 description 8
• PFMAFXYUHZDKPY-UHFFFAOYSA-N 1-[(4-fluorophenyl)carbamoyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(F)C=CC=1NC(=O)C1(C(=O)O)CC1 PFMAFXYUHZDKPY-UHFFFAOYSA-N 0.000 description 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• 206010041067 Small cell lung cancer Diseases 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 238000001574 biopsy Methods 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• 239000011159 matrix material Substances 0.000 description 7
• 208000000587 small cell lung carcinoma Diseases 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 238000002560 therapeutic procedure Methods 0.000 description 7
• 238000011144 upstream manufacturing Methods 0.000 description 7
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 6
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 6
• 101710168331 ALK tyrosine kinase receptor Proteins 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• 206010069754 Acquired gene mutation Diseases 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• 229940126394 ROS1 tyrosine kinase inhibitor Drugs 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 230000003321 amplification Effects 0.000 description 6
• 229910052799 carbon Inorganic materials 0.000 description 6
• 235000010980 cellulose Nutrition 0.000 description 6
• 229920002678 cellulose Polymers 0.000 description 6
• 239000001913 cellulose Substances 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• 235000019441 ethanol Nutrition 0.000 description 6
• 238000003018 immunoassay Methods 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
• 238000003199 nucleic acid amplification method Methods 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 238000012216 screening Methods 0.000 description 6
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• 230000037439 somatic mutation Effects 0.000 description 6
• 238000013519 translation Methods 0.000 description 6
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
• JQWTVIFNRAALHM-UHFFFAOYSA-N 1-[(4-fluorophenyl)carbamoyl]cyclopropane-1-carbonyl chloride Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(Cl)=O)CC1 JQWTVIFNRAALHM-UHFFFAOYSA-N 0.000 description 5
• WRVHQEYBCDPZEU-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinoline Chemical compound C1=CC(Cl)=C2C=C(OC)C(OC)=CC2=N1 WRVHQEYBCDPZEU-UHFFFAOYSA-N 0.000 description 5
• WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 5
• 108091023037 Aptamer Proteins 0.000 description 5
• 229920002785 Croscarmellose sodium Polymers 0.000 description 5
• 230000004544 DNA amplification Effects 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 108091028043 Nucleic acid sequence Proteins 0.000 description 5
• 229910019213 POCl3 Inorganic materials 0.000 description 5
• 102100037220 Syndecan-4 Human genes 0.000 description 5
• 150000001408 amides Chemical group 0.000 description 5
• 125000000539 amino acid group Chemical group 0.000 description 5
• 230000008711 chromosomal rearrangement Effects 0.000 description 5
• 230000000875 corresponding effect Effects 0.000 description 5
• 239000003995 emulsifying agent Substances 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 238000003364 immunohistochemistry Methods 0.000 description 5
• 235000011090 malic acid Nutrition 0.000 description 5
• 238000012544 monitoring process Methods 0.000 description 5
• 229910052757 nitrogen Inorganic materials 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 238000001556 precipitation Methods 0.000 description 5
• 230000002265 prevention Effects 0.000 description 5
• 239000002987 primer (paints) Substances 0.000 description 5
• 230000035755 proliferation Effects 0.000 description 5
• 230000008707 rearrangement Effects 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 238000013518 transcription Methods 0.000 description 5
• 230000035897 transcription Effects 0.000 description 5
• 238000001262 western blot Methods 0.000 description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 4
• KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 4
• 208000005443 Circulating Neoplastic Cells Diseases 0.000 description 4
• 102000001301 EGF receptor Human genes 0.000 description 4
• 108060006698 EGF receptor Proteins 0.000 description 4
• 238000002965 ELISA Methods 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 208000034951 Genetic Translocation Diseases 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 4
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 4
• 230000001594 aberrant effect Effects 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 230000005754 cellular signaling Effects 0.000 description 4
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 239000000975 dye Substances 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 230000007717 exclusion Effects 0.000 description 4
• 101150016193 fig gene Proteins 0.000 description 4
• 239000012530 fluid Substances 0.000 description 4
• 239000007850 fluorescent dye Substances 0.000 description 4
• 208000005017 glioblastoma Diseases 0.000 description 4
• 235000011187 glycerol Nutrition 0.000 description 4
• 230000036541 health Effects 0.000 description 4
• 229940116298 l- malic acid Drugs 0.000 description 4
• 238000002372 labelling Methods 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• 239000001630 malic acid Substances 0.000 description 4
• 229940099690 malic acid Drugs 0.000 description 4
• 238000013507 mapping Methods 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 230000002685 pulmonary effect Effects 0.000 description 4
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
• 230000035945 sensitivity Effects 0.000 description 4
• 238000003756 stirring Methods 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 4
• 239000013598 vector Substances 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 101001072499 Homo sapiens Golgi-associated PDZ and coiled-coil motif-containing protein Proteins 0.000 description 3
• 101000740519 Homo sapiens Syndecan-4 Proteins 0.000 description 3
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 238000012408 PCR amplification Methods 0.000 description 3
• 229920001213 Polysorbate 20 Polymers 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 108010076504 Protein Sorting Signals Proteins 0.000 description 3
• 239000012980 RPMI-1640 medium Substances 0.000 description 3
• 101150045592 RSC1 gene Proteins 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 102100033080 Tropomyosin alpha-3 chain Human genes 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 238000004873 anchoring Methods 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 230000000903 blocking effect Effects 0.000 description 3
• 239000006172 buffering agent Substances 0.000 description 3
• 229910002092 carbon dioxide Inorganic materials 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 239000000460 chlorine Chemical group 0.000 description 3
• 208000006990 cholangiocarcinoma Diseases 0.000 description 3
• 238000012790 confirmation Methods 0.000 description 3
• 229960001681 croscarmellose sodium Drugs 0.000 description 3
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 235000005911 diet Nutrition 0.000 description 3
• 230000037213 diet Effects 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 208000014018 liver neoplasm Diseases 0.000 description 3
• 210000005265 lung cell Anatomy 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
• 235000011181 potassium carbonates Nutrition 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 229960004063 propylene glycol Drugs 0.000 description 3
• 238000003127 radioimmunoassay Methods 0.000 description 3
• 238000003753 real-time PCR Methods 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 235000012239 silicon dioxide Nutrition 0.000 description 3
• CGRKYEALWSRNJS-UHFFFAOYSA-N sodium;2-methylbutan-2-olate Chemical compound [Na+].CCC(C)(C)[O-] CGRKYEALWSRNJS-UHFFFAOYSA-N 0.000 description 3
• 239000007909 solid dosage form Substances 0.000 description 3
• 230000000392 somatic effect Effects 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 229940032147 starch Drugs 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 230000001629 suppression Effects 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• 238000011285 therapeutic regimen Methods 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
• 239000003981 vehicle Substances 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
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
• 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 2
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
• FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• QOGPNCUTXVZQSL-UHFFFAOYSA-N 6,7-dimethoxy-1h-quinolin-4-one Chemical compound C1=CC(O)=C2C=C(OC)C(OC)=CC2=N1 QOGPNCUTXVZQSL-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 241000283707 Capra Species 0.000 description 2
• 108010078791 Carrier Proteins Proteins 0.000 description 2
• 102000053642 Catalytic RNA Human genes 0.000 description 2
• 108090000994 Catalytic RNA Proteins 0.000 description 2
• 206010061764 Chromosomal deletion Diseases 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• 239000003155 DNA primer Substances 0.000 description 2
• 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 2
• 102100020903 Ezrin Human genes 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 108091093094 Glycol nucleic acid Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 102100036675 Golgi-associated PDZ and coiled-coil motif-containing protein Human genes 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 101000854648 Homo sapiens Ezrin Proteins 0.000 description 2
• 101001017855 Homo sapiens Leucine-rich repeats and immunoglobulin-like domains protein 3 Proteins 0.000 description 2
• 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 2
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
• 101100187408 Homo sapiens SLC34A2 gene Proteins 0.000 description 2
• 101000604039 Homo sapiens Sodium-dependent phosphate transport protein 2B Proteins 0.000 description 2
• 101000850794 Homo sapiens Tropomyosin alpha-3 chain Proteins 0.000 description 2
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 2
• 102100033284 Leucine-rich repeats and immunoglobulin-like domains protein 3 Human genes 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 238000000636 Northern blotting Methods 0.000 description 2
• 102000003992 Peroxidases Human genes 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 238000002105 Southern blotting Methods 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 108010055215 Syndecan-4 Proteins 0.000 description 2
• 101710120037 Toxin CcdB Proteins 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 230000000996 additive effect Effects 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 210000001124 body fluid Anatomy 0.000 description 2
• 239000010839 body fluid Substances 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• HFCFMRYTXDINDK-WNQIDUERSA-N cabozantinib malate Chemical compound OC(=O)[C@@H](O)CC(O)=O.C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 HFCFMRYTXDINDK-WNQIDUERSA-N 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 229960004926 chlorobutanol Drugs 0.000 description 2
• 235000015165 citric acid Nutrition 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 229940034568 cometriq Drugs 0.000 description 2
• 229960005168 croscarmellose Drugs 0.000 description 2
• 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 229940127089 cytotoxic agent Drugs 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 238000002405 diagnostic procedure Methods 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 238000006471 dimerization reaction Methods 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• 239000013604 expression vector Substances 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 238000007667 floating Methods 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 229960002584 gefitinib Drugs 0.000 description 2
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 2
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 2
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 2
• 239000003906 humectant Substances 0.000 description 2
• 238000011532 immunohistochemical staining Methods 0.000 description 2
• 238000012744 immunostaining Methods 0.000 description 2
• 238000009169 immunotherapy Methods 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 229910052740 iodine Chemical group 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
• 229940011051 isopropyl acetate Drugs 0.000 description 2
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 238000007834 ligase chain reaction Methods 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 238000004020 luminiscence type Methods 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• 230000001394 metastastic effect Effects 0.000 description 2
• 206010061289 metastatic neoplasm Diseases 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
• 210000003097 mucus Anatomy 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• 235000008390 olive oil Nutrition 0.000 description 2
• 231100000590 oncogenic Toxicity 0.000 description 2
• 230000002246 oncogenic effect Effects 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• 108040007629 peroxidase activity proteins Proteins 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 108020001580 protein domains Proteins 0.000 description 2
• 108091092562 ribozyme Proteins 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 229960004889 salicylic acid Drugs 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 229910052709 silver Inorganic materials 0.000 description 2
• 239000004332 silver Substances 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 125000001424 substituent group Chemical group 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• 229940049068 xalkori Drugs 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• KUHSEZKIEJYEHN-BXRBKJIMSA-N (2s)-2-amino-3-hydroxypropanoic acid;(2s)-2-aminopropanoic acid Chemical compound C[C@H](N)C(O)=O.OC[C@H](N)C(O)=O KUHSEZKIEJYEHN-BXRBKJIMSA-N 0.000 description 1
• PSLCKQYQNVNTQI-BHFSHLQUSA-N (2s)-2-aminobutanedioic acid;(2s)-2-aminopentanedioic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O.OC(=O)[C@@H](N)CCC(O)=O PSLCKQYQNVNTQI-BHFSHLQUSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• QAPSNMNOIOSXSQ-YNEHKIRRSA-N 1-[(2r,4s,5r)-4-[tert-butyl(dimethyl)silyl]oxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C1 QAPSNMNOIOSXSQ-YNEHKIRRSA-N 0.000 description 1
• HXGYPQKHBCZWKO-UHFFFAOYSA-N 1-[[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]carbamoyl]cyclopropane-1-carboxylic acid Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC(C=C1)=CC=C1NC(=O)C1(C(O)=O)CC1 HXGYPQKHBCZWKO-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
• GNENVASJJIUNER-UHFFFAOYSA-N 2,4,6-tricyclohexyloxy-1,3,5,2,4,6-trioxatriborinane Chemical compound C1CCCCC1OB1OB(OC2CCCCC2)OB(OC2CCCCC2)O1 GNENVASJJIUNER-UHFFFAOYSA-N 0.000 description 1
• NXRGKFVQYZGDIY-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1.CC1=CC=CC(C)=N1 NXRGKFVQYZGDIY-UHFFFAOYSA-N 0.000 description 1
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
• UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
• XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
• YRYKZXCOGVCXBN-UHFFFAOYSA-N 6,7-dimethoxy-4-(4-nitrophenoxy)quinoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C([N+]([O-])=O)C=C1 YRYKZXCOGVCXBN-UHFFFAOYSA-N 0.000 description 1
• PCDPMVJGEGAJBI-UHFFFAOYSA-N 6,7-dimethoxyquinoline Chemical compound C1=CN=C2C=C(OC)C(OC)=CC2=C1 PCDPMVJGEGAJBI-UHFFFAOYSA-N 0.000 description 1
• IRECQXWRHWPICF-UHFFFAOYSA-N 6,7-dimethyl-4-(4-nitrophenoxy)quinoline Chemical compound C=12C=C(C)C(C)=CC2=NC=CC=1OC1=CC=C([N+]([O-])=O)C=C1 IRECQXWRHWPICF-UHFFFAOYSA-N 0.000 description 1
• XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 101000686029 Arabidopsis thaliana DNA glycosylase/AP lyase ROS1 Proteins 0.000 description 1
• 229930091051 Arenine Natural products 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• 206010004593 Bile duct cancer Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000016718 Chromosome Inversion Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 1
• 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• YTBSYETUWUMLBZ-QWWZWVQMSA-N D-threose Chemical compound OC[C@@H](O)[C@H](O)C=O YTBSYETUWUMLBZ-QWWZWVQMSA-N 0.000 description 1
• 108020001019 DNA Primers Proteins 0.000 description 1
• 108020003215 DNA Probes Proteins 0.000 description 1
• 238000007400 DNA extraction Methods 0.000 description 1
• 238000000018 DNA microarray Methods 0.000 description 1
• 239000003298 DNA probe Substances 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
• 206010013710 Drug interaction Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 102000016359 Fibronectins Human genes 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• 241000206672 Gelidium Species 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102000006354 HLA-DR Antigens Human genes 0.000 description 1
• 108010058597 HLA-DR Antigens Proteins 0.000 description 1
• 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
• 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
• 101100091500 Homo sapiens ROS1 gene Proteins 0.000 description 1
• 102000003839 Human Proteins Human genes 0.000 description 1
• 108090000144 Human Proteins Proteins 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 101150023321 KIF5B gene Proteins 0.000 description 1
• 102000010638 Kinesin Human genes 0.000 description 1
• 108010063296 Kinesin Proteins 0.000 description 1
• 150000008575 L-amino acids Chemical class 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
• 238000007397 LAMP assay Methods 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• 108090001030 Lipoproteins Proteins 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000009018 Medullary thyroid cancer Diseases 0.000 description 1
• 102000018697 Membrane Proteins Human genes 0.000 description 1
• 108010052285 Membrane Proteins Proteins 0.000 description 1
• TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 108010021466 Mutant Proteins Proteins 0.000 description 1
• 102000008300 Mutant Proteins Human genes 0.000 description 1
• 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
• 229910020700 Na3VO4 Inorganic materials 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 239000000020 Nitrocellulose Substances 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 108010038807 Oligopeptides Proteins 0.000 description 1
• 102000015636 Oligopeptides Human genes 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 102000038030 PI3Ks Human genes 0.000 description 1
• 108091007960 PI3Ks Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 108010092528 Phosphate Transport Proteins Proteins 0.000 description 1
• 102000016462 Phosphate Transport Proteins Human genes 0.000 description 1
• 208000002151 Pleural effusion Diseases 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004952 Polyamide Substances 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 1
• 201000003454 Pulmonary alveolar microlithiasis Diseases 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 108091030071 RNAI Proteins 0.000 description 1
• 108020004511 Recombinant DNA Proteins 0.000 description 1
• 108700005075 Regulator Genes Proteins 0.000 description 1
• 101150077555 Ret gene Proteins 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 229910006024 SO2Cl2 Inorganic materials 0.000 description 1
• 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
• 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
• 108091027967 Small hairpin RNA Proteins 0.000 description 1
• 108020004459 Small interfering RNA Proteins 0.000 description 1
• 102000013996 Sodium-dependent phosphate transport protein 2B Human genes 0.000 description 1
• 108050003877 Sodium-dependent phosphate transport protein 2B Proteins 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 235000019486 Sunflower oil Nutrition 0.000 description 1
• 102220600990 Syndecan-4_E34R_mutation Human genes 0.000 description 1
• 108010006785 Taq Polymerase Proteins 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 101710091952 Tropomyosin alpha-3 chain Proteins 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
• NZTHDEBIUKWGSX-UHFFFAOYSA-K [Na+].[Mg++].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O Chemical compound [Na+].[Mg++].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O NZTHDEBIUKWGSX-UHFFFAOYSA-K 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 238000000246 agarose gel electrophoresis Methods 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
• 235000008206 alpha-amino acids Nutrition 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 229960004977 anhydrous lactose Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 108010062796 arginyllysine Proteins 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 238000013475 authorization Methods 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 102000005936 beta-Galactosidase Human genes 0.000 description 1
• 108010005774 beta-Galactosidase Proteins 0.000 description 1
• 208000026900 bile duct neoplasm Diseases 0.000 description 1
• 239000011230 binding agent Substances 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
• OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 230000003139 buffering effect Effects 0.000 description 1
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
• 238000010805 cDNA synthesis kit Methods 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 239000012295 chemical reaction liquid Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 229960004106 citric acid Drugs 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 230000006552 constitutive activation Effects 0.000 description 1
• 239000012059 conventional drug carrier Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• FDKLLWKMYAMLIF-UHFFFAOYSA-N cyclopropane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC1 FDKLLWKMYAMLIF-UHFFFAOYSA-N 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 231100000517 death Toxicity 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000002939 deleterious effect 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
• 238000013461 design Methods 0.000 description 1
• MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• NVJBFARDFTXOTO-UHFFFAOYSA-N diethyl sulfite Chemical compound CCOS(=O)OCC NVJBFARDFTXOTO-UHFFFAOYSA-N 0.000 description 1
• 230000001079 digestive effect Effects 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• VNEBWJSWMVTSHK-UHFFFAOYSA-L disodium;3-hydroxynaphthalene-2,7-disulfonate Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=CC2=C1 VNEBWJSWMVTSHK-UHFFFAOYSA-L 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 229940088679 drug related substance Drugs 0.000 description 1
• 239000008393 encapsulating agent Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• 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 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
• 229960005542 ethidium bromide Drugs 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 230000008622 extracellular signaling Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000003885 eye ointment Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 229940125777 fusion inhibitor Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 230000009368 gene silencing by RNA Effects 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 238000003205 genotyping method Methods 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 238000002657 hormone replacement therapy Methods 0.000 description 1
• 238000001794 hormone therapy Methods 0.000 description 1
• 102000054387 human GOPC Human genes 0.000 description 1
• 102000049336 human SLC34A2 Human genes 0.000 description 1
• 210000004408 hybridoma Anatomy 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
• QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 238000003317 immunochromatography Methods 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 238000001114 immunoprecipitation Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 108010028930 invariant chain Proteins 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 239000011630 iodine Chemical group 0.000 description 1
• 229940036571 iodine therapy Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• 238000011901 isothermal amplification Methods 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000003292 kidney cell Anatomy 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960001375 lactose Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 210000004901 leucine-rich repeat Anatomy 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 201000009546 lung large cell carcinoma Diseases 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 238000007403 mPCR Methods 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 229940126601 medicinal product Drugs 0.000 description 1
• 239000012907 medicinal substance Substances 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 238000001465 metallisation Methods 0.000 description 1
• 208000037819 metastatic cancer Diseases 0.000 description 1
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 108091070501 miRNA Proteins 0.000 description 1
• 239000002679 microRNA Substances 0.000 description 1
• 238000002493 microarray Methods 0.000 description 1
• 238000010208 microarray analysis Methods 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 108010029942 microperoxidase Proteins 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• WVKNBCACIPKHEW-UHFFFAOYSA-N n,n-diethylethanamine;n,n-dimethylformamide Chemical compound CN(C)C=O.CCN(CC)CC WVKNBCACIPKHEW-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 229920001220 nitrocellulos Polymers 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 230000004650 oncogenic pathway Effects 0.000 description 1
• 102000027450 oncoproteins Human genes 0.000 description 1
• 108091008819 oncoproteins Proteins 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
• 239000006179 pH buffering agent Substances 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 108010091212 pepstatin Proteins 0.000 description 1
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 238000002823 phage display Methods 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 229960003742 phenol Drugs 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003905 phosphatidylinositols Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229960000502 poloxamer Drugs 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920002647 polyamide Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 description 1
• WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
• 235000012015 potatoes Nutrition 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• VYXXMAGSIYIYGD-NWAYQTQBSA-N propan-2-yl 2-[[[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(pyrimidine-4-carbonylamino)phosphoryl]amino]-2-methylpropanoate Chemical compound CC(C)OC(=O)C(C)(C)NP(=O)(CO[C@H](C)Cn1cnc2c(N)ncnc12)NC(=O)c1ccncn1 VYXXMAGSIYIYGD-NWAYQTQBSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 239000000941 radioactive substance Substances 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 208000016691 refractory malignant neoplasm Diseases 0.000 description 1
• 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 239000012723 sample buffer Substances 0.000 description 1
• 238000003118 sandwich ELISA Methods 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 239000012679 serum free medium Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000008054 signal transmission Effects 0.000 description 1
• 239000002924 silencing RNA Substances 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 239000004055 small Interfering RNA Substances 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
• 229940048086 sodium pyrophosphate Drugs 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 229940035044 sorbitan monolaurate Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 238000011895 specific detection Methods 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 238000010183 spectrum analysis Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 239000002600 sunflower oil Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 238000002626 targeted therapy Methods 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
• 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
• 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 102000027257 transmembrane receptors Human genes 0.000 description 1
• 108091008578 transmembrane receptors Proteins 0.000 description 1
• 229960000575 trastuzumab Drugs 0.000 description 1
• 229940117013 triethanolamine oleate Drugs 0.000 description 1
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
• 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000002699 waste material Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1