CN103957923A - 用于抑制包括癌干细胞在内的干细胞的增殖、发育或分化的hs.459642单基因簇产物的拮抗剂 - Google Patents
用于抑制包括癌干细胞在内的干细胞的增殖、发育或分化的hs.459642单基因簇产物的拮抗剂 Download PDFInfo
- Publication number
- CN103957923A CN103957923A CN201280055308.5A CN201280055308A CN103957923A CN 103957923 A CN103957923 A CN 103957923A CN 201280055308 A CN201280055308 A CN 201280055308A CN 103957923 A CN103957923 A CN 103957923A
- Authority
- CN
- China
- Prior art keywords
- cell
- antibody
- gene bunch
- cancer
- stem cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 178
- 201000011510 cancer Diseases 0.000 title claims abstract description 123
- 210000000130 stem cell Anatomy 0.000 title claims abstract description 103
- 239000005557 antagonist Substances 0.000 title claims abstract description 33
- 230000004069 differentiation Effects 0.000 title claims abstract description 29
- 238000011161 development Methods 0.000 title abstract description 10
- 230000018109 developmental process Effects 0.000 title abstract description 10
- 230000035755 proliferation Effects 0.000 title abstract description 6
- 230000002401 inhibitory effect Effects 0.000 title abstract 2
- 238000000034 method Methods 0.000 claims abstract description 59
- 101000932804 Homo sapiens Voltage-dependent T-type calcium channel subunit alpha-1H Proteins 0.000 claims abstract description 51
- 102000014835 CACNA1H Human genes 0.000 claims abstract description 50
- 239000000203 mixture Substances 0.000 claims abstract description 37
- 239000000074 antisense oligonucleotide Substances 0.000 claims abstract description 29
- 238000012230 antisense oligonucleotides Methods 0.000 claims abstract description 29
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims abstract 3
- 108091034117 Oligonucleotide Proteins 0.000 claims description 35
- 230000012010 growth Effects 0.000 claims description 25
- 238000011319 anticancer therapy Methods 0.000 claims description 16
- 230000001225 therapeutic effect Effects 0.000 claims description 15
- 230000008485 antagonism Effects 0.000 claims description 7
- 238000001959 radiotherapy Methods 0.000 claims description 4
- 230000002101 lytic effect Effects 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 52
- 238000011282 treatment Methods 0.000 abstract description 49
- 238000002648 combination therapy Methods 0.000 abstract description 11
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 136
- 239000000047 product Substances 0.000 description 87
- 108090000623 proteins and genes Proteins 0.000 description 44
- 102000004169 proteins and genes Human genes 0.000 description 33
- 235000018102 proteins Nutrition 0.000 description 32
- 108090000765 processed proteins & peptides Proteins 0.000 description 30
- 230000000694 effects Effects 0.000 description 27
- 239000000523 sample Substances 0.000 description 23
- 108020004459 Small interfering RNA Proteins 0.000 description 22
- 230000005764 inhibitory process Effects 0.000 description 20
- 125000003729 nucleotide group Chemical group 0.000 description 20
- 239000011575 calcium Substances 0.000 description 19
- 108090000312 Calcium Channels Proteins 0.000 description 18
- 102000003922 Calcium Channels Human genes 0.000 description 18
- 230000014509 gene expression Effects 0.000 description 18
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 17
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 17
- 229960004964 temozolomide Drugs 0.000 description 17
- 239000002773 nucleotide Substances 0.000 description 16
- 108020004999 messenger RNA Proteins 0.000 description 15
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 239000012634 fragment Substances 0.000 description 13
- 229920001184 polypeptide Polymers 0.000 description 13
- 230000004044 response Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 12
- 239000003005 anticarcinogenic agent Substances 0.000 description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 10
- 102000053642 Catalytic RNA Human genes 0.000 description 10
- 108090000994 Catalytic RNA Proteins 0.000 description 10
- 241000282414 Homo sapiens Species 0.000 description 10
- HBNPJJILLOYFJU-VMPREFPWSA-N Mibefradil Chemical compound C1CC2=CC(F)=CC=C2[C@H](C(C)C)[C@@]1(OC(=O)COC)CCN(C)CCCC1=NC2=CC=CC=C2N1 HBNPJJILLOYFJU-VMPREFPWSA-N 0.000 description 10
- 229910052791 calcium Inorganic materials 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 108091092562 ribozyme Proteins 0.000 description 10
- 230000000295 complement effect Effects 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 230000008685 targeting Effects 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 238000002512 chemotherapy Methods 0.000 description 8
- 230000009368 gene silencing by RNA Effects 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 229960004438 mibefradil Drugs 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 241001093575 Alma Species 0.000 description 7
- 108091030071 RNAI Proteins 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 description 6
- 230000010261 cell growth Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 210000001671 embryonic stem cell Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 210000004881 tumor cell Anatomy 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 102000014837 CACNA1G Human genes 0.000 description 5
- 102000014836 CACNA1I Human genes 0.000 description 5
- 229940127291 Calcium channel antagonist Drugs 0.000 description 5
- 208000032612 Glial tumor Diseases 0.000 description 5
- 206010018338 Glioma Diseases 0.000 description 5
- 101000867850 Homo sapiens Voltage-dependent T-type calcium channel subunit alpha-1G Proteins 0.000 description 5
- 101000932785 Homo sapiens Voltage-dependent T-type calcium channel subunit alpha-1I Proteins 0.000 description 5
- 230000003302 anti-idiotype Effects 0.000 description 5
- 239000000480 calcium channel blocker Substances 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 238000005520 cutting process Methods 0.000 description 5
- 231100000599 cytotoxic agent Toxicity 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000008030 elimination Effects 0.000 description 5
- 238000003379 elimination reaction Methods 0.000 description 5
- 208000005017 glioblastoma Diseases 0.000 description 5
- 238000003018 immunoassay Methods 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 201000000050 myeloid neoplasm Diseases 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241001597008 Nomeidae Species 0.000 description 4
- 210000004504 adult stem cell Anatomy 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- -1 antibody Proteins 0.000 description 4
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000032823 cell division Effects 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 239000002254 cytotoxic agent Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 210000003754 fetus Anatomy 0.000 description 4
- 230000002779 inactivation Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Chemical compound CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 229960001438 immunostimulant agent Drugs 0.000 description 3
- 239000003022 immunostimulating agent Substances 0.000 description 3
- 230000003308 immunostimulating effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000000415 inactivating effect Effects 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 230000028161 membrane depolarization Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000012797 qualification Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 210000004988 splenocyte Anatomy 0.000 description 3
- 230000003068 static effect Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- VPFUWHKTPYPNGT-UHFFFAOYSA-N 3-(3,4-dihydroxyphenyl)-1-(5-hydroxy-2,2-dimethylchromen-6-yl)propan-1-one Chemical compound OC1=C2C=CC(C)(C)OC2=CC=C1C(=O)CCC1=CC=C(O)C(O)=C1 VPFUWHKTPYPNGT-UHFFFAOYSA-N 0.000 description 2
- 108010066676 Abrin Proteins 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 108091060211 Expressed sequence tag Proteins 0.000 description 2
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000003693 Hedgehog Proteins Human genes 0.000 description 2
- 108090000031 Hedgehog Proteins Proteins 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 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
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010039491 Ricin Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229940124650 anti-cancer therapies Drugs 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 210000003969 blast cell Anatomy 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 2
- 229930195731 calicheamicin Natural products 0.000 description 2
- 239000012830 cancer therapeutic Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000007910 cell fusion Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 210000004754 hybrid cell Anatomy 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002991 immunohistochemical analysis Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 230000001613 neoplastic effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000002688 persistence Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 238000002823 phage display Methods 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
- 210000001778 pluripotent stem cell Anatomy 0.000 description 2
- 229920002627 poly(phosphazenes) Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- SVJMLYUFVDMUHP-XIFFEERXSA-N (4S)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid O5-[3-(4,4-diphenyl-1-piperidinyl)propyl] ester O3-methyl ester Chemical compound C1([C@@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)OCCCN2CCC(CC2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC([N+]([O-])=O)=C1 SVJMLYUFVDMUHP-XIFFEERXSA-N 0.000 description 1
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 1
- PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 1
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- FBUTXZSKZCQABC-UHFFFAOYSA-N 2-amino-1-methyl-7h-purine-6-thione Chemical compound S=C1N(C)C(N)=NC2=C1NC=N2 FBUTXZSKZCQABC-UHFFFAOYSA-N 0.000 description 1
- QSVVHABHJUTSQN-UHFFFAOYSA-N 3-phosphonothiophene-2-carboxylic acid Chemical group P(=O)(O)(O)C1=C(SC=C1)C(=O)O QSVVHABHJUTSQN-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 244000123550 Adenia heterophylla Species 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 229930195573 Amycin Natural products 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 101000669426 Aspergillus restrictus Ribonuclease mitogillin Proteins 0.000 description 1
- 108091007065 BIRCs Proteins 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- OYPRJOBELJOOCE-IGMARMGPSA-N Calcium-40 Chemical compound [40Ca] OYPRJOBELJOOCE-IGMARMGPSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- 108700032819 Croton tiglium crotin II Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- XQLWNAFCTODIRK-UHFFFAOYSA-N Gallopamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 XQLWNAFCTODIRK-UHFFFAOYSA-N 0.000 description 1
- 108700004714 Gelonium multiflorum GEL Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 244000283207 Indigofera tinctoria Species 0.000 description 1
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 102000000704 Interleukin-7 Human genes 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 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
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- LPGWZGMPDKDHEP-HLTPFJCJSA-N Leurosine Chemical compound C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC LPGWZGMPDKDHEP-HLTPFJCJSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699729 Muridae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- BCCQNBXHUMKLFW-HNQRYHMESA-N NNC 55-0396 dihydrochloride Chemical compound Cl.Cl.O([C@]1(CCN(C)CCCC=2NC3=CC=CC=C3N=2)CCC2=CC(F)=CC=C2[C@@H]1C(C)C)C(=O)C1CC1 BCCQNBXHUMKLFW-HNQRYHMESA-N 0.000 description 1
- 206010061864 Neoplasm recurrence Diseases 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000003946 Saponaria officinalis Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 229940123582 Telomerase inhibitor Drugs 0.000 description 1
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-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
- 208000033781 Thyroid carcinoma Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010015780 Viral Core Proteins Proteins 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 201000005179 adrenal carcinoma Diseases 0.000 description 1
- 201000005188 adrenal gland cancer Diseases 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 108010001818 alpha-sarcin Proteins 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 150000008038 benzoazepines Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229940126587 biotherapeutics Drugs 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 230000000086 blastomogenic effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 206010006007 bone sarcoma Diseases 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000004611 cancer cell death Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 229930003827 cannabinoid Natural products 0.000 description 1
- 239000003557 cannabinoid Substances 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000005059 dormancy Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 108010028531 enomycin Proteins 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 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
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 238000010304 firing Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 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 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 201000007487 gallbladder carcinoma Diseases 0.000 description 1
- 229960000457 gallopamil Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 230000004034 genetic regulation Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 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
- 150000004676 glycans Chemical class 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 210000003677 hemocyte Anatomy 0.000 description 1
- 229940000351 hemocyte Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000000951 immunodiffusion Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 229940100994 interleukin-7 Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000904 isoindolyl group Chemical class C=1(NC=C2C=CC=CC12)* 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
- 229960004427 isradipine Drugs 0.000 description 1
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000011645 metastatic carcinoma Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 108010010621 modeccin Proteins 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 208000018389 neoplasm of cerebral hemisphere Diseases 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229950010800 niguldipine Drugs 0.000 description 1
- VZWXXKDFACOXNT-UHFFFAOYSA-N niludipine Chemical compound CCCOCCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCOCCC)C1C1=CC=CC([N+]([O-])=O)=C1 VZWXXKDFACOXNT-UHFFFAOYSA-N 0.000 description 1
- 229950000109 niludipine Drugs 0.000 description 1
- 229960000227 nisoldipine Drugs 0.000 description 1
- 229960005425 nitrendipine Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 208000030940 penile carcinoma Diseases 0.000 description 1
- 201000008174 penis carcinoma Diseases 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 210000004332 phalangeal cell Anatomy 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- YVUQSNJEYSNKRX-UHFFFAOYSA-N pimozide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 YVUQSNJEYSNKRX-UHFFFAOYSA-N 0.000 description 1
- 229960003634 pimozide Drugs 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 230000032361 posttranscriptional gene silencing Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 208000011581 secondary neoplasm Diseases 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 239000003277 telomerase inhibitor Substances 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 210000005102 tumor initiating cell Anatomy 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 210000002444 unipotent stem cell Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Plant Pathology (AREA)
- Immunology (AREA)
- Mycology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims (22)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161533545P | 2011-09-12 | 2011-09-12 | |
US61/533,545 | 2011-09-12 | ||
PCT/US2012/054567 WO2013039859A1 (en) | 2011-09-12 | 2012-09-11 | Antagonists of products of the hs.459642 unigene cluster for the inhibition of proliferation, development or differentiation of stem cells including cancer stem cells |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103957923A true CN103957923A (zh) | 2014-07-30 |
CN103957923B CN103957923B (zh) | 2018-05-25 |
Family
ID=47830014
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201280055308.5A Expired - Fee Related CN103957923B (zh) | 2011-09-12 | 2012-09-11 | 用于抑制包括癌干细胞在内的干细胞的增殖、发育或分化的hs.459642单基因簇产物的拮抗剂 |
Country Status (12)
Country | Link |
---|---|
US (2) | US20130064814A1 (zh) |
EP (1) | EP2755674A4 (zh) |
JP (1) | JP2014526475A (zh) |
KR (1) | KR20140084034A (zh) |
CN (1) | CN103957923B (zh) |
AU (1) | AU2012309800B2 (zh) |
CA (1) | CA2848311A1 (zh) |
HK (1) | HK1200120A1 (zh) |
IL (1) | IL231385A0 (zh) |
MX (1) | MX2014002967A (zh) |
SG (2) | SG11201400526TA (zh) |
WO (1) | WO2013039859A1 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018058489A1 (zh) * | 2016-09-30 | 2018-04-05 | 武汉华大吉诺因生物科技有限公司 | Cacna1h衍生的肿瘤抗原多肽及其应用 |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9427429B2 (en) | 2010-03-01 | 2016-08-30 | Tau Therapeutics Llc | Cancer diagnosis and imaging |
JP2017031059A (ja) * | 2014-01-29 | 2017-02-09 | 学校法人慶應義塾 | がん幹細胞の増殖抑制剤および細胞内活性酸素蓄積誘導剤 |
JP6876502B2 (ja) * | 2016-04-25 | 2021-05-26 | クラシエホールディングス株式会社 | 未分化細胞除去剤 |
UY37341A (es) | 2016-07-22 | 2017-11-30 | Flamel Ireland Ltd | Formulaciones de gamma-hidroxibutirato de liberación modificada con farmacocinética mejorada |
US11602513B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11602512B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11504347B1 (en) | 2016-07-22 | 2022-11-22 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11986451B1 (en) | 2016-07-22 | 2024-05-21 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
WO2019103578A1 (ko) * | 2017-11-27 | 2019-05-31 | (주)프로스테믹스 | 올리고뉴클레오티드 및 이를 포함하는 암의 예방 또는 치료용 약학적 조성물 |
CN113473980A (zh) | 2019-03-01 | 2021-10-01 | 弗拉梅尔爱尔兰有限公司 | 在进食状态下具有改善的药代动力学的γ-羟基丁酸酯组合物 |
US11583510B1 (en) | 2022-02-07 | 2023-02-21 | Flamel Ireland Limited | Methods of administering gamma hydroxybutyrate formulations after a high-fat meal |
US11779557B1 (en) | 2022-02-07 | 2023-10-10 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101854802A (zh) * | 2007-09-10 | 2010-10-06 | 波士顿生物医药公司 | 用于癌症治疗的新组合物和方法 |
CN102112490A (zh) * | 2008-07-08 | 2011-06-29 | 昂考梅德药品有限公司 | Notch1受体结合剂和其使用方法 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
AU633698B2 (en) | 1990-01-12 | 1993-02-04 | Amgen Fremont Inc. | Generation of xenogeneic antibodies |
BR9707529A (pt) | 1996-02-14 | 2000-01-04 | Isis Pharmaceuticals Inc | Oligunucleotìdeo especificamente hibridizável com dna ou rna. |
US6251886B1 (en) * | 1998-12-07 | 2001-06-26 | Schering Corporation | Methods of using temozolomide in the treatment of cancers |
ZA200305980B (en) * | 2001-02-12 | 2007-01-31 | Res Dev Foundation | Modified proteins, designer toxins, and methods of making thereof |
NZ533126A (en) | 2002-01-17 | 2006-04-28 | Univ British Columbia | Bispecific antisense oligonucleotides that inhibit IGFBP-2 and IGFBP-5 and methods of using same |
JP2008501633A (ja) * | 2004-02-11 | 2008-01-24 | ユニバーシティ オブ ヴァージニア パテント ファウンデーション | 癌の診断及び治療のためのCav3アイソフォーム及びそのδ25スプライスバリアントの阻害 |
US7662240B2 (en) * | 2004-06-22 | 2010-02-16 | The Timken Company | Seal for worm gear speed reducer |
KR100743255B1 (ko) * | 2006-05-04 | 2007-07-27 | 한국과학기술연구원 | T-형 칼슘 채널에 활성을 지닌 신규1,3-다이옥소아이소인돌 유도체 |
TW200831538A (en) * | 2006-12-19 | 2008-08-01 | Genentech Inc | VEGF-specific antagonists for adjuvant and neoadjuvant therapy and the treatment of early stage tumors |
US20120088807A1 (en) * | 2009-06-05 | 2012-04-12 | Tau Therapeutics Llc | Interlaced method for treating cancer or a precancerous condition |
-
2012
- 2012-09-11 AU AU2012309800A patent/AU2012309800B2/en not_active Ceased
- 2012-09-11 JP JP2014529965A patent/JP2014526475A/ja active Pending
- 2012-09-11 MX MX2014002967A patent/MX2014002967A/es unknown
- 2012-09-11 CA CA2848311A patent/CA2848311A1/en not_active Abandoned
- 2012-09-11 CN CN201280055308.5A patent/CN103957923B/zh not_active Expired - Fee Related
- 2012-09-11 WO PCT/US2012/054567 patent/WO2013039859A1/en active Application Filing
- 2012-09-11 US US13/609,942 patent/US20130064814A1/en not_active Abandoned
- 2012-09-11 EP EP12832679.0A patent/EP2755674A4/en not_active Withdrawn
- 2012-09-11 SG SG11201400526TA patent/SG11201400526TA/en unknown
- 2012-09-11 SG SG10201601917XA patent/SG10201601917XA/en unknown
- 2012-09-11 KR KR1020147009726A patent/KR20140084034A/ko not_active Application Discontinuation
-
2014
- 2014-03-06 IL IL231385A patent/IL231385A0/en unknown
-
2015
- 2015-01-21 HK HK15100687.1A patent/HK1200120A1/zh unknown
-
2019
- 2019-11-15 US US16/685,279 patent/US20200197516A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101854802A (zh) * | 2007-09-10 | 2010-10-06 | 波士顿生物医药公司 | 用于癌症治疗的新组合物和方法 |
CN102112490A (zh) * | 2008-07-08 | 2011-06-29 | 昂考梅德药品有限公司 | Notch1受体结合剂和其使用方法 |
Non-Patent Citations (4)
Title |
---|
JAE HO HEO ET AL: "T-type Ca2+ channel blockers suppress the growth of human cancer cells", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
JAMES T.TAYLOR ET AL: "Selective blockade of T-type Ca2+ channels suppresses human breast cancer cell proliferation", 《CANCER LETTERS》 * |
王跃群等: "人类T型钙通道α1H亚单位基因在细胞增殖中的功能研究", 《遗传学报》, vol. 29, no. 8, 31 August 2002 (2002-08-31), pages 659 - 665 * |
黄香: "靶向肿瘤干细胞治疗策略的研究进展", 《癌症进展》, vol. 9, no. 1, 31 January 2011 (2011-01-31), pages 48 - 54 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018058489A1 (zh) * | 2016-09-30 | 2018-04-05 | 武汉华大吉诺因生物科技有限公司 | Cacna1h衍生的肿瘤抗原多肽及其应用 |
CN109790224A (zh) * | 2016-09-30 | 2019-05-21 | 武汉华大吉诺因生物科技有限公司 | Cacna1h衍生的肿瘤抗原多肽及其应用 |
US11548925B2 (en) | 2016-09-30 | 2023-01-10 | Genoimmune Therapeutics Co., Ltd. | CACNA1H-derived tumor antigen polypeptide and use thereof |
Also Published As
Publication number | Publication date |
---|---|
US20130064814A1 (en) | 2013-03-14 |
MX2014002967A (es) | 2015-04-13 |
AU2012309800A1 (en) | 2014-05-01 |
JP2014526475A (ja) | 2014-10-06 |
CN103957923B (zh) | 2018-05-25 |
HK1200120A1 (zh) | 2015-07-31 |
EP2755674A1 (en) | 2014-07-23 |
SG10201601917XA (en) | 2016-04-28 |
CA2848311A1 (en) | 2013-03-21 |
AU2012309800B2 (en) | 2017-10-05 |
IL231385A0 (en) | 2014-04-30 |
US20200197516A1 (en) | 2020-06-25 |
KR20140084034A (ko) | 2014-07-04 |
EP2755674A4 (en) | 2015-04-08 |
WO2013039859A1 (en) | 2013-03-21 |
SG11201400526TA (en) | 2014-04-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103957923A (zh) | 用于抑制包括癌干细胞在内的干细胞的增殖、发育或分化的hs.459642单基因簇产物的拮抗剂 | |
JP2014526475A5 (zh) | ||
Li et al. | Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion | |
KR101847523B1 (ko) | 조절자 T 세포에 특이적으로 존재하는 새로운 표면단백질 Lrig-1의 용도 | |
CN101605560A (zh) | 治疗胆管癌的药物组合物、抑制胆管癌生长或侵入的方法和治疗胆管癌的方法 | |
CA2968352A1 (en) | Methods for upregulating immune responses using combinations of anti-rgmb and anti-pd-1 agents | |
CN101528926A (zh) | 过表达reg4或kiaa0101的癌症的治疗或预防 | |
US20140378531A1 (en) | Inhibition of pattern recognition receptors in pancreatic cancer treatment using tlr inhibitors | |
KR20180022761A (ko) | 조절자 T 세포에 특이적으로 존재하는 새로운 표면단백질 Lrig-1의 용도 | |
EP1854473A1 (en) | Preventive/therapeutic agent for cancer | |
CN109468380B (zh) | Il1r2在乳腺癌预后评估与靶向治疗中的应用 | |
JP5704722B2 (ja) | 細胞接着阻害剤およびその用途 | |
KR102067402B1 (ko) | 조절자 T 세포에 특이적으로 존재하는 새로운 표면단백질 Lrig-1의 용도 | |
KR20200076660A (ko) | Drg2 억제제를 유효성분으로 포함하는 항암용 조성물 | |
Chen et al. | Prolactin enhances T regulatory cell promotion of breast cancer through the long form prolactin receptor | |
JP7231917B2 (ja) | 癌細胞における免疫チェックポイント因子の発現抑制剤及び癌治療用医薬組成物 | |
JP6029019B2 (ja) | 細胞接着阻害剤、細胞増殖阻害剤、並びに癌の検査方法および検査用キット | |
Zhou et al. | Knockdown of the long non‑coding RNA CACNA1G‑AS1 enhances cytotoxicity and apoptosis of human diffuse large B cell lymphoma by regulating miR‑3160‑5p | |
US20240083990A1 (en) | Novel stim1 splicing variants and uses thereof | |
KR102094747B1 (ko) | 조절자 T 세포에 특이적으로 존재하는 새로운 표면단백질 Lrig-1의 용도 | |
EP1521591B1 (fr) | UTILISATION D'UN ANTICORPS ANTI-PTHrP(34-53) COMME ANTAGONISTE DE LA PTHrP POUR TRAITER LE CARCINOME A CELLULES RENALES | |
Liu | The Role of Mir-218 in Breast Cancer Bone Metastasis | |
小林慎太 et al. | Identification and Characterization of Cancer Stem Cells Responsible for Drug-Resistance and Metastasis | |
US20100086911A1 (en) | Preventive/therapeutic agent for cancer | |
KR101521981B1 (ko) | 혈액암 줄기세포 증식 또는 생착 억제용 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20170411 Address after: Charlottetown Canada Applicant after: CAVION, Inc. Address before: Charlottetown Canada Applicant before: Card viand LLC Effective date of registration: 20170411 Address after: Charlottetown Canada Applicant after: Card viand LLC Address before: Virginia Applicant before: TAU Therapy Co.,Ltd. |
|
TA01 | Transfer of patent application right | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180525 Termination date: 20190911 |
|
CF01 | Termination of patent right due to non-payment of annual fee |