JP5993390B2 - がん幹細胞を標的とするための新規の化合物および組成物 - Google Patents
がん幹細胞を標的とするための新規の化合物および組成物 Download PDFInfo
- Publication number
- JP5993390B2 JP5993390B2 JP2014040225A JP2014040225A JP5993390B2 JP 5993390 B2 JP5993390 B2 JP 5993390B2 JP 2014040225 A JP2014040225 A JP 2014040225A JP 2014040225 A JP2014040225 A JP 2014040225A JP 5993390 B2 JP5993390 B2 JP 5993390B2
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- cancer
- polymorph
- compound
- composition according
- 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.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims description 287
- 206010028980 Neoplasm Diseases 0.000 title claims description 279
- 201000011510 cancer Diseases 0.000 title claims description 192
- 239000000203 mixture Substances 0.000 title claims description 110
- 210000000130 stem cell Anatomy 0.000 title description 61
- 230000008685 targeting Effects 0.000 title description 6
- 239000002245 particle Substances 0.000 claims description 438
- 239000008194 pharmaceutical composition Substances 0.000 claims description 170
- 238000000034 method Methods 0.000 claims description 167
- 238000011282 treatment Methods 0.000 claims description 65
- 238000009826 distribution Methods 0.000 claims description 56
- 239000003814 drug Substances 0.000 claims description 54
- 229940079593 drug Drugs 0.000 claims description 51
- 241000282414 Homo sapiens Species 0.000 claims description 47
- 239000008280 blood Substances 0.000 claims description 34
- 210000004369 blood Anatomy 0.000 claims description 34
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 24
- 201000010536 head and neck cancer Diseases 0.000 claims description 21
- 108010017324 STAT3 Transcription Factor Proteins 0.000 claims description 19
- 230000004083 survival effect Effects 0.000 claims description 19
- 206010006187 Breast cancer Diseases 0.000 claims description 18
- 208000026310 Breast neoplasm Diseases 0.000 claims description 18
- 239000000654 additive Substances 0.000 claims description 18
- 206010009944 Colon cancer Diseases 0.000 claims description 17
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 16
- 206010033128 Ovarian cancer Diseases 0.000 claims description 16
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 16
- 201000005202 lung cancer Diseases 0.000 claims description 16
- 208000020816 lung neoplasm Diseases 0.000 claims description 16
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 14
- 201000001441 melanoma Diseases 0.000 claims description 13
- 230000000996 additive effect Effects 0.000 claims description 12
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 9
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 9
- 201000002528 pancreatic cancer Diseases 0.000 claims description 9
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 9
- 239000004094 surface-active agent Substances 0.000 claims description 9
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 206010039491 Sarcoma Diseases 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 150000002314 glycerols Chemical class 0.000 claims description 7
- 229940074046 glyceryl laurate Drugs 0.000 claims description 7
- 150000002632 lipids Chemical class 0.000 claims description 7
- ARIWANIATODDMH-UHFFFAOYSA-N rac-1-monolauroylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 claims description 7
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 235000006708 antioxidants Nutrition 0.000 claims description 6
- 208000016691 refractory malignant neoplasm Diseases 0.000 claims description 6
- 201000003076 Angiosarcoma Diseases 0.000 claims description 5
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 5
- 206010038111 Recurrent cancer Diseases 0.000 claims description 5
- 206010070308 Refractory cancer Diseases 0.000 claims description 5
- 238000004458 analytical method Methods 0.000 claims description 5
- 208000037819 metastatic cancer Diseases 0.000 claims description 5
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 5
- 229920000053 polysorbate 80 Polymers 0.000 claims description 5
- 238000010298 pulverizing process Methods 0.000 claims description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- 238000007563 acoustic spectroscopy Methods 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 238000001493 electron microscopy Methods 0.000 claims description 4
- 238000004062 sedimentation Methods 0.000 claims description 4
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 3
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 3
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 3
- 229930182558 Sterol Natural products 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 201000006585 gastric adenocarcinoma Diseases 0.000 claims description 3
- 238000000399 optical microscopy Methods 0.000 claims description 3
- 230000002018 overexpression Effects 0.000 claims description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 3
- 206010038038 rectal cancer Diseases 0.000 claims description 3
- 201000001275 rectum cancer Diseases 0.000 claims description 3
- 235000003702 sterols Nutrition 0.000 claims description 3
- 150000003432 sterols Chemical class 0.000 claims description 3
- 229920002675 Polyoxyl Polymers 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims 1
- 206010004992 Bladder adenocarcinoma stage unspecified Diseases 0.000 claims 1
- 102000004495 STAT3 Transcription Factor Human genes 0.000 claims 1
- 201000006587 bladder adenocarcinoma Diseases 0.000 claims 1
- 201000010897 colon adenocarcinoma Diseases 0.000 claims 1
- 229940047135 glycate Drugs 0.000 claims 1
- 125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 238000002441 X-ray diffraction Methods 0.000 description 215
- 229940125904 compound 1 Drugs 0.000 description 171
- DPHUWDIXHNQOSY-UHFFFAOYSA-N napabucasin Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1OC(C(=O)C)=C2 DPHUWDIXHNQOSY-UHFFFAOYSA-N 0.000 description 159
- 210000004027 cell Anatomy 0.000 description 123
- KUJTUBMARVZCNB-UHFFFAOYSA-N 1-(4,9-dihydrobenzo[f][1]benzofuran-2-yl)ethanone Chemical compound C(C)(=O)C1=CC2=C(O1)CC1=CC=CC=C1C2 KUJTUBMARVZCNB-UHFFFAOYSA-N 0.000 description 114
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
- 230000008569 process Effects 0.000 description 63
- -1 naphthofuran compound Chemical class 0.000 description 53
- 239000000047 product Substances 0.000 description 51
- 230000000259 anti-tumor effect Effects 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 47
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical group C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 46
- 239000013078 crystal Substances 0.000 description 45
- CSFWPUWCSPOLJW-UHFFFAOYSA-N lawsone Chemical compound C1=CC=C2C(=O)C(O)=CC(=O)C2=C1 CSFWPUWCSPOLJW-UHFFFAOYSA-N 0.000 description 45
- MFMVRILBADIIJO-UHFFFAOYSA-N benzo[e][1]benzofuran Chemical class C1=CC=C2C(C=CO3)=C3C=CC2=C1 MFMVRILBADIIJO-UHFFFAOYSA-N 0.000 description 44
- 239000007787 solid Substances 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 238000004128 high performance liquid chromatography Methods 0.000 description 39
- 241001465754 Metazoa Species 0.000 description 38
- 239000002904 solvent Substances 0.000 description 32
- 125000000623 heterocyclic group Chemical group 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- 231100000419 toxicity Toxicity 0.000 description 29
- 230000001988 toxicity Effects 0.000 description 29
- SAXKEWRSGLPYPB-UHFFFAOYSA-N 2-(1-hydroxyethyl)benzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1OC(C(O)C)=C2 SAXKEWRSGLPYPB-UHFFFAOYSA-N 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 229910052739 hydrogen Inorganic materials 0.000 description 27
- 238000000227 grinding Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 230000000694 effects Effects 0.000 description 24
- 150000003839 salts Chemical class 0.000 description 24
- 239000001257 hydrogen Substances 0.000 description 23
- 239000012535 impurity Substances 0.000 description 23
- 208000035269 cancer or benign tumor Diseases 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 21
- 210000005170 neoplastic cell Anatomy 0.000 description 21
- 239000004480 active ingredient Substances 0.000 description 20
- 230000001186 cumulative effect Effects 0.000 description 20
- 150000002431 hydrogen Chemical class 0.000 description 20
- 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 description 20
- 238000002360 preparation method Methods 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000012453 solvate Substances 0.000 description 20
- 238000002512 chemotherapy Methods 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- 239000003981 vehicle Substances 0.000 description 19
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 18
- 238000002425 crystallisation Methods 0.000 description 18
- 230000008025 crystallization Effects 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 17
- 229910052731 fluorine Inorganic materials 0.000 description 17
- 230000001965 increasing effect Effects 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 description 16
- 230000001976 improved effect Effects 0.000 description 16
- QORFLTDEUGKOSZ-UHFFFAOYSA-N 2-ethylbenzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1OC(CC)=C2 QORFLTDEUGKOSZ-UHFFFAOYSA-N 0.000 description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 15
- 241000124008 Mammalia Species 0.000 description 15
- 229910052794 bromium Inorganic materials 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 239000011737 fluorine Substances 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 15
- 238000004519 manufacturing process Methods 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 239000002002 slurry Substances 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 14
- 239000000460 chlorine Substances 0.000 description 14
- 230000001613 neoplastic effect Effects 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 13
- QMKMOPXRLXYBLI-UHFFFAOYSA-N benzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1OC=C2 QMKMOPXRLXYBLI-UHFFFAOYSA-N 0.000 description 13
- 239000002552 dosage form Substances 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- RVIUPSHRLLQFOH-UHFFFAOYSA-N 2-acetyl-7-chlorobenzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC(Cl)=CC=C2C(=O)C2=C1OC(C(=O)C)=C2 RVIUPSHRLLQFOH-UHFFFAOYSA-N 0.000 description 12
- RPCXZIRGAHYOKZ-UHFFFAOYSA-N 2-acetyl-7-fluorobenzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC(F)=CC=C2C(=O)C2=C1OC(C(=O)C)=C2 RPCXZIRGAHYOKZ-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 230000036470 plasma concentration Effects 0.000 description 12
- 125000000547 substituted alkyl group Chemical group 0.000 description 12
- 125000003107 substituted aryl group Chemical group 0.000 description 12
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 12
- 206010027476 Metastases Diseases 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 11
- 230000036515 potency Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
- 241000282412 Homo Species 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 206010061289 metastatic neoplasm Diseases 0.000 description 10
- 238000001959 radiotherapy Methods 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 229920002554 vinyl polymer Polymers 0.000 description 10
- AGHIQBRPBAHPMV-UHFFFAOYSA-N 3-bromobut-3-en-2-one Chemical compound CC(=O)C(Br)=C AGHIQBRPBAHPMV-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 208000003174 Brain Neoplasms Diseases 0.000 description 9
- 208000005718 Stomach Neoplasms Diseases 0.000 description 9
- 239000002246 antineoplastic agent Substances 0.000 description 9
- 206010017758 gastric cancer Diseases 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 230000009401 metastasis Effects 0.000 description 9
- 201000011549 stomach cancer Diseases 0.000 description 9
- 125000004426 substituted alkynyl group Chemical group 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- ALOLHIXWHIWOHM-UHFFFAOYSA-N 2-acetyl-2,3,4,9-tetrahydronaphtho[2,3-b]furan-4,9-dione Natural products O=C1C2=CC=CC=C2C(=O)C2=C1OC(C(=O)C)C2 ALOLHIXWHIWOHM-UHFFFAOYSA-N 0.000 description 8
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 8
- 208000005623 Carcinogenesis Diseases 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 206010060862 Prostate cancer Diseases 0.000 description 8
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 8
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 8
- 230000036952 cancer formation Effects 0.000 description 8
- 231100000504 carcinogenesis Toxicity 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 229940127089 cytotoxic agent Drugs 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 208000032839 leukemia Diseases 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical group O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 230000037361 pathway Effects 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 238000000634 powder X-ray diffraction Methods 0.000 description 8
- 238000007920 subcutaneous administration Methods 0.000 description 8
- 125000005017 substituted alkenyl group Chemical group 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 8
- JPXSZZLSOYKPTA-UHFFFAOYSA-N 2,3-dihydrobenzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1OCC2 JPXSZZLSOYKPTA-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 208000034578 Multiple myelomas Diseases 0.000 description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 description 7
- 230000001093 anti-cancer Effects 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 230000002147 killing effect Effects 0.000 description 7
- 230000003902 lesion Effects 0.000 description 7
- 210000004379 membrane Anatomy 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 230000001394 metastastic effect Effects 0.000 description 7
- 230000035699 permeability Effects 0.000 description 7
- 230000002035 prolonged effect Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- SKUFZJDSGCDXDR-UHFFFAOYSA-N 1-(4,9-dioxo-3a,9a-dihydrobenzo[f][1]benzofuran-2-yl)ethenyl dimethyl phosphate Chemical compound C1=CC=C2C(=O)C3C=C(C(=C)OP(=O)(OC)OC)OC3C(=O)C2=C1 SKUFZJDSGCDXDR-UHFFFAOYSA-N 0.000 description 6
- 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 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 206010025323 Lymphomas Diseases 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 230000002411 adverse Effects 0.000 description 6
- 230000032823 cell division Effects 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 6
- 229940000406 drug candidate Drugs 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000007800 oxidant agent Substances 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 229920000728 polyester Polymers 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000000381 tumorigenic effect Effects 0.000 description 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 5
- 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- GQTBUPKXORMCKS-UHFFFAOYSA-N OP(O)(=O)OC1=CC2C(O1)C(=O)C1=C(C=CC=C1)C2=O Chemical compound OP(O)(=O)OC1=CC2C(O1)C(=O)C1=C(C=CC=C1)C2=O GQTBUPKXORMCKS-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 238000010902 jet-milling Methods 0.000 description 5
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 231100000588 tumorigenic Toxicity 0.000 description 5
- 210000002700 urine Anatomy 0.000 description 5
- 229920001567 vinyl ester resin Polymers 0.000 description 5
- FHRKNQJXHSDMGJ-UHFFFAOYSA-N 3,4-dibromobut-3-en-2-one Chemical compound CC(=O)C(Br)=CBr FHRKNQJXHSDMGJ-UHFFFAOYSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- 206010055114 Colon cancer metastatic Diseases 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000031709 bromination Effects 0.000 description 4
- 238000005893 bromination reaction Methods 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 230000019522 cellular metabolic process Effects 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 238000007256 debromination reaction Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- 239000007937 lozenge Substances 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 230000002246 oncogenic effect Effects 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 150000004671 saturated fatty acids Chemical class 0.000 description 4
- 235000003441 saturated fatty acids Nutrition 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000003944 tolyl group Chemical group 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- QTEYOHOQLZFKFU-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-c][1,3]diazepine Chemical compound C1CCNCN2CCCC=C21 QTEYOHOQLZFKFU-UHFFFAOYSA-N 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010090306 Member 2 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000000118 anti-neoplastic effect Effects 0.000 description 3
- 238000000498 ball milling Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 230000004611 cancer cell death Effects 0.000 description 3
- 239000007894 caplet Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000001934 delay Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000005315 distribution function Methods 0.000 description 3
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 238000003801 milling Methods 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000006186 oral dosage form Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- 239000013557 residual solvent Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000005029 sieve analysis Methods 0.000 description 3
- 238000007873 sieving Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 210000001988 somatic stem cell Anatomy 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000001238 wet grinding Methods 0.000 description 3
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 2
- NBFNRWYMOPMUDP-UHFFFAOYSA-N 1-(4,9-dihydroxybenzo[f][1]benzofuran-2-yl)ethanone Chemical compound C1=CC=C2C(O)=C(OC(C(=O)C)=C3)C3=C(O)C2=C1 NBFNRWYMOPMUDP-UHFFFAOYSA-N 0.000 description 2
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 2
- GYJHMCZCUSPKNU-UHFFFAOYSA-N 2,7-diacetylbenzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC(C(C)=O)=CC=C2C(=O)C2=C1OC(C(=O)C)=C2 GYJHMCZCUSPKNU-UHFFFAOYSA-N 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
- BYWHACZSGKDRSQ-UHFFFAOYSA-N 3-acetylbenzo[f][1]benzofuran-4,9-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(C(=O)C)=CO2 BYWHACZSGKDRSQ-UHFFFAOYSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010004593 Bile duct cancer Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 206010005949 Bone cancer Diseases 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
- 101000823298 Homo sapiens Broad substrate specificity ATP-binding cassette transporter ABCG2 Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 208000000172 Medulloblastoma Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 2
- 206010061934 Salivary gland cancer Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 239000004904 UV filter Substances 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 208000037844 advanced solid tumor Diseases 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229940124650 anti-cancer therapies Drugs 0.000 description 2
- 238000011319 anticancer therapy Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 238000011717 athymic nude mouse Methods 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- ZLNMFKYGGBXDJX-UHFFFAOYSA-N benzo[f][1]benzofuran-4,9-diol Chemical compound C1=CC=C2C(O)=C(C=CO3)C3=C(O)C2=C1 ZLNMFKYGGBXDJX-UHFFFAOYSA-N 0.000 description 2
- 208000026900 bile duct neoplasm Diseases 0.000 description 2
- 201000008211 brain sarcoma Diseases 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000011254 conventional chemotherapy Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000007269 dehydrobromination reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000009837 dry grinding Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 210000001842 enterocyte Anatomy 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 208000024519 eye neoplasm Diseases 0.000 description 2
- 239000010419 fine particle Substances 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 201000010175 gallbladder cancer Diseases 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 230000003676 hair loss Effects 0.000 description 2
- 208000024963 hair loss Diseases 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 239000011572 manganese Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000036457 multidrug resistance Effects 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 210000000441 neoplastic stem cell Anatomy 0.000 description 2
- 230000006911 nucleation Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 235000021231 nutrient uptake Nutrition 0.000 description 2
- 201000008106 ocular cancer Diseases 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 238000003921 particle size analysis Methods 0.000 description 2
- 238000010951 particle size reduction Methods 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 201000002511 pituitary cancer Diseases 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 210000001646 side-population cell Anatomy 0.000 description 2
- 231100000161 signs of toxicity Toxicity 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000003746 surface roughness Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 210000005102 tumor initiating cell Anatomy 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 238000012447 xenograft mouse model Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DMLHCDWQBHPTPM-UHFFFAOYSA-N 1-(2-acetylbenzo[f][1]benzofuran-6-yl)ethanone Chemical compound C(C)(=O)C1=CC2=C(O1)C=C1C=CC(=CC1=C2)C(C)=O DMLHCDWQBHPTPM-UHFFFAOYSA-N 0.000 description 1
- XFJYHILCBBEPTC-UHFFFAOYSA-N 1-(4,9-dioxo-3a,9a-dihydrobenzo[f][1]benzofuran-2-yl)ethenyl dihydrogen phosphate Chemical compound C1=CC=C2C(=O)C3C=C(C(=C)OP(O)(=O)O)OC3C(=O)C2=C1 XFJYHILCBBEPTC-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-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
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 1
- GHHURQMJLARIDK-UHFFFAOYSA-N 2-hydroxypropyl octanoate Chemical compound CCCCCCCC(=O)OCC(C)O GHHURQMJLARIDK-UHFFFAOYSA-N 0.000 description 1
- DRSZTATWOSZRAK-UHFFFAOYSA-N 3,4-dibromobutan-2-one Chemical compound CC(=O)C(Br)CBr DRSZTATWOSZRAK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 description 1
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 description 1
- 102100021501 ATP-binding cassette sub-family B member 5 Human genes 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 240000000146 Agaricus augustus Species 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- RKGJOORQQFSCFF-UHFFFAOYSA-N C(C)(=O)C1=CC2=C(O1)C=C1C=C(C=CC1=C2)Cl Chemical compound C(C)(=O)C1=CC2=C(O1)C=C1C=C(C=CC1=C2)Cl RKGJOORQQFSCFF-UHFFFAOYSA-N 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 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
- 230000033616 DNA repair Effects 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 206010066476 Haematological malignancy Diseases 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
- 101000677872 Homo sapiens ATP-binding cassette sub-family B member 5 Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 102000015617 Janus Kinases Human genes 0.000 description 1
- 108010024121 Janus Kinases Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 206010034811 Pharyngeal cancer Diseases 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 241001632427 Radiola Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 101150099493 STAT3 gene Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000000763 Survivin Human genes 0.000 description 1
- 108010002687 Survivin Proteins 0.000 description 1
- 240000001949 Taraxacum officinale Species 0.000 description 1
- 235000005187 Taraxacum officinale ssp. officinale Nutrition 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000004504 adult stem cell Anatomy 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000005880 cancer cell killing Effects 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000003822 cell turnover Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000011262 co‐therapy Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 201000011587 gastric lymphoma Diseases 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 231100000405 induce cancer Toxicity 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000009061 membrane transport Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229940041676 mucosal spray Drugs 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000028 nontoxic concentration Toxicity 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229960003552 other antineoplastic agent in atc Drugs 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 235000012771 pancakes Nutrition 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011255 standard chemotherapy Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 208000013066 thyroid gland cancer Diseases 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- 230000004614 tumor growth Effects 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
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/92—Naphthofurans; Hydrogenated naphthofurans
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/14—Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Reproductive Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pregnancy & Childbirth (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Gynecology & Obstetrics (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31588610P | 2010-03-19 | 2010-03-19 | |
| US31589010P | 2010-03-19 | 2010-03-19 | |
| US61/315,890 | 2010-03-19 | ||
| US61/315,886 | 2010-03-19 | ||
| US32581410P | 2010-04-19 | 2010-04-19 | |
| US61/325,814 | 2010-04-19 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013500246A Division JP5602935B2 (ja) | 2010-03-19 | 2011-03-21 | がん幹細胞を標的とするための新規の化合物および組成物 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015035285A Division JP2015098489A (ja) | 2010-03-19 | 2015-02-25 | がん幹細胞を標的とするための新規の化合物および組成物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014098048A JP2014098048A (ja) | 2014-05-29 |
| JP2014098048A5 JP2014098048A5 (enExample) | 2014-12-04 |
| JP5993390B2 true JP5993390B2 (ja) | 2016-09-14 |
Family
ID=50940329
Family Applications (11)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014040225A Expired - Fee Related JP5993390B2 (ja) | 2010-03-19 | 2014-03-03 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2014040227A Withdrawn JP2014098050A (ja) | 2010-03-19 | 2014-03-03 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2014040226A Withdrawn JP2014098049A (ja) | 2010-03-19 | 2014-03-03 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2015035285A Pending JP2015098489A (ja) | 2010-03-19 | 2015-02-25 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2015179115A Expired - Fee Related JP6246169B2 (ja) | 2010-03-19 | 2015-09-11 | がん幹細胞を標的とするための新規の方法 |
| JP2016194176A Withdrawn JP2016222723A (ja) | 2010-03-19 | 2016-09-30 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2017199380A Withdrawn JP2018002744A (ja) | 2010-03-19 | 2017-10-13 | がん幹細胞を標的とするための新規の方法 |
| JP2018081329A Withdrawn JP2018115209A (ja) | 2010-03-19 | 2018-04-20 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2020014705A Withdrawn JP2020063308A (ja) | 2010-03-19 | 2020-01-31 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2020082479A Pending JP2020114888A (ja) | 2010-03-19 | 2020-05-08 | がん幹細胞を標的とするための新規の方法 |
| JP2021197732A Pending JP2022020002A (ja) | 2010-03-19 | 2021-12-06 | がん幹細胞を標的とするための新規の化合物および組成物 |
Family Applications After (10)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014040227A Withdrawn JP2014098050A (ja) | 2010-03-19 | 2014-03-03 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2014040226A Withdrawn JP2014098049A (ja) | 2010-03-19 | 2014-03-03 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2015035285A Pending JP2015098489A (ja) | 2010-03-19 | 2015-02-25 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2015179115A Expired - Fee Related JP6246169B2 (ja) | 2010-03-19 | 2015-09-11 | がん幹細胞を標的とするための新規の方法 |
| JP2016194176A Withdrawn JP2016222723A (ja) | 2010-03-19 | 2016-09-30 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2017199380A Withdrawn JP2018002744A (ja) | 2010-03-19 | 2017-10-13 | がん幹細胞を標的とするための新規の方法 |
| JP2018081329A Withdrawn JP2018115209A (ja) | 2010-03-19 | 2018-04-20 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2020014705A Withdrawn JP2020063308A (ja) | 2010-03-19 | 2020-01-31 | がん幹細胞を標的とするための新規の化合物および組成物 |
| JP2020082479A Pending JP2020114888A (ja) | 2010-03-19 | 2020-05-08 | がん幹細胞を標的とするための新規の方法 |
| JP2021197732A Pending JP2022020002A (ja) | 2010-03-19 | 2021-12-06 | がん幹細胞を標的とするための新規の化合物および組成物 |
Country Status (11)
| Country | Link |
|---|---|
| EP (2) | EP3295796A1 (enExample) |
| JP (11) | JP5993390B2 (enExample) |
| CN (3) | CN104016951B (enExample) |
| CA (3) | CA2993363A1 (enExample) |
| DK (1) | DK3108750T3 (enExample) |
| ES (1) | ES2689928T3 (enExample) |
| HU (1) | HUE066482T2 (enExample) |
| NZ (2) | NZ701237A (enExample) |
| PT (1) | PT2547205T (enExample) |
| RU (2) | RU2657750C1 (enExample) |
| SG (3) | SG10201502079VA (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2190429B1 (en) | 2007-09-10 | 2016-04-20 | Boston Biomedical, Inc. | A novel group of stat3 pathway inhibitors and cancer stem cell pathway inhibitors |
| CN104016951B (zh) * | 2010-03-19 | 2016-07-13 | 北京强新生物科技有限公司 | 靶向癌症干细胞的化合物和组合物 |
| DK2547205T3 (da) * | 2010-03-19 | 2024-05-27 | 1Globe Biomedical Co Ltd | Hidtil ukendte fremgangsmåder til målretning mod cancerstamceller |
| US20160030384A1 (en) | 2013-04-09 | 2016-02-04 | Boston Biomedical, Inc. | 2-acetylnaphtho[2,3-b]furan -4,9-dione for use on treating cancer |
| WO2016196935A1 (en) * | 2015-06-03 | 2016-12-08 | Boston Biomedical, Inc. | Compositions comprising a cancer stemness inhibitor and an immunotherapeutic agent for use in treating cancer |
| GB201515391D0 (en) * | 2015-08-28 | 2015-10-14 | Amazentis Sa | Compositions |
| GB201515387D0 (en) * | 2015-08-28 | 2015-10-14 | Amazentis Sa | Compositions |
| JP6751658B2 (ja) | 2016-11-15 | 2020-09-09 | クラリオン株式会社 | 音声認識装置、音声認識システム |
| CA3045306A1 (en) | 2016-11-29 | 2018-06-07 | Boston Biomedical, Inc. | Naphthofuran derivatives, preparation, and methods of use thereof |
| JP2020520923A (ja) | 2017-05-17 | 2020-07-16 | ボストン バイオメディカル， インコーポレイテッド | がんを処置するための方法 |
| KR20240012436A (ko) * | 2021-05-25 | 2024-01-29 | 액티브 바이오테크 에이비 | 복수의 타스퀴니모드 입자 및 그 용도 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61205257A (ja) * | 1985-03-08 | 1986-09-11 | Ishihara Sangyo Kaisha Ltd | ベンゾイルウレア系化合物、その製法及びそれを含有する抗ガン剤 |
| EP0945131A1 (de) * | 1998-03-27 | 1999-09-29 | Boehringer Ingelheim Pharma KG | Perorale Wirkstoff-Suspension |
| JP2003525862A (ja) * | 1999-01-27 | 2003-09-02 | ザ ユニヴァーシティー オブ サウス フロリダ | ヒト癌の治療のためのｓｔａｔ３シグナル伝達の阻害 |
| WO2004026253A2 (en) * | 2002-09-17 | 2004-04-01 | Arqule, Inc. | Novel lapacho compounds and methods of use thereof |
| AR042052A1 (es) * | 2002-11-15 | 2005-06-08 | Vertex Pharma | Diaminotriazoles utiles como inhibidores de proteinquinasas |
| WO2006087919A1 (ja) * | 2005-01-28 | 2006-08-24 | Takeda Pharmaceutical Company Limited | 難水溶性物質含有微細化組成物 |
| JP2006290871A (ja) * | 2005-03-16 | 2006-10-26 | Taheebo Japan Kk | 抗癌性を示す化合物およびその中間体ならびにそれらの製造方法 |
| TW200803854A (en) * | 2005-09-30 | 2008-01-16 | Smithkline Beecham Corp | Pharmaceutical compositions |
| EP1860126A1 (en) * | 2006-05-26 | 2007-11-28 | INEOS Manufacturing Belgium NV | Polyolefin powder |
| EP2190429B1 (en) | 2007-09-10 | 2016-04-20 | Boston Biomedical, Inc. | A novel group of stat3 pathway inhibitors and cancer stem cell pathway inhibitors |
| KR20110031370A (ko) * | 2008-07-08 | 2011-03-25 | 베타 파마, 인크. | 염산 ｉｃｏｔｉｎｉｂ, 합성, 결정형, 약학적 조성물 및 이의 사용 |
| NZ602328A (en) * | 2010-03-19 | 2014-11-28 | Boston Biomedical Inc | Novel compounds and compositions for targeting cancer stem cells |
| DK2547205T3 (da) * | 2010-03-19 | 2024-05-27 | 1Globe Biomedical Co Ltd | Hidtil ukendte fremgangsmåder til målretning mod cancerstamceller |
| CN104016951B (zh) * | 2010-03-19 | 2016-07-13 | 北京强新生物科技有限公司 | 靶向癌症干细胞的化合物和组合物 |
-
2011
- 2011-03-21 CN CN201410101861.9A patent/CN104016951B/zh active Active
- 2011-03-21 ES ES16182813.2T patent/ES2689928T3/es active Active
- 2011-03-21 RU RU2016123004A patent/RU2657750C1/ru active
- 2011-03-21 SG SG10201502079VA patent/SG10201502079VA/en unknown
- 2011-03-21 SG SG10201704745UA patent/SG10201704745UA/en unknown
- 2011-03-21 DK DK16182813.2T patent/DK3108750T3/en active
- 2011-03-21 CN CN201710134235.3A patent/CN106860443A/zh active Pending
- 2011-03-21 RU RU2015142279A patent/RU2015142279A/ru not_active Application Discontinuation
- 2011-03-21 CN CN201710613672.3A patent/CN107311969B/zh active Active
- 2011-03-21 CA CA2993363A patent/CA2993363A1/en not_active Abandoned
- 2011-03-21 EP EP17196754.0A patent/EP3295796A1/en active Pending
- 2011-03-21 EP EP16182813.2A patent/EP3108750B1/en active Active
- 2011-03-21 NZ NZ701237A patent/NZ701237A/en not_active IP Right Cessation
- 2011-03-21 SG SG10201706265PA patent/SG10201706265PA/en unknown
- 2011-03-21 CA CA2959951A patent/CA2959951A1/en not_active Abandoned
- 2011-03-21 NZ NZ712826A patent/NZ712826A/en unknown
- 2011-03-21 HU HUE11757135A patent/HUE066482T2/hu unknown
- 2011-03-21 CA CA2959931A patent/CA2959931A1/en not_active Abandoned
- 2011-03-21 PT PT117571356T patent/PT2547205T/pt unknown
-
2014
- 2014-03-03 JP JP2014040225A patent/JP5993390B2/ja not_active Expired - Fee Related
- 2014-03-03 JP JP2014040227A patent/JP2014098050A/ja not_active Withdrawn
- 2014-03-03 JP JP2014040226A patent/JP2014098049A/ja not_active Withdrawn
-
2015
- 2015-02-25 JP JP2015035285A patent/JP2015098489A/ja active Pending
- 2015-09-11 JP JP2015179115A patent/JP6246169B2/ja not_active Expired - Fee Related
-
2016
- 2016-09-30 JP JP2016194176A patent/JP2016222723A/ja not_active Withdrawn
-
2017
- 2017-10-13 JP JP2017199380A patent/JP2018002744A/ja not_active Withdrawn
-
2018
- 2018-04-20 JP JP2018081329A patent/JP2018115209A/ja not_active Withdrawn
-
2020
- 2020-01-31 JP JP2020014705A patent/JP2020063308A/ja not_active Withdrawn
- 2020-05-08 JP JP2020082479A patent/JP2020114888A/ja active Pending
-
2021
- 2021-12-06 JP JP2021197732A patent/JP2022020002A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5602935B2 (ja) | がん幹細胞を標的とするための新規の化合物および組成物 | |
| JP6246169B2 (ja) | がん幹細胞を標的とするための新規の方法 | |
| JP2013522326A (ja) | がん幹細胞を標的とするための新規の方法 | |
| JP6433085B2 (ja) | がんの処置に使用するための２−アセチルナフト［２，３−ｂ］フラン−４，９−ジオン | |
| AU2015218436B9 (en) | Novel Methods For Targeting Cancer Stem Cells | |
| HK1239527A1 (en) | Novel compounds and compositions for targeting cancer stem cells | |
| HK1229744A1 (en) | 2-acetylnaphtho[2,3-b]furan -4,9-dione for use on treating cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140401 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20141017 |
|
| A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20141106 |
|
| A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20141120 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141203 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150218 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150525 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150824 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20151006 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160623 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160819 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5993390 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |