TWI632912B - 布魯東氏（ｂｒｕｔｏｎ'ｓ）酪胺酸激酶抑制劑之醫藥調配物 - Google Patents

Info

Publication number

TWI632912B

TWI632912B TW105106446A TW105106446A TWI632912B TW I632912 B TWI632912 B TW I632912B TW 105106446 A TW105106446 A TW 105106446A TW 105106446 A TW105106446 A TW 105106446A TW I632912 B TWI632912 B TW I632912B

Authority

TW

Taiwan

Prior art keywords

amount

load solid

lozenge formulation

ibrutinib

solid lozenge

Prior art date

2015-03-03

Links

• Espacenet
• Global Dossier
• Discuss

• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 176
• 229940125814 BTK kinase inhibitor Drugs 0.000 title abstract description 3
• XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims abstract description 232
• 238000000034 method Methods 0.000 claims abstract description 186
• 239000003814 drug Substances 0.000 claims abstract description 22
• 239000000203 mixture Substances 0.000 claims description 330
• 238000009472 formulation Methods 0.000 claims description 320
• 239000007937 lozenge Substances 0.000 claims description 252
• 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 224
• 229960001507 ibrutinib Drugs 0.000 claims description 224
• 239000007787 solid Substances 0.000 claims description 198
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 189
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 184
• 229920002785 Croscarmellose sodium Polymers 0.000 claims description 178
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 157
• 229960001681 croscarmellose sodium Drugs 0.000 claims description 156
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 151
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 148
• 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 142
• 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 142
• 239000008108 microcrystalline cellulose Substances 0.000 claims description 142
• 229940016286 microcrystalline cellulose Drugs 0.000 claims description 142
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 140
• 229960001375 lactose Drugs 0.000 claims description 130
• 239000008101 lactose Substances 0.000 claims description 130
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 106
• 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 106
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 92
• 235000019359 magnesium stearate Nutrition 0.000 claims description 92
• 229940125904 compound 1 Drugs 0.000 claims description 87
• 239000003085 diluting agent Substances 0.000 claims description 76
• 239000008119 colloidal silica Substances 0.000 claims description 73
• 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 67
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 67
• 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 61
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 44
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 44
• 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 44
• 238000005550 wet granulation Methods 0.000 claims description 38
• 239000011230 binding agent Substances 0.000 claims description 37
• 230000000694 effects Effects 0.000 claims description 37
• 239000007884 disintegrant Substances 0.000 claims description 34
• 150000001875 compounds Chemical class 0.000 claims description 32
• 239000000377 silicon dioxide Substances 0.000 claims description 30
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 claims description 27
• 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 claims description 27
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 23
• 229920002472 Starch Polymers 0.000 claims description 22
• 229960005168 croscarmellose Drugs 0.000 claims description 22
• 229940032147 starch Drugs 0.000 claims description 22
• 239000008107 starch Substances 0.000 claims description 22
• 235000019698 starch Nutrition 0.000 claims description 22
• WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 18
• 239000008187 granular material Substances 0.000 claims description 17
• 229960001021 lactose monohydrate Drugs 0.000 claims description 17
• 229920000881 Modified starch Polymers 0.000 claims description 15
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 14
• 235000010980 cellulose Nutrition 0.000 claims description 14
• 229920002678 cellulose Polymers 0.000 claims description 14
• 239000001913 cellulose Substances 0.000 claims description 14
• 229960000913 crospovidone Drugs 0.000 claims description 14
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 14
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 14
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 13
• 229940071676 hydroxypropylcellulose Drugs 0.000 claims description 13
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 12
• 229920000609 methyl cellulose Polymers 0.000 claims description 11
• 235000010981 methylcellulose Nutrition 0.000 claims description 11
• 239000001923 methylcellulose Substances 0.000 claims description 11
• 229960002900 methylcellulose Drugs 0.000 claims description 11
• 235000012239 silicon dioxide Nutrition 0.000 claims description 11
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 8
• 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 claims description 8
• 239000004927 clay Substances 0.000 claims description 8
• 239000000084 colloidal system Substances 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 239000002245 particle Substances 0.000 claims description 8
• 235000010413 sodium alginate Nutrition 0.000 claims description 8
• 239000000661 sodium alginate Substances 0.000 claims description 8
• 229940005550 sodium alginate Drugs 0.000 claims description 8
• 229940080313 sodium starch Drugs 0.000 claims description 8
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 7
• 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 claims description 7
• 229920000858 Cyclodextrin Polymers 0.000 claims description 7
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 7
• 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 claims description 7
• 239000005913 Maltodextrin Substances 0.000 claims description 7
• 229920002774 Maltodextrin Polymers 0.000 claims description 7
• 239000004368 Modified starch Substances 0.000 claims description 7
• 229930006000 Sucrose Natural products 0.000 claims description 7
• 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 claims description 7
• TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 7
• 239000001506 calcium phosphate Substances 0.000 claims description 7
• 229910000389 calcium phosphate Inorganic materials 0.000 claims description 7
• 235000011010 calcium phosphates Nutrition 0.000 claims description 7
• 235000011132 calcium sulphate Nutrition 0.000 claims description 7
• 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 7
• 229920006037 cross link polymer Polymers 0.000 claims description 7
• 239000008121 dextrose Substances 0.000 claims description 7
• 239000003292 glue Substances 0.000 claims description 7
• 229940035034 maltodextrin Drugs 0.000 claims description 7
• HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 7
• 235000019426 modified starch Nutrition 0.000 claims description 7
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 7
• 229940079832 sodium starch glycolate Drugs 0.000 claims description 7
• 239000008109 sodium starch glycolate Substances 0.000 claims description 7
• 229920003109 sodium starch glycolate Polymers 0.000 claims description 7
• 239000000600 sorbitol Substances 0.000 claims description 7
• 235000010356 sorbitol Nutrition 0.000 claims description 7
• 239000005720 sucrose Substances 0.000 claims description 7
• 239000000454 talc Substances 0.000 claims description 7
• 229910052623 talc Inorganic materials 0.000 claims description 7
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 7
• 235000010447 xylitol Nutrition 0.000 claims description 7
• 239000000811 xylitol Substances 0.000 claims description 7
• HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 7
• 229960002675 xylitol Drugs 0.000 claims description 7
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 6
• 229930195725 Mannitol Natural products 0.000 claims description 6
• 239000008103 glucose Substances 0.000 claims description 6
• 239000000594 mannitol Substances 0.000 claims description 6
• 235000010355 mannitol Nutrition 0.000 claims description 6
• 229960001855 mannitol Drugs 0.000 claims description 6
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
• 238000002156 mixing Methods 0.000 claims description 5
• 229940069328 povidone Drugs 0.000 claims description 5
• 229960002920 sorbitol Drugs 0.000 claims description 5
• 239000007788 liquid Substances 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 238000005469 granulation Methods 0.000 claims description 3
• 230000003179 granulation Effects 0.000 claims description 3
• 229940057948 magnesium stearate Drugs 0.000 claims description 3
• 229920001296 polysiloxane Polymers 0.000 claims description 2
• 239000007916 tablet composition Substances 0.000 claims description 2
• 238000000227 grinding Methods 0.000 claims 2
• DKXULEFCEORBJK-UHFFFAOYSA-N magnesium;octadecanoic acid Chemical compound [Mg].CCCCCCCCCCCCCCCCCC(O)=O DKXULEFCEORBJK-UHFFFAOYSA-N 0.000 claims 2
• 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 claims 1
• 229920002307 Dextran Polymers 0.000 claims 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
• 238000001035 drying Methods 0.000 claims 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims 1
• 239000008213 purified water Substances 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 abstract description 137
• 206010025323 Lymphomas Diseases 0.000 abstract description 51
• 229940124291 BTK inhibitor Drugs 0.000 abstract description 23
• 208000023275 Autoimmune disease Diseases 0.000 abstract description 10
• 229940124597 therapeutic agent Drugs 0.000 abstract description 9
• 208000027866 inflammatory disease Diseases 0.000 abstract description 8
• 208000026278 immune system disease Diseases 0.000 abstract description 2
• 201000011510 cancer Diseases 0.000 description 115
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 83
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 73
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 67
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 63
• 238000011282 treatment Methods 0.000 description 63
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 59
• 201000010099 disease Diseases 0.000 description 52
• 210000003719 b-lymphocyte Anatomy 0.000 description 48
• 210000004027 cell Anatomy 0.000 description 45
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 38
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 35
• 206010066476 Haematological malignancy Diseases 0.000 description 32
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 32
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 30
• 206010035226 Plasma cell myeloma Diseases 0.000 description 30
• 208000035475 disorder Diseases 0.000 description 30
• 208000011691 Burkitt lymphomas Diseases 0.000 description 25
• 208000032839 leukemia Diseases 0.000 description 25
• 150000003839 salts Chemical class 0.000 description 25
• 239000000314 lubricant Substances 0.000 description 24
• 230000036210 malignancy Effects 0.000 description 24
• 239000012748 slip agent Substances 0.000 description 24
• 239000004094 surface-active agent Substances 0.000 description 23
• 201000003444 follicular lymphoma Diseases 0.000 description 22
• 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 20
• 208000021937 marginal zone lymphoma Diseases 0.000 description 20
• 208000034578 Multiple myelomas Diseases 0.000 description 19
• 230000002062 proliferating effect Effects 0.000 description 18
• 108010057466 NF-kappa B Proteins 0.000 description 17
• 102000003945 NF-kappa B Human genes 0.000 description 17
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 17
• 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 16
• 208000003950 B-cell lymphoma Diseases 0.000 description 15
• 210000001185 bone marrow Anatomy 0.000 description 15
• 108090000623 proteins and genes Proteins 0.000 description 15
• 239000012453 solvate Substances 0.000 description 13
• 208000024891 symptom Diseases 0.000 description 13
• 201000003791 MALT lymphoma Diseases 0.000 description 11
• 230000004071 biological effect Effects 0.000 description 11
• 210000001165 lymph node Anatomy 0.000 description 11
• 208000017426 precursor B-cell acute lymphoblastic leukemia Diseases 0.000 description 11
• 102000004169 proteins and genes Human genes 0.000 description 11
• 230000004044 response Effects 0.000 description 11
• 108091008875 B cell receptors Proteins 0.000 description 10
• 206010016654 Fibrosis Diseases 0.000 description 10
• 241000124008 Mammalia Species 0.000 description 10
• 210000001744 T-lymphocyte Anatomy 0.000 description 10
• 210000004369 blood Anatomy 0.000 description 10
• 239000008280 blood Substances 0.000 description 10
• 230000001684 chronic effect Effects 0.000 description 10
• 230000005764 inhibitory process Effects 0.000 description 10
• 230000002427 irreversible effect Effects 0.000 description 10
• 201000000050 myeloid neoplasm Diseases 0.000 description 10
• 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 10
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 9
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• 230000004761 fibrosis Effects 0.000 description 9
• 230000035772 mutation Effects 0.000 description 9
• 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 9
• 235000018102 proteins Nutrition 0.000 description 9
• -1 4-phenoxyphenyl Chemical group 0.000 description 8
• 210000000265 leukocyte Anatomy 0.000 description 8
• 230000011664 signaling Effects 0.000 description 8
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 7
• 206010039491 Sarcoma Diseases 0.000 description 7
• 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 7
• 238000002648 combination therapy Methods 0.000 description 7
• 230000003325 follicular Effects 0.000 description 7
• 239000003112 inhibitor Substances 0.000 description 7
• 206010025135 lupus erythematosus Diseases 0.000 description 7
• 230000019491 signal transduction Effects 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 6
• 206010005003 Bladder cancer Diseases 0.000 description 6
• 206010006187 Breast cancer Diseases 0.000 description 6
• 208000026310 Breast neoplasm Diseases 0.000 description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
• 208000009329 Graft vs Host Disease Diseases 0.000 description 6
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 6
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 6
• 230000001154 acute effect Effects 0.000 description 6
• 208000009956 adenocarcinoma Diseases 0.000 description 6
• 210000003169 central nervous system Anatomy 0.000 description 6
• 208000006990 cholangiocarcinoma Diseases 0.000 description 6
• 208000024908 graft versus host disease Diseases 0.000 description 6
• 208000026876 intravascular large B-cell lymphoma Diseases 0.000 description 6
• 210000004698 lymphocyte Anatomy 0.000 description 6
• 230000037361 pathway Effects 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 201000006845 reticulosarcoma Diseases 0.000 description 6
• 208000029922 reticulum cell sarcoma Diseases 0.000 description 6
• 230000004083 survival effect Effects 0.000 description 6
• 208000011580 syndromic disease Diseases 0.000 description 6
• 201000005112 urinary bladder cancer Diseases 0.000 description 6
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 5
• 102100024965 Caspase recruitment domain-containing protein 11 Human genes 0.000 description 5
• 206010009944 Colon cancer Diseases 0.000 description 5
• 206010014967 Ependymoma Diseases 0.000 description 5
• 206010018691 Granuloma Diseases 0.000 description 5
• 101000761179 Homo sapiens Caspase recruitment domain-containing protein 11 Proteins 0.000 description 5
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 206010033128 Ovarian cancer Diseases 0.000 description 5
• 108091000080 Phosphotransferase Proteins 0.000 description 5
• 208000007452 Plasmacytoma Diseases 0.000 description 5
• 206010039710 Scleroderma Diseases 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 230000006907 apoptotic process Effects 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 201000005202 lung cancer Diseases 0.000 description 5
• 208000020816 lung neoplasm Diseases 0.000 description 5
• 208000003747 lymphoid leukemia Diseases 0.000 description 5
• 210000003563 lymphoid tissue Anatomy 0.000 description 5
• 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 5
• 102000020233 phosphotransferase Human genes 0.000 description 5
• 230000036470 plasma concentration Effects 0.000 description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• 210000001541 thymus gland Anatomy 0.000 description 5
• 206010003571 Astrocytoma Diseases 0.000 description 4
• 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 4
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
• 208000023611 Burkitt leukaemia Diseases 0.000 description 4
• 201000004085 CLL/SLL Diseases 0.000 description 4
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
• 201000008808 Fibrosarcoma Diseases 0.000 description 4
• 241000282414 Homo sapiens Species 0.000 description 4
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 4
• 206010052178 Lymphocytic lymphoma Diseases 0.000 description 4
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 description 4
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
• 206010035664 Pneumonia Diseases 0.000 description 4
• 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 4
• 206010060862 Prostate cancer Diseases 0.000 description 4
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 4
• 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 4
• 230000002159 abnormal effect Effects 0.000 description 4
• 210000000601 blood cell Anatomy 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 238000002512 chemotherapy Methods 0.000 description 4
• 208000023738 chronic lymphocytic leukemia/small lymphocytic lymphoma Diseases 0.000 description 4
• 230000002708 enhancing effect Effects 0.000 description 4
• 201000009277 hairy cell leukemia Diseases 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 230000000670 limiting effect Effects 0.000 description 4
• 210000002751 lymph Anatomy 0.000 description 4
• 230000003211 malignant effect Effects 0.000 description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
• 239000002207 metabolite Substances 0.000 description 4
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
• 210000000056 organ Anatomy 0.000 description 4
• 201000002528 pancreatic cancer Diseases 0.000 description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 210000000952 spleen Anatomy 0.000 description 4
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 3
• 108700024832 B-Cell CLL-Lymphoma 10 Proteins 0.000 description 3
• 102100037598 B-cell lymphoma/leukemia 10 Human genes 0.000 description 3
• 208000025321 B-lymphoblastic leukemia/lymphoma Diseases 0.000 description 3
• 101150074953 BCL10 gene Proteins 0.000 description 3
• 208000006386 Bone Resorption Diseases 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 206010018338 Glioma Diseases 0.000 description 3
• 208000017604 Hodgkin disease Diseases 0.000 description 3
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 3
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 3
• 206010020751 Hypersensitivity Diseases 0.000 description 3
• 208000028018 Lymphocytic leukaemia Diseases 0.000 description 3
• 101150113681 MALT1 gene Proteins 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 108700026676 Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Proteins 0.000 description 3
• 102100038732 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 Human genes 0.000 description 3
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
• 201000010133 Oligodendroglioma Diseases 0.000 description 3
• 208000001132 Osteoporosis Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 208000033014 Plasma cell tumor Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 201000004681 Psoriasis Diseases 0.000 description 3
• 206010042971 T-cell lymphoma Diseases 0.000 description 3
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000007815 allergy Effects 0.000 description 3
• 150000001413 amino acids Chemical group 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 230000024279 bone resorption Effects 0.000 description 3
• 239000007963 capsule composition Substances 0.000 description 3
• 230000001413 cellular effect Effects 0.000 description 3
• 230000005754 cellular signaling Effects 0.000 description 3
• 201000001352 cholecystitis Diseases 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 208000029742 colonic neoplasm Diseases 0.000 description 3
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
• 238000003745 diagnosis Methods 0.000 description 3
• 210000001280 germinal center Anatomy 0.000 description 3
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
• 208000006454 hepatitis Diseases 0.000 description 3
• 231100000283 hepatitis Toxicity 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 239000013038 irreversible inhibitor Substances 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 206010024627 liposarcoma Diseases 0.000 description 3
• 230000007774 longterm Effects 0.000 description 3
• 210000004324 lymphatic system Anatomy 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 230000009826 neoplastic cell growth Effects 0.000 description 3
• 239000006186 oral dosage form Substances 0.000 description 3
• 208000010626 plasma cell neoplasm Diseases 0.000 description 3
• 210000004180 plasmocyte Anatomy 0.000 description 3
• 239000002243 precursor Substances 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 201000006037 primary mediastinal B-cell lymphoma Diseases 0.000 description 3
• 230000035755 proliferation Effects 0.000 description 3
• 238000001959 radiotherapy Methods 0.000 description 3
• 230000000306 recurrent effect Effects 0.000 description 3
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 230000009424 thromboembolic effect Effects 0.000 description 3
• 206010000830 Acute leukaemia Diseases 0.000 description 2
• 208000026872 Addison Disease Diseases 0.000 description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 2
• 208000032467 Aplastic anaemia Diseases 0.000 description 2
• 206010003827 Autoimmune hepatitis Diseases 0.000 description 2
• 206010003840 Autonomic nervous system imbalance Diseases 0.000 description 2
• 102100027205 B-cell antigen receptor complex-associated protein alpha chain Human genes 0.000 description 2
• 102100027203 B-cell antigen receptor complex-associated protein beta chain Human genes 0.000 description 2
• 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 2
• 208000023328 Basedow disease Diseases 0.000 description 2
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 2
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 2
• 208000003174 Brain Neoplasms Diseases 0.000 description 2
• 206010006448 Bronchiolitis Diseases 0.000 description 2
• 206010006811 Bursitis Diseases 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 2
• 206010008342 Cervix carcinoma Diseases 0.000 description 2
• 208000005243 Chondrosarcoma Diseases 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 208000015943 Coeliac disease Diseases 0.000 description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
• 206010010741 Conjunctivitis Diseases 0.000 description 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
• 201000009273 Endometriosis Diseases 0.000 description 2
• 208000004145 Endometritis Diseases 0.000 description 2
• 208000004232 Enteritis Diseases 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 201000011275 Epicondylitis Diseases 0.000 description 2
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
• 206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 description 2
• 206010016228 Fasciitis Diseases 0.000 description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
• 208000007882 Gastritis Diseases 0.000 description 2
• 208000005577 Gastroenteritis Diseases 0.000 description 2
• 208000007465 Giant cell arteritis Diseases 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 208000015023 Graves' disease Diseases 0.000 description 2
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
• 101000914489 Homo sapiens B-cell antigen receptor complex-associated protein alpha chain Proteins 0.000 description 2
• 101000914491 Homo sapiens B-cell antigen receptor complex-associated protein beta chain Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 2
• 102000009438 IgE Receptors Human genes 0.000 description 2
• 108010073816 IgE Receptors Proteins 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• 208000005615 Interstitial Cystitis Diseases 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 208000003456 Juvenile Arthritis Diseases 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• 206010023774 Large cell lung cancer Diseases 0.000 description 2
• 201000008197 Laryngitis Diseases 0.000 description 2
• 208000030289 Lymphoproliferative disease Diseases 0.000 description 2
• 201000009906 Meningitis Diseases 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 208000005647 Mumps Diseases 0.000 description 2
• 208000003926 Myelitis Diseases 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• 208000009525 Myocarditis Diseases 0.000 description 2
• 208000002033 Myoclonus Diseases 0.000 description 2
• 201000002481 Myositis Diseases 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• 206010029260 Neuroblastoma Diseases 0.000 description 2
• 235000007413 Nigella arvensis Nutrition 0.000 description 2
• 244000090896 Nigella sativa Species 0.000 description 2
• 235000016698 Nigella sativa Nutrition 0.000 description 2
• 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 2
• RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
• 208000005141 Otitis Diseases 0.000 description 2
• 208000002193 Pain Diseases 0.000 description 2
• 206010033645 Pancreatitis Diseases 0.000 description 2
• 201000007100 Pharyngitis Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 206010036524 Precursor B-lymphoblastic lymphomas Diseases 0.000 description 2
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 2
• 206010036774 Proctitis Diseases 0.000 description 2
• 208000033766 Prolymphocytic Leukemia Diseases 0.000 description 2
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
• 206010037596 Pyelonephritis Diseases 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 208000015634 Rectal Neoplasms Diseases 0.000 description 2
• 206010038389 Renal cancer Diseases 0.000 description 2
• 208000007893 Salpingitis Diseases 0.000 description 2
• 208000021386 Sjogren Syndrome Diseases 0.000 description 2
• 208000000453 Skin Neoplasms Diseases 0.000 description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 description 2
• 208000004350 Strabismus Diseases 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 208000000491 Tendinopathy Diseases 0.000 description 2
• 206010043255 Tendonitis Diseases 0.000 description 2
• 208000024313 Testicular Neoplasms Diseases 0.000 description 2
• 206010057644 Testis cancer Diseases 0.000 description 2
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
• 208000024770 Thyroid neoplasm Diseases 0.000 description 2
• 108020000411 Toll-like receptor Proteins 0.000 description 2
• 102000002689 Toll-like receptor Human genes 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
• 208000006374 Uterine Cervicitis Diseases 0.000 description 2
• 206010046851 Uveitis Diseases 0.000 description 2
• 206010046914 Vaginal infection Diseases 0.000 description 2
• 201000008100 Vaginitis Diseases 0.000 description 2
• 206010047115 Vasculitis Diseases 0.000 description 2
• 210000001015 abdomen Anatomy 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 208000004631 alopecia areata Diseases 0.000 description 2
• 229960004977 anhydrous lactose Drugs 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 206010003230 arteritis Diseases 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
• 230000005784 autoimmunity Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 201000000053 blastoma Diseases 0.000 description 2
• 208000010217 blepharitis Diseases 0.000 description 2
• 230000017531 blood circulation Effects 0.000 description 2
• 210000002798 bone marrow cell Anatomy 0.000 description 2
• 238000010322 bone marrow transplantation Methods 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 201000010983 breast ductal carcinoma Diseases 0.000 description 2
• 206010006451 bronchitis Diseases 0.000 description 2
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
• 208000035269 cancer or benign tumor Diseases 0.000 description 2
• 230000011712 cell development Effects 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 201000010881 cervical cancer Diseases 0.000 description 2
• 206010008323 cervicitis Diseases 0.000 description 2
• 238000006243 chemical reaction Methods 0.000 description 2
• 208000003167 cholangitis Diseases 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 208000024207 chronic leukemia Diseases 0.000 description 2
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 2
• 208000019425 cirrhosis of liver Diseases 0.000 description 2
• 206010009887 colitis Diseases 0.000 description 2
• 230000037011 constitutive activity Effects 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 235000018417 cysteine Nutrition 0.000 description 2
• 201000003146 cystitis Diseases 0.000 description 2
• 201000004400 dacryoadenitis Diseases 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 201000001981 dermatomyositis Diseases 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 230000009977 dual effect Effects 0.000 description 2
• 208000019258 ear infection Diseases 0.000 description 2
• 201000008184 embryoma Diseases 0.000 description 2
• 206010014599 encephalitis Diseases 0.000 description 2
• 206010014665 endocarditis Diseases 0.000 description 2
• 208000010227 enterocolitis Diseases 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 201000010063 epididymitis Diseases 0.000 description 2
• 230000009786 epithelial differentiation Effects 0.000 description 2
• 201000004101 esophageal cancer Diseases 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 206010016256 fatigue Diseases 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 208000005017 glioblastoma Diseases 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 230000003862 health status Effects 0.000 description 2
• 206010020718 hyperplasia Diseases 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 201000010982 kidney cancer Diseases 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 201000007270 liver cancer Diseases 0.000 description 2
• 208000014018 liver neoplasm Diseases 0.000 description 2
• 201000009546 lung large cell carcinoma Diseases 0.000 description 2
• 201000011649 lymphoblastic lymphoma Diseases 0.000 description 2
• 201000000564 macroglobulinemia Diseases 0.000 description 2
• 208000004396 mastitis Diseases 0.000 description 2
• 208000008585 mastocytosis Diseases 0.000 description 2
• 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 230000000877 morphologic effect Effects 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 208000010805 mumps infectious disease Diseases 0.000 description 2
• 208000025113 myeloid leukemia Diseases 0.000 description 2
• 201000008383 nephritis Diseases 0.000 description 2
• 230000002232 neuromuscular Effects 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• 201000008968 osteosarcoma Diseases 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 208000008494 pericarditis Diseases 0.000 description 2
• 206010034674 peritonitis Diseases 0.000 description 2
• 230000002085 persistent effect Effects 0.000 description 2
• 208000001297 phlebitis Diseases 0.000 description 2
• 208000008423 pleurisy Diseases 0.000 description 2
• 229920006316 polyvinylpyrrolidine Polymers 0.000 description 2
• 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 2
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 2
• 229940002612 prodrug Drugs 0.000 description 2
• 239000000651 prodrug Substances 0.000 description 2
• 238000004393 prognosis Methods 0.000 description 2
• 201000007094 prostatitis Diseases 0.000 description 2
• 206010038038 rectal cancer Diseases 0.000 description 2
• 201000001275 rectum cancer Diseases 0.000 description 2
• 206010039083 rhinitis Diseases 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 201000009890 sinusitis Diseases 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 201000000849 skin cancer Diseases 0.000 description 2
• 208000000649 small cell carcinoma Diseases 0.000 description 2
• HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 0.000 description 2
• 239000000243 solution Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 201000011549 stomach cancer Diseases 0.000 description 2
• 208000003265 stomatitis Diseases 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 201000004595 synovitis Diseases 0.000 description 2
• 230000001839 systemic circulation Effects 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 206010043207 temporal arteritis Diseases 0.000 description 2
• 201000004415 tendinitis Diseases 0.000 description 2
• 201000003120 testicular cancer Diseases 0.000 description 2
• 201000002510 thyroid cancer Diseases 0.000 description 2
• 206010043778 thyroiditis Diseases 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 206010044008 tonsillitis Diseases 0.000 description 2
• 230000005945 translocation Effects 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 206010046885 vaginal cancer Diseases 0.000 description 2
• 208000013139 vaginal neoplasm Diseases 0.000 description 2
• 208000002003 vulvitis Diseases 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• XYFPWWZEPKGCCK-SFHVURJKSA-N 1-[(3s)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-SFHVURJKSA-N 0.000 description 1
• XYFPWWZEPKGCCK-UHFFFAOYSA-N 1-[3-[4-amino-3-(4-phenoxyphenyl)-1-pyrazolo[3,4-d]pyrimidinyl]-1-piperidinyl]-2-propen-1-one Chemical compound C1=2C(N)=NC=NC=2N(C2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-UHFFFAOYSA-N 0.000 description 1
• QPRMGHKASRLPJP-UHFFFAOYSA-N 12-(5-hydroxy-6-methylpiperidin-2-yl)dodecan-2-one Chemical compound CC1NC(CCCCCCCCCCC(C)=O)CCC1O QPRMGHKASRLPJP-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 1
• 241000238876 Acari Species 0.000 description 1
• 206010069754 Acquired gene mutation Diseases 0.000 description 1
• 208000003200 Adenoma Diseases 0.000 description 1
• 206010001233 Adenoma benign Diseases 0.000 description 1
• 206010001488 Aggression Diseases 0.000 description 1
• 208000037540 Alveolar soft tissue sarcoma Diseases 0.000 description 1
• 206010061424 Anal cancer Diseases 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 206010002388 Angina unstable Diseases 0.000 description 1
• 201000003076 Angiosarcoma Diseases 0.000 description 1
• 108010083359 Antigen Receptors Proteins 0.000 description 1
• 102000006306 Antigen Receptors Human genes 0.000 description 1
• 208000007860 Anus Neoplasms Diseases 0.000 description 1
• 206010003011 Appendicitis Diseases 0.000 description 1
• 206010073360 Appendix cancer Diseases 0.000 description 1
• 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
• 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 1
• 208000012526 B-cell neoplasm Diseases 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 208000027496 Behcet disease Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 206010004992 Bladder adenocarcinoma stage unspecified Diseases 0.000 description 1
• 241001674044 Blattodea Species 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 208000016778 CD4+/CD56+ hematodermic neoplasm Diseases 0.000 description 1
• 241001164374 Calyx Species 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• OGPQOSAKRHKIHW-UHFFFAOYSA-N Cassin Natural products CC(CCCCCCCCCC1CCC(O)C(C)N1)C(=O)C OGPQOSAKRHKIHW-UHFFFAOYSA-N 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 208000031404 Chromosome Aberrations Diseases 0.000 description 1
• 208000000668 Chronic Pancreatitis Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 206010073140 Clear cell sarcoma of soft tissue Diseases 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 208000035984 Colonic Polyps Diseases 0.000 description 1
• 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
• 102000006311 Cyclin D1 Human genes 0.000 description 1
• 108010058546 Cyclin D1 Proteins 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 206010073135 Dedifferentiated liposarcoma Diseases 0.000 description 1
• 206010051055 Deep vein thrombosis Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 206010015108 Epstein-Barr virus infection Diseases 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 description 1
• 201000001342 Fallopian tube cancer Diseases 0.000 description 1
• 201000006107 Familial adenomatous polyposis Diseases 0.000 description 1
• 208000001640 Fibromyalgia Diseases 0.000 description 1
• 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
• 206010061968 Gastric neoplasm Diseases 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
• 208000034951 Genetic Translocation Diseases 0.000 description 1
• 208000007569 Giant Cell Tumors Diseases 0.000 description 1
• 208000024869 Goodpasture syndrome Diseases 0.000 description 1
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
• 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000002125 Hemangioendothelioma Diseases 0.000 description 1
• 208000006050 Hemangiopericytoma Diseases 0.000 description 1
• 208000001258 Hemangiosarcoma Diseases 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 1
• 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 1
• 101000986087 Homo sapiens HLA class I histocompatibility antigen, B alpha chain Proteins 0.000 description 1
• 101100521072 Homo sapiens PRDM1 gene Proteins 0.000 description 1
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
• 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
• 101000772888 Homo sapiens Ubiquitin-protein ligase E3A Proteins 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 208000001718 Immediate Hypersensitivity Diseases 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 206010023347 Keratoacanthoma Diseases 0.000 description 1
• 208000021605 Large-Cell Immunoblastic Lymphoma Diseases 0.000 description 1
• 206010023825 Laryngeal cancer Diseases 0.000 description 1
• 244000147568 Laurus nobilis Species 0.000 description 1
• 235000017858 Laurus nobilis Nutrition 0.000 description 1
• 206010073099 Lobular breast carcinoma in situ Diseases 0.000 description 1
• 206010025280 Lymphocytosis Diseases 0.000 description 1
• 101150053046 MYD88 gene Proteins 0.000 description 1
• 206010073059 Malignant neoplasm of unknown primary site Diseases 0.000 description 1
• 208000033724 Malignant tumor of fallopian tubes Diseases 0.000 description 1
• 208000032271 Malignant tumor of penis Diseases 0.000 description 1
• 102100025169 Max-binding protein MNT Human genes 0.000 description 1
• 201000009574 Mesenchymal Chondrosarcoma Diseases 0.000 description 1
• 229920003091 Methocel™ Polymers 0.000 description 1
• 238000006957 Michael reaction Methods 0.000 description 1
• 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
• 208000003445 Mouth Neoplasms Diseases 0.000 description 1
• 208000007727 Muscle Tissue Neoplasms Diseases 0.000 description 1
• 206010028372 Muscular weakness Diseases 0.000 description 1
• 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 1
• 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 1
• 102100024134 Myeloid differentiation primary response protein MyD88 Human genes 0.000 description 1
• 206010073137 Myxoid liposarcoma Diseases 0.000 description 1
• 206010061309 Neoplasm progression Diseases 0.000 description 1
• 206010029240 Neuritis Diseases 0.000 description 1
• 208000033383 Neuroendocrine tumor of pancreas Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 102100023059 Nuclear factor NF-kappa-B p100 subunit Human genes 0.000 description 1
• 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
• 208000003435 Optic Neuritis Diseases 0.000 description 1
• 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010033649 Pancreatitis chronic Diseases 0.000 description 1
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 206010034299 Penile cancer Diseases 0.000 description 1
• 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
• 208000031839 Peripheral nerve sheath tumour malignant Diseases 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 201000010395 Pleomorphic liposarcoma Diseases 0.000 description 1
• 229920003080 Povidone K 25 Polymers 0.000 description 1
• 229920003081 Povidone K 30 Polymers 0.000 description 1
• 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 101710188314 Protein V Proteins 0.000 description 1
• 102000000850 Proto-Oncogene Proteins c-rel Human genes 0.000 description 1
• 108010001859 Proto-Oncogene Proteins c-rel Proteins 0.000 description 1
• 208000010378 Pulmonary Embolism Diseases 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 206010038563 Reocclusion Diseases 0.000 description 1
• 206010039085 Rhinitis allergic Diseases 0.000 description 1
• 208000034712 Rickettsia Infections Diseases 0.000 description 1
• 208000033220 Rickettsial disease Diseases 0.000 description 1
• 206010061495 Rickettsiosis Diseases 0.000 description 1
• 206010073139 Round cell liposarcoma Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 102100029064 Serine/threonine-protein kinase WNK1 Human genes 0.000 description 1
• 201000011683 Small Cell Sarcoma Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 206010041660 Splenomegaly Diseases 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 206010043189 Telangiectasia Diseases 0.000 description 1
• 235000005212 Terminalia tomentosa Nutrition 0.000 description 1
• 206010043515 Throat cancer Diseases 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000004357 Transferases Human genes 0.000 description 1
• 108090000992 Transferases Proteins 0.000 description 1
• 208000037280 Trisomy Diseases 0.000 description 1
• 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 description 1
• 206010045240 Type I hypersensitivity Diseases 0.000 description 1
• 208000007814 Unstable Angina Diseases 0.000 description 1
• 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 206010046798 Uterine leiomyoma Diseases 0.000 description 1
• 206010047249 Venous thrombosis Diseases 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 102000007624 ZAP-70 Protein-Tyrosine Kinase Human genes 0.000 description 1
• 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
• 201000005188 adrenal gland cancer Diseases 0.000 description 1
• 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 230000016571 aggressive behavior Effects 0.000 description 1
• 208000012761 aggressive behavior Diseases 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 208000002205 allergic conjunctivitis Diseases 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 201000010105 allergic rhinitis Diseases 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 206010065867 alveolar rhabdomyosarcoma Diseases 0.000 description 1
• 208000008524 alveolar soft part sarcoma Diseases 0.000 description 1
• 208000010029 ameloblastoma Diseases 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 238000005280 amorphization Methods 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 201000011165 anus cancer Diseases 0.000 description 1
• 208000021780 appendiceal neoplasm Diseases 0.000 description 1
• 159000000032 aromatic acids Chemical class 0.000 description 1
• 208000021328 arterial occlusion Diseases 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
• 208000024998 atopic conjunctivitis Diseases 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 238000001815 biotherapy Methods 0.000 description 1
• 201000006587 bladder adenocarcinoma Diseases 0.000 description 1
• 238000004820 blood count Methods 0.000 description 1
• 210000001772 blood platelet Anatomy 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 206010006007 bone sarcoma Diseases 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 201000005389 breast carcinoma in situ Diseases 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 201000010882 cellular myxoid liposarcoma Diseases 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
• 201000000292 clear cell sarcoma Diseases 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 201000002758 colorectal adenoma Diseases 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 230000002559 cytogenic effect Effects 0.000 description 1
• 108010057085 cytokine receptors Proteins 0.000 description 1
• 102000003675 cytokine receptors Human genes 0.000 description 1
• 210000005220 cytoplasmic tail Anatomy 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 231100000517 death Toxicity 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 229940096516 dextrates Drugs 0.000 description 1
• 238000007435 diagnostic evaluation Methods 0.000 description 1
• 238000002405 diagnostic procedure Methods 0.000 description 1
• 150000001991 dicarboxylic acids Chemical group 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000007908 dry granulation Methods 0.000 description 1
• 239000000428 dust Substances 0.000 description 1
• 230000003511 endothelial effect Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000036566 epidermal hyperplasia Effects 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 210000003743 erythrocyte Anatomy 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000013265 extended release Methods 0.000 description 1
• 201000006544 extraosseous Ewings sarcoma-primitive neuroepithelial tumor Diseases 0.000 description 1
• 201000008815 extraosseous osteosarcoma Diseases 0.000 description 1
• 208000024519 eye neoplasm Diseases 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 230000003328 fibroblastic effect Effects 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
• 208000017215 gastric mucosa-associated lymphoid tissue lymphoma Diseases 0.000 description 1
• 210000001102 germinal center b cell Anatomy 0.000 description 1
• 229960001031 glucose Drugs 0.000 description 1
• 230000007773 growth pattern Effects 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 210000002768 hair cell Anatomy 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 208000007475 hemolytic anemia Diseases 0.000 description 1
• 208000002557 hidradenitis Diseases 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 238000012760 immunocytochemical staining Methods 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000000415 inactivating effect Effects 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 208000015266 indolent plasma cell myeloma Diseases 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
• 229940011051 isopropyl acetate Drugs 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• 208000003849 large cell carcinoma Diseases 0.000 description 1
• 206010023841 laryngeal neoplasm Diseases 0.000 description 1
• 239000004816 latex Substances 0.000 description 1
• 229920000126 latex Polymers 0.000 description 1
• 201000010260 leiomyoma Diseases 0.000 description 1
• 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 201000011059 lobular neoplasia Diseases 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 201000009020 malignant peripheral nerve sheath tumor Diseases 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 210000003826 marginal zone b cell Anatomy 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 210000001370 mediastinum Anatomy 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 206010027743 mixed astrocytoma-ependymoma Diseases 0.000 description 1
• 201000002447 mixed astrocytoma-ependymoma-oligodendroglioma Diseases 0.000 description 1
• 201000010225 mixed cell type cancer Diseases 0.000 description 1
• 208000029638 mixed neoplasm Diseases 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 230000036473 myasthenia Effects 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 208000024305 myofibroblastoma Diseases 0.000 description 1
• 201000009500 myxoid chondrosarcoma Diseases 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 210000000822 natural killer cell Anatomy 0.000 description 1
• 230000011234 negative regulation of signal transduction Effects 0.000 description 1
• 210000005170 neoplastic cell Anatomy 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 230000010309 neoplastic transformation Effects 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 210000000276 neural tube Anatomy 0.000 description 1
• 208000029974 neurofibrosarcoma Diseases 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 201000008106 ocular cancer Diseases 0.000 description 1
• 206010073131 oligoastrocytoma Diseases 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 210000001328 optic nerve Anatomy 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 210000002741 palatine tonsil Anatomy 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 201000002530 pancreatic endocrine carcinoma Diseases 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 201000010198 papillary carcinoma Diseases 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 201000003434 periosteal osteogenic sarcoma Diseases 0.000 description 1
• 230000002093 peripheral 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
• 239000010452 phosphate Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 208000010916 pituitary tumor Diseases 0.000 description 1
• 201000010968 pleomorphic carcinoma Diseases 0.000 description 1
• 239000002574 poison Substances 0.000 description 1
• 231100000614 poison Toxicity 0.000 description 1
• 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 208000014081 polyp of colon Diseases 0.000 description 1
• 229920002717 polyvinylpyridine Polymers 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 230000004850 protein–protein interaction Effects 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 201000000443 refractory hairy cell leukemia Diseases 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 208000014653 solitary fibrous tumor Diseases 0.000 description 1
• 230000000392 somatic effect Effects 0.000 description 1
• 230000037439 somatic mutation Effects 0.000 description 1
• 208000021550 spleen neoplasm Diseases 0.000 description 1
• 238000010911 splenectomy Methods 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000011272 standard treatment Methods 0.000 description 1
• 238000011476 stem cell transplantation Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 208000028210 stromal sarcoma Diseases 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000008961 swelling Effects 0.000 description 1
• 206010042863 synovial sarcoma Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 208000009056 telangiectasis Diseases 0.000 description 1
• ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 108091006107 transcriptional repressors Proteins 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 230000006433 tumor necrosis factor production Effects 0.000 description 1
• 230000005751 tumor progression Effects 0.000 description 1
• 230000009959 type I hypersensitivity Effects 0.000 description 1
• 230000004222 uncontrolled growth Effects 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 208000037964 urogenital cancer Diseases 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1