AU2019443366A1 - Combination therapies comprising apremilast and Tyk2 inhibitors - Google Patents
Combination therapies comprising apremilast and Tyk2 inhibitors Download PDFInfo
- Publication number
- AU2019443366A1 AU2019443366A1 AU2019443366A AU2019443366A AU2019443366A1 AU 2019443366 A1 AU2019443366 A1 AU 2019443366A1 AU 2019443366 A AU2019443366 A AU 2019443366A AU 2019443366 A AU2019443366 A AU 2019443366A AU 2019443366 A1 AU2019443366 A1 AU 2019443366A1
- Authority
- AU
- Australia
- Prior art keywords
- day
- substituted
- per day
- dioxo
- methylsulfonyl
- 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.)
- Abandoned
Links
- IMOZEMNVLZVGJZ-QGZVFWFLSA-N apremilast Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CS(C)(=O)=O)N2C(C3=C(NC(C)=O)C=CC=C3C2=O)=O)=C1 IMOZEMNVLZVGJZ-QGZVFWFLSA-N 0.000 title claims abstract description 240
- 229940123371 Tyrosine kinase 2 inhibitor Drugs 0.000 title claims abstract description 105
- 229960001164 apremilast Drugs 0.000 title abstract description 203
- 238000002648 combination therapy Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 81
- 230000005764 inhibitory process Effects 0.000 claims abstract description 44
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims description 84
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 62
- 125000005842 heteroatom Chemical group 0.000 claims description 56
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 52
- 229910052760 oxygen Inorganic materials 0.000 claims description 51
- 150000002431 hydrogen Chemical class 0.000 claims description 50
- 125000004432 carbon atom Chemical group C* 0.000 claims description 48
- 229910052717 sulfur Inorganic materials 0.000 claims description 44
- 201000010099 disease Diseases 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 37
- 208000035475 disorder Diseases 0.000 claims description 33
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 24
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 22
- 201000004681 Psoriasis Diseases 0.000 claims description 21
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 229910052794 bromium Inorganic materials 0.000 claims description 16
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 11
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 11
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 10
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 238000004448 titration Methods 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 9
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 7
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 6
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 229910052805 deuterium Inorganic materials 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 206010025135 lupus erythematosus Diseases 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 206010012442 Dermatitis contact Diseases 0.000 claims description 4
- 108010010057 TYK2 Kinase Proteins 0.000 claims description 4
- 102000015774 TYK2 Kinase Human genes 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 208000010247 contact dermatitis Diseases 0.000 claims description 4
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 238000001126 phototherapy Methods 0.000 claims description 4
- 230000009897 systematic effect Effects 0.000 claims description 4
- 230000009885 systemic effect Effects 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 3
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000013265 extended release Methods 0.000 claims description 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 208000009137 Behcet syndrome Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
- 206010070517 Type 2 lepra reaction Diseases 0.000 claims description 2
- 208000027418 Wounds and injury Diseases 0.000 claims description 2
- 230000000172 allergic effect Effects 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- 230000002068 genetic effect Effects 0.000 claims description 2
- 230000000222 hyperoxic effect Effects 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 208000026350 Inborn Genetic disease Diseases 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 208000016361 genetic disease Diseases 0.000 claims 1
- 208000037765 diseases and disorders Diseases 0.000 abstract description 2
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 abstract 1
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 40
- 108010065637 Interleukin-23 Proteins 0.000 description 40
- 102000013264 Interleukin-23 Human genes 0.000 description 40
- 229940124829 interleukin-23 Drugs 0.000 description 40
- 102000013691 Interleukin-17 Human genes 0.000 description 38
- 108050003558 Interleukin-17 Proteins 0.000 description 38
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 38
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 35
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 35
- 230000000638 stimulation Effects 0.000 description 34
- 238000011282 treatment Methods 0.000 description 29
- 239000002158 endotoxin Substances 0.000 description 28
- 229920006008 lipopolysaccharide Polymers 0.000 description 28
- 230000016396 cytokine production Effects 0.000 description 26
- 102000004127 Cytokines Human genes 0.000 description 25
- 108090000695 Cytokines Proteins 0.000 description 25
- 210000004369 blood Anatomy 0.000 description 25
- 239000008280 blood Substances 0.000 description 25
- 150000001875 compounds Chemical class 0.000 description 23
- 230000014509 gene expression Effects 0.000 description 23
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 22
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 22
- 108090001005 Interleukin-6 Proteins 0.000 description 19
- 108010074109 interleukin-22 Proteins 0.000 description 19
- 238000003556 assay Methods 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 16
- BZZKEPGENYLQSC-FIBGUPNXSA-N 6-(cyclopropanecarbonylamino)-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide Chemical compound C1(CC1)C(=O)NC1=CC(=C(N=N1)C(=O)NC([2H])([2H])[2H])NC1=C(C(=CC=C1)C1=NN(C=N1)C)OC BZZKEPGENYLQSC-FIBGUPNXSA-N 0.000 description 15
- 229940124282 BMS-986165 Drugs 0.000 description 14
- 102100030703 Interleukin-22 Human genes 0.000 description 13
- 230000003247 decreasing effect Effects 0.000 description 13
- 108010065805 Interleukin-12 Proteins 0.000 description 12
- 102000013462 Interleukin-12 Human genes 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 102000008070 Interferon-gamma Human genes 0.000 description 8
- 108010074328 Interferon-gamma Proteins 0.000 description 8
- 229960003130 interferon gamma Drugs 0.000 description 8
- 238000007619 statistical method Methods 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 230000006698 induction Effects 0.000 description 7
- 102000000018 Chemokine CCL2 Human genes 0.000 description 6
- -1 IL-1b Proteins 0.000 description 6
- 238000000540 analysis of variance Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 230000002195 synergetic effect Effects 0.000 description 6
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 5
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 5
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 230000000295 complement effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000013389 whole blood assay Methods 0.000 description 4
- 108010044467 Isoenzymes Proteins 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 208000025113 myeloid leukemia Diseases 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
- 101150015280 Cel gene Proteins 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 230000002301 combined effect Effects 0.000 description 2
- 238000013503 de-identification Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000012997 ficoll-paque Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 230000013462 interleukin-17F production Effects 0.000 description 2
- 230000003704 interleukin-23 production Effects 0.000 description 2
- 208000003747 lymphoid leukemia Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000023185 monocyte chemotactic protein-1 production Effects 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000003359 percent control normalization Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 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
- 238000011269 treatment regimen Methods 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZNEMGFATAVGQSF-UHFFFAOYSA-N 1-(2-amino-6,7-dihydro-4H-[1,3]thiazolo[4,5-c]pyridin-5-yl)-2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound NC=1SC2=C(CN(CC2)C(CC=2OC(=NN=2)C=2C=NC(=NC=2)NC2CC3=CC=CC=C3C2)=O)N=1 ZNEMGFATAVGQSF-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 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 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 201000003883 Cystic fibrosis 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
- 238000002965 ELISA Methods 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000001617 Interferon Receptors Human genes 0.000 description 1
- 108010054267 Interferon Receptors Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 208000035490 Megakaryoblastic Acute Leukemia Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 1
- 101100371345 Mus musculus Tyk2 gene Proteins 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010053879 Sepsis syndrome Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 206010051379 Systemic Inflammatory Response Syndrome 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
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000037831 acute erythroleukemic leukemia Diseases 0.000 description 1
- 208000037832 acute lymphoblastic B-cell leukemia Diseases 0.000 description 1
- 208000037833 acute lymphoblastic T-cell leukemia Diseases 0.000 description 1
- 208000013593 acute megakaryoblastic leukemia Diseases 0.000 description 1
- 208000020700 acute megakaryocytic leukemia Diseases 0.000 description 1
- 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 201000007180 bile duct carcinoma Diseases 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000007016 complementary pharmacologic effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000007821 culture assay Methods 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 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
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 208000037828 epithelial carcinoma Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 208000029824 high grade glioma Diseases 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 208000037829 lymphangioendotheliosarcoma Diseases 0.000 description 1
- 208000012804 lymphangiosarcoma Diseases 0.000 description 1
- 238000002794 lymphocyte assay Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 201000011614 malignant glioma Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000011201 multiple comparisons test Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000001611 myxosarcoma Diseases 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012735 once-a-day formulation Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229940011530 otezla Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 238000001907 polarising light microscopy Methods 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 201000010965 sweat gland carcinoma Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 206010047470 viral myocarditis Diseases 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
-
- 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
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Indole Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2019/029772 WO2020222773A1 (en) | 2019-04-30 | 2019-04-30 | Combination therapies comprising apremilast and tyk2 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2019443366A1 true AU2019443366A1 (en) | 2021-12-02 |
Family
ID=66476870
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2019443366A Abandoned AU2019443366A1 (en) | 2019-04-30 | 2019-04-30 | Combination therapies comprising apremilast and Tyk2 inhibitors |
| AU2020266143A Pending AU2020266143A1 (en) | 2019-04-30 | 2020-04-30 | Combination therapies comprising apremilast and Tyk2 inhibitors |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2020266143A Pending AU2020266143A1 (en) | 2019-04-30 | 2020-04-30 | Combination therapies comprising apremilast and Tyk2 inhibitors |
Country Status (14)
| Country | Link |
|---|---|
| EP (2) | EP3962475A1 (es) |
| JP (2) | JP2022537877A (es) |
| KR (2) | KR20220002488A (es) |
| CN (2) | CN114269336A (es) |
| AU (2) | AU2019443366A1 (es) |
| BR (2) | BR112021021809A2 (es) |
| CA (2) | CA3138473A1 (es) |
| CL (1) | CL2021002847A1 (es) |
| CO (2) | CO2021015622A2 (es) |
| IL (2) | IL287665A (es) |
| MA (1) | MA55799A (es) |
| MX (2) | MX2021013317A (es) |
| SG (2) | SG11202112043PA (es) |
| WO (2) | WO2020222773A1 (es) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11202112043PA (en) | 2019-04-30 | 2021-11-29 | Celgene Corp | Combination therapies comprising apremilast and tyk2 inhibitors |
| TW202246232A (zh) | 2021-02-19 | 2022-12-01 | 英商蘇多生物科學有限公司 | Ｔｙｋ２抑制劑及其用途 |
| AU2022350509A1 (en) * | 2021-09-23 | 2024-04-04 | Bristol-Myers Squibb Company | Methods of treating hair-loss disorders with tyk2 inhibitors |
| CA3236262A1 (en) | 2021-10-25 | 2023-05-04 | Isaac Marx | Tyk2 degraders and uses thereof |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6962940B2 (en) * | 2002-03-20 | 2005-11-08 | Celgene Corporation | (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
| US7893101B2 (en) | 2002-03-20 | 2011-02-22 | Celgene Corporation | Solid forms comprising (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, compositions thereof, and uses thereof |
| GB0709031D0 (en) | 2007-05-10 | 2007-06-20 | Sareum Ltd | Pharmaceutical compounds |
| GB0820819D0 (en) | 2008-11-13 | 2008-12-24 | Sareum Ltd | Pharmaceutical compounds |
| US8367689B2 (en) * | 2009-05-06 | 2013-02-05 | Portola Pharmaceuticals, Inc. | Inhibitors of JAK |
| AU2011328237A1 (en) | 2010-11-09 | 2013-05-23 | Cellzome Limited | Pyridine compounds and aza analogues thereof as TYK2 inhibitors |
| WO2012149251A1 (en) * | 2011-04-28 | 2012-11-01 | Celgene Corporation | Methods and compositions using pde4 inhibitors for the treatment and management of autoimmune and inflammatory diseases |
| UA113750C2 (xx) | 2011-12-27 | 2017-03-10 | Склад (+)-2-$1-(3-етокси-4-метоксифеніл)-2-метансульфонілетил]-4-ацетиламіноізоіндолін-1,3-діону | |
| RU2627661C2 (ru) | 2012-01-10 | 2017-08-09 | Ф. Хоффманн-Ля Рош Аг | Соединения пиридазинамида и их применение в качестве ингибиторов тирозинкиназы селезенки (syk) |
| EP2832734A4 (en) | 2012-03-28 | 2015-08-26 | Takeda Pharmaceutical | HETEROCYCLIC CONNECTION |
| US9296725B2 (en) | 2012-05-24 | 2016-03-29 | Cellzome Limited | Heterocyclyl pyrimidine analogues as TYK2 inhibitors |
| UY35126A (es) | 2012-11-08 | 2014-05-30 | Bristol Myers Squibb Co | Ojo es alfa |
| EA028052B1 (ru) * | 2012-11-08 | 2017-10-31 | Бристол-Майерс Сквибб Компани | АЛКИЛАМИДЗАМЕЩЁННЫЕ ПИРИМИДИНОВЫЕ СОЕДИНЕНИЯ, ПРИГОДНЫЕ ДЛЯ МОДУЛЯЦИИ IL-12, IL-23 И/ИЛИ IFNα |
| WO2014151180A1 (en) * | 2013-03-14 | 2014-09-25 | Celgene Corporation | Treatment of psoriatic arthritis using apremilast |
| EP3029031A4 (en) | 2013-07-30 | 2017-01-11 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| WO2015032423A1 (en) | 2013-09-03 | 2015-03-12 | Sareum Limited | Pharmaceutical compounds |
| AR094537A1 (es) | 2013-11-07 | 2015-08-12 | Bristol Myers Squibb Co | COMPUESTOS DE PIRIDILO SUSTITUIDOS CON ALQUILAMIDA ÚTILES COMO MODULADORES DE LAS RESPUESTAS DE IL-12, IL-23 Y/O IFNa |
| CN105992768B (zh) | 2013-12-10 | 2018-04-20 | 百时美施贵宝公司 | 用作IL‑12、IL‑23和/或IFNα响应的调节剂的咪唑并哒嗪化合物 |
| WO2015091584A1 (en) | 2013-12-18 | 2015-06-25 | F. Hoffmann-La Roche Ag | Thiazolopyridine compounds, compositions and their use as tyk2 kinase inhibitors |
| WO2015123453A1 (en) | 2014-02-14 | 2015-08-20 | Portola Pharmaceuticals, Inc. | Pyridazine compounds as jak inhibitors |
| ES2921874T3 (es) | 2014-02-28 | 2022-09-01 | Nimbus Lakshmi Inc | Inhibidores de TYK2 y usos de los mismos |
| EP3157520B1 (en) | 2014-06-23 | 2019-09-04 | Celgene Corporation | Apremilast for the treatment of a liver disease or a liver function abnormality |
| US10092541B2 (en) * | 2014-08-15 | 2018-10-09 | Celgene Corporation | Methods for the treatment of diseases ameliorated by PDE4 inhibition using dosage titration of apremilast |
| NO2721710T3 (es) | 2014-08-21 | 2018-03-31 | ||
| WO2016047678A1 (ja) | 2014-09-25 | 2016-03-31 | 武田薬品工業株式会社 | 複素環化合物 |
| TWI788655B (zh) | 2015-02-27 | 2023-01-01 | 美商林伯士拉克許米公司 | 酪胺酸蛋白質激酶2(tyk2)抑制劑及其用途 |
| EP4327809A3 (en) | 2015-09-02 | 2024-04-17 | Takeda Pharmaceutical Company Limited | Tyk2 inhibitors and uses thereof |
| DK3419978T3 (da) | 2016-02-24 | 2020-06-02 | Pfizer | Pyrazolo[1,5-A]pyrazin-4-yl-derivater som JAK-hæmmere |
| ES2902995T3 (es) | 2016-10-07 | 2022-03-30 | Bristol Myers Squibb Co | Compuestos de imidazopiridazina útiles como moduladores de respuestas a IL-12, IL-23 y/o IFN alfa |
| US10323036B2 (en) | 2016-10-14 | 2019-06-18 | Nimbus Lakshmi, Inc. | TYK2 inhibitors and uses thereof |
| WO2018075937A1 (en) | 2016-10-21 | 2018-04-26 | Nimbus Lakshmi, Inc. | Tyk2 inhibitors and uses thereof |
| WO2018081488A1 (en) | 2016-10-28 | 2018-05-03 | Bristol-Myers Squibb Company | Heterobicyclic compounds useful as modulators of il-12, il-23 and/or ifn alpha responses |
| CN110191887B (zh) | 2016-11-17 | 2022-02-18 | 百时美施贵宝公司 | IL-12、IL-23和/或IFN-α的咪唑并哒嗪调节剂 |
| GB2562702B (en) | 2017-03-06 | 2022-05-18 | Linear Shaped Ltd | Frame and linear shaped charge |
| TW202321243A (zh) * | 2017-03-08 | 2023-06-01 | 美商林伯士拉克許米公司 | Ｔｙｋ２抑制劑之生產方法 |
| SG11202112043PA (en) | 2019-04-30 | 2021-11-29 | Celgene Corp | Combination therapies comprising apremilast and tyk2 inhibitors |
-
2019
- 2019-04-30 SG SG11202112043PA patent/SG11202112043PA/en unknown
- 2019-04-30 EP EP19723291.1A patent/EP3962475A1/en active Pending
- 2019-04-30 MX MX2021013317A patent/MX2021013317A/es unknown
- 2019-04-30 WO PCT/US2019/029772 patent/WO2020222773A1/en unknown
- 2019-04-30 KR KR1020217038511A patent/KR20220002488A/ko unknown
- 2019-04-30 CN CN201980097711.6A patent/CN114269336A/zh active Pending
- 2019-04-30 CA CA3138473A patent/CA3138473A1/en active Pending
- 2019-04-30 BR BR112021021809A patent/BR112021021809A2/pt unknown
- 2019-04-30 AU AU2019443366A patent/AU2019443366A1/en not_active Abandoned
- 2019-04-30 IL IL287665A patent/IL287665A/en unknown
- 2019-04-30 JP JP2021564469A patent/JP2022537877A/ja not_active Abandoned
-
2020
- 2020-04-30 WO PCT/US2020/030608 patent/WO2020223431A1/en unknown
- 2020-04-30 CA CA3138686A patent/CA3138686A1/en active Pending
- 2020-04-30 SG SG11202112018YA patent/SG11202112018YA/en unknown
- 2020-04-30 BR BR112021021826A patent/BR112021021826A8/pt unknown
- 2020-04-30 JP JP2021564471A patent/JP7453251B2/ja active Active
- 2020-04-30 CN CN202080046457.XA patent/CN114206333A/zh active Pending
- 2020-04-30 MA MA055799A patent/MA55799A/fr unknown
- 2020-04-30 EP EP20725978.9A patent/EP3962476A1/en active Pending
- 2020-04-30 MX MX2021013318A patent/MX2021013318A/es unknown
- 2020-04-30 AU AU2020266143A patent/AU2020266143A1/en active Pending
- 2020-04-30 KR KR1020217038512A patent/KR20220002489A/ko unknown
-
2021
- 2021-10-28 IL IL287670A patent/IL287670A/en unknown
- 2021-10-29 CL CL2021002847A patent/CL2021002847A1/es unknown
- 2021-11-22 CO CONC2021/0015622A patent/CO2021015622A2/es unknown
- 2021-11-22 CO CONC2021/0015614A patent/CO2021015614A2/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20220002489A (ko) | 2022-01-06 |
| CL2021002847A1 (es) | 2022-07-22 |
| CA3138473A1 (en) | 2020-11-05 |
| JP7453251B2 (ja) | 2024-03-19 |
| IL287670A (en) | 2021-12-01 |
| EP3962476A1 (en) | 2022-03-09 |
| IL287665A (en) | 2022-07-01 |
| MA55799A (fr) | 2022-03-09 |
| AU2020266143A1 (en) | 2021-12-02 |
| CN114206333A (zh) | 2022-03-18 |
| JP2022537877A (ja) | 2022-08-31 |
| MX2021013317A (es) | 2022-01-18 |
| CA3138686A1 (en) | 2020-11-05 |
| MX2021013318A (es) | 2022-01-31 |
| SG11202112018YA (en) | 2021-11-29 |
| EP3962475A1 (en) | 2022-03-09 |
| WO2020222773A1 (en) | 2020-11-05 |
| KR20220002488A (ko) | 2022-01-06 |
| BR112021021809A2 (pt) | 2022-01-04 |
| BR112021021826A2 (pt) | 2022-01-04 |
| CN114269336A (zh) | 2022-04-01 |
| BR112021021826A8 (pt) | 2022-06-21 |
| WO2020223431A1 (en) | 2020-11-05 |
| CO2021015614A2 (es) | 2021-12-10 |
| SG11202112043PA (en) | 2021-11-29 |
| JP2022537878A (ja) | 2022-08-31 |
| CO2021015622A2 (es) | 2022-02-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11357775B2 (en) | Combination therapies comprising apremilast and Tyk2 inhibitors | |
| WO2020222773A1 (en) | Combination therapies comprising apremilast and tyk2 inhibitors | |
| RU2316318C2 (ru) | Фармацевтическая композиция, включающая ингибитор ренина, блокатор кальциевых каналов и диуретик | |
| JP2006176542A (ja) | フェニルエテンスルホンアミド誘導体含有医薬 | |
| KR102303052B1 (ko) | Jak 저해제를 포함하는 제약 조성물 | |
| JP2019537615A (ja) | シェーグレン症候群の治療におけるペオニフロリン−６’−ｏ−ベンゼンスルホン酸の使用 | |
| JP2022538403A (ja) | がんの治療のためのｅｇｆｒ阻害剤 | |
| JP6775699B2 (ja) | インドール化合物を用いた疼痛又は間質性膀胱炎の治療方法 | |
| WO2003065970A2 (en) | Treatment of fibromyalgia and related fatigue syndromes using pindolol | |
| US20220009889A1 (en) | Polymorphic form of meisoindigo and modified formulation of meisoindigo | |
| WO2020078445A1 (zh) | 一种治疗纤维化疾病的药物组合或药物组合物 | |
| US20070082903A1 (en) | Remedy for rheumatoid arthritis | |
| WO2021224494A1 (en) | New treatments of viral infections | |
| AU2016212625B2 (en) | Prevention or treatment of uric acid or gout disease | |
| JPH03130218A (ja) | 子宮弛緩剤及び膀胱弛緩剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |