AU2015296010A1 - Biomarkers for predicting response of DLBCL to treatment with a BTK inhibitor - Google Patents
Biomarkers for predicting response of DLBCL to treatment with a BTK inhibitor Download PDFInfo
- Publication number
- AU2015296010A1 AU2015296010A1 AU2015296010A AU2015296010A AU2015296010A1 AU 2015296010 A1 AU2015296010 A1 AU 2015296010A1 AU 2015296010 A AU2015296010 A AU 2015296010A AU 2015296010 A AU2015296010 A AU 2015296010A AU 2015296010 A1 AU2015296010 A1 AU 2015296010A1
- Authority
- AU
- Australia
- Prior art keywords
- dlbcl
- lymphoma
- inhibitor
- cell
- ibrutinib
- 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
- 239000000090 biomarker Substances 0.000 title claims abstract description 199
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 title claims description 328
- 238000011282 treatment Methods 0.000 title description 107
- 229940124291 BTK inhibitor Drugs 0.000 title description 90
- 230000004044 response Effects 0.000 title description 25
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 189
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 315
- 230000004048 modification Effects 0.000 claims description 294
- 238000012986 modification Methods 0.000 claims description 294
- 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 description 207
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 204
- 229960001507 ibrutinib Drugs 0.000 claims description 204
- -1 TNFRSF11 A Proteins 0.000 claims description 164
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 106
- 101001003194 Eleusine coracana Alpha-amylase/trypsin inhibitor Proteins 0.000 claims description 86
- 101001064870 Homo sapiens Lon protease homolog, mitochondrial Proteins 0.000 claims description 81
- 101000595531 Homo sapiens Serine/threonine-protein kinase pim-1 Proteins 0.000 claims description 81
- 101000601724 Homo sapiens Paired box protein Pax-5 Proteins 0.000 claims description 71
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 claims description 71
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 claims description 71
- 102100037504 Paired box protein Pax-5 Human genes 0.000 claims description 71
- 108010038036 Receptor Activator of Nuclear Factor-kappa B Proteins 0.000 claims description 52
- 102100028787 Tumor necrosis factor receptor superfamily member 11A Human genes 0.000 claims description 52
- 102100027768 Histone-lysine N-methyltransferase 2D Human genes 0.000 claims description 51
- 101001045848 Homo sapiens Histone-lysine N-methyltransferase 2B Proteins 0.000 claims description 51
- 101001008894 Homo sapiens Histone-lysine N-methyltransferase 2D Proteins 0.000 claims description 51
- 102100038885 Histone acetyltransferase p300 Human genes 0.000 claims description 50
- 101000882390 Homo sapiens Histone acetyltransferase p300 Proteins 0.000 claims description 50
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 49
- 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 claims description 48
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 claims description 48
- 125000000539 amino acid group Chemical group 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 101000761179 Homo sapiens Caspase recruitment domain-containing protein 11 Proteins 0.000 claims description 28
- 102100024965 Caspase recruitment domain-containing protein 11 Human genes 0.000 claims description 26
- 230000000750 progressive effect Effects 0.000 claims description 13
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 claims description 12
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 claims description 12
- 210000001102 germinal center b cell Anatomy 0.000 claims description 11
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims description 10
- 108091012583 BCL2 Proteins 0.000 claims description 6
- 102220225706 rs1014627144 Human genes 0.000 claims description 6
- 102200026940 rs148685531 Human genes 0.000 claims description 6
- 102200049724 rs1555765564 Human genes 0.000 claims description 4
- 101000984620 Homo sapiens Low-density lipoprotein receptor-related protein 1B Proteins 0.000 claims 5
- 101000795659 Homo sapiens Tuberin Proteins 0.000 claims 5
- 102100031955 Lon protease homolog, mitochondrial Human genes 0.000 claims 5
- 102100027121 Low-density lipoprotein receptor-related protein 1B Human genes 0.000 claims 5
- 102100031638 Tuberin Human genes 0.000 claims 5
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims 4
- 101150053046 MYD88 gene Proteins 0.000 claims 4
- 102100024134 Myeloid differentiation primary response protein MyD88 Human genes 0.000 claims 4
- 102100027203 B-cell antigen receptor complex-associated protein beta chain Human genes 0.000 claims 3
- 101000914491 Homo sapiens B-cell antigen receptor complex-associated protein beta chain Proteins 0.000 claims 3
- 102200104802 rs13406336 Human genes 0.000 claims 2
- 102200088456 rs17220206 Human genes 0.000 claims 1
- 102220280387 rs201054129 Human genes 0.000 claims 1
- 102220005330 rs34956202 Human genes 0.000 claims 1
- 102220028791 rs398123246 Human genes 0.000 claims 1
- 102200111144 rs61751411 Human genes 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 106
- 239000000203 mixture Substances 0.000 abstract description 13
- 238000003491 array Methods 0.000 abstract description 11
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 131
- 239000000523 sample Substances 0.000 description 114
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 107
- 235000001014 amino acid Nutrition 0.000 description 97
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 96
- 230000035772 mutation Effects 0.000 description 88
- 108700019205 Tuberous Sclerosis Complex 2 Proteins 0.000 description 84
- 102000044633 Tuberous Sclerosis Complex 2 Human genes 0.000 description 81
- 239000003112 inhibitor Substances 0.000 description 80
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 78
- 230000014509 gene expression Effects 0.000 description 78
- 206010066476 Haematological malignancy Diseases 0.000 description 76
- 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 description 76
- 102000039446 nucleic acids Human genes 0.000 description 76
- 108020004707 nucleic acids Proteins 0.000 description 76
- 150000007523 nucleic acids Chemical class 0.000 description 76
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 70
- 102100040177 Tyrosine-protein kinase Tec Human genes 0.000 description 70
- 206010028980 Neoplasm Diseases 0.000 description 67
- RRHONYZEMUNMJX-UHFFFAOYSA-N N-[5-[[5-[(4-acetyl-1-piperazinyl)-oxomethyl]-4-methoxy-2-methylphenyl]thio]-2-thiazolyl]-4-[(3-methylbutan-2-ylamino)methyl]benzamide Chemical compound C1=C(C(=O)N2CCN(CC2)C(C)=O)C(OC)=CC(C)=C1SC(S1)=CN=C1NC(=O)C1=CC=C(CNC(C)C(C)C)C=C1 RRHONYZEMUNMJX-UHFFFAOYSA-N 0.000 description 63
- 210000004027 cell Anatomy 0.000 description 60
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical group C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 description 54
- 229960001183 venetoclax Drugs 0.000 description 54
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 52
- 238000002560 therapeutic procedure Methods 0.000 description 52
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 50
- 201000003444 follicular lymphoma Diseases 0.000 description 49
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 48
- 239000003814 drug Substances 0.000 description 42
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 38
- 108020004414 DNA Proteins 0.000 description 37
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 33
- 201000011510 cancer Diseases 0.000 description 31
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 30
- 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 29
- 101000864342 Homo sapiens Tyrosine-protein kinase BTK Proteins 0.000 description 27
- 230000036210 malignancy Effects 0.000 description 27
- 238000012544 monitoring process Methods 0.000 description 27
- 108700041737 bcl-2 Genes Proteins 0.000 description 26
- 229940104302 cytosine Drugs 0.000 description 26
- 208000037821 progressive disease Diseases 0.000 description 26
- 206010025323 Lymphomas Diseases 0.000 description 25
- 229940113082 thymine Drugs 0.000 description 24
- 208000011691 Burkitt lymphomas Diseases 0.000 description 22
- 108010058544 Cyclin D2 Proteins 0.000 description 22
- 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 description 22
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 22
- 102100033467 L-selectin Human genes 0.000 description 22
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 22
- 239000002853 nucleic acid probe Substances 0.000 description 22
- 102100022454 Actin, gamma-enteric smooth muscle Human genes 0.000 description 21
- 101000678433 Homo sapiens Actin, gamma-enteric smooth muscle Proteins 0.000 description 21
- 101000923016 Homo sapiens Protein GAPT Proteins 0.000 description 21
- 102100031784 Loricrin Human genes 0.000 description 21
- 102100031494 Protein GAPT Human genes 0.000 description 21
- 229960003957 dexamethasone Drugs 0.000 description 21
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 21
- 108020000318 saccharopine dehydrogenase Proteins 0.000 description 21
- 229940124597 therapeutic agent Drugs 0.000 description 21
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 description 20
- 210000000349 chromosome Anatomy 0.000 description 20
- 201000010099 disease Diseases 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 description 20
- 229930024421 Adenine Natural products 0.000 description 19
- 208000002460 Enteropathy-Associated T-Cell Lymphoma Diseases 0.000 description 19
- 206010036524 Precursor B-lymphoblastic lymphomas Diseases 0.000 description 19
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 19
- 229960000643 adenine Drugs 0.000 description 19
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 19
- 201000006845 reticulosarcoma Diseases 0.000 description 19
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 19
- 238000003752 polymerase chain reaction Methods 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 108091008875 B cell receptors Proteins 0.000 description 17
- 230000037429 base substitution Effects 0.000 description 17
- 230000010261 cell growth Effects 0.000 description 17
- 238000012217 deletion Methods 0.000 description 17
- 230000037430 deletion Effects 0.000 description 17
- 239000012664 BCL-2-inhibitor Substances 0.000 description 16
- 229940123711 Bcl2 inhibitor Drugs 0.000 description 16
- 238000003780 insertion Methods 0.000 description 16
- 230000037431 insertion Effects 0.000 description 16
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 15
- 102100038720 Histone deacetylase 9 Human genes 0.000 description 15
- 239000000427 antigen Substances 0.000 description 15
- 108091007433 antigens Proteins 0.000 description 15
- 102000036639 antigens Human genes 0.000 description 15
- 201000009277 hairy cell leukemia Diseases 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 description 15
- 208000021937 marginal zone lymphoma Diseases 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 210000001185 bone marrow Anatomy 0.000 description 14
- 230000008707 rearrangement Effects 0.000 description 14
- SJVQHLPISAIATJ-ZDUSSCGKSA-N 8-chloro-2-phenyl-3-[(1S)-1-(7H-purin-6-ylamino)ethyl]-1-isoquinolinone Chemical group C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=CC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1 SJVQHLPISAIATJ-ZDUSSCGKSA-N 0.000 description 13
- 101100278318 Dictyostelium discoideum dohh-2 gene Proteins 0.000 description 13
- 206010035226 Plasma cell myeloma Diseases 0.000 description 13
- 230000004075 alteration Effects 0.000 description 13
- 239000002246 antineoplastic agent Substances 0.000 description 13
- 230000027455 binding Effects 0.000 description 13
- 238000001574 biopsy Methods 0.000 description 13
- 238000012545 processing Methods 0.000 description 13
- 102220218221 rs778408360 Human genes 0.000 description 13
- 101150015280 Cel gene Proteins 0.000 description 12
- 208000031404 Chromosome Aberrations Diseases 0.000 description 12
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 12
- 108060003951 Immunoglobulin Proteins 0.000 description 12
- 206010042971 T-cell lymphoma Diseases 0.000 description 12
- 230000003321 amplification Effects 0.000 description 12
- 230000000875 corresponding effect Effects 0.000 description 12
- 229940127089 cytotoxic agent Drugs 0.000 description 12
- 102000018358 immunoglobulin Human genes 0.000 description 12
- 238000003199 nucleic acid amplification method Methods 0.000 description 12
- 102200162764 rs1057519825 Human genes 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 230000011664 signaling Effects 0.000 description 11
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 description 10
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 description 10
- 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 10
- 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 10
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 10
- 230000002159 abnormal effect Effects 0.000 description 10
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 10
- 210000002751 lymph Anatomy 0.000 description 10
- 201000005962 mycosis fungoides Diseases 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 208000020982 T-lymphoblastic lymphoma Diseases 0.000 description 9
- 210000001744 T-lymphocyte Anatomy 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000019491 signal transduction Effects 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 8
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 8
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 8
- 206010061818 Disease progression Diseases 0.000 description 8
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 description 8
- 208000034578 Multiple myelomas Diseases 0.000 description 8
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 8
- 239000012491 analyte Substances 0.000 description 8
- 230000005750 disease progression Effects 0.000 description 8
- 201000006037 primary mediastinal B-cell lymphoma Diseases 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- 230000006907 apoptotic process Effects 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 229940072221 immunoglobulins Drugs 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 238000011269 treatment regimen Methods 0.000 description 7
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 6
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 6
- 102100031162 Collagen alpha-1(XVIII) chain Human genes 0.000 description 6
- 108010079505 Endostatins Proteins 0.000 description 6
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 6
- 229940126656 GS-4224 Drugs 0.000 description 6
- 208000017604 Hodgkin disease Diseases 0.000 description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 6
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 6
- 229930012538 Paclitaxel Natural products 0.000 description 6
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 238000001994 activation Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- ABSXPNGWJFAPRT-UHFFFAOYSA-N benzenesulfonic acid;n-[3-[[5-fluoro-2-[4-(2-methoxyethoxy)anilino]pyrimidin-4-yl]amino]phenyl]prop-2-enamide Chemical compound OS(=O)(=O)C1=CC=CC=C1.C1=CC(OCCOC)=CC=C1NC1=NC=C(F)C(NC=2C=C(NC(=O)C=C)C=CC=2)=N1 ABSXPNGWJFAPRT-UHFFFAOYSA-N 0.000 description 6
- 229960001467 bortezomib Drugs 0.000 description 6
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 6
- 229960004630 chlorambucil Drugs 0.000 description 6
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 6
- 229960003668 docetaxel Drugs 0.000 description 6
- 229960004679 doxorubicin Drugs 0.000 description 6
- 229960005167 everolimus Drugs 0.000 description 6
- 229960000390 fludarabine Drugs 0.000 description 6
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 6
- 229950005309 fostamatinib Drugs 0.000 description 6
- GKDRMWXFWHEQQT-UHFFFAOYSA-N fostamatinib Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(NC=3N=C4N(COP(O)(O)=O)C(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=C1 GKDRMWXFWHEQQT-UHFFFAOYSA-N 0.000 description 6
- 229960003445 idelalisib Drugs 0.000 description 6
- IFSDAJWBUCMOAH-HNNXBMFYSA-N idelalisib Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)CC)=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1 IFSDAJWBUCMOAH-HNNXBMFYSA-N 0.000 description 6
- 229960001101 ifosfamide Drugs 0.000 description 6
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 6
- 238000011901 isothermal amplification Methods 0.000 description 6
- 229960004942 lenalidomide Drugs 0.000 description 6
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 6
- 208000032839 leukemia Diseases 0.000 description 6
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 6
- 229960004963 mesalazine Drugs 0.000 description 6
- 231100000310 mutation rate increase Toxicity 0.000 description 6
- 229960002450 ofatumumab Drugs 0.000 description 6
- 229960001592 paclitaxel Drugs 0.000 description 6
- 229960002340 pentostatin Drugs 0.000 description 6
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 6
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 6
- 229960004618 prednisone Drugs 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- 229960004641 rituximab Drugs 0.000 description 6
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 6
- 229960000235 temsirolimus Drugs 0.000 description 6
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 6
- 229960003433 thalidomide Drugs 0.000 description 6
- 238000011285 therapeutic regimen Methods 0.000 description 6
- 229960005267 tositumomab Drugs 0.000 description 6
- 102100031585 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Human genes 0.000 description 5
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 5
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 5
- 101000777636 Homo sapiens ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 Proteins 0.000 description 5
- 108020004485 Nonsense Codon Proteins 0.000 description 5
- 239000012828 PI3K inhibitor Substances 0.000 description 5
- 206010063092 Trisomy 12 Diseases 0.000 description 5
- 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 5
- 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000003246 corticosteroid Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 210000001165 lymph node Anatomy 0.000 description 5
- 201000000050 myeloid neoplasm Diseases 0.000 description 5
- 230000037434 nonsense mutation Effects 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 5
- 102220332621 rs1394261454 Human genes 0.000 description 5
- 102220005204 rs63750783 Human genes 0.000 description 5
- 102200006385 rs769382085 Human genes 0.000 description 5
- 102220242532 rs779472232 Human genes 0.000 description 5
- 102220166788 rs886046933 Human genes 0.000 description 5
- 230000037436 splice-site mutation Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 230000005945 translocation Effects 0.000 description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- 206010002412 Angiocentric lymphomas 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
- 201000004085 CLL/SLL Diseases 0.000 description 4
- 101100016516 Caenorhabditis elegans hbl-1 gene Proteins 0.000 description 4
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 4
- 102100027907 Cytoplasmic tyrosine-protein kinase BMX Human genes 0.000 description 4
- 101000935548 Homo sapiens Cytoplasmic tyrosine-protein kinase BMX Proteins 0.000 description 4
- 201000003791 MALT lymphoma Diseases 0.000 description 4
- 206010029461 Nodal marginal zone B-cell lymphomas Diseases 0.000 description 4
- 208000010954 Partial deletion of the long arm of chromosome 7 Diseases 0.000 description 4
- 208000007452 Plasmacytoma Diseases 0.000 description 4
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 description 4
- 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 102000052575 Proto-Oncogene Human genes 0.000 description 4
- 108700020978 Proto-Oncogene Proteins 0.000 description 4
- 102100039079 Tyrosine-protein kinase TXK Human genes 0.000 description 4
- 208000023738 chronic lymphocytic leukemia/small lymphocytic lymphoma Diseases 0.000 description 4
- 238000011223 gene expression profiling Methods 0.000 description 4
- 208000021173 high grade B-cell lymphoma Diseases 0.000 description 4
- 208000026876 intravascular large B-cell lymphoma Diseases 0.000 description 4
- 208000006116 lymphomatoid granulomatosis Diseases 0.000 description 4
- 238000007899 nucleic acid hybridization Methods 0.000 description 4
- 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- RNOAOAWBMHREKO-QFIPXVFZSA-N (7S)-2-(4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C(C=C)(=O)N1CCC(CC1)[C@@H]1CCNC=2N1N=C(C=2C(=O)N)C1=CC=C(C=C1)OC1=CC=CC=C1 RNOAOAWBMHREKO-QFIPXVFZSA-N 0.000 description 3
- LCFFREMLXLZNHE-GBOLQPHISA-N (e)-2-[(3r)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(/C#N)=C/C(C)(C)N2CCN(CC2)C2COC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 LCFFREMLXLZNHE-GBOLQPHISA-N 0.000 description 3
- SMOPKEHQPPXRSH-UHFFFAOYSA-N 2-methyl-n-[2-[3-[[2-(prop-2-enoylamino)acetyl]amino]anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide Chemical compound C1=C(C(=O)NC=2C=NC(NC=3C=C(NC(=O)CNC(=O)C=C)C=CC=3)=NC=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 SMOPKEHQPPXRSH-UHFFFAOYSA-N 0.000 description 3
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 3
- VVLHQJDAUIPZFH-UHFFFAOYSA-N 4-[4-[[5-fluoro-4-[3-(prop-2-enoylamino)anilino]pyrimidin-2-yl]amino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC=3N=C(NC=4C=C(NC(=O)C=C)C=CC=4)C(F)=CN=3)=CC=2)=C1 VVLHQJDAUIPZFH-UHFFFAOYSA-N 0.000 description 3
- JIFCFQDXHMUPGP-UHFFFAOYSA-N 4-tert-butyl-n-[2-methyl-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]benzamide Chemical compound C1=CC=C(C=2N=C(NC=3C=CC(=CC=3)C(=O)N3CCOCC3)C(=O)N(C)C=2)C(C)=C1NC(=O)C1=CC=C(C(C)(C)C)C=C1 JIFCFQDXHMUPGP-UHFFFAOYSA-N 0.000 description 3
- SEJLPXCPMNSRAM-GOSISDBHSA-N 6-amino-9-[(3r)-1-but-2-ynoylpyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one Chemical compound C1N(C(=O)C#CC)CC[C@H]1N1C(=O)N(C=2C=CC(OC=3C=CC=CC=3)=CC=2)C2=C(N)N=CN=C21 SEJLPXCPMNSRAM-GOSISDBHSA-N 0.000 description 3
- ZTUJNJAKTLHBEX-UHFFFAOYSA-N 6-cyclopropyl-8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]-6-oxopyridin-3-yl]phenyl]isoquinolin-1-one Chemical compound C1CN(C)CCN1C(C=N1)=CC=C1NC1=CC(C=2C(=C(C=CC=2)N2C(C3=C(F)C=C(C=C3C=C2)C2CC2)=O)CO)=CN(C)C1=O ZTUJNJAKTLHBEX-UHFFFAOYSA-N 0.000 description 3
- BSSBAJKNZOHHCA-UHFFFAOYSA-N 7-benzyl-1-(3-piperidin-1-ylpropyl)-2-(4-pyridin-4-ylphenyl)-5h-imidazo[4,5-g]quinoxalin-6-one Chemical compound C1CCCCN1CCCN1C=2C=C3N=C(CC=4C=CC=CC=4)C(=O)NC3=CC=2N=C1C(C=C1)=CC=C1C1=CC=NC=C1 BSSBAJKNZOHHCA-UHFFFAOYSA-N 0.000 description 3
- 102100027205 B-cell antigen receptor complex-associated protein alpha chain Human genes 0.000 description 3
- 208000003950 B-cell lymphoma Diseases 0.000 description 3
- 102220544638 Cell cycle progression protein 1_Y418H_mutation Human genes 0.000 description 3
- 108010009356 Cyclin-Dependent Kinase Inhibitor p15 Proteins 0.000 description 3
- 102000009512 Cyclin-Dependent Kinase Inhibitor p15 Human genes 0.000 description 3
- 108010009392 Cyclin-Dependent Kinase Inhibitor p16 Proteins 0.000 description 3
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 3
- 102220500865 F-box only protein 38_S592P_mutation Human genes 0.000 description 3
- 102220552010 Gamma-aminobutyric acid receptor subunit beta-1_I429N_mutation Human genes 0.000 description 3
- 102000003886 Glycoproteins Human genes 0.000 description 3
- 108090000288 Glycoproteins Proteins 0.000 description 3
- 101000914489 Homo sapiens B-cell antigen receptor complex-associated protein alpha chain Proteins 0.000 description 3
- 101001077600 Homo sapiens Insulin receptor substrate 2 Proteins 0.000 description 3
- 101100128894 Homo sapiens LRP1B gene Proteins 0.000 description 3
- 101000721646 Homo sapiens Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma Proteins 0.000 description 3
- 102100025092 Insulin receptor substrate 2 Human genes 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 3
- UVSVTDVJQAJIFG-VURMDHGXSA-N LFM-A13 Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC(Br)=CC=C1Br UVSVTDVJQAJIFG-VURMDHGXSA-N 0.000 description 3
- 101150001102 LRP1B gene Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- ZHXNIYGJAOPMSO-UHFFFAOYSA-N N-[5-[[5-[(4-acetyl-1-piperazinyl)-oxomethyl]-4-methoxy-2-methylphenyl]thio]-2-thiazolyl]-4-[(3,3-dimethylbutan-2-ylamino)methyl]benzamide Chemical compound C1=C(C(=O)N2CCN(CC2)C(C)=O)C(OC)=CC(C)=C1SC(S1)=CN=C1NC(=O)C1=CC=C(CNC(C)C(C)(C)C)C=C1 ZHXNIYGJAOPMSO-UHFFFAOYSA-N 0.000 description 3
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 3
- 102220497999 Neuronal growth regulator 1_G594E_mutation Human genes 0.000 description 3
- 244000061176 Nicotiana tabacum Species 0.000 description 3
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 3
- 101100179449 Nicotiana tabacum A622 gene Proteins 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- 102100025063 Phosphatidylinositol 3-kinase C2 domain-containing subunit gamma Human genes 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 101150056413 Pim1 gene Proteins 0.000 description 3
- 102220469108 S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1_G462V_mutation Human genes 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 102220564469 Tyrosine-protein kinase BTK_A508D_mutation Human genes 0.000 description 3
- 102220564531 Tyrosine-protein kinase BTK_A523E_mutation Human genes 0.000 description 3
- 102220564345 Tyrosine-protein kinase BTK_C502F_mutation Human genes 0.000 description 3
- 102220564360 Tyrosine-protein kinase BTK_C502W_mutation Human genes 0.000 description 3
- 102220564477 Tyrosine-protein kinase BTK_D521H_mutation Human genes 0.000 description 3
- 102220564376 Tyrosine-protein kinase BTK_E589D_mutation Human genes 0.000 description 3
- 102220563343 Tyrosine-protein kinase BTK_F25S_mutation Human genes 0.000 description 3
- 102220564537 Tyrosine-protein kinase BTK_F559S_mutation Human genes 0.000 description 3
- 102220564363 Tyrosine-protein kinase BTK_F583S_mutation Human genes 0.000 description 3
- 102220564257 Tyrosine-protein kinase BTK_H364P_mutation Human genes 0.000 description 3
- 102220564322 Tyrosine-protein kinase BTK_I370M_mutation Human genes 0.000 description 3
- 102220563159 Tyrosine-protein kinase BTK_I61N_mutation Human genes 0.000 description 3
- 102220563339 Tyrosine-protein kinase BTK_K12R_mutation Human genes 0.000 description 3
- 102220563342 Tyrosine-protein kinase BTK_K19E_mutation Human genes 0.000 description 3
- 102220563350 Tyrosine-protein kinase BTK_K27R_mutation Human genes 0.000 description 3
- 102220564470 Tyrosine-protein kinase BTK_M509I_mutation Human genes 0.000 description 3
- 102220563341 Tyrosine-protein kinase BTK_R28C_mutation Human genes 0.000 description 3
- 102220563347 Tyrosine-protein kinase BTK_R28P_mutation Human genes 0.000 description 3
- 102220564277 Tyrosine-protein kinase BTK_R307T_mutation Human genes 0.000 description 3
- 102220564539 Tyrosine-protein kinase BTK_R525P_mutation Human genes 0.000 description 3
- 102220564516 Tyrosine-protein kinase BTK_R544G_mutation Human genes 0.000 description 3
- 102220563160 Tyrosine-protein kinase BTK_R82K_mutation Human genes 0.000 description 3
- 102220564312 Tyrosine-protein kinase BTK_S366F_mutation Human genes 0.000 description 3
- 102220563168 Tyrosine-protein kinase BTK_T117P_mutation Human genes 0.000 description 3
- 102220563165 Tyrosine-protein kinase BTK_T184P_mutation Human genes 0.000 description 3
- 102220564252 Tyrosine-protein kinase BTK_V319A_mutation Human genes 0.000 description 3
- 102220564532 Tyrosine-protein kinase BTK_V535F_mutation Human genes 0.000 description 3
- 102220563164 Tyrosine-protein kinase BTK_V64D_mutation Human genes 0.000 description 3
- 102220563151 Tyrosine-protein kinase BTK_V64F_mutation Human genes 0.000 description 3
- 102220577218 Tyrosine-protein kinase BTK_W251L_mutation Human genes 0.000 description 3
- 102220563349 Tyrosine-protein kinase BTK_Y40N_mutation Human genes 0.000 description 3
- 102220564356 Tyrosine-protein kinase BTK_Y476D_mutation Human genes 0.000 description 3
- 102220577209 Tyrosine-protein kinase BTK_Y551F_mutation Human genes 0.000 description 3
- WDENQIQQYWYTPO-IBGZPJMESA-N acalabrutinib Chemical compound CC#CC(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C(=O)NC=2N=CC=CC=2)=C2N1C=CN=C2N WDENQIQQYWYTPO-IBGZPJMESA-N 0.000 description 3
- 102220359327 c.1086C>G Human genes 0.000 description 3
- 102220352968 c.1573C>G Human genes 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 210000001280 germinal center Anatomy 0.000 description 3
- 239000001806 glycerol esters of wood rosin Substances 0.000 description 3
- 235000010985 glycerol esters of wood rosin Nutrition 0.000 description 3
- 238000002493 microarray Methods 0.000 description 3
- IJMHHZDBRUGXNO-UHFFFAOYSA-N n-[3-(8-anilinoimidazo[1,2-a]pyrazin-6-yl)phenyl]-4-tert-butylbenzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)NC1=CC=CC(C=2N=C(NC=3C=CC=CC=3)C3=NC=CN3C=2)=C1 IJMHHZDBRUGXNO-UHFFFAOYSA-N 0.000 description 3
- CDOOFZZILLRUQH-GDLZYMKVSA-N n-[3-[6-[4-[(2r)-1,4-dimethyl-3-oxopiperazin-2-yl]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide Chemical compound CN1CCN(C)C(=O)[C@H]1C(C=C1)=CC=C1NC1=NC(C=2C(=C(NC(=O)C=3SC=4CCCCC=4C=3)C=CC=2)C)=CN(C)C1=O CDOOFZZILLRUQH-GDLZYMKVSA-N 0.000 description 3
- DQPJVNQWPBLBAB-UHFFFAOYSA-N n-[5-[[3-(4-acetylpiperazine-1-carbonyl)-4,5-dimethylphenyl]methylsulfanyl]-1,3-thiazol-2-yl]-4-[(3,3-dimethylbutan-2-ylamino)methyl]benzamide Chemical compound C1=CC(CNC(C)C(C)(C)C)=CC=C1C(=O)NC(S1)=NC=C1SCC1=CC(C)=C(C)C(C(=O)N2CCN(CC2)C(C)=O)=C1 DQPJVNQWPBLBAB-UHFFFAOYSA-N 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 229940018008 rilzabrutinib Drugs 0.000 description 3
- 102200152049 rs104894770 Human genes 0.000 description 3
- 102200061354 rs104894866 Human genes 0.000 description 3
- 102220032552 rs104895389 Human genes 0.000 description 3
- 102200152078 rs1057520045 Human genes 0.000 description 3
- 102200149745 rs1057521103 Human genes 0.000 description 3
- 102200104413 rs1060501202 Human genes 0.000 description 3
- 102200073080 rs119463988 Human genes 0.000 description 3
- 102200162761 rs128620184 Human genes 0.000 description 3
- 102200162820 rs128620185 Human genes 0.000 description 3
- 102200162818 rs128620189 Human genes 0.000 description 3
- 102200162840 rs128621194 Human genes 0.000 description 3
- 102200162723 rs128621196 Human genes 0.000 description 3
- 102200162705 rs128621198 Human genes 0.000 description 3
- 102200162742 rs128621200 Human genes 0.000 description 3
- 102200162744 rs128621202 Human genes 0.000 description 3
- 102200152272 rs128621203 Human genes 0.000 description 3
- 102200152048 rs128621204 Human genes 0.000 description 3
- 102200152070 rs128621206 Human genes 0.000 description 3
- 102200152011 rs128621208 Human genes 0.000 description 3
- 102200035386 rs137853120 Human genes 0.000 description 3
- 102200117384 rs13926 Human genes 0.000 description 3
- 102220206630 rs140636792 Human genes 0.000 description 3
- 102220015163 rs144152046 Human genes 0.000 description 3
- 102220092500 rs145292219 Human genes 0.000 description 3
- 102220078390 rs147904927 Human genes 0.000 description 3
- 102220159983 rs150268016 Human genes 0.000 description 3
- 102220248763 rs1555781403 Human genes 0.000 description 3
- 102200152047 rs1555977474 Human genes 0.000 description 3
- 102200162816 rs1555980875 Human genes 0.000 description 3
- 102220309786 rs200117340 Human genes 0.000 description 3
- 102200071189 rs28934595 Human genes 0.000 description 3
- 102200162721 rs28935478 Human genes 0.000 description 3
- 102220340945 rs376480977 Human genes 0.000 description 3
- 102220229129 rs376675270 Human genes 0.000 description 3
- 102220083511 rs377620735 Human genes 0.000 description 3
- 102200050881 rs386833797 Human genes 0.000 description 3
- 102220012214 rs397515909 Human genes 0.000 description 3
- 102220029805 rs398123662 Human genes 0.000 description 3
- 102220018495 rs45509791 Human genes 0.000 description 3
- 102220024644 rs57877560 Human genes 0.000 description 3
- 102200142926 rs61752138 Human genes 0.000 description 3
- 102200022513 rs727502811 Human genes 0.000 description 3
- 102220056431 rs730880077 Human genes 0.000 description 3
- 102220242295 rs746383238 Human genes 0.000 description 3
- 102200091861 rs75709682 Human genes 0.000 description 3
- 102220242307 rs760486704 Human genes 0.000 description 3
- 102220169800 rs761985295 Human genes 0.000 description 3
- 102220021072 rs80356939 Human genes 0.000 description 3
- 102200128929 rs838827 Human genes 0.000 description 3
- 102200139137 rs864622780 Human genes 0.000 description 3
- 102220103922 rs878854913 Human genes 0.000 description 3
- 102200037645 rs879254535 Human genes 0.000 description 3
- 102220166430 rs886050759 Human genes 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- HEUVRFNVTLGKMZ-SANMLTNESA-N 4-[(2s)-2-(4-cyanophenyl)-2-hydroxy-2-(3-methylimidazol-4-yl)ethoxy]-3-[4-(trifluoromethoxy)phenyl]benzonitrile Chemical compound CN1C=NC=C1[C@@](O)(C=1C=CC(=CC=1)C#N)COC1=CC=C(C#N)C=C1C1=CC=C(OC(F)(F)F)C=C1 HEUVRFNVTLGKMZ-SANMLTNESA-N 0.000 description 2
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 2
- 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 2
- 108700024832 B-Cell CLL-Lymphoma 10 Proteins 0.000 description 2
- 102100037598 B-cell lymphoma/leukemia 10 Human genes 0.000 description 2
- 101150074953 BCL10 gene Proteins 0.000 description 2
- 101100160805 Bacillus subtilis (strain 168) yxaF gene Proteins 0.000 description 2
- 108010087819 Fc receptors Proteins 0.000 description 2
- 102000009109 Fc receptors Human genes 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 101150113681 MALT1 gene Proteins 0.000 description 2
- 108700026676 Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Proteins 0.000 description 2
- 102100038732 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 Human genes 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- 102000038030 PI3Ks Human genes 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- 101150035397 Ros1 gene Proteins 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 2
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 2
- 102220564389 Tyrosine-protein kinase BTK_A622P_mutation Human genes 0.000 description 2
- 102220577206 Tyrosine-protein kinase BTK_C633Y_mutation Human genes 0.000 description 2
- 102220577207 Tyrosine-protein kinase BTK_F644L_mutation Human genes 0.000 description 2
- 102220577204 Tyrosine-protein kinase BTK_M630I_mutation Human genes 0.000 description 2
- 102220577202 Tyrosine-protein kinase BTK_M630T_mutation Human genes 0.000 description 2
- 102220564387 Tyrosine-protein kinase BTK_P619A_mutation Human genes 0.000 description 2
- 102220577205 Tyrosine-protein kinase BTK_R641C_mutation Human genes 0.000 description 2
- 102220563337 Tyrosine-protein kinase BTK_S14F_mutation Human genes 0.000 description 2
- 102220577212 Tyrosine-protein kinase BTK_Y617E_mutation Human genes 0.000 description 2
- 102100038183 Tyrosine-protein kinase SYK Human genes 0.000 description 2
- 201000006966 adult T-cell leukemia Diseases 0.000 description 2
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 102200105112 c.1855C>T Human genes 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- 230000037011 constitutive activity Effects 0.000 description 2
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 238000003500 gene array Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000010208 microarray analysis Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 208000037922 refractory disease Diseases 0.000 description 2
- 102220206928 rs1057521812 Human genes 0.000 description 2
- 102200162849 rs128621190 Human genes 0.000 description 2
- 102200152010 rs128621209 Human genes 0.000 description 2
- 102200152109 rs128621210 Human genes 0.000 description 2
- 102200152132 rs128622212 Human genes 0.000 description 2
- 102220326635 rs1555420162 Human genes 0.000 description 2
- 102220332763 rs1555917318 Human genes 0.000 description 2
- 102220197676 rs1557036757 Human genes 0.000 description 2
- 102220093404 rs574202204 Human genes 0.000 description 2
- 102220098772 rs878853359 Human genes 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000011301 standard therapy Methods 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 239000000225 tumor suppressor protein Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010053754 Aldehyde reductase Proteins 0.000 description 1
- 102100027265 Aldo-keto reductase family 1 member B1 Human genes 0.000 description 1
- 102100027308 Apoptosis regulator BAX Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102100021631 B-cell lymphoma 6 protein Human genes 0.000 description 1
- 208000016778 CD4+/CD56+ hematodermic neoplasm Diseases 0.000 description 1
- 244000045232 Canavalia ensiformis Species 0.000 description 1
- 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
- 102220583052 Cellular tumor antigen p53_K24N_mutation Human genes 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 102100031048 Coiled-coil domain-containing protein 6 Human genes 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 102100039368 ER lumen protein-retaining receptor 2 Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000016937 Extranodal nasal NK/T cell lymphoma Diseases 0.000 description 1
- 102100020903 Ezrin Human genes 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
- 208000034951 Genetic Translocation Diseases 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
- 101710175981 Hamartin Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 101000971234 Homo sapiens B-cell lymphoma 6 protein Proteins 0.000 description 1
- 101000777370 Homo sapiens Coiled-coil domain-containing protein 6 Proteins 0.000 description 1
- 101000812465 Homo sapiens ER lumen protein-retaining receptor 2 Proteins 0.000 description 1
- 101000854648 Homo sapiens Ezrin Proteins 0.000 description 1
- 101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
- 101000795643 Homo sapiens Hamartin Proteins 0.000 description 1
- 101001055315 Homo sapiens Immunoglobulin heavy constant alpha 1 Proteins 0.000 description 1
- 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 1
- 101001017855 Homo sapiens Leucine-rich repeats and immunoglobulin-like domains protein 3 Proteins 0.000 description 1
- 101000740519 Homo sapiens Syndecan-4 Proteins 0.000 description 1
- 101000850794 Homo sapiens Tropomyosin alpha-3 chain Proteins 0.000 description 1
- 101000912503 Homo sapiens Tyrosine-protein kinase Fgr Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 102100026217 Immunoglobulin heavy constant alpha 1 Human genes 0.000 description 1
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 102000042838 JAK family Human genes 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 102000006259 LDL-Receptor Related Proteins Human genes 0.000 description 1
- 108010058141 LDL-Receptor Related Proteins Proteins 0.000 description 1
- 102100033284 Leucine-rich repeats and immunoglobulin-like domains protein 3 Human genes 0.000 description 1
- 208000008771 Lymphadenopathy Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 230000037364 MAPK/ERK pathway Effects 0.000 description 1
- 102000004318 Matrilysin Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100091501 Mus musculus Ros1 gene Proteins 0.000 description 1
- 102220483691 Myb/SANT-like DNA-binding domain-containing protein 1_Q25L_mutation Human genes 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 235000010617 Phaseolus lunatus Nutrition 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102220558511 Proteinase-activated receptor 3_L15S_mutation Human genes 0.000 description 1
- 108010001859 Proto-Oncogene Proteins c-rel Proteins 0.000 description 1
- 102000000850 Proto-Oncogene Proteins c-rel Human genes 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 108050002653 Retinoblastoma protein Proteins 0.000 description 1
- 102100038042 Retinoblastoma-associated protein Human genes 0.000 description 1
- 208000034712 Rickettsia Infections Diseases 0.000 description 1
- 206010061495 Rickettsiosis Diseases 0.000 description 1
- 102100031773 SH2 domain-containing adapter protein F Human genes 0.000 description 1
- 108091006576 SLC34A2 Proteins 0.000 description 1
- 101710204410 Scaffold protein Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 1
- 102220489125 Serine/threonine-protein kinase pim-1_N82K_mutation Human genes 0.000 description 1
- 102100038437 Sodium-dependent phosphate transport protein 2B Human genes 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108010016672 Syk Kinase Proteins 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 102100037220 Syndecan-4 Human genes 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 102100033080 Tropomyosin alpha-3 chain Human genes 0.000 description 1
- 102000044632 Tuberous Sclerosis Complex 1 Human genes 0.000 description 1
- 102100026150 Tyrosine-protein kinase Fgr Human genes 0.000 description 1
- 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 description 1
- 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 description 1
- 102100021657 Tyrosine-protein phosphatase non-receptor type 6 Human genes 0.000 description 1
- 101710128901 Tyrosine-protein phosphatase non-receptor type 6 Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 102220359152 c.170C>T Human genes 0.000 description 1
- 102220360487 c.268C>T Human genes 0.000 description 1
- 102200047322 c.322T>C Human genes 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000012412 chemical coupling Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 230000009629 growth pathway Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 230000006548 oncogenic transformation Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 239000000092 prognostic biomarker Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 102200078033 rs104895335 Human genes 0.000 description 1
- 102220321988 rs1390412870 Human genes 0.000 description 1
- 102220125995 rs144185168 Human genes 0.000 description 1
- 102220340221 rs1555191880 Human genes 0.000 description 1
- 102200043251 rs281875267 Human genes 0.000 description 1
- 102200082896 rs34769005 Human genes 0.000 description 1
- 102200065863 rs387906775 Human genes 0.000 description 1
- 102220093873 rs781163298 Human genes 0.000 description 1
- 102200026754 rs80356672 Human genes 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 238000010911 splenectomy Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000004654 survival pathway Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/156—Polymorphic or mutational markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
- G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
- G01N2333/4701—Details
- G01N2333/4703—Regulators; Modulating activity
- G01N2333/4706—Regulators; Modulating activity stimulating, promoting or activating activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/82—Translation products from oncogenes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2440/00—Post-translational modifications [PTMs] in chemical analysis of biological material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Hospice & Palliative Care (AREA)
- Physics & Mathematics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462032430P | 2014-08-01 | 2014-08-01 | |
| US62/032,430 | 2014-08-01 | ||
| US201562119668P | 2015-02-23 | 2015-02-23 | |
| US62/119,668 | 2015-02-23 | ||
| US201562127484P | 2015-03-03 | 2015-03-03 | |
| US62/127,484 | 2015-03-03 | ||
| PCT/US2015/043300 WO2016019341A1 (en) | 2014-08-01 | 2015-07-31 | Biomarkers for predicting response of dlbcl to treatment with a btk inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2015296010A1 true AU2015296010A1 (en) | 2017-02-02 |
Family
ID=55179406
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2015296010A Abandoned AU2015296010A1 (en) | 2014-08-01 | 2015-07-31 | Biomarkers for predicting response of DLBCL to treatment with a BTK inhibitor |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20160032404A1 (enExample) |
| EP (1) | EP3185870A4 (enExample) |
| JP (1) | JP2017523188A (enExample) |
| KR (1) | KR20170042614A (enExample) |
| CN (1) | CN106714804A (enExample) |
| AU (1) | AU2015296010A1 (enExample) |
| BR (1) | BR112017001677A2 (enExample) |
| CA (1) | CA2955744A1 (enExample) |
| IL (1) | IL250221A0 (enExample) |
| MX (1) | MX2017001302A (enExample) |
| RU (1) | RU2017106794A (enExample) |
| SG (1) | SG11201700774UA (enExample) |
| WO (1) | WO2016019341A1 (enExample) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2350075T1 (sl) | 2008-09-22 | 2014-06-30 | Array Biopharma, Inc. | Substituirane imidazo (1,2b)piridazinske spojine kot Trk kinazni inhibitorji |
| SG10201914059WA (en) | 2008-10-22 | 2020-03-30 | Array Biopharma Inc | Substituted pyrazolo[1,5-a]pyrimidine compounds as trk kinase inhibitors |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| EP2918588B1 (en) | 2010-05-20 | 2017-05-03 | Array Biopharma, Inc. | Macrocyclic compounds as TRK kinase inhibitors |
| NZ604040A (en) | 2010-06-03 | 2015-02-27 | Pharmacyclics Inc | The use of inhibitors of bruton’s tyrosine kinase (btk) |
| KR20150032340A (ko) | 2012-07-24 | 2015-03-25 | 파마시클릭스, 인코포레이티드 | 브루톤 티로신 키나제(btk)의 억제제에 대한 내성과 관련된 돌연변이 |
| WO2016071770A2 (en) * | 2014-11-05 | 2016-05-12 | Janssen Pharmaceutica Nv | Biological markers for identifying ibrutinib resistance in patients having mantle cell lymphoma and methods of using the same |
| US10799505B2 (en) | 2014-11-16 | 2020-10-13 | Array Biopharma, Inc. | Crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-A]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate |
| MA54411B1 (fr) | 2015-04-06 | 2023-11-30 | Janssen Pharmaceutica Nv | Compositions contenant de l'ibrutinib |
| JP2018534296A (ja) | 2015-10-26 | 2018-11-22 | ロクソ オンコロジー, インコーポレイテッドLoxo Oncology, Inc. | Trk阻害薬耐性がんにおける点変異およびそれに関連する方法 |
| MX386416B (es) | 2016-04-04 | 2025-03-18 | Loxo Oncology Inc | Formulaciones liquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida. |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| HUE063877T2 (hu) | 2016-05-18 | 2024-02-28 | Loxo Oncology Inc | (S)-N-(5-((R)-2-(2,5-dlfluorofenil)pirolidin-1-il)plrazolo[1,5-A]pirimidin-3-il) -3-hidroxipirolidin-1-karboxamid elõállítása |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JP7356351B2 (ja) * | 2016-12-12 | 2023-10-04 | エクセラ・バイオサイエンシーズ・インコーポレイテッド | マイクロキャピラリーアレイを使用したスクリーニングのための方法およびシステム |
| US11085039B2 (en) | 2016-12-12 | 2021-08-10 | xCella Biosciences, Inc. | Methods and systems for screening using microcapillary arrays |
| WO2018125832A1 (en) | 2016-12-30 | 2018-07-05 | xCella Biosciences, Inc. | Multi-stage sample recovery system |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| EP3612192A4 (en) * | 2017-06-08 | 2020-05-27 | Enlivex Therapeutics Ltd. | THERAPEUTIC APOPTOTIC CELLS FOR CANCER THERAPY |
| CZ2017787A3 (cs) | 2017-12-08 | 2019-06-19 | Zentiva, K.S. | Farmaceutické kompozice obsahující ibrutinib |
| CN112292117B (zh) * | 2018-06-15 | 2024-06-07 | 詹森药业有限公司 | 包含依鲁替尼的配制品/组合物 |
| GB2577909B (en) * | 2018-10-10 | 2020-11-18 | Symetrica Ltd | Gamma-ray spectrum classification |
| MX2021006368A (es) * | 2018-11-30 | 2021-10-13 | Janssen Biotech Inc | Métodos para tratar el linfoma folicular. |
| ES3039910T3 (en) | 2018-12-06 | 2025-10-27 | Xcella Biosciences Inc | Lateral loading of microcapillary arrays |
| WO2021087044A1 (en) * | 2019-10-30 | 2021-05-06 | Celgene Corporation | Methods for predicting responsiveness of lymphoma to drug and methods for treating lymphoma |
| CA3209784A1 (en) * | 2021-02-03 | 2022-08-11 | Curis Inc. | Biomarkers for fimepinostat therapy |
| WO2023275330A1 (en) * | 2021-06-30 | 2023-01-05 | Janssen Pharmaceutica Nv | Treatments for diffuse large b-cell lymphoma |
| MX2023015147A (es) * | 2021-06-30 | 2024-04-01 | Janssen Pharmaceutica Nv | Inhibidores de la tirosina quinasa de bruton y métodos de su uso. |
| JP7423090B2 (ja) * | 2022-04-07 | 2024-01-29 | 学校法人藤田学園 | 不明熱患者のb細胞リンパ腫診断補助キットおよび情報提供方法 |
| WO2025080543A1 (en) * | 2023-10-09 | 2025-04-17 | Bristol-Myers Squibb Company | Methods for predicting responsiveness of lymphoma to drug and methods for treating lymphoma |
| JP7696987B1 (ja) * | 2023-12-22 | 2025-06-23 | 東洋鋼鈑株式会社 | 遺伝子変異を検出する方法 |
| JP7698850B1 (ja) * | 2023-12-22 | 2025-06-26 | 東洋鋼鈑株式会社 | 遺伝子変異評価用キット |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ604040A (en) * | 2010-06-03 | 2015-02-27 | Pharmacyclics Inc | The use of inhibitors of bruton’s tyrosine kinase (btk) |
| CA2841142C (en) * | 2010-06-23 | 2020-12-15 | Ryan D. Morin | Biomarkers for non-hodgkin lymphomas and uses thereof |
| EP2771010A4 (en) * | 2011-10-19 | 2015-04-01 | Pharmacyclics Inc | USE OF BRUTON TYROSINE KINASE (BTK) INHIBITORS |
| EP2770830A4 (en) * | 2011-10-28 | 2015-05-27 | Celgene Avilomics Res Inc | METHODS OF TREATING A DISEASE OR DISEASE ASSOCIATED WITH TYROSINE KINASE BTK (BRUTON'S TYROSINE KINASE) |
| EA201492082A1 (ru) * | 2012-06-04 | 2015-03-31 | Фармасайкликс, Инк. | Кристаллические формы ингибитора тирозинкиназы брутона |
| KR20150032340A (ko) * | 2012-07-24 | 2015-03-25 | 파마시클릭스, 인코포레이티드 | 브루톤 티로신 키나제(btk)의 억제제에 대한 내성과 관련된 돌연변이 |
| AU2014205577A1 (en) * | 2013-01-10 | 2015-05-28 | Nimbus Iris, Inc. | IRAK inhibitors and uses thereof |
-
2015
- 2015-07-31 AU AU2015296010A patent/AU2015296010A1/en not_active Abandoned
- 2015-07-31 CN CN201580049596.7A patent/CN106714804A/zh active Pending
- 2015-07-31 BR BR112017001677-0A patent/BR112017001677A2/pt not_active Application Discontinuation
- 2015-07-31 CA CA2955744A patent/CA2955744A1/en not_active Abandoned
- 2015-07-31 EP EP15828160.0A patent/EP3185870A4/en not_active Withdrawn
- 2015-07-31 JP JP2017504752A patent/JP2017523188A/ja active Pending
- 2015-07-31 MX MX2017001302A patent/MX2017001302A/es unknown
- 2015-07-31 RU RU2017106794A patent/RU2017106794A/ru not_active Application Discontinuation
- 2015-07-31 SG SG11201700774UA patent/SG11201700774UA/en unknown
- 2015-07-31 KR KR1020177005365A patent/KR20170042614A/ko not_active Withdrawn
- 2015-07-31 WO PCT/US2015/043300 patent/WO2016019341A1/en not_active Ceased
- 2015-07-31 US US14/815,921 patent/US20160032404A1/en not_active Abandoned
-
2017
- 2017-01-22 IL IL250221A patent/IL250221A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RU2017106794A (ru) | 2018-09-03 |
| US20160032404A1 (en) | 2016-02-04 |
| RU2017106794A3 (enExample) | 2019-02-27 |
| IL250221A0 (en) | 2017-03-30 |
| WO2016019341A1 (en) | 2016-02-04 |
| EP3185870A4 (en) | 2018-06-20 |
| MX2017001302A (es) | 2017-10-11 |
| JP2017523188A (ja) | 2017-08-17 |
| CA2955744A1 (en) | 2016-02-04 |
| CN106714804A (zh) | 2017-05-24 |
| BR112017001677A2 (pt) | 2018-07-17 |
| SG11201700774UA (en) | 2017-02-27 |
| KR20170042614A (ko) | 2017-04-19 |
| EP3185870A1 (en) | 2017-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11318138B2 (en) | Methods for treating B cell proliferative disorders | |
| US20160032404A1 (en) | Biomarkers for predicting response of dlbcl to treatment with a btk inhibitor | |
| US9730938B2 (en) | Bruton's tyrosine kinase inhibitor combinations and uses thereof | |
| US20220249494A1 (en) | Use of inhibitors of brutons tyrosine kinase (btk) | |
| KR102054468B1 (ko) | 브루톤 티로신 인산화효소(btk)의 억제제의 용도 | |
| US20220242868A1 (en) | Co-crystals of a bruton's tyrosine kinase inhibitor | |
| US20220106317A1 (en) | Solvated forms of a bruton's tyrosine kinase inhibitor | |
| WO2016123504A1 (en) | Btk inhibitor combinations and multidrug-resistance | |
| US20170360796A1 (en) | Btk inhibitor combinations and dosing regimen | |
| US20200030330A1 (en) | Bruton's tyrosine kinase inhibitor combinations and uses thereof | |
| CN117642168A (zh) | 布鲁顿酪氨酸激酶的抑制剂及其使用方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |