TWI649081B - 治療固態腫瘤之方法 - Google Patents
治療固態腫瘤之方法 Download PDFInfo
- Publication number
- TWI649081B TWI649081B TW103126513A TW103126513A TWI649081B TW I649081 B TWI649081 B TW I649081B TW 103126513 A TW103126513 A TW 103126513A TW 103126513 A TW103126513 A TW 103126513A TW I649081 B TWI649081 B TW I649081B
- Authority
- TW
- Taiwan
- Prior art keywords
- cancer
- combination
- carcinoma
- composition
- substituted
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 262
- 238000000034 method Methods 0.000 title description 34
- 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 191
- 229960001507 ibrutinib Drugs 0.000 claims description 191
- 239000000203 mixture Substances 0.000 claims description 89
- 238000011282 treatment Methods 0.000 claims description 87
- 201000009030 Carcinoma Diseases 0.000 claims description 82
- -1 hydroxylaminomethyl Chemical group 0.000 claims description 70
- 206010039491 Sarcoma Diseases 0.000 claims description 69
- 201000011510 cancer Diseases 0.000 claims description 57
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 49
- 206010005003 Bladder cancer Diseases 0.000 claims description 47
- 208000009956 adenocarcinoma Diseases 0.000 claims description 47
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 46
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 46
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 44
- 201000005202 lung cancer Diseases 0.000 claims description 44
- 208000020816 lung neoplasm Diseases 0.000 claims description 44
- 206010033128 Ovarian cancer Diseases 0.000 claims description 39
- 208000026310 Breast neoplasm Diseases 0.000 claims description 35
- 206010006187 Breast cancer Diseases 0.000 claims description 34
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 31
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 31
- 201000002528 pancreatic cancer Diseases 0.000 claims description 31
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 31
- 206010009944 Colon cancer Diseases 0.000 claims description 28
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 28
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 27
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 27
- 206010060862 Prostate cancer Diseases 0.000 claims description 26
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 26
- 239000002552 dosage form Substances 0.000 claims description 24
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 24
- MAUCONCHVWBMHK-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide Chemical compound O1C2=CC=CC=C2C(CN(C)C)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 MAUCONCHVWBMHK-UHFFFAOYSA-N 0.000 claims description 22
- 229950008805 abexinostat Drugs 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 19
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 18
- 208000000649 small cell carcinoma Diseases 0.000 claims description 18
- 206010023774 Large cell lung cancer Diseases 0.000 claims description 17
- 201000009546 lung large cell carcinoma Diseases 0.000 claims description 17
- 239000002775 capsule Substances 0.000 claims description 15
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 13
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 13
- 208000029742 colonic neoplasm Diseases 0.000 claims description 12
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 11
- 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 claims description 11
- 201000001441 melanoma Diseases 0.000 claims description 11
- 208000014081 polyp of colon Diseases 0.000 claims description 11
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 10
- 201000001342 Fallopian tube cancer Diseases 0.000 claims description 10
- 206010073099 Lobular breast carcinoma in situ Diseases 0.000 claims description 10
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 10
- 201000010881 cervical cancer Diseases 0.000 claims description 10
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 10
- 206010061424 Anal cancer Diseases 0.000 claims description 9
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 9
- 206010073360 Appendix cancer Diseases 0.000 claims description 9
- 206010004992 Bladder adenocarcinoma stage unspecified Diseases 0.000 claims description 9
- 208000009458 Carcinoma in Situ Diseases 0.000 claims description 9
- 201000006107 Familial adenomatous polyposis Diseases 0.000 claims description 9
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 9
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 9
- 206010038389 Renal cancer Diseases 0.000 claims description 9
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 9
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 9
- 206010057644 Testis cancer Diseases 0.000 claims description 9
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 9
- 201000008395 adenosquamous carcinoma Diseases 0.000 claims description 9
- 201000011165 anus cancer Diseases 0.000 claims description 9
- 208000021780 appendiceal neoplasm Diseases 0.000 claims description 9
- 201000009036 biliary tract cancer Diseases 0.000 claims description 9
- 208000020790 biliary tract neoplasm Diseases 0.000 claims description 9
- 201000006587 bladder adenocarcinoma Diseases 0.000 claims description 9
- 201000005389 breast carcinoma in situ Diseases 0.000 claims description 9
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 claims description 9
- 208000024519 eye neoplasm Diseases 0.000 claims description 9
- 206010017758 gastric cancer Diseases 0.000 claims description 9
- 201000004933 in situ carcinoma Diseases 0.000 claims description 9
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 claims description 9
- 201000010982 kidney cancer Diseases 0.000 claims description 9
- 208000003849 large cell carcinoma Diseases 0.000 claims description 9
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 9
- 201000007270 liver cancer Diseases 0.000 claims description 9
- 208000014018 liver neoplasm Diseases 0.000 claims description 9
- 201000011059 lobular neoplasia Diseases 0.000 claims description 9
- 201000005243 lung squamous cell carcinoma Diseases 0.000 claims description 9
- 201000008106 ocular cancer Diseases 0.000 claims description 9
- 201000002530 pancreatic endocrine carcinoma Diseases 0.000 claims description 9
- 201000011549 stomach cancer Diseases 0.000 claims description 9
- 201000003120 testicular cancer Diseases 0.000 claims description 9
- 201000002510 thyroid cancer Diseases 0.000 claims description 9
- 206010023825 Laryngeal cancer Diseases 0.000 claims description 8
- 208000000172 Medulloblastoma Diseases 0.000 claims description 8
- 208000013612 Parathyroid disease Diseases 0.000 claims description 8
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 8
- 206010047741 Vulval cancer Diseases 0.000 claims description 8
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims description 8
- 206010023841 laryngeal neoplasm Diseases 0.000 claims description 8
- 208000022560 parathyroid gland disease Diseases 0.000 claims description 8
- 206010046766 uterine cancer Diseases 0.000 claims description 8
- 206010046885 vaginal cancer Diseases 0.000 claims description 8
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 8
- 201000005102 vulva cancer Diseases 0.000 claims description 8
- 208000035984 Colonic Polyps Diseases 0.000 claims description 7
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 7
- 208000033724 Malignant tumor of fallopian tubes Diseases 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 7
- 230000003412 degenerative effect Effects 0.000 claims description 7
- 201000004101 esophageal cancer Diseases 0.000 claims description 7
- 238000001990 intravenous administration Methods 0.000 claims description 6
- 239000007909 solid dosage form Substances 0.000 claims description 6
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 4
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 201000000849 skin cancer Diseases 0.000 claims description 4
- 208000013452 Fallopian tube neoplasm Diseases 0.000 claims description 3
- 206010038038 rectal cancer Diseases 0.000 claims description 3
- 201000001275 rectum cancer Diseases 0.000 claims description 3
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 208000010576 undifferentiated carcinoma Diseases 0.000 claims description 2
- 206010051589 Large intestine polyp Diseases 0.000 claims 1
- 208000024312 invasive carcinoma Diseases 0.000 claims 1
- 102100036409 Activated CDC42 kinase 1 Human genes 0.000 abstract description 132
- 101000928956 Homo sapiens Activated CDC42 kinase 1 Proteins 0.000 abstract description 132
- 239000003112 inhibitor Substances 0.000 abstract description 125
- 239000003276 histone deacetylase inhibitor Substances 0.000 abstract description 100
- 229940121372 histone deacetylase inhibitor Drugs 0.000 abstract description 82
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 39
- 201000010099 disease Diseases 0.000 abstract description 36
- 238000011161 development Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 description 142
- 125000000217 alkyl group Chemical group 0.000 description 107
- 229940124291 BTK inhibitor Drugs 0.000 description 101
- 239000003814 drug Substances 0.000 description 80
- 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 78
- 229910052799 carbon Inorganic materials 0.000 description 60
- 125000001072 heteroaryl group Chemical group 0.000 description 60
- 241000699670 Mus sp. Species 0.000 description 56
- 125000003118 aryl group Chemical group 0.000 description 54
- 230000002427 irreversible effect Effects 0.000 description 52
- 210000004027 cell Anatomy 0.000 description 48
- 101150015280 Cel gene Proteins 0.000 description 39
- 125000000753 cycloalkyl group Chemical group 0.000 description 39
- 125000000623 heterocyclic group Chemical group 0.000 description 39
- 229940079593 drug Drugs 0.000 description 35
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 32
- 201000008968 osteosarcoma Diseases 0.000 description 30
- 125000003342 alkenyl group Chemical group 0.000 description 29
- 238000011260 co-administration Methods 0.000 description 29
- 125000004429 atom Chemical group 0.000 description 26
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 25
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 25
- 125000000304 alkynyl group Chemical group 0.000 description 22
- 238000009472 formulation Methods 0.000 description 22
- 229910052739 hydrogen Inorganic materials 0.000 description 22
- 239000001257 hydrogen Substances 0.000 description 22
- 125000005842 heteroatom Chemical group 0.000 description 20
- 208000005243 Chondrosarcoma Diseases 0.000 description 19
- 201000008808 Fibrosarcoma Diseases 0.000 description 19
- 206010024627 liposarcoma Diseases 0.000 description 19
- 229910052760 oxygen Inorganic materials 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 19
- 229910052717 sulfur Inorganic materials 0.000 description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 16
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 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 15
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 15
- 210000004072 lung Anatomy 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 238000001356 surgical procedure Methods 0.000 description 15
- 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 14
- 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 14
- 206010027476 Metastases Diseases 0.000 description 14
- 125000004122 cyclic group Chemical group 0.000 description 14
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 14
- 230000002757 inflammatory effect Effects 0.000 description 14
- 230000003211 malignant effect Effects 0.000 description 14
- 230000009401 metastasis Effects 0.000 description 14
- 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 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 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 13
- 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 13
- 229940126656 GS-4224 Drugs 0.000 description 13
- 101100153369 Mus musculus Tle1 gene Proteins 0.000 description 13
- 206010073137 Myxoid liposarcoma Diseases 0.000 description 13
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 13
- 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 13
- 235000018417 cysteine Nutrition 0.000 description 13
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 13
- 125000005843 halogen group Chemical group 0.000 description 13
- 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 13
- 230000004044 response Effects 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- 238000011830 transgenic mouse model Methods 0.000 description 12
- 238000011160 research Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 10
- 125000004404 heteroalkyl group Chemical group 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 206010019280 Heart failures Diseases 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 8
- 125000004414 alkyl thio group Chemical group 0.000 description 8
- 230000001640 apoptogenic effect Effects 0.000 description 8
- 210000000988 bone and bone Anatomy 0.000 description 8
- 229940109239 creatinine Drugs 0.000 description 8
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 8
- 238000013461 design Methods 0.000 description 8
- 125000001188 haloalkyl group Chemical group 0.000 description 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 210000002540 macrophage Anatomy 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 230000007115 recruitment Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 230000004083 survival effect Effects 0.000 description 8
- QEVHRUUCFGRFIF-UHFFFAOYSA-N 6,18-dimethoxy-17-[oxo-(3,4,5-trimethoxyphenyl)methoxy]-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylic acid methyl ester Chemical compound C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-UHFFFAOYSA-N 0.000 description 7
- 201000003076 Angiosarcoma Diseases 0.000 description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 206010007559 Cardiac failure congestive Diseases 0.000 description 7
- 201000009047 Chordoma Diseases 0.000 description 7
- 206010061818 Disease progression Diseases 0.000 description 7
- 208000007207 Epithelioid hemangioendothelioma Diseases 0.000 description 7
- 201000005231 Epithelioid sarcoma Diseases 0.000 description 7
- 208000006168 Ewing Sarcoma Diseases 0.000 description 7
- 208000007569 Giant Cell Tumors Diseases 0.000 description 7
- 208000006050 Hemangiopericytoma Diseases 0.000 description 7
- 208000001258 Hemangiosarcoma Diseases 0.000 description 7
- 208000032843 Hemorrhage Diseases 0.000 description 7
- 208000007766 Kaposi sarcoma Diseases 0.000 description 7
- 201000009574 Mesenchymal Chondrosarcoma Diseases 0.000 description 7
- 208000007727 Muscle Tissue Neoplasms Diseases 0.000 description 7
- 206010029260 Neuroblastoma Diseases 0.000 description 7
- 208000033383 Neuroendocrine tumor of pancreas Diseases 0.000 description 7
- 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 7
- 208000010029 ameloblastoma Diseases 0.000 description 7
- 208000034158 bleeding Diseases 0.000 description 7
- 230000000740 bleeding effect Effects 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 description 7
- 230000005750 disease progression Effects 0.000 description 7
- 210000003237 epithelioid cell Anatomy 0.000 description 7
- 230000007717 exclusion Effects 0.000 description 7
- 201000008815 extraosseous osteosarcoma Diseases 0.000 description 7
- 230000003328 fibroblastic effect Effects 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 206010020718 hyperplasia Diseases 0.000 description 7
- 230000002390 hyperplastic effect Effects 0.000 description 7
- 208000024305 myofibroblastoma Diseases 0.000 description 7
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 206010042863 synovial sarcoma Diseases 0.000 description 7
- 210000002700 urine Anatomy 0.000 description 7
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 6
- 206010065859 Congenital fibrosarcoma Diseases 0.000 description 6
- 206010073135 Dedifferentiated liposarcoma Diseases 0.000 description 6
- 208000032271 Malignant tumor of penis Diseases 0.000 description 6
- 208000002471 Penile Neoplasms Diseases 0.000 description 6
- 206010034299 Penile cancer Diseases 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 6
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 6
- 206010073139 Round cell liposarcoma Diseases 0.000 description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000009534 blood test Methods 0.000 description 6
- 201000010882 cellular myxoid liposarcoma Diseases 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 150000001924 cycloalkanes Chemical class 0.000 description 6
- 230000004069 differentiation Effects 0.000 description 6
- 238000001839 endoscopy Methods 0.000 description 6
- 206010016629 fibroma Diseases 0.000 description 6
- 125000004438 haloalkoxy group Chemical group 0.000 description 6
- 125000004475 heteroaralkyl group Chemical group 0.000 description 6
- 125000004447 heteroarylalkenyl group Chemical group 0.000 description 6
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000013038 irreversible inhibitor Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 125000004660 phenylalkylthio group Chemical group 0.000 description 6
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 201000008864 small cell osteogenic sarcoma Diseases 0.000 description 6
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 5
- 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
- 101150065749 Churc1 gene Proteins 0.000 description 5
- 208000009738 Connective Tissue Neoplasms Diseases 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 5
- 102100038239 Protein Churchill Human genes 0.000 description 5
- 206010039710 Scleroderma Diseases 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 125000003275 alpha amino acid group Chemical group 0.000 description 5
- 206010003119 arrhythmia Diseases 0.000 description 5
- 230000006793 arrhythmia Effects 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 230000024245 cell differentiation Effects 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000008595 infiltration Effects 0.000 description 5
- 238000001764 infiltration Methods 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 206010061289 metastatic neoplasm Diseases 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 208000010125 myocardial infarction Diseases 0.000 description 5
- 208000029974 neurofibrosarcoma Diseases 0.000 description 5
- 239000001301 oxygen Chemical group 0.000 description 5
- 201000010198 papillary carcinoma Diseases 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 201000003434 periosteal osteogenic sarcoma Diseases 0.000 description 5
- 238000001959 radiotherapy Methods 0.000 description 5
- 238000009121 systemic therapy Methods 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 206010044412 transitional cell carcinoma Diseases 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- WJJSZTJGFCFNKI-UHFFFAOYSA-N 1,3-oxathiolane Chemical compound C1CSCO1 WJJSZTJGFCFNKI-UHFFFAOYSA-N 0.000 description 4
- 206010002388 Angina unstable Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 208000007814 Unstable Angina Diseases 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 150000003973 alkyl amines Chemical class 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000002591 computed tomography Methods 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 201000006544 extraosseous Ewings sarcoma-primitive neuroepithelial tumor Diseases 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 4
- 150000003278 haem Chemical class 0.000 description 4
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 210000003097 mucus Anatomy 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 208000010916 pituitary tumor Diseases 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 208000037821 progressive disease Diseases 0.000 description 4
- 238000002271 resection Methods 0.000 description 4
- 239000011593 sulfur Chemical group 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 3
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 3
- 208000031839 Peripheral nerve sheath tumour malignant Diseases 0.000 description 3
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 3
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 150000001345 alkine derivatives Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 239000003098 androgen Substances 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000013068 control sample Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 208000019622 heart disease Diseases 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000002595 magnetic resonance imaging Methods 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 201000009020 malignant peripheral nerve sheath tumor Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000002085 persistent effect Effects 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 239000008223 sterile water Substances 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 2
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 2
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 2
- 125000005330 8 membered heterocyclic group Chemical group 0.000 description 2
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- 108700020463 BRCA1 Proteins 0.000 description 2
- 102000036365 BRCA1 Human genes 0.000 description 2
- 101150072950 BRCA1 gene Proteins 0.000 description 2
- 206010061809 Cervix carcinoma stage 0 Diseases 0.000 description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- 206010011878 Deafness Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 206010053717 Fibrous histiocytoma Diseases 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- 101001010823 Homo sapiens Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 206010059282 Metastases to central nervous system Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 208000006735 Periostitis Diseases 0.000 description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 150000001412 amines Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical class 0.000 description 2
- 238000011225 antiretroviral therapy Methods 0.000 description 2
- 125000005228 aryl sulfonate group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000997 bicalutamide Drugs 0.000 description 2
- 206010005084 bladder transitional cell carcinoma Diseases 0.000 description 2
- 201000001528 bladder urothelial carcinoma Diseases 0.000 description 2
- 201000008791 bone leiomyosarcoma Diseases 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000012321 colectomy Methods 0.000 description 2
- 201000010897 colon adenocarcinoma Diseases 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 238000012325 curative resection Methods 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000009786 epithelial differentiation Effects 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 229960002074 flutamide Drugs 0.000 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 230000003862 health status Effects 0.000 description 2
- 230000010370 hearing loss Effects 0.000 description 2
- 231100000888 hearing loss Toxicity 0.000 description 2
- 208000016354 hearing loss disease Diseases 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 201000000284 histiocytoma Diseases 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000007386 incisional biopsy Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 208000010658 metastatic prostate carcinoma Diseases 0.000 description 2
- 208000007538 neurilemmoma Diseases 0.000 description 2
- 230000009251 neurologic dysfunction Effects 0.000 description 2
- 208000015015 neurological dysfunction Diseases 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 2
- 229960002653 nilutamide Drugs 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 230000000683 nonmetastatic effect Effects 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 210000003460 periosteum Anatomy 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 238000009597 pregnancy test Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 206010039667 schwannoma Diseases 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 208000020352 skin basal cell carcinoma Diseases 0.000 description 2
- 201000008261 skin carcinoma Diseases 0.000 description 2
- 201000010106 skin squamous cell carcinoma Diseases 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 238000009495 sugar coating Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 150000007970 thio esters Chemical group 0.000 description 2
- 238000012384 transportation and delivery Methods 0.000 description 2
- 230000008736 traumatic injury Effects 0.000 description 2
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000005748 tumor development Effects 0.000 description 2
- 210000001635 urinary tract Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- 125000005943 1,2,3,6-tetrahydropyridyl group Chemical group 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- LKLLNYWECKEQIB-UHFFFAOYSA-N 1,3,5-triazinane Chemical compound C1NCNCN1 LKLLNYWECKEQIB-UHFFFAOYSA-N 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- DXSUORGKJZADET-UHFFFAOYSA-N 3,3-dimethylbutan-2-amine Chemical compound CC(N)C(C)(C)C DXSUORGKJZADET-UHFFFAOYSA-N 0.000 description 1
- YYVUOZULIDAKRN-UHFFFAOYSA-N 3-(4-phenoxyphenyl)-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C=12C(N)=NC=NC2=NNC=1C(C=C1)=CC=C1OC1=CC=CC=C1 YYVUOZULIDAKRN-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- PGXIIVWUFFAYLC-UHFFFAOYSA-N 4H-1,3-dioxine Chemical compound C1OCC=CO1.C1OCC=CO1 PGXIIVWUFFAYLC-UHFFFAOYSA-N 0.000 description 1
- MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010060921 Abdominal abscess Diseases 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 206010001367 Adrenal insufficiency Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010056375 Bile duct obstruction Diseases 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 description 1
- 206010058354 Bronchioloalveolar carcinoma Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 108010051219 Cre recombinase Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229940122964 Deacetylase inhibitor Drugs 0.000 description 1
- 208000001154 Dermoid Cyst Diseases 0.000 description 1
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 1
- 208000002251 Dissecting Aneurysm Diseases 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001125671 Eretmochelys imbricata Species 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010016717 Fistula Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017886 Gastroduodenal ulcer Diseases 0.000 description 1
- 206010018001 Gastrointestinal perforation Diseases 0.000 description 1
- 208000009139 Gilbert Disease Diseases 0.000 description 1
- 208000022412 Gilbert syndrome Diseases 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 1
- 101000984551 Homo sapiens Tyrosine-protein kinase Blk Proteins 0.000 description 1
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 101001047681 Homo sapiens Tyrosine-protein kinase Lck Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 description 1
- 208000007666 Klatskin Tumor Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- 206010062049 Lymphocytic infiltration Diseases 0.000 description 1
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 206010025557 Malignant fibrous histiocytoma of bone Diseases 0.000 description 1
- 206010025652 Malignant melanoma in situ Diseases 0.000 description 1
- 206010073059 Malignant neoplasm of unknown primary site Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010027450 Metastases to abdominal cavity Diseases 0.000 description 1
- 206010027457 Metastases to liver Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- 208000000160 Olfactory Esthesioneuroblastoma Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 208000005228 Pericardial Effusion Diseases 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000026149 Primary peritoneal carcinoma Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 108010009978 Tec protein-tyrosine kinase Proteins 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000018452 Torsade de pointes Diseases 0.000 description 1
- 208000002363 Torsades de Pointes Diseases 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 102100027053 Tyrosine-protein kinase Blk Human genes 0.000 description 1
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 1
- 102100024036 Tyrosine-protein kinase Lck Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 208000011930 active peptic ulcer disease Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 208000017515 adrenocortical insufficiency Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000011292 agonist therapy Methods 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005084 alkoxyalkylaminoalkyl group Chemical group 0.000 description 1
- 125000005055 alkyl alkoxy group Chemical group 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 206010002895 aortic dissection Diseases 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 201000007180 bile duct carcinoma Diseases 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 208000015294 blood coagulation disease Diseases 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037180 bone health Effects 0.000 description 1
- 206010006007 bone sarcoma Diseases 0.000 description 1
- 238000007469 bone scintigraphy Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 208000011825 carcinoma of the ampulla of vater Diseases 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 238000011976 chest X-ray Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 201000004365 colon carcinoma in situ Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 208000030381 cutaneous melanoma Diseases 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000000991 decompressive effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 201000007273 ductal carcinoma in situ Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 201000011523 endocrine gland cancer Diseases 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 208000032099 esthesioneuroblastoma Diseases 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 231100000029 gastro-duodenal ulcer Toxicity 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 239000002434 gonadorelin derivative Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 208000018060 hilar cholangiocarcinoma Diseases 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 102000053810 human ERBB4 Human genes 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 125000005181 hydroxyalkylaminoalkyl group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 201000009939 hypertensive encephalopathy Diseases 0.000 description 1
- 239000002117 illicit drug Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 201000007450 intrahepatic cholangiocarcinoma Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical group 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000016992 lung adenocarcinoma in situ Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- FLCWYEUDIOQXEB-UHFFFAOYSA-N morpholin-4-yl(phenyl)methanone Chemical group C=1C=CC=CC=1C(=O)N1CCOCC1 FLCWYEUDIOQXEB-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000001095 motoneuron effect Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 201000009500 myxoid chondrosarcoma Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 201000002120 neuroendocrine carcinoma Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 description 1
- 229960000572 olaparib Drugs 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- SFJGCXYXEFWEBK-UHFFFAOYSA-N oxazepine Chemical compound O1C=CC=CC=N1 SFJGCXYXEFWEBK-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003551 oxepanyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 230000009996 pancreatic endocrine effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000015356 pericytic neoplasm Diseases 0.000 description 1
- 201000008944 perivascular tumor Diseases 0.000 description 1
- 239000011129 pharmaceutical packaging material Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- 239000000955 prescription drug Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 201000001474 proteinuria Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- QFYXSLAAXZTRLG-UHFFFAOYSA-N pyrrolidine-2,3-dione Chemical compound O=C1CCNC1=O QFYXSLAAXZTRLG-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- 201000011164 rectum carcinoma in situ Diseases 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000009589 serological test Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 125000004149 thio group Chemical group *S* 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 125000005503 thioxanyl group Chemical group 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 208000018417 undifferentiated high grade pleomorphic sarcoma of bone Diseases 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 208000029584 urinary system neoplasm Diseases 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 210000000504 visceral peritoneum Anatomy 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229960005080 warfarin Drugs 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
- A61K31/495—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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361861853P | 2013-08-02 | 2013-08-02 | |
| US61/861,853 | 2013-08-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201601727A TW201601727A (zh) | 2016-01-16 |
| TWI649081B true TWI649081B (zh) | 2019-02-01 |
Family
ID=52428222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW103126513A TWI649081B (zh) | 2013-08-02 | 2014-08-01 | 治療固態腫瘤之方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US9421208B2 (enExample) |
| EP (1) | EP3027192A4 (enExample) |
| JP (1) | JP6800750B2 (enExample) |
| AR (1) | AR097204A1 (enExample) |
| CA (1) | CA2919996A1 (enExample) |
| TW (1) | TWI649081B (enExample) |
| WO (1) | WO2015017812A1 (enExample) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2663116C (en) | 2006-09-22 | 2014-06-10 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| US8809273B2 (en) | 2007-03-28 | 2014-08-19 | Pharmacyclics, Inc. | Inhibitors of Bruton's tyrosine kinase |
| CA3031835C (en) | 2008-06-27 | 2021-09-07 | Celgene Car Llc | Heteroaryl compounds and uses thereof |
| US11351168B1 (en) | 2008-06-27 | 2022-06-07 | Celgene Car Llc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| CN102159214A (zh) | 2008-07-16 | 2011-08-17 | 药品循环公司 | 用于实体肿瘤的治疗的布鲁顿酪氨酸激酶的抑制剂 |
| US8603521B2 (en) | 2009-04-17 | 2013-12-10 | Pharmacyclics, Inc. | Formulations of histone deacetylase inhibitor and uses thereof |
| CN102482277B (zh) | 2009-05-05 | 2017-09-19 | 达纳-法伯癌症研究所有限公司 | 表皮生长因子受体抑制剂及治疗障碍的方法 |
| MX342405B (es) | 2010-06-03 | 2016-09-28 | Pharmacyclics Inc | El uso de inhibidores de la tirosina quinasa de bruton (btk). |
| WO2012008514A1 (ja) * | 2010-07-15 | 2012-01-19 | シャープ株式会社 | 画像のイントラ予測モード推定装置、画像符号化装置、画像復号装置、及び画像の符号化データ |
| CN105566229A (zh) | 2010-08-10 | 2016-05-11 | 西建阿维拉米斯研究公司 | Btk抑制剂的苯磺酸盐及其用途和制备方法 |
| RU2644151C2 (ru) | 2010-11-01 | 2018-02-08 | Селджен Авиломикс Рисерч, Инк. | Гетероциклические соединения и их применение |
| US9238629B2 (en) | 2010-11-01 | 2016-01-19 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| WO2012064706A1 (en) | 2010-11-10 | 2012-05-18 | Avila Therapeutics, Inc. | Mutant-selective egfr inhibitors and uses thereof |
| EA201490265A1 (ru) | 2011-07-13 | 2014-12-30 | Фармасайкликс, Инк. | Ингибиторы тирозинкиназы брутона |
| CA2845806C (en) | 2011-09-13 | 2019-06-11 | Pharmacyclics, Inc. | Formulations of histone deacetylase inhibitor in combination with bendamustine and uses thereof |
| US9364476B2 (en) | 2011-10-28 | 2016-06-14 | Celgene Avilomics Research, Inc. | Methods of treating a Bruton's Tyrosine Kinase disease or disorder |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| TWI662964B (zh) | 2012-06-04 | 2019-06-21 | 美商製藥有限責任公司 | 布魯頓氏酪胺酸激酶抑制劑之結晶形式 |
| CN104704129A (zh) | 2012-07-24 | 2015-06-10 | 药品循环公司 | 与对布鲁顿酪氨酸激酶(btk)抑制剂的抗性相关的突变 |
| CN104854107A (zh) | 2012-11-15 | 2015-08-19 | 药品循环公司 | 作为激酶抑制剂的吡咯并嘧啶化合物 |
| EP2935226A4 (en) | 2012-12-21 | 2016-11-02 | Celgene Avilomics Res Inc | HETEROARYL COMPOUNDS AND USES THEREOF |
| US9145387B2 (en) | 2013-02-08 | 2015-09-29 | Celgene Avilomics Research, Inc. | ERK inhibitors and uses thereof |
| EP3033079B1 (en) | 2013-08-12 | 2018-10-31 | Pharmacyclics LLC | Methods for the treatment of her2 amplified cancer |
| US9492471B2 (en) | 2013-08-27 | 2016-11-15 | Celgene Avilomics Research, Inc. | Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase |
| CA2925124A1 (en) | 2013-09-30 | 2015-04-02 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| JP2017509336A (ja) | 2014-03-20 | 2017-04-06 | ファーマサイクリックス エルエルシー | ホスホリパーゼcガンマ2及び耐性に関連した変異 |
| WO2015187848A1 (en) * | 2014-06-04 | 2015-12-10 | Sampath Deepa | Hdac inhibitor and btk inhibitor combinations |
| WO2016019233A1 (en) | 2014-08-01 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| SG11201700849XA (en) | 2014-08-07 | 2017-03-30 | Pharmacyclics Llc | Novel formulations of a bruton's tyrosine kinase inhibitor |
| ES2741785T3 (es) | 2014-08-13 | 2020-02-12 | Celgene Car Llc | Formas y composiciones de un inhibidor de ERK |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| EP3284466A4 (en) | 2015-04-13 | 2018-12-05 | Daiichi Sankyo Company, Limited | Treatment method combining mdm2 inhibitor and btk inhibitor |
| CN105753863B (zh) * | 2015-09-11 | 2018-07-31 | 东莞市真兴贝特医药技术有限公司 | 氧代二氢咪唑并吡啶类化合物及其应用 |
| GB201703876D0 (en) | 2017-03-10 | 2017-04-26 | Berlin-Chemie Ag | Pharmaceutical combinations |
| MX2022015410A (es) | 2020-06-05 | 2023-03-13 | Kinnate Biopharma Inc | Inhibidores de las cinasas receptoras del factor de crecimiento de fibroblastos. |
| USD910604S1 (en) * | 2020-07-22 | 2021-02-16 | Crown Tech Llc | Microphone isolation shield |
| USD905022S1 (en) * | 2020-07-22 | 2020-12-15 | Crown Tech Llc | Microphone isolation shield |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130178483A1 (en) * | 2011-06-28 | 2013-07-11 | Pharmacyclics, Inc. | Methods and Compositions for Inhibition of Bone Resorption |
Family Cites Families (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE794063A (fr) | 1972-01-17 | 1973-07-16 | Henkel & Cie Gmbh | Anti-inflammatoires pour compositions cosmetiques |
| EP0084236A3 (en) | 1981-12-22 | 1983-08-03 | Fbc Limited | Fungicidal heterocyclic compounds and compositions containing them |
| EP0394440B1 (en) | 1987-10-20 | 1994-05-11 | Otsuka Pharmaceutical Co., Ltd. | Phenylcarboxylic acid derivatives |
| JPH03215470A (ja) | 1990-01-22 | 1991-09-20 | Suntory Ltd | プロピオン酸アミド誘導体,その製造法及びそれを有効成分として含有する除草剤 |
| DE4124345A1 (de) | 1991-07-23 | 1993-01-28 | Gruenenthal Gmbh | Substituierte 3,4-dihydronaphthaline, diese verbindungen enthaltende arzneimittel und verfahren zur herstellung dieser verbindungen und arzneimittel |
| GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
| DE4327365A1 (de) | 1993-08-14 | 1995-02-16 | Boehringer Mannheim Gmbh | Verwendung von Phenolen und Phenolderivaten als Arzneimittel mit fibrinogensenkender Wirkung |
| US6326469B1 (en) | 1994-04-22 | 2001-12-04 | Sugen, Inc. | Megakaryocytic protein tyrosine kinases |
| US5593997A (en) | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
| CH690773A5 (de) | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| US5958957A (en) | 1996-04-19 | 1999-09-28 | Novo Nordisk A/S | Modulators of molecules with phosphotyrosine recognition units |
| HUP0102661A2 (hu) | 1998-04-17 | 2001-11-28 | Parker Hughes Institute | BTK-inhibitorok és a BTK-inhibitorok azonosítására szolgáló eljárások, valamint alkalmazásuk |
| US6303652B1 (en) | 1998-08-21 | 2001-10-16 | Hughes Institute | BTK inhibitors and methods for their identification and use |
| US6335155B1 (en) | 1998-06-26 | 2002-01-01 | Sunesis Pharmaceuticals, Inc. | Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules |
| US20050287596A9 (en) | 1998-06-26 | 2005-12-29 | Braisted Andrew C | Novel ligands and libraries of ligands |
| US6998233B2 (en) | 1998-06-26 | 2006-02-14 | Sunesis Pharmaceuticals, Inc. | Methods for ligand discovery |
| US6211197B1 (en) | 1998-10-07 | 2001-04-03 | Merck Frosst Canada & Co. | Prostaglandin receptor ligands |
| US6306897B1 (en) | 1999-03-19 | 2001-10-23 | Parker Hughes Institute | Calanolides for inhibiting BTK |
| WO2001014331A2 (en) | 1999-08-24 | 2001-03-01 | Regents Of The University Of California | Non-quinoline inhibitors of malaria parasites |
| DK1212327T3 (da) | 1999-09-17 | 2003-12-15 | Abbott Gmbh & Co Kg | Pyrazolopyrimidiner som terapeutiske midler |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| US6506769B2 (en) | 1999-10-06 | 2003-01-14 | Boehringer Ingelheim Pharmaceuticals, Inc. | Heterocyclic compounds useful as inhibitors of tyrosine kinases |
| DE60014130T2 (de) | 1999-10-06 | 2006-03-09 | Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield | Heterocyclische verbindungen verwendbar als tyrosinkinase inhibitoren |
| ATE514674T1 (de) | 1999-11-23 | 2011-07-15 | Methylgene Inc | Inhibitoren für histone-deacetylase |
| CA2390857A1 (en) | 1999-11-30 | 2001-06-14 | Fatih M. Uckun | Inhibitors of collagen-induced platelet aggregation |
| CA2394650A1 (en) | 1999-12-17 | 2001-06-21 | Chi B. Vu | Novel heterocycles |
| GB0005345D0 (en) | 2000-03-06 | 2000-04-26 | Mathilda & Terence Kennedy Ins | Methods of treating sepsis septic shock and inflammation |
| GB0023983D0 (en) | 2000-09-29 | 2000-11-15 | Prolifix Ltd | Therapeutic compounds |
| CA2423744C (en) | 2000-09-29 | 2012-04-03 | Prolifix Limited | Hydroxamic acid compounds comprising a sulfonamide linkage as hdac inhibitors |
| MX242553B (es) | 2000-10-20 | 2006-12-06 | Eisai Co Ltd | Derivados aromaticos que contienen nitrogeno. |
| JP2004533209A (ja) | 2000-10-23 | 2004-11-04 | ブリストル−マイヤーズ スクイブ カンパニー | ブルトンチロシンキナーゼおよびブルトンチロシンキナーゼ媒体のモデュレーターおよびその同定方法および骨粗鬆症および関連疾患状態の治療および予防におけるその使用 |
| AU2002232492A1 (en) | 2000-12-06 | 2002-06-18 | Pharmacia Corporation | Rapidly dispersing pharmaceutical composition comprising effervescent agents |
| MXPA03008560A (es) | 2001-03-22 | 2004-06-30 | Abbot Gmbh & Co Kg | Pirazolopirimidinas como agentes terapeuticos. |
| US8306897B2 (en) | 2001-05-04 | 2012-11-06 | Stockshield, Inc. | Method and system for insuring against investment loss |
| EP1463742A4 (en) | 2001-06-21 | 2006-05-10 | Ariad Pharma Inc | NEW PYRAZOLO AND PYRROLO PYRIMIDINES AND THEIR USES |
| CA2450777C (en) | 2001-08-10 | 2013-04-09 | Novartis Ag | Use of c-src inhibitors alone or in combination with sti571 for the treatment of leukaemia |
| WO2003016338A1 (en) | 2001-08-15 | 2003-02-27 | Parker Hughes Institute | Crystal structure of the btk kinase domain |
| JP4391237B2 (ja) | 2001-11-21 | 2009-12-24 | サネシス ファーマシューティカルズ, インコーポレイテッド | リガンド発見のための方法 |
| AU2003211362A1 (en) | 2002-02-21 | 2003-09-09 | Osaka Industrial Promotion Organization | N-hydroxycarboxamide derivative |
| US20040132825A1 (en) | 2002-03-04 | 2004-07-08 | Bacopoulos Nicholas G. | Methods of treating cancer with HDAC inhibitors |
| US20050084905A1 (en) | 2002-03-21 | 2005-04-21 | Prescott John C. | Identification of kinase inhibitors |
| GB2388594A (en) | 2002-05-16 | 2003-11-19 | Bayer Ag | Imidazo-triazine PDE 4 inhibitors |
| CA2494114A1 (en) | 2002-08-02 | 2004-02-12 | Argenta Discovery Limited | Substituted thienyl-hydroxamic acids as histone deacetylase inhibitors |
| AU2003257094A1 (en) | 2002-08-08 | 2004-02-25 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted benzimidazole compounds |
| GB0303910D0 (en) | 2003-02-20 | 2003-03-26 | Merck Sharp & Dohme | Therapeutic agents |
| EP1608628A2 (en) | 2003-03-17 | 2005-12-28 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| WO2004092115A2 (en) | 2003-04-07 | 2004-10-28 | Axys Pharmaceuticals Inc. | Hydroxamates as therapeutic agents |
| US7687506B2 (en) | 2003-04-11 | 2010-03-30 | The Regents Of The University Of California | Selective serine/threonine kinase inhibitors |
| US20050008640A1 (en) | 2003-04-23 | 2005-01-13 | Wendy Waegell | Method of treating transplant rejection |
| EP1473039A1 (en) | 2003-05-02 | 2004-11-03 | Centre National De La Recherche Scientifique (Cnrs) | Use of inhibitors and antisense oligonucleotides of BTK for the treatment of proliferative mastocytosis |
| WO2005014599A1 (en) | 2003-06-04 | 2005-02-17 | Cellular Genomics, Inc. | Imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of bruton’s tyrosine kinase by such compounds |
| US7393848B2 (en) | 2003-06-30 | 2008-07-01 | Cgi Pharmaceuticals, Inc. | Certain heterocyclic substituted imidazo[1,2-A]pyrazin-8-ylamines and methods of inhibition of Bruton's tyrosine kinase by such compounds |
| US8131475B2 (en) | 2003-09-03 | 2012-03-06 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Methods for identifying, diagnosing, and predicting survival of lymphomas |
| CN1897950A (zh) | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| US20070196395A1 (en) | 2003-12-12 | 2007-08-23 | Mackerell Alexander | Immunomodulatory compounds that target and inhibit the py'binding site of tyrosene kinase p56 lck sh2 domain |
| US20070281907A1 (en) | 2003-12-22 | 2007-12-06 | Watkins William J | Kinase Inhibitor Phosphonate Conjugates |
| AU2005228845A1 (en) | 2004-01-26 | 2005-10-13 | Vertex Pharmaceuticals Incorporated | Compositions useful as inhibitors of protein kinases |
| JP2007520559A (ja) | 2004-02-03 | 2007-07-26 | アボット・ラボラトリーズ | 治療薬としてのアミノベンゾオキサゾール類 |
| WO2005097770A1 (en) | 2004-04-07 | 2005-10-20 | Pharmacyclics, Inc. | Novel hydroxamates as therapeutic agents |
| WO2005117980A1 (en) | 2004-06-04 | 2005-12-15 | Pfizer Products Inc. | Method for treating abnormal cell growth |
| WO2006036941A2 (en) | 2004-09-27 | 2006-04-06 | Kosan Biosciences Incorporated | Specific kinase inhibitors |
| EA200700757A1 (ru) | 2004-09-28 | 2007-10-26 | Янссен Фармацевтика Н.В. | Замещённые дипиперидиновые антагонисты ccr2 |
| TW200621240A (en) | 2004-11-05 | 2006-07-01 | Salmedix Inc | Cancer treatments |
| RU2007121508A (ru) | 2004-11-10 | 2008-12-20 | Сги Фармасьютиклз | Определенные имидазо[1, 2-а]пиразин-8-иламины, методы их получения и методы их применения |
| GB0425035D0 (en) | 2004-11-12 | 2004-12-15 | Novartis Ag | Organic compounds |
| AU2006223409B2 (en) | 2005-03-10 | 2011-07-21 | Gilead Connecticut, Inc. | Certain substituted amides, method of making, and method of use thereof |
| BRPI0610278A2 (pt) | 2005-05-13 | 2010-06-08 | Irm Llc | compostos e composições como inibidores de proteìna cinase |
| WO2007002325A1 (en) | 2005-06-22 | 2007-01-04 | Plexxikon, Inc. | Pyrrolo[2,3-b] pyridine derivatives as protein kinase inhibitors |
| CA2629314A1 (en) | 2005-11-12 | 2007-05-24 | Boehringer Ingelheim International Gmbh | Tec kinase inhibitors |
| US7933820B2 (en) | 2006-01-13 | 2011-04-26 | Data Trace Information Services, Llc | Method and apparatus for compiling data from property title documents |
| KR20080098490A (ko) | 2006-01-13 | 2008-11-10 | 파마시클릭스, 인코포레이티드 | 티로신 키나제 억제제 및 이의 용도 |
| EP1984030B1 (en) | 2006-01-30 | 2013-05-08 | The Scripps Research Institute | Methods for detection of circulating tumor cells and methods of diagnosis of cancer in a mammalian subject |
| US20090098137A1 (en) * | 2006-04-05 | 2009-04-16 | Novartis Ag | Combinations of therapeutic agents for treating cancer |
| EP2865381A1 (en) | 2006-05-18 | 2015-04-29 | Pharmacyclics, Inc. | ITK inhibitors for treating blood cell malignancies |
| HRP20130080T1 (hr) | 2006-09-15 | 2013-02-28 | Janssen Pharmaceutica Nv | Inhibitori histonske deacetilaze sa spojenom aktivnosti protiv histonskih deacetilaza klase-i i klase-iib u kombinaciji sa inhibitorima proteasoma |
| CA2663116C (en) | 2006-09-22 | 2014-06-10 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| CA2668286C (en) | 2006-11-03 | 2014-09-16 | Pharmacyclics, Inc. | Bruton's tyrosine kinase activity probe and method of using |
| KR20120090100A (ko) | 2006-12-26 | 2012-08-16 | 파마시클릭스, 인코포레이티드 | 병용 치료에 있어서 히스톤 디아세틸라제 억제제 이용 및 생체표지 감시 방법 |
| US7838234B2 (en) | 2007-01-30 | 2010-11-23 | Pharmacyclics, Inc. | Methods for determining cancer resistance to histone deacetylase inhibitors |
| NL2000640C2 (nl) | 2007-03-05 | 2008-09-08 | Stichting Wetsus Ct Of Excelle | Werkwijze en systeem voor het zuiveren van een vloeistof. |
| US20120065201A1 (en) | 2007-03-28 | 2012-03-15 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
| US8809273B2 (en) | 2007-03-28 | 2014-08-19 | Pharmacyclics, Inc. | Inhibitors of Bruton's tyrosine kinase |
| EP2560007A1 (en) | 2007-03-28 | 2013-02-20 | Pharmacyclics, Inc. | Identification of bruton's tyrosine kinase inhibitors |
| AU2008314632B2 (en) | 2007-10-19 | 2015-05-28 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| US7989465B2 (en) | 2007-10-19 | 2011-08-02 | Avila Therapeutics, Inc. | 4,6-disubstituted pyrimidines useful as kinase inhibitors |
| CA2701275C (en) | 2007-10-23 | 2016-06-21 | F. Hoffmann-La Roche Ag | Kinase inhibitors |
| US8426441B2 (en) | 2007-12-14 | 2013-04-23 | Roche Palo Alto Llc | Inhibitors of bruton's tyrosine kinase |
| EP2110377A1 (en) | 2008-04-15 | 2009-10-21 | DAC S.r.l. | Spirocyclic derivatives as histone deacetylase inhibitors |
| CA3031835C (en) | 2008-06-27 | 2021-09-07 | Celgene Car Llc | Heteroaryl compounds and uses thereof |
| CN102159214A (zh) | 2008-07-16 | 2011-08-17 | 药品循环公司 | 用于实体肿瘤的治疗的布鲁顿酪氨酸激酶的抑制剂 |
| US8603521B2 (en) | 2009-04-17 | 2013-12-10 | Pharmacyclics, Inc. | Formulations of histone deacetylase inhibitor and uses thereof |
| JP5656976B2 (ja) | 2009-04-29 | 2015-01-21 | ローカス ファーマシューティカルズ インコーポレイテッド | ピロロトリアジン化合物 |
| NZ598705A (en) | 2009-09-16 | 2014-06-27 | Celgene Avilomics Res Inc | Protein kinase conjugates and inhibitors |
| US7718662B1 (en) | 2009-10-12 | 2010-05-18 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of bruton's tyrosine kinase |
| US20120071497A1 (en) | 2010-06-03 | 2012-03-22 | Pharmacyclics, Inc. | Methods of treating abc-dlbcl using inhibitors of bruton's tyrosine kinase |
| MX342405B (es) | 2010-06-03 | 2016-09-28 | Pharmacyclics Inc | El uso de inhibidores de la tirosina quinasa de bruton (btk). |
| PT2975042T (pt) | 2010-06-23 | 2019-01-11 | Hanmi Science Co Ltd | Novos derivados de pirimidina fundidos para inibição de atividade de tirosina-quinase |
| CN105566229A (zh) | 2010-08-10 | 2016-05-11 | 西建阿维拉米斯研究公司 | Btk抑制剂的苯磺酸盐及其用途和制备方法 |
| UY34295A (es) | 2011-09-08 | 2013-04-30 | Servier Lab | Nuevo esquema de administración de la n-hidroxi -4- {2-[3- (n,ndimetilaminometil)benzofuran -2- ilcarbonilamino]etoxi}benzamida |
| US8501724B1 (en) | 2012-01-31 | 2013-08-06 | Pharmacyclics, Inc. | Purinone compounds as kinase inhibitors |
| BR112015010059A2 (pt) * | 2012-11-02 | 2017-07-11 | Pharmacyclics Inc | terapia adjuvante com inibidor da quinase da família tec |
| HK1215374A1 (zh) * | 2013-04-08 | 2016-08-26 | Pharmacyclics Llc | 依鲁替尼联合疗法 |
| TWI660739B (zh) | 2013-10-25 | 2019-06-01 | 製藥公司 | 使用布魯頓氏酪胺酸激酶抑制劑之治療及免疫療法 |
| CN105949197A (zh) | 2014-01-29 | 2016-09-21 | 苏州晶云药物科技有限公司 | 依鲁替尼的新晶型及其制备方法 |
-
2014
- 2014-08-01 TW TW103126513A patent/TWI649081B/zh not_active IP Right Cessation
- 2014-08-01 EP EP14831872.8A patent/EP3027192A4/en not_active Withdrawn
- 2014-08-01 WO PCT/US2014/049459 patent/WO2015017812A1/en not_active Ceased
- 2014-08-01 US US14/450,068 patent/US9421208B2/en active Active
- 2014-08-01 CA CA2919996A patent/CA2919996A1/en not_active Abandoned
- 2014-08-01 JP JP2016531935A patent/JP6800750B2/ja not_active Expired - Fee Related
- 2014-08-01 AR ARP140102910A patent/AR097204A1/es unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130178483A1 (en) * | 2011-06-28 | 2013-07-11 | Pharmacyclics, Inc. | Methods and Compositions for Inhibition of Bone Resorption |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3027192A4 (en) | 2017-03-22 |
| US9421208B2 (en) | 2016-08-23 |
| AR097204A1 (es) | 2016-02-24 |
| TW201601727A (zh) | 2016-01-16 |
| US20150038518A1 (en) | 2015-02-05 |
| JP6800750B2 (ja) | 2020-12-16 |
| EP3027192A1 (en) | 2016-06-08 |
| CA2919996A1 (en) | 2015-02-05 |
| WO2015017812A1 (en) | 2015-02-05 |
| JP2016529245A (ja) | 2016-09-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI649081B (zh) | 治療固態腫瘤之方法 | |
| CN104519887B (zh) | 包含B‑Raf抑制剂、EGFR抑制剂和任选PI3Kα抑制剂的药物组合 | |
| BR112021001233A2 (pt) | método para tratar câncer em um paciente, uso de uma quantidade terapeuticamente eficaz de gdc-0077 e quantidade terapeuticamente eficaz de gdc-0077 | |
| RU2630975C2 (ru) | Режим дозирования pi-3 киназы | |
| RU2640180C2 (ru) | Способ адъювантного лечения рака | |
| TW202027736A (zh) | 用PI3Kα抑制劑及二甲雙胍治療癌症之方法 | |
| KR20210106484A (ko) | Hdm2-p53 상호작용 억제제와 bcl2 억제제의 조합 및 암 치료를 위한 이의 용도 | |
| US20220193076A1 (en) | Methods of treating breast cancer with tucatinib | |
| TWI866427B (zh) | 雌激素受體降解劑之給藥方案 | |
| CN106794180A (zh) | 联合疗法 | |
| JP2020519576A (ja) | 肝細胞癌の治療 | |
| TW202120086A (zh) | 治療癌症之方法 | |
| CN114746094A (zh) | 图卡替尼联合卡培他滨和曲妥珠单抗治疗her2阳性乳腺癌的方法 | |
| TW202521120A (zh) | 藥物組合物及其應用 | |
| KR20220098175A (ko) | B 세포 악성 종양을 치료하기 위한 아칼라브루티닙 및 카피바세르팁의 치료 조합 | |
| UA128539C2 (uk) | Чіаураніб для лікування дрібноклітинного раку легенів | |
| KR20210060642A (ko) | 성장 관련 질환 및/또는 그것의 임상적 상태를 억제 및/또는 치료하기 위한 조성물 및 방법 | |
| CA3019682A1 (en) | Treatment of renal cell carcinoma with lenvatinib and everolimus | |
| RU2784869C1 (ru) | Чиаураниб для лечения мелкоклеточного рака легкого | |
| WO2024015506A1 (en) | Methods of treating estrogen receptor-mediated disorders | |
| TW201130819A (en) | Antitumor agent or postoperative adjuvant chemotherapeutic agent for treatment of hepatocellular carcinoma | |
| EP4598520A1 (en) | Methods of treating estrogen receptor-mediated disorders | |
| WO2024076633A1 (en) | Methods of treating estrogen receptor-mediated disorders | |
| Zhao et al. | Construction and Preclinical evaluation of BCL3-Degrading PROTACs for Enhanced Colorectal Cancer Therapy | |
| WO2025199434A1 (en) | Methods of treating breast cancer using a pyrazole compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |