CA2746085A1 - Enzastaurin for the treatment of cancer - Google Patents
Enzastaurin for the treatment of cancer Download PDFInfo
- Publication number
- CA2746085A1 CA2746085A1 CA2746085A CA2746085A CA2746085A1 CA 2746085 A1 CA2746085 A1 CA 2746085A1 CA 2746085 A CA2746085 A CA 2746085A CA 2746085 A CA2746085 A CA 2746085A CA 2746085 A1 CA2746085 A1 CA 2746085A1
- Authority
- CA
- Canada
- Prior art keywords
- cancer
- patient
- hdac2
- enzastaurin
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 57
- AXRCEOKUDYDWLF-UHFFFAOYSA-N 3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(C)C=C1C(C(NC1=O)=O)=C1C(C1=CC=CC=C11)=CN1C(CC1)CCN1CC1=CC=CC=N1 AXRCEOKUDYDWLF-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 201000011510 cancer Diseases 0.000 title claims abstract description 50
- 229950002189 enzastaurin Drugs 0.000 title claims abstract description 50
- 238000011282 treatment Methods 0.000 title description 13
- 102100039999 Histone deacetylase 2 Human genes 0.000 claims abstract description 50
- 101001035011 Homo sapiens Histone deacetylase 2 Proteins 0.000 claims abstract description 50
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims abstract description 19
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims abstract description 17
- 210000004027 cell Anatomy 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- 239000000523 sample Substances 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims description 15
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 claims description 10
- 108020004485 Nonsense Codon Proteins 0.000 claims description 7
- 230000037433 frameshift Effects 0.000 claims description 7
- 230000037434 nonsense mutation Effects 0.000 claims description 7
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- JWOGUUIOCYMBPV-GMFLJSBRSA-N (3S,6S,9S,12R)-3-[(2S)-Butan-2-yl]-6-[(1-methoxyindol-3-yl)methyl]-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone Chemical compound N1C(=O)[C@H](CCCCCC(=O)CC)NC(=O)[C@H]2CCCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CC1=CN(OC)C2=CC=CC=C12 JWOGUUIOCYMBPV-GMFLJSBRSA-N 0.000 claims description 5
- 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 5
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 claims description 5
- KQGPQDMPQIWCMX-UHFFFAOYSA-N 4-pyridin-4-yl-1,3-dihydroimidazole-2-thione Chemical compound N1C(S)=NC(C=2C=CN=CC=2)=C1 KQGPQDMPQIWCMX-UHFFFAOYSA-N 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 108010002156 Depsipeptides Proteins 0.000 claims description 5
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 5
- 206010025323 Lymphomas Diseases 0.000 claims description 5
- IDQPVOFTURLJPT-UHFFFAOYSA-N N,N'-dihydroxyoctanediamide Chemical compound ONC(=O)CCCCCCC(=O)NO IDQPVOFTURLJPT-UHFFFAOYSA-N 0.000 claims description 5
- AJRGHIGYPXNABY-UHFFFAOYSA-N N-hydroxy-1-[(4-methoxyphenyl)methyl]-6-indolecarboxamide Chemical compound C1=CC(OC)=CC=C1CN1C2=CC(C(=O)NO)=CC=C2C=C1 AJRGHIGYPXNABY-UHFFFAOYSA-N 0.000 claims description 5
- JWOGUUIOCYMBPV-UHFFFAOYSA-N OT-Key 11219 Natural products N1C(=O)C(CCCCCC(=O)CC)NC(=O)C2CCCCN2C(=O)C(C(C)CC)NC(=O)C1CC1=CN(OC)C2=CC=CC=C12 JWOGUUIOCYMBPV-UHFFFAOYSA-N 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
- 229930189037 Trapoxin Natural products 0.000 claims description 5
- 229950008805 abexinostat Drugs 0.000 claims description 5
- 108010082820 apicidin Proteins 0.000 claims description 5
- 229930186608 apicidin Natural products 0.000 claims description 5
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 claims description 5
- 229960003094 belinostat Drugs 0.000 claims description 5
- QOXHZZQZTIGPEV-UHFFFAOYSA-K cyclopenta-1,3-diene;titanium(4+);trichloride Chemical compound Cl[Ti+](Cl)Cl.C=1C=C[CH-]C=1 QOXHZZQZTIGPEV-UHFFFAOYSA-K 0.000 claims description 5
- 150000001993 dienes Chemical class 0.000 claims description 5
- 208000005017 glioblastoma Diseases 0.000 claims description 5
- MUTBJZVSRNUIHA-UHFFFAOYSA-N n-hydroxy-2-(4-naphthalen-2-ylsulfonylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound N1=CC(C(=O)NO)=CN=C1N1CCN(S(=O)(=O)C=2C=C3C=CC=CC3=CC=2)CC1 MUTBJZVSRNUIHA-UHFFFAOYSA-N 0.000 claims description 5
- 201000002528 pancreatic cancer Diseases 0.000 claims description 5
- 229960005184 panobinostat Drugs 0.000 claims description 5
- FWZRWHZDXBDTFK-ZHACJKMWSA-N panobinostat Chemical compound CC1=NC2=CC=C[CH]C2=C1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FWZRWHZDXBDTFK-ZHACJKMWSA-N 0.000 claims description 5
- 239000013610 patient sample Substances 0.000 claims description 5
- 229950009215 phenylbutanoic acid Drugs 0.000 claims description 5
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 claims description 5
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 claims description 5
- 108010060597 trapoxin A Proteins 0.000 claims description 5
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 claims description 5
- 229960000604 valproic acid Drugs 0.000 claims description 5
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical group ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 claims description 5
- 229960000237 vorinostat Drugs 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010014733 Endometrial cancer Diseases 0.000 claims description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- HRNLUBSXIHFDHP-UHFFFAOYSA-N N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC1=NC=CC(C=2C=NC=CC=2)=N1 HRNLUBSXIHFDHP-UHFFFAOYSA-N 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 4
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 201000005962 mycosis fungoides Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 239000000090 biomarker Substances 0.000 abstract description 8
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 230000014509 gene expression Effects 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 13
- 108020004459 Small interfering RNA Proteins 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102000003964 Histone deacetylase Human genes 0.000 description 9
- 108090000353 Histone deacetylase Proteins 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 239000012091 fetal bovine serum Substances 0.000 description 8
- 238000003364 immunohistochemistry Methods 0.000 description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- 229930182816 L-glutamine Natural products 0.000 description 6
- 238000003752 polymerase chain reaction Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 5
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- -1 MGCDO103 Chemical compound 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 102100022524 Alpha-1-antichymotrypsin Human genes 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 101000678026 Homo sapiens Alpha-1-antichymotrypsin Proteins 0.000 description 2
- 238000011529 RT qPCR Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000012054 celltiter-glo Methods 0.000 description 2
- 229940000425 combination drug Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 230000002357 endometrial effect Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010061968 Gastric neoplasm Diseases 0.000 description 1
- 101150098261 Hdac2 gene Proteins 0.000 description 1
- 102000003893 Histone acetyltransferases Human genes 0.000 description 1
- 108090000246 Histone acetyltransferases Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 238000010805 cDNA synthesis kit Methods 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 201000011024 colonic benign neoplasm Diseases 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000023965 endometrium neoplasm Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013077 scoring method Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000013517 stratification Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009044 synergistic interaction Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000013076 thyroid tumor Diseases 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091006105 transcriptional corepressors Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/15—Depsipeptides; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12245108P | 2008-12-15 | 2008-12-15 | |
| US61/122,451 | 2008-12-15 | ||
| PCT/US2009/066925 WO2010074936A2 (en) | 2008-12-15 | 2009-12-07 | Enzastaurin for the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2746085A1 true CA2746085A1 (en) | 2010-07-01 |
Family
ID=41785627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2746085A Abandoned CA2746085A1 (en) | 2008-12-15 | 2009-12-07 | Enzastaurin for the treatment of cancer |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20110288032A1 (https=) |
| EP (1) | EP2376081A2 (https=) |
| JP (1) | JP2012512157A (https=) |
| KR (1) | KR20110084533A (https=) |
| CN (1) | CN102245184A (https=) |
| AU (1) | AU2009330492A1 (https=) |
| BR (1) | BRPI0922367A2 (https=) |
| CA (1) | CA2746085A1 (https=) |
| EA (1) | EA201170821A1 (https=) |
| MX (1) | MX2011006433A (https=) |
| WO (1) | WO2010074936A2 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3007787C (en) | 2010-06-03 | 2020-03-10 | Pharmacyclics Llc | The use of inhibitors of bruton's tyrosine kinase (btk) |
| CA2862492A1 (en) * | 2012-01-24 | 2013-08-01 | Millennium Pharmaceuticals, Inc. | Methods of treatment of cancer |
| EP2812338A4 (en) * | 2012-01-24 | 2015-09-23 | Millennium Pharm Inc | METHOD FOR THE TREATMENT OF NASOPHARYNGEAL CANCER |
| AU2013221298A1 (en) * | 2012-02-17 | 2014-08-28 | Pharmacyclics Llc | Combinations of histone deacetylase inhibitor and pazopanib and uses thereof |
| 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 |
| MX372671B (es) * | 2013-07-19 | 2020-04-23 | Onyx Therapeutics Inc | Inhibidores de proteasoma de epoxicetona peptídica en combinacion con inhibidores de cinasa pim para el tratamiento de canceres. |
| US9885086B2 (en) | 2014-03-20 | 2018-02-06 | Pharmacyclics Llc | Phospholipase C gamma 2 and resistance associated mutations |
| WO2017011314A1 (en) * | 2015-07-10 | 2017-01-19 | Paharmacyclics Llc | Btk and hdac combinations |
| EP3963092A1 (en) * | 2019-05-02 | 2022-03-09 | Predictive Technology Group, Inc. | Somatic cancer driver mutations in endometriosis lesions contribute to secondary cancer risk |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2179650C (en) | 1993-12-23 | 2007-10-30 | William Francis Heath, Jr. | Bisindolemaleimides and their use as protein kinase c inhibitors |
| US20080096923A1 (en) * | 2004-07-23 | 2008-04-24 | Aniz Girach | Methods For Diagnosing And Treating Diabetic Microvascular Complications |
| WO2006135733A2 (en) * | 2005-06-10 | 2006-12-21 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Modulation of peripheral clocks in adipose tissue |
-
2009
- 2009-12-07 KR KR1020117013612A patent/KR20110084533A/ko not_active Ceased
- 2009-12-07 WO PCT/US2009/066925 patent/WO2010074936A2/en not_active Ceased
- 2009-12-07 BR BRPI0922367A patent/BRPI0922367A2/pt not_active IP Right Cessation
- 2009-12-07 JP JP2011540796A patent/JP2012512157A/ja not_active Withdrawn
- 2009-12-07 CN CN2009801503024A patent/CN102245184A/zh active Pending
- 2009-12-07 CA CA2746085A patent/CA2746085A1/en not_active Abandoned
- 2009-12-07 MX MX2011006433A patent/MX2011006433A/es not_active Application Discontinuation
- 2009-12-07 EP EP09768467A patent/EP2376081A2/en not_active Withdrawn
- 2009-12-07 EA EA201170821A patent/EA201170821A1/ru unknown
- 2009-12-07 AU AU2009330492A patent/AU2009330492A1/en not_active Abandoned
- 2009-12-07 US US13/130,104 patent/US20110288032A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010074936A3 (en) | 2010-09-16 |
| US20110288032A1 (en) | 2011-11-24 |
| EA201170821A1 (ru) | 2011-12-30 |
| KR20110084533A (ko) | 2011-07-25 |
| EP2376081A2 (en) | 2011-10-19 |
| WO2010074936A2 (en) | 2010-07-01 |
| CN102245184A (zh) | 2011-11-16 |
| BRPI0922367A2 (pt) | 2016-05-24 |
| AU2009330492A1 (en) | 2010-07-01 |
| MX2011006433A (es) | 2011-07-19 |
| JP2012512157A (ja) | 2012-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pan et al. | The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma | |
| Wasko et al. | Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer | |
| US20110288032A1 (en) | Enzastaurin for the treatment of cancer | |
| Lissanu Deribe et al. | Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer | |
| Agnihotri et al. | Alkylpurine–DNA–N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients | |
| Gooding et al. | The lncRNA BORG facilitates the survival and chemoresistance of triple-negative breast cancers | |
| Thatikonda et al. | Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance | |
| US12006553B2 (en) | Companion diagnostics for mitochondrial inhibitors | |
| Wang et al. | LncRNA MALAT1 accelerates non‐small cell lung cancer progression via regulating miR‐185‐5p/MDM4 axis | |
| Lu et al. | SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers | |
| Gruhn et al. | The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia | |
| Shah et al. | Targeting ribonucleotide reductase M2 and NF-κB activation with didox to circumvent tamoxifen resistance in breast cancer | |
| Li et al. | BCL6 is regulated by the MAPK/ELK1 axis and promotes KRAS-driven lung cancer | |
| Bell et al. | MNK inhibition disrupts mesenchymal glioma stem cells and prolongs survival in a mouse model of glioblastoma | |
| JP2019508440A (ja) | 固形腫瘍の治療における使用のための、ｌｓｄ１阻害剤の組合せ | |
| US20150025017A1 (en) | Compositions and methods for treating cancer | |
| Mus et al. | The ETS transcription factor ETV5 is a target of activated ALK in neuroblastoma contributing to increased tumour aggressiveness | |
| Lee et al. | Genome‐scale CRISPR screening identifies cell cycle and protein ubiquitination processes as druggable targets for erlotinib‐resistant lung cancer | |
| Raghava Kurup et al. | ADAR3 activates NF-κB signaling and promotes glioblastoma cell resistance to temozolomide | |
| Wang et al. | Oncogenic K-ras confers SAHA resistance by up-regulating HDAC6 and c-myc expression | |
| Rao et al. | Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by sponging miR‐30a to regulate COX‐2/BCL9 pathway | |
| Lai et al. | HAF mediates the evasive resistance of anti-angiogenesis TKI through disrupting HIF-1α and HIF-2α balance in renal cell carcinoma | |
| Welti et al. | NXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth | |
| EP4244391A1 (en) | Methods and compositions for predicting and treating uveal melanoma | |
| KR101999476B1 (ko) | Alk 저해제에 내성을 획득한 eml4-alk 양성 비소세포폐암의 치료를 위한 약물 선택의 정보 제공 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20141209 |