JP2013502424A - 熱ショックタンパク質結合化合物、組成物、およびそれらを製造するための方法 - Google Patents
熱ショックタンパク質結合化合物、組成物、およびそれらを製造するための方法 Download PDFInfo
- Publication number
- JP2013502424A JP2013502424A JP2012525652A JP2012525652A JP2013502424A JP 2013502424 A JP2013502424 A JP 2013502424A JP 2012525652 A JP2012525652 A JP 2012525652A JP 2012525652 A JP2012525652 A JP 2012525652A JP 2013502424 A JP2013502424 A JP 2013502424A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- alkenyl
- alkynyl
- group
- saturated
- 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.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 207
- 238000000034 method Methods 0.000 title claims abstract description 63
- 230000027455 binding Effects 0.000 title claims description 54
- 238000009739 binding Methods 0.000 title claims description 54
- 239000000203 mixture Substances 0.000 title description 47
- 102000002812 Heat-Shock Proteins Human genes 0.000 title description 5
- 108010004889 Heat-Shock Proteins Proteins 0.000 title description 5
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 claims abstract description 128
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 67
- 150000003839 salts Chemical class 0.000 claims abstract description 56
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 52
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 230000002062 proliferating effect Effects 0.000 claims abstract description 22
- 108010036652 HSC70 Heat-Shock Proteins Proteins 0.000 claims abstract description 19
- 102000012215 HSC70 Heat-Shock Proteins Human genes 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 238000012544 monitoring process Methods 0.000 claims abstract 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 325
- 125000003545 alkoxy group Chemical group 0.000 claims description 317
- 125000000217 alkyl group Chemical group 0.000 claims description 280
- 229920006395 saturated elastomer Polymers 0.000 claims description 267
- 125000000304 alkynyl group Chemical group 0.000 claims description 227
- 125000003118 aryl group Chemical group 0.000 claims description 202
- 125000003282 alkyl amino group Chemical group 0.000 claims description 171
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 170
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 170
- 125000004986 diarylamino group Chemical group 0.000 claims description 170
- 125000001769 aryl amino group Chemical group 0.000 claims description 169
- 125000000623 heterocyclic group Chemical group 0.000 claims description 155
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 154
- 229910052736 halogen Inorganic materials 0.000 claims description 146
- 150000002367 halogens Chemical class 0.000 claims description 146
- 210000004027 cell Anatomy 0.000 claims description 145
- 229910052739 hydrogen Inorganic materials 0.000 claims description 145
- 239000001257 hydrogen Substances 0.000 claims description 142
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 138
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 135
- 125000004442 acylamino group Chemical group 0.000 claims description 134
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 133
- 150000001408 amides Chemical class 0.000 claims description 131
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 127
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 127
- -1 trihaloalkyl carbon Chemical compound 0.000 claims description 127
- 125000004104 aryloxy group Chemical group 0.000 claims description 126
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 106
- 229940124530 sulfonamide Drugs 0.000 claims description 95
- 150000003456 sulfonamides Chemical class 0.000 claims description 95
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 94
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 92
- 125000004001 thioalkyl group Chemical group 0.000 claims description 88
- 125000005647 linker group Chemical group 0.000 claims description 55
- 235000018102 proteins Nutrition 0.000 claims description 47
- 230000000694 effects Effects 0.000 claims description 45
- 201000011510 cancer Diseases 0.000 claims description 44
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 42
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims description 42
- 229910052799 carbon Inorganic materials 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 41
- 239000003112 inhibitor Substances 0.000 claims description 28
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 25
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 25
- 206010006187 Breast cancer Diseases 0.000 claims description 20
- 208000026310 Breast neoplasm Diseases 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000002837 carbocyclic group Chemical group 0.000 claims description 17
- 239000003446 ligand Substances 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 230000006907 apoptotic process Effects 0.000 claims description 16
- 238000003556 assay Methods 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 14
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 14
- 230000015556 catabolic process Effects 0.000 claims description 13
- 238000006731 degradation reaction Methods 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 11
- 230000008856 allosteric binding Effects 0.000 claims description 11
- 238000003776 cleavage reaction Methods 0.000 claims description 11
- 230000001965 increasing effect Effects 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 230000007017 scission Effects 0.000 claims description 11
- 230000010261 cell growth Effects 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 8
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 claims description 8
- 235000001014 amino acid Nutrition 0.000 claims description 8
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 238000012545 processing Methods 0.000 claims description 8
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 8
- 238000012360 testing method Methods 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 102000011727 Caspases Human genes 0.000 claims description 7
- 108010076667 Caspases Proteins 0.000 claims description 7
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 claims description 7
- 230000001640 apoptogenic effect Effects 0.000 claims description 7
- 230000007423 decrease Effects 0.000 claims description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
- 238000002875 fluorescence polarization Methods 0.000 claims description 7
- 230000002779 inactivation Effects 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 6
- 230000004913 activation Effects 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 238000013500 data storage Methods 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 230000009036 growth inhibition Effects 0.000 claims description 6
- 230000001939 inductive effect Effects 0.000 claims description 6
- 108020001756 ligand binding domains Proteins 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 238000012216 screening Methods 0.000 claims description 6
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 6
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 102100023038 WD and tetratricopeptide repeats protein 1 Human genes 0.000 claims description 5
- 239000002773 nucleotide Substances 0.000 claims description 5
- 125000003729 nucleotide group Chemical group 0.000 claims description 5
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical class CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 4
- 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 claims description 4
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 claims description 4
- 125000005250 alkyl acrylate group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 230000009286 beneficial effect Effects 0.000 claims description 4
- 230000002860 competitive effect Effects 0.000 claims description 4
- 230000006698 induction Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000003936 working memory Effects 0.000 claims description 4
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 3
- 102000014150 Interferons Human genes 0.000 claims description 3
- 108010050904 Interferons Proteins 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 230000017066 negative regulation of growth Effects 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 210000004881 tumor cell Anatomy 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 210000004204 blood vessel Anatomy 0.000 claims description 2
- 239000007850 fluorescent dye Substances 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 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 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 36
- 239000012472 biological sample Substances 0.000 claims 5
- 208000037824 growth disorder Diseases 0.000 claims 1
- 229940079322 interferon Drugs 0.000 claims 1
- 201000001037 lung lymphoma Diseases 0.000 claims 1
- OSGZIPATAUFTOB-UHFFFAOYSA-N n-[2-[2-(4-methylpiperazin-1-yl)-4-phenylmethoxypyrimidin-5-yl]sulfanylpyrimidin-4-yl]prop-2-enamide Chemical compound C1CN(C)CCN1C(N=C1OCC=2C=CC=CC=2)=NC=C1SC1=NC=CC(NC(=O)C=C)=N1 OSGZIPATAUFTOB-UHFFFAOYSA-N 0.000 claims 1
- OFOBBRIOXWIASO-UHFFFAOYSA-N n-[2-[4,6-dimethoxy-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]sulfanylpyrimidin-4-yl]prop-2-enamide Chemical compound COC1=NC(N2CCN(C)CC2)=NC(OC)=C1SC1=NC=CC(NC(=O)C=C)=N1 OFOBBRIOXWIASO-UHFFFAOYSA-N 0.000 claims 1
- SXCYNWXZUZUHKI-UHFFFAOYSA-N n-[3-[2-(4-methylpiperazin-1-yl)-4-phenylmethoxypyrimidin-5-yl]sulfanylphenyl]acetamide Chemical compound C1CN(C)CCN1C(N=C1OCC=2C=CC=CC=2)=NC=C1SC1=CC=CC(NC(C)=O)=C1 SXCYNWXZUZUHKI-UHFFFAOYSA-N 0.000 claims 1
- DNCACTLFFFYPLO-UHFFFAOYSA-N n-[3-[2-(4-methylpiperazin-1-yl)-4-phenylmethoxypyrimidin-5-yl]sulfanylphenyl]benzamide Chemical compound C1CN(C)CCN1C(N=C1OCC=2C=CC=CC=2)=NC=C1SC1=CC=CC(NC(=O)C=2C=CC=CC=2)=C1 DNCACTLFFFYPLO-UHFFFAOYSA-N 0.000 claims 1
- NVOGKZHADXJLOK-UHFFFAOYSA-N n-[3-[2-(4-methylpiperazin-1-yl)-4-phenylmethoxypyrimidin-5-yl]sulfanylphenyl]prop-2-enamide Chemical compound C1CN(C)CCN1C(N=C1OCC=2C=CC=CC=2)=NC=C1SC1=CC=CC(NC(=O)C=C)=C1 NVOGKZHADXJLOK-UHFFFAOYSA-N 0.000 claims 1
- YBBRZWICSZOVDL-UHFFFAOYSA-N n-[6-amino-2-[4,6-diethoxy-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]sulfanylpyrimidin-4-yl]prop-2-enamide Chemical compound CCOC1=NC(N2CCN(C)CC2)=NC(OCC)=C1SC1=NC(N)=CC(NC(=O)C=C)=N1 YBBRZWICSZOVDL-UHFFFAOYSA-N 0.000 claims 1
- ZYAVZIQPWICPQI-UHFFFAOYSA-N n-[6-amino-2-[4,6-dimethoxy-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]sulfanylpyrimidin-4-yl]prop-2-enamide Chemical compound COC1=NC(N2CCN(C)CC2)=NC(OC)=C1SC1=NC(N)=CC(NC(=O)C=C)=N1 ZYAVZIQPWICPQI-UHFFFAOYSA-N 0.000 claims 1
- 239000000523 sample Substances 0.000 claims 1
- 239000011232 storage material Substances 0.000 claims 1
- 230000035939 shock Effects 0.000 abstract description 6
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 abstract description 4
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000011394 anticancer treatment Methods 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 106
- 239000011324 bead Substances 0.000 description 41
- 238000005481 NMR spectroscopy Methods 0.000 description 34
- 230000005764 inhibitory process Effects 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 238000001262 western blot Methods 0.000 description 27
- 230000002829 reductive effect Effects 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 102000043276 Oncogene Human genes 0.000 description 24
- 108091008819 oncoproteins Proteins 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 22
- 208000035475 disorder Diseases 0.000 description 22
- 239000000284 extract Substances 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000003981 vehicle Substances 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 17
- 238000004440 column chromatography Methods 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- 108010090804 Streptavidin Proteins 0.000 description 14
- 230000006870 function Effects 0.000 description 14
- 230000007246 mechanism Effects 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 10
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 150000003384 small molecules Chemical class 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- 239000013543 active substance Substances 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 235000000638 D-biotin Nutrition 0.000 description 8
- 239000011665 D-biotin Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000003281 allosteric effect Effects 0.000 description 8
- 230000003993 interaction Effects 0.000 description 8
- 230000003211 malignant effect Effects 0.000 description 8
- 102000000521 Immunophilins Human genes 0.000 description 7
- 108010016648 Immunophilins Proteins 0.000 description 7
- 102000007474 Multiprotein Complexes Human genes 0.000 description 7
- 108010085220 Multiprotein Complexes Proteins 0.000 description 7
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000006882 induction of apoptosis Effects 0.000 description 7
- 238000012746 preparative thin layer chromatography Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000037361 pathway Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- QCAWOHUJKPKOMD-UHFFFAOYSA-N 4,6-diamino-1h-pyrimidine-2-thione Chemical compound NC1=CC(N)=NC(S)=N1 QCAWOHUJKPKOMD-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 108010042283 HSP40 Heat-Shock Proteins Proteins 0.000 description 5
- 102000004447 HSP40 Heat-Shock Proteins Human genes 0.000 description 5
- 108010006519 Molecular Chaperones Proteins 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 4
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 4
- ISYXPRJYSJTAIH-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1CC1=CC=NC(N)=N1 ISYXPRJYSJTAIH-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 4
- 102100028642 Prostaglandin E synthase 3 Human genes 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 4
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 239000012190 activator Substances 0.000 description 4
- 230000001028 anti-proliverative effect Effects 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 230000006369 cell cycle progression Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000002648 combination therapy Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000001114 immunoprecipitation Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000036210 malignancy Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108090001008 Avidin Proteins 0.000 description 3
- 108090000397 Caspase 3 Proteins 0.000 description 3
- 102100029855 Caspase-3 Human genes 0.000 description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 3
- 108700020796 Oncogene Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 3
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 231100000504 carcinogenesis Toxicity 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 238000009388 chemical precipitation Methods 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- BXVSAYBZSGIURM-UHFFFAOYSA-N 2-phenoxy-4h-1,3,2$l^{5}-benzodioxaphosphinine 2-oxide Chemical compound O1CC2=CC=CC=C2OP1(=O)OC1=CC=CC=C1 BXVSAYBZSGIURM-UHFFFAOYSA-N 0.000 description 2
- KYUTTZLLGAWFAP-UHFFFAOYSA-N 2-pyrimidin-5-ylsulfanylpyrimidine Chemical group N=1C=CC=NC=1SC1=CN=CN=C1 KYUTTZLLGAWFAP-UHFFFAOYSA-N 0.000 description 2
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 2
- KCIOVTSUEXGUFJ-UHFFFAOYSA-N 8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-pent-4-yn-1-yl-9H-purin-6-amine Chemical compound COC1=C(OC)C(OC)=CC(CC=2N(C3=NC(F)=NC(N)=C3N=2)CCCC#C)=C1Cl KCIOVTSUEXGUFJ-UHFFFAOYSA-N 0.000 description 2
- 108091006112 ATPases Proteins 0.000 description 2
- 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 206010000830 Acute leukaemia Diseases 0.000 description 2
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 101150099575 CDC37 gene Proteins 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101150112743 HSPA5 gene Proteins 0.000 description 2
- 101150101832 HSPA9 gene Proteins 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 2
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 2
- 108091008611 Protein Kinase B Proteins 0.000 description 2
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 2
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000036676 acute undifferentiated leukemia Diseases 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 231100000315 carcinogenic Toxicity 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000001876 chaperonelike Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 150000001924 cycloalkanes Chemical class 0.000 description 2
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 230000030609 dephosphorylation Effects 0.000 description 2
- 238000006209 dephosphorylation reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000004980 dosimetry Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 239000012145 high-salt buffer Substances 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000005414 inactive ingredient Substances 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000009456 molecular mechanism Effects 0.000 description 2
- 230000010309 neoplastic transformation Effects 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000012342 propidium iodide staining Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000006920 protein precipitation Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 229910052721 tungsten Inorganic materials 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- SUPVGFZUWFMATN-UHFFFAOYSA-N zelavespib Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4OCOC=4C=3)I)=NC2=C1N SUPVGFZUWFMATN-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- KWMLJOLKUYYJFJ-GASJEMHNSA-N (2xi)-D-gluco-heptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C(O)=O KWMLJOLKUYYJFJ-GASJEMHNSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RBNPOMFGQQGHHO-UHFFFAOYSA-N -2,3-Dihydroxypropanoic acid Natural products OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- WLXGQMVCYPUOLM-UHFFFAOYSA-N 1-hydroxyethanesulfonic acid Chemical compound CC(O)S(O)(=O)=O WLXGQMVCYPUOLM-UHFFFAOYSA-N 0.000 description 1
- MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- FGYADSCZTQOAFK-UHFFFAOYSA-N 1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C=NC2=C1 FGYADSCZTQOAFK-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 description 1
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
- QAFDFEXCGOCOGG-UHFFFAOYSA-N 2-(cyanoamino)-2-oxoacetic acid Chemical compound OC(=O)C(=O)NC#N QAFDFEXCGOCOGG-UHFFFAOYSA-N 0.000 description 1
- DLOKUYYLDQGBIB-UHFFFAOYSA-N 2-[2-[bis[(4-methoxyphenyl)methyl]amino]-4,6-diethoxypyrimidin-5-yl]sulfanylpyrimidine-4,6-diamine Chemical compound CCOC1=NC(N(CC=2C=CC(OC)=CC=2)CC=2C=CC(OC)=CC=2)=NC(OCC)=C1SC1=NC(N)=CC(N)=N1 DLOKUYYLDQGBIB-UHFFFAOYSA-N 0.000 description 1
- AZOMAPVTQSPORF-UHFFFAOYSA-N 2-[2-[bis[(4-methoxyphenyl)methyl]amino]-4,6-dimethoxypyrimidin-5-yl]sulfanylpyrimidine-4,6-diamine Chemical compound C1=CC(OC)=CC=C1CN(C=1N=C(OC)C(SC=2N=C(N)C=C(N)N=2)=C(OC)N=1)CC1=CC=C(OC)C=C1 AZOMAPVTQSPORF-UHFFFAOYSA-N 0.000 description 1
- GXKUNEURMIPZNE-UHFFFAOYSA-N 2-[4,6-dimethoxy-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]sulfanylpyrimidine-4,6-diamine Chemical compound COC1=NC(N2CCN(C)CC2)=NC(OC)=C1SC1=NC(N)=CC(N)=N1 GXKUNEURMIPZNE-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 101710128979 23 kDa piroplasm membrane protein Proteins 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- QMEQBOSUJUOXMX-UHFFFAOYSA-N 2h-oxadiazine Chemical compound N1OC=CC=N1 QMEQBOSUJUOXMX-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- UNTNRNUQVKDIPV-UHFFFAOYSA-N 3h-dithiazole Chemical compound N1SSC=C1 UNTNRNUQVKDIPV-UHFFFAOYSA-N 0.000 description 1
- KWIVRAVCZJXOQC-UHFFFAOYSA-N 3h-oxathiazole Chemical compound N1SOC=C1 KWIVRAVCZJXOQC-UHFFFAOYSA-N 0.000 description 1
- JPZOAVGMSDSWSW-UHFFFAOYSA-N 4,6-dichloropyrimidin-2-amine Chemical compound NC1=NC(Cl)=CC(Cl)=N1 JPZOAVGMSDSWSW-UHFFFAOYSA-N 0.000 description 1
- LVFRCHIUUKWBLR-UHFFFAOYSA-N 4,6-dimethoxypyrimidin-2-amine Chemical compound COC1=CC(OC)=NC(N)=N1 LVFRCHIUUKWBLR-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 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
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 102100032187 Androgen receptor Human genes 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- RBNPOMFGQQGHHO-UWTATZPHSA-N D-glyceric acid Chemical compound OC[C@@H](O)C(O)=O RBNPOMFGQQGHHO-UWTATZPHSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102100022207 E3 ubiquitin-protein ligase parkin Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 101710113436 GTPase KRas Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 101150051208 HSPH1 gene Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000967216 Homo sapiens Eosinophil cationic protein Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 1
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 1
- 101001095089 Homo sapiens PML-RARA-regulated adapter molecule 1 Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101001116548 Homo sapiens Protein CBFA2T1 Proteins 0.000 description 1
- 101000712530 Homo sapiens RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 235000008694 Humulus lupulus Nutrition 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 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
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 101710159527 Maturation protein A Proteins 0.000 description 1
- 101710091157 Maturation protein A2 Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000005431 Molecular Chaperones Human genes 0.000 description 1
- 101100381978 Mus musculus Braf gene Proteins 0.000 description 1
- 101100339694 Mus musculus Hspa1b gene Proteins 0.000 description 1
- 101100451677 Mus musculus Hspa4 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 108010058765 Oncogene Protein pp60(v-src) Proteins 0.000 description 1
- 102100037019 PML-RARA-regulated adapter molecule 1 Human genes 0.000 description 1
- 101710177166 Phosphoprotein Proteins 0.000 description 1
- 102000007982 Phosphoproteins Human genes 0.000 description 1
- 108010089430 Phosphoproteins Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 102100024952 Protein CBFA2T1 Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000055027 Protein Methyltransferases Human genes 0.000 description 1
- 108700040121 Protein Methyltransferases Proteins 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101710094326 Ras-related protein R-Ras Proteins 0.000 description 1
- 101100339690 Rattus norvegicus Hspa1a gene Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108010017842 Telomerase Proteins 0.000 description 1
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 1
- JZFICWYCTCCINF-UHFFFAOYSA-N Thiadiazin Chemical compound S=C1SC(C)NC(C)N1CCN1C(=S)SC(C)NC1C JZFICWYCTCCINF-UHFFFAOYSA-N 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- 101710157927 Translationally-controlled tumor protein Proteins 0.000 description 1
- 101710175870 Translationally-controlled tumor protein homolog Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000004062 acenaphthenyl group Chemical group C1(CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 229960000250 adipic acid Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 238000003349 alamar blue assay Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000006323 alkenyl amino group Chemical group 0.000 description 1
- 125000005422 alkyl sulfonamido group Chemical group 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000005122 aminoalkylamino group Chemical group 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 150000001540 azides Chemical group 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N beta-hydroxyethanesulfonic acid Natural products OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 201000002136 bile duct sarcoma Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
- 210000003969 blast cell Anatomy 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical class [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 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 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- WBZKQQHYRPRKNJ-UHFFFAOYSA-N disulfurous acid Chemical compound OS(=O)S(O)(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-N 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- MNQDKWZEUULFPX-UHFFFAOYSA-M dithiazanine iodide Chemical compound [I-].S1C2=CC=CC=C2[N+](CC)=C1C=CC=CC=C1N(CC)C2=CC=CC=C2S1 MNQDKWZEUULFPX-UHFFFAOYSA-M 0.000 description 1
- USIWYKJRJIVHBN-UHFFFAOYSA-N dodecyl hydrogen sulfite Chemical compound CCCCCCCCCCCCOS(O)=O USIWYKJRJIVHBN-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000010410 dusting Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- JOXWSDNHLSQKCC-UHFFFAOYSA-N ethenesulfonamide Chemical compound NS(=O)(=O)C=C JOXWSDNHLSQKCC-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000034725 extrinsic apoptotic signaling pathway Effects 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000010820 immunofluorescence microscopy Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 239000006207 intravenous dosage form Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 125000002463 lignoceryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000005741 malignant process Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- SCFCEBRAZKHPRE-UHFFFAOYSA-N n-[6-acetamido-2-(2-amino-4,6-diethoxypyrimidin-5-yl)sulfanylpyrimidin-4-yl]acetamide Chemical compound CCOC1=NC(N)=NC(OCC)=C1SC1=NC(NC(C)=O)=CC(NC(C)=O)=N1 SCFCEBRAZKHPRE-UHFFFAOYSA-N 0.000 description 1
- CDMJDESECCKWAX-UHFFFAOYSA-N n-[6-acetamido-2-(2-amino-4,6-dimethoxypyrimidin-5-yl)sulfanylpyrimidin-4-yl]acetamide Chemical compound COC1=NC(N)=NC(OC)=C1SC1=NC(NC(C)=O)=CC(NC(C)=O)=N1 CDMJDESECCKWAX-UHFFFAOYSA-N 0.000 description 1
- IXTJNKWOABHKLQ-UHFFFAOYSA-N n-[6-acetamido-2-(2-fluoro-4,6-dimethoxypyrimidin-5-yl)sulfanylpyrimidin-4-yl]acetamide Chemical compound COC1=NC(F)=NC(OC)=C1SC1=NC(NC(C)=O)=CC(NC(C)=O)=N1 IXTJNKWOABHKLQ-UHFFFAOYSA-N 0.000 description 1
- APZOXZKAXJLYJZ-UHFFFAOYSA-N n-[6-acetamido-2-(4,6-diethoxy-2-fluoropyrimidin-5-yl)sulfanylpyrimidin-4-yl]acetamide Chemical compound CCOC1=NC(F)=NC(OCC)=C1SC1=NC(NC(C)=O)=CC(NC(C)=O)=N1 APZOXZKAXJLYJZ-UHFFFAOYSA-N 0.000 description 1
- MBALKHXJZPESLC-UHFFFAOYSA-N n-[6-acetamido-2-[2-[bis[(4-methoxyphenyl)methyl]amino]-4,6-diethoxypyrimidin-5-yl]sulfanylpyrimidin-4-yl]acetamide Chemical compound CCOC1=NC(N(CC=2C=CC(OC)=CC=2)CC=2C=CC(OC)=CC=2)=NC(OCC)=C1SC1=NC(NC(C)=O)=CC(NC(C)=O)=N1 MBALKHXJZPESLC-UHFFFAOYSA-N 0.000 description 1
- WODPSWGZCWMLKK-UHFFFAOYSA-N n-[6-acetamido-2-[2-[bis[(4-methoxyphenyl)methyl]amino]-4,6-dimethoxypyrimidin-5-yl]sulfanylpyrimidin-4-yl]acetamide Chemical compound C1=CC(OC)=CC=C1CN(C=1N=C(OC)C(SC=2N=C(NC(C)=O)C=C(NC(C)=O)N=2)=C(OC)N=1)CC1=CC=C(OC)C=C1 WODPSWGZCWMLKK-UHFFFAOYSA-N 0.000 description 1
- QSAIGIDPEGEHQC-UHFFFAOYSA-N n-[6-acetamido-2-[4,6-diethoxy-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]sulfanylpyrimidin-4-yl]acetamide Chemical compound CCOC1=NC(N2CCN(C)CC2)=NC(OCC)=C1SC1=NC(NC(C)=O)=CC(NC(C)=O)=N1 QSAIGIDPEGEHQC-UHFFFAOYSA-N 0.000 description 1
- KYBGKFLSHRWLAB-UHFFFAOYSA-N n-[6-acetamido-2-[4,6-dimethoxy-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]sulfanylpyrimidin-4-yl]acetamide Chemical compound COC1=NC(N2CCN(C)CC2)=NC(OC)=C1SC1=NC(NC(C)=O)=CC(NC(C)=O)=N1 KYBGKFLSHRWLAB-UHFFFAOYSA-N 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
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 231100001222 nononcogenic Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- LTHCSWBWNVGEFE-UHFFFAOYSA-N octanamide Chemical compound CCCCCCCC(N)=O LTHCSWBWNVGEFE-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004650 oncogenic pathway Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- GMQOZFVOGGIFIX-UHFFFAOYSA-N oxathiazolidine Chemical compound C1COSN1 GMQOZFVOGGIFIX-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000026938 proteasomal ubiquitin-dependent protein catabolic process Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000004063 proteosomal degradation Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000006479 redox reaction Methods 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 108010051423 streptavidin-agarose Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- YGNGABUJMXJPIJ-UHFFFAOYSA-N thiatriazole Chemical compound C1=NN=NS1 YGNGABUJMXJPIJ-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000003041 virtual screening Methods 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 229940045860 white wax 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Cosmetics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27210109P | 2009-08-17 | 2009-08-17 | |
| US61/272,101 | 2009-08-17 | ||
| PCT/US2010/045817 WO2011022440A2 (en) | 2009-08-17 | 2010-08-17 | Heat shock protein binding compounds, compositions, and methods for making and using same |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015160345A Division JP6465774B2 (ja) | 2009-08-17 | 2015-08-17 | 熱ショックタンパク質結合化合物、組成物、およびそれらを製造するための方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013502424A true JP2013502424A (ja) | 2013-01-24 |
| JP2013502424A5 JP2013502424A5 (https=) | 2013-10-03 |
Family
ID=43607564
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012525652A Ceased JP2013502424A (ja) | 2009-08-17 | 2010-08-17 | 熱ショックタンパク質結合化合物、組成物、およびそれらを製造するための方法 |
| JP2015160345A Expired - Fee Related JP6465774B2 (ja) | 2009-08-17 | 2015-08-17 | 熱ショックタンパク質結合化合物、組成物、およびそれらを製造するための方法 |
| JP2018158360A Withdrawn JP2018188476A (ja) | 2009-08-17 | 2018-08-27 | 熱ショックタンパク質結合化合物、組成物、ならびにそれらを製造および使用するための方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015160345A Expired - Fee Related JP6465774B2 (ja) | 2009-08-17 | 2015-08-17 | 熱ショックタンパク質結合化合物、組成物、およびそれらを製造するための方法 |
| JP2018158360A Withdrawn JP2018188476A (ja) | 2009-08-17 | 2018-08-27 | 熱ショックタンパク質結合化合物、組成物、ならびにそれらを製造および使用するための方法 |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US9567318B2 (https=) |
| EP (2) | EP3205647B1 (https=) |
| JP (3) | JP2013502424A (https=) |
| KR (1) | KR101906146B1 (https=) |
| CN (2) | CN108752280A (https=) |
| AU (1) | AU2010284255B2 (https=) |
| BR (1) | BR112012003637A2 (https=) |
| CA (1) | CA2771190C (https=) |
| EA (1) | EA201290062A1 (https=) |
| ES (2) | ES2608670T3 (https=) |
| MX (1) | MX353747B (https=) |
| NZ (3) | NZ713361A (https=) |
| WO (1) | WO2011022440A2 (https=) |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017502994A (ja) * | 2014-01-17 | 2017-01-26 | ノバルティス アーゲー | Ｓｈｐ２の活性を阻害するための１−（トリアジン−３−イル／ピリダジン−３−イル）−ピペリジン／ピペラジン誘導体およびその組成物 |
| JP2017515857A (ja) * | 2014-05-13 | 2017-06-15 | メモリアル スローン−ケタリング キャンサー センター | Ｈｓｐ７０モジュレーターならびにその作製および使用方法 |
| WO2017111076A1 (ja) * | 2015-12-24 | 2017-06-29 | 協和発酵キリン株式会社 | α、β不飽和アミド化合物 |
| WO2018235926A1 (ja) * | 2017-06-23 | 2018-12-27 | 協和発酵キリン株式会社 | α、β不飽和アミド化合物 |
| JP2019527728A (ja) * | 2016-07-12 | 2019-10-03 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としての２，５−二置換３−メチルピラジンおよび２，５，６−三置換３−メチルピラジン |
| JP2020536881A (ja) * | 2017-10-12 | 2020-12-17 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としてのピリジン、ピラジンおよびトリアジン化合物 |
| JP2021523104A (ja) * | 2018-04-30 | 2021-09-02 | ライボン・セラピューティクス・インコーポレイテッドＲｉｂｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | Ｐａｒｐ７阻害剤としてのピリダジノン |
| JP2022534788A (ja) * | 2019-06-07 | 2022-08-03 | レヴォリューション・メディスンズ，インコーポレイテッド | Ｓｈｐ２阻害物質である｛６－［（２－アミノ－３－クロロピリジン－４－イル）スルファニル］－３－［（３ｓ，４ｓ）－４－アミノ－３－メチル－２－オキサ－８－アザスピロ［４．５］デカン－８－イル］－５－メチルピラジン－２－イル｝メタノールの固体形態 |
| WO2022191253A1 (ja) * | 2021-03-10 | 2022-09-15 | 住友ファーマ株式会社 | 融合タンパク質の製造方法 |
| US11673901B2 (en) | 2017-12-15 | 2023-06-13 | Revolution Medicines, Inc. | Polycyclic compounds as allosteric SHP2 inhibitors |
| US11691969B2 (en) | 2019-10-30 | 2023-07-04 | Ribon Therapeutics, Inc. | Pyridazinones as PARP7 inhibtors |
| JP2023541992A (ja) * | 2020-09-18 | 2023-10-04 | ボロノイバイオ インコーポレイテッド | ヘテロアリール誘導体、そのヘテロアリール誘導体の調製方法、及びそのヘテロアリール誘導体を活性成分として含む医薬組成物 |
| US12371421B2 (en) | 2019-04-29 | 2025-07-29 | Ribon Therapeutics, Inc. | Solid forms of a PARP7 inhibitor |
| US12617782B2 (en) | 2023-05-12 | 2026-05-05 | Ribon Therapeutics, Inc. | Pyridazinones as PARP7 inhibitors |
Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| MX353308B (es) | 2008-05-21 | 2018-01-08 | Ariad Pharma Inc | Derivados fosforosos como inhibidores de cinasa. |
| NZ713361A (en) | 2009-08-17 | 2017-06-30 | Memorial Sloan Kettering Cancer Center | Heat shock protein binding compounds, compositions, and methods for making and using same |
| BR112013027448A2 (pt) * | 2011-04-28 | 2020-09-01 | Sloan-Kettering Institute For Cancer Research | terapia de combinação com hsp90 |
| EP2704572B1 (en) | 2011-05-04 | 2015-12-30 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| EA201490230A1 (ru) | 2011-07-08 | 2014-06-30 | Слоан-Кеттеринг Инститьют Фор Кэнсер Рисерч | Применение меченых ингибиторов hsp90 |
| US9696313B2 (en) * | 2011-10-06 | 2017-07-04 | Whitehead Institute For Biomedical Research | HSF1 as a marker in tumor prognosis and treatment |
| WO2013169401A1 (en) | 2012-05-05 | 2013-11-14 | Ariad Pharmaceuticals, Inc. | Compounds for inhibiting cell proliferation in egfr-driven cancers |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN105492429A (zh) | 2013-07-02 | 2016-04-13 | 米伦纽姆医药公司 | Sumo活化酶的杂芳基抑制剂 |
| TW201605812A (zh) | 2013-09-16 | 2016-02-16 | 拜耳製藥股份有限公司 | 經雙取代之三氟甲基嘧啶酮類及其用途 |
| US9353078B2 (en) | 2013-10-01 | 2016-05-31 | New York University | Amino, amido and heterocyclic compounds as modulators of rage activity and uses thereof |
| CA2934891C (en) | 2014-01-16 | 2023-02-28 | Nicholas Ryan DEPREZ | Pyrimidinyloxy benzene derivatives as herbicides |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| ES2699351T3 (es) | 2014-01-17 | 2019-02-08 | Novartis Ag | Derivados de 1-piridazin/triazin-3-il-piper(-azina)/idina/pirolidina y composiciones de las mismas para inhibir la actividad de SHP2 |
| BR112016030787B1 (pt) | 2014-07-01 | 2022-12-20 | Takeda Pharmaceutical Company Limited | Entidade química, composição farmacêutica e seu uso |
| CR20170077A (es) | 2014-08-04 | 2017-06-26 | Nuevolution As | Derivados de heterociclilo opcionalmente condensados de pirimidina útiles para el tratamiento de enfermedades inflamatorias, metabólicas, oncológicas y autoinmunitarias |
| MX387627B (es) | 2014-09-17 | 2025-03-18 | Memorial Sloan Kettering Cancer Center | Formación de imágenes de inflamación e infección dirigida a hsp90 y terapia |
| WO2016113205A1 (de) | 2015-01-13 | 2016-07-21 | Bayer Pharma Aktiengesellschaft | Substituierte pentafluorethylpyrimidinone und ihre verwendung |
| WO2016149315A1 (en) | 2015-03-18 | 2016-09-22 | E. I. Du Pont De Nemours And Company | Substituted pyrimidinyloxy pyridine derivatives as herbicides |
| WO2016176675A2 (en) | 2015-04-30 | 2016-11-03 | Nant Holdings Ip, Llc | Patient treatment via teratogenic pharmaceutical compounds |
| TWI713530B (zh) | 2015-06-05 | 2020-12-21 | 美商艾佛艾姆希公司 | 作為除草劑之嘧啶氧基苯衍生物 |
| WO2016203405A1 (en) | 2015-06-19 | 2016-12-22 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
| US10485235B2 (en) | 2015-07-13 | 2019-11-26 | Fmc Corporation | Aryloxypyrimidinyl ethers as herbicides |
| GB201514021D0 (en) | 2015-08-07 | 2015-09-23 | Arner Elias Set Jeno | Novel Pyridines and their use in the treatment of cancer |
| SG11201801856XA (en) | 2015-09-18 | 2018-04-27 | Kaken Pharmaceutical Co Ltd | Biaryl derivative and medicine containing same |
| US20180280397A1 (en) | 2015-10-05 | 2018-10-04 | Memorial Sloan Kettering Cancer Center | Rational combination therapy for the treatment of cancer |
| KR102720461B1 (ko) | 2016-01-22 | 2024-10-21 | 잔센파마슈티카엔.브이. | Nik 억제제로서의 신규 6원 헤테로방향족 치환된 시아노인돌린 유도체 |
| JP6910359B2 (ja) | 2016-01-22 | 2021-07-28 | ヤンセン ファーマシューティカ エヌ．ベー． | Ｎｉｋ阻害剤としての新たな置換されたシアノインドリン誘導体 |
| WO2017160569A1 (en) * | 2016-03-14 | 2017-09-21 | Afferent Pharmaceuticals Inc. | Pyrimidines and variants thereof, and uses therefor |
| MX388576B (es) | 2016-06-07 | 2025-03-20 | Jacobio Pharmaceuticals Co Ltd | Derivados heterociclicos novedosos utiles como inhibidores de shp2. |
| WO2017216706A1 (en) | 2016-06-14 | 2017-12-21 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
| WO2018002219A1 (en) | 2016-06-30 | 2018-01-04 | Janssen Pharmaceutica Nv | Cyanoindoline derivatives as nik inhibitors |
| ES2805976T3 (es) | 2016-06-30 | 2021-02-16 | Janssen Pharmaceutica Nv | Derivados heteroaromáticos en calidad de inhibidores de NIK |
| WO2018118015A1 (en) | 2016-12-19 | 2018-06-28 | Morehouse School Of Medicine | Compositions and methods for treating diseases by inhibiting exosome release |
| CA3048340A1 (en) | 2017-01-10 | 2018-07-19 | Novartis Ag | Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor |
| JP7240319B2 (ja) | 2017-01-23 | 2023-03-15 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としての二環式化合物 |
| KR20190110588A (ko) | 2017-01-23 | 2019-09-30 | 레볼루션 메디슨즈, 인크. | 알로스테릭 shp2 억제제로서의 피리딘 화합물 |
| AU2018218521C1 (en) | 2017-02-07 | 2022-06-09 | Oblique Therapeutics Ab | Heterocyclylsulfonyl-substituted pyridines and their use in the treatment of cancer |
| MA47450A (fr) | 2017-02-07 | 2019-12-18 | Oblique Therapeutics Ab | Sulfinylpyridines et leur utilisation dans le traitement du cancer |
| JP2020507625A (ja) | 2017-02-07 | 2020-03-12 | オブリーク セラピューティクス アーベー | ヘテロアリールスルホニル置換ピリジンおよび癌の治療におけるそれらの使用 |
| CA3051539A1 (en) | 2017-02-07 | 2018-08-16 | Oblique Therapeutics Ab | Hydrocarbylsulfonyl-substituted pyridines and their use in the treatment of cancer |
| LT3483164T (lt) | 2017-03-20 | 2020-05-11 | Forma Therapeutics, Inc. | Pirolpirolo kompozicijos kaip piruvato kinazės (pkr) aktyvatoriai |
| EA202190196A1 (ru) | 2017-03-23 | 2021-08-31 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| CN110785413B (zh) | 2017-05-02 | 2024-08-02 | Fmc公司 | 作为除草剂的嘧啶氧基苯并稠合化合物 |
| CA3074690A1 (en) | 2017-09-07 | 2019-03-14 | Revolution Medicines, Inc. | Shp2 inhibitor compositions and methods for treating cancer |
| US11801284B2 (en) * | 2017-12-13 | 2023-10-31 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for treating motor neuron diseases |
| WO2019177375A1 (ko) * | 2018-03-13 | 2019-09-19 | 포로노이바이오 주식회사 | 2, 4, 5-치환된 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 암의 예방 또는 치료용 약학적 조성물 |
| RU2020133727A (ru) * | 2018-03-21 | 2022-04-21 | Сучжоу Пухе Биофарма Ко., Лтд. | Ингибиторы shp2 и их применение |
| MX2020010719A (es) | 2018-04-10 | 2020-11-06 | Revolution Medicines Inc | Composiciones de inhibidores de shp2, metodos para tratar el cancer y metodos para identificar a un sujeto con mutaciones en shp2. |
| MX2020011565A (es) | 2018-05-01 | 2021-01-29 | Revolution Medicines Inc | Analogos de rapamicina ligados a c40, c28 y c-32 como inhibidores de mtor. |
| IL312291A (en) | 2018-05-01 | 2024-06-01 | Revolution Medicines Inc | C-26-linked rapamycin analogs as MTOR inhibitors |
| EP3853206B1 (en) | 2018-09-19 | 2024-04-10 | Novo Nordisk Health Care AG | Treating sickle cell disease with a pyruvate kinase r activating compound |
| EP3852791B1 (en) | 2018-09-19 | 2024-07-03 | Novo Nordisk Health Care AG | Activating pyruvate kinase r |
| US20210393623A1 (en) | 2018-09-26 | 2021-12-23 | Jacobio Pharmaceuticals Co., Ltd. | Novel Heterocyclic Derivatives Useful as SHP2 Inhibitors |
| JP2022508651A (ja) | 2018-10-08 | 2022-01-19 | レヴォリューション・メディスンズ，インコーポレイテッド | 癌を処置するためのｓｈｐ２阻害剤組成物および方法 |
| MX2021010319A (es) | 2019-03-01 | 2021-12-10 | Revolution Medicines Inc | Compuestos biciclicos de heteroarilo y usos de estos. |
| MX2021010323A (es) | 2019-03-01 | 2021-12-10 | Revolution Medicines Inc | Compuestos bicíclicos de heterociclilo y usos de este. |
| US12157730B2 (en) | 2019-03-19 | 2024-12-03 | Voronoi Inc. | Heteroaryl derivative, method for producing same, and pharmaceutical composition comprising same as effective component |
| PT3943491T (pt) | 2019-03-19 | 2025-07-28 | Voronoi Inc | Derivado de heteroarilo, método para a produção do mesmo e composição farmacêutica que compreende o mesmo como componente eficaz |
| MA55909A (fr) | 2019-05-05 | 2022-03-16 | Qilu Regor Therapeutics Inc | Inhibiteurs de cdk |
| EP3994132A1 (en) | 2019-07-03 | 2022-05-11 | Sumitomo Dainippon Pharma Oncology, Inc. | Tyrosine kinase non-receptor 1 (tnk1) inhibitors and uses thereof |
| HRP20251148T1 (hr) | 2019-09-19 | 2025-11-21 | Novo Nordisk Health Care Ag | Pripravci koji aktiviraju piruvat-kinazu r (pkr) |
| TW202132316A (zh) | 2019-11-04 | 2021-09-01 | 美商銳新醫藥公司 | Ｒａｓ抑制劑 |
| IL322454A (en) | 2019-11-04 | 2025-09-01 | Revolution Medicines Inc | ras inhibitors |
| AU2020377925A1 (en) | 2019-11-04 | 2022-05-05 | Revolution Medicines, Inc. | Ras inhibitors |
| CN110702483B (zh) * | 2019-11-07 | 2022-05-10 | 上海海洋大学 | 一种超快速鉴别海鲜或肉类的预处理方法 |
| CA3156359A1 (en) | 2019-11-08 | 2021-05-14 | Adrian Liam Gill | Bicyclic heteroaryl compounds and uses thereof |
| CN111646956B (zh) * | 2019-11-14 | 2022-06-03 | 中山万远新药研发有限公司 | 一种哌嗪基取代的二苯基亚砜类化合物及其组合物和应用 |
| EP4065231A1 (en) | 2019-11-27 | 2022-10-05 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| UY38994A (es) | 2019-12-20 | 2021-07-30 | Nuevolution As | Compuestos activos frente a receptores nucleares |
| MX2022007265A (es) | 2019-12-20 | 2022-09-09 | Nuevolution As | Compuestos activos frente a receptores nucleares. |
| WO2021142026A1 (en) | 2020-01-07 | 2021-07-15 | Revolution Medicines, Inc. | Shp2 inhibitor dosing and methods of treating cancer |
| WO2021198956A1 (en) | 2020-03-31 | 2021-10-07 | Nuevolution A/S | Compounds active towards nuclear receptors |
| AU2021245397A1 (en) | 2020-03-31 | 2022-10-20 | Nuevolution A/S | Compounds active towards nuclear receptors |
| TWI782504B (zh) | 2020-05-08 | 2022-11-01 | 美商美國禮來大藥廠 | (三氟甲基)嘧啶-2-胺化合物 |
| CN112487680B (zh) * | 2020-11-27 | 2024-05-03 | 西安空间无线电技术研究所 | 一种用于评价和调控离子阱非谐性势的方法 |
| JP7849366B2 (ja) | 2020-12-22 | 2026-04-21 | キル・レガー・セラピューティクス・インコーポレーテッド | Ｓｏｓ１阻害剤およびその使用 |
| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
| CA3256390A1 (en) | 2022-05-25 | 2023-11-30 | Revolution Medicines, Inc. | CANCER TREATMENT METHODS USING AN MTOR INHIBITOR |
| TW202542151A (zh) | 2023-12-22 | 2025-11-01 | 美商銳格醫藥有限公司 | Ｓｏｓ１抑制劑及其用途 |
| CN118389553A (zh) * | 2024-03-01 | 2024-07-26 | 中国科学技术大学 | 免疫增效rna分子及其组合物、疫苗与试剂盒 |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3154551A (en) * | 1959-03-17 | 1964-10-27 | Burroughs Wellcome Co | 4-piperazino-5-arylmercapto pyrimidines |
| US3248393A (en) * | 1960-06-23 | 1966-04-26 | Burroughs Wellcome Co | 1, 3-diazaphenothiazines and method |
| JPS5191273A (https=) * | 1974-12-24 | 1976-08-10 | ||
| JPS5273896A (en) * | 1975-12-09 | 1977-06-21 | Merck & Co Inc | Novel substituted imidazo*1*22a* pyridine |
| JPS59184167A (ja) * | 1983-03-30 | 1984-10-19 | バイエル・アクチエンゲゼルシヤフト | 尿素誘導体 |
| US5707930A (en) * | 1996-09-16 | 1998-01-13 | Zeneca Limited | 4-cycloalkyl-5-substituted pyrimidine compounds useful as crop protection agents |
| JP2004523474A (ja) * | 2000-09-20 | 2004-08-05 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | チロシンキナーゼモジュレーターとしてのピラジン誘導体 |
| JP2004528293A (ja) * | 2001-02-01 | 2004-09-16 | ドゥーケーン ユニバーシティ オブ ザ ホーリー ゴースト | ピリミジン化合物並びに該化合物の製造及び使用方法 |
| JP2007526268A (ja) * | 2004-03-05 | 2007-09-13 | エフ．ホフマン−ラ ロシュ アーゲー | Ｐ２ｘ３およびｐ２ｘ２／３アンタゴニストとしてのジアミノピリミジン |
| WO2008092199A1 (en) * | 2007-01-31 | 2008-08-07 | Cytopia Research Pty Ltd | Thiopyrimidine-based compounds and uses thereof |
| JP2008533166A (ja) * | 2005-03-16 | 2008-08-21 | ターゲジェン インコーポレーティッド | ピリミジン化合物および使用法 |
| WO2009067081A1 (en) * | 2007-11-22 | 2009-05-28 | Astrazeneca Ab | Pyrimidine derivatives for the treatment of asthma, copd, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, cancer, hepatitis b, hepatitis c, hiv, hpv, bacterial infections and dermatosis |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB990857A (en) | 1961-10-13 | 1965-05-05 | Wellcome Found | 1,3-diazaphenothiazines |
| US4039543A (en) | 1974-12-24 | 1977-08-02 | Hoffmann-La Roche Inc. | Benzylpyrimidines |
| US4911920A (en) | 1986-07-30 | 1990-03-27 | Alcon Laboratories, Inc. | Sustained release, comfort formulation for glaucoma therapy |
| FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
| JP2594486B2 (ja) | 1991-01-15 | 1997-03-26 | アルコン ラボラトリーズ インコーポレイテッド | 局所的眼薬組成物 |
| US5212162A (en) | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
| BR9407799A (pt) * | 1993-10-12 | 1997-05-06 | Du Pont Merck Pharma | Composição de matéria método de tratamento e composição farmaceutica |
| DE4423098A1 (de) * | 1994-07-01 | 1996-01-04 | Hoechst Ag | Verwendung von Pyrimidingruppen enthaltenden konjugierten Verbindungen als Elektrolumineszenzmaterialien |
| US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
| JPH09236070A (ja) | 1996-02-29 | 1997-09-09 | Denso Corp | スタータ |
| AU4198400A (en) | 1999-04-06 | 2000-10-23 | Krenitsky Pharmaceuticals Inc. | Neurotrophic thio substituted pyrimidines |
| AU2002227984B8 (en) | 2000-12-18 | 2007-01-04 | Actelion Pharmaceuticals Ltd. | Novel sulfamides and their use as endothelin receptor antagonists |
| US7501429B2 (en) | 2001-04-11 | 2009-03-10 | Queen's University At Kingston | Pyrimidine compounds as anti-ictogenic and/or anti-epileptogenic agents |
| ATE374753T1 (de) | 2001-12-21 | 2007-10-15 | Vernalis Cambridge Ltd | 3-(2,4)dihydroxyphenyl-4-phenylpyrazole und deren medizinische verwendung |
| HRP20050089B1 (hr) | 2002-07-29 | 2015-06-19 | Rigel Pharmaceuticals | Upotreba 2,4 pirimidindiaminskog spoja za proizvodnju lijeka za lijeäśenje ili sprjeäśavanje autoimunosne bolesti |
| NZ540791A (en) | 2003-02-13 | 2009-09-25 | Banyu Pharma Co Ltd | Novel 2-pyridinecarboxamide derivatives |
| NZ546044A (en) * | 2003-08-29 | 2009-09-25 | Vernalis Cambridge Ltd | Pyrimidothiophene compounds |
| US20050070712A1 (en) * | 2003-09-26 | 2005-03-31 | Christi Kosogof | Pyrimidine derivatives as ghrelin receptor modulators |
| JP4906715B2 (ja) * | 2004-05-08 | 2012-03-28 | ニューロジェン・コーポレーション | ４，５−ジ置換−２−アリールピリミジン類 |
| ES2562056T3 (es) | 2005-09-01 | 2016-03-02 | F. Hoffmann-La Roche Ag | Diaminopirimidinas como moduladores P2X3 y P2X2/3 |
| WO2007131034A1 (en) | 2006-05-03 | 2007-11-15 | The Regents Of The University Of Michigan | Pyrimidone derivatives which are modulators of heat shock protein (hsp) 70 |
| JP2008081492A (ja) * | 2006-08-31 | 2008-04-10 | Banyu Pharmaceut Co Ltd | オーロラａ選択的阻害作用を有する新規アミノピリジン誘導体 |
| US20080124407A1 (en) | 2006-10-10 | 2008-05-29 | University Of Washington | Inhibiting cyp3a4 induction |
| EA017405B9 (ru) | 2006-12-08 | 2014-05-30 | АйАрЭм ЭлЭлСи | Соединения и композиции в качестве ингибиторов протеинкиназы |
| TW200911240A (en) | 2007-06-11 | 2009-03-16 | Kyowa Hakko Kogyo Kk | Anti-tumor agent |
| WO2009023846A2 (en) * | 2007-08-15 | 2009-02-19 | The Research Foundation Of State University Of New York | Methods for heat shock protein dependent cancer treatment |
| WO2009061345A2 (en) | 2007-11-07 | 2009-05-14 | Cornell Research Foundation, Inc. | Targeting cdk4 and cdk6 in cancer therapy |
| JP2012529512A (ja) | 2009-06-08 | 2012-11-22 | アブラクシス バイオサイエンス リミテッド ライアビリティー カンパニー | トリアジン誘導体類及びそれらの治療応用 |
| NZ713361A (en) | 2009-08-17 | 2017-06-30 | Memorial Sloan Kettering Cancer Center | Heat shock protein binding compounds, compositions, and methods for making and using same |
| WO2014078294A1 (en) | 2012-11-13 | 2014-05-22 | Memorial Sloan-Kettering Cancer Center | Indole compounds and their use as antimicrobials |
| JP6607870B2 (ja) | 2014-05-13 | 2019-11-20 | メモリアル スローン ケタリング キャンサー センター | Ｈｓｐ７０モジュレーターならびにその作製および使用方法 |
| WO2016203405A1 (en) | 2015-06-19 | 2016-12-22 | Novartis Ag | Compounds and compositions for inhibiting the activity of shp2 |
| CA2998753A1 (en) | 2015-09-18 | 2017-03-23 | St. Jude Children's Research Hospital | Methods and compositions of inhibiting dcn1-ubc12 interaction |
-
2010
- 2010-08-17 NZ NZ713361A patent/NZ713361A/en not_active IP Right Cessation
- 2010-08-17 NZ NZ623069A patent/NZ623069A/en not_active IP Right Cessation
- 2010-08-17 AU AU2010284255A patent/AU2010284255B2/en not_active Ceased
- 2010-08-17 NZ NZ59826210A patent/NZ598262A/en not_active IP Right Cessation
- 2010-08-17 CN CN201810695781.9A patent/CN108752280A/zh active Pending
- 2010-08-17 ES ES10810519.8T patent/ES2608670T3/es active Active
- 2010-08-17 MX MX2012001993A patent/MX353747B/es active IP Right Grant
- 2010-08-17 BR BR112012003637A patent/BR112012003637A2/pt not_active IP Right Cessation
- 2010-08-17 CN CN2010800368189A patent/CN102753177A/zh active Pending
- 2010-08-17 CA CA2771190A patent/CA2771190C/en not_active Expired - Fee Related
- 2010-08-17 ES ES16189468T patent/ES2817700T3/es active Active
- 2010-08-17 KR KR1020127006838A patent/KR101906146B1/ko not_active Expired - Fee Related
- 2010-08-17 EP EP16189468.8A patent/EP3205647B1/en active Active
- 2010-08-17 US US13/391,148 patent/US9567318B2/en active Active
- 2010-08-17 EP EP10810519.8A patent/EP2467142B1/en active Active
- 2010-08-17 EA EA201290062A patent/EA201290062A1/ru unknown
- 2010-08-17 JP JP2012525652A patent/JP2013502424A/ja not_active Ceased
- 2010-08-17 WO PCT/US2010/045817 patent/WO2011022440A2/en not_active Ceased
-
2015
- 2015-08-17 JP JP2015160345A patent/JP6465774B2/ja not_active Expired - Fee Related
-
2016
- 2016-08-08 US US15/230,700 patent/US10052325B2/en active Active
-
2018
- 2018-07-17 US US16/037,160 patent/US10758538B2/en active Active
- 2018-08-27 JP JP2018158360A patent/JP2018188476A/ja not_active Withdrawn
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3154551A (en) * | 1959-03-17 | 1964-10-27 | Burroughs Wellcome Co | 4-piperazino-5-arylmercapto pyrimidines |
| US3248393A (en) * | 1960-06-23 | 1966-04-26 | Burroughs Wellcome Co | 1, 3-diazaphenothiazines and method |
| JPS5191273A (https=) * | 1974-12-24 | 1976-08-10 | ||
| JPS5273896A (en) * | 1975-12-09 | 1977-06-21 | Merck & Co Inc | Novel substituted imidazo*1*22a* pyridine |
| JPS59184167A (ja) * | 1983-03-30 | 1984-10-19 | バイエル・アクチエンゲゼルシヤフト | 尿素誘導体 |
| US5707930A (en) * | 1996-09-16 | 1998-01-13 | Zeneca Limited | 4-cycloalkyl-5-substituted pyrimidine compounds useful as crop protection agents |
| JP2004523474A (ja) * | 2000-09-20 | 2004-08-05 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | チロシンキナーゼモジュレーターとしてのピラジン誘導体 |
| JP2004528293A (ja) * | 2001-02-01 | 2004-09-16 | ドゥーケーン ユニバーシティ オブ ザ ホーリー ゴースト | ピリミジン化合物並びに該化合物の製造及び使用方法 |
| JP2007526268A (ja) * | 2004-03-05 | 2007-09-13 | エフ．ホフマン−ラ ロシュ アーゲー | Ｐ２ｘ３およびｐ２ｘ２／３アンタゴニストとしてのジアミノピリミジン |
| JP2008533166A (ja) * | 2005-03-16 | 2008-08-21 | ターゲジェン インコーポレーティッド | ピリミジン化合物および使用法 |
| WO2008092199A1 (en) * | 2007-01-31 | 2008-08-07 | Cytopia Research Pty Ltd | Thiopyrimidine-based compounds and uses thereof |
| WO2009067081A1 (en) * | 2007-11-22 | 2009-05-28 | Astrazeneca Ab | Pyrimidine derivatives for the treatment of asthma, copd, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, cancer, hepatitis b, hepatitis c, hiv, hpv, bacterial infections and dermatosis |
Non-Patent Citations (5)
| Title |
|---|
| JPN6015015041; ＫＡＺＵＡＫＩ ＳＵＧＩＹＡＭＡ， ｅｔ ａｌ．: 'Ｓｔｕｄｉｅｓ ｏｎ １， ４-Ｂｅｎｚｏｔｈｉａｚｉｎｅｓ． ＩＶ． Ｒｅａｃｔｉｏｎｓ ｏｆ ２-Ａｃｙｌ-４Ｈ-１， ４-ｂｅｎｚｏｔｈｉａｚｉｎｅｓ ｗｉｔｈ Ｈｙｄｒｏｘｙｌａｍｉｎｅ， Ｈ' Ｃｈｅｍｉｃａｌ ａｎｄ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ Ｖｏｌ．３２ Ｎｏ．４, 1984, ｐｐ．１５９３-１５９６ * |
| JPN6015015044; Ｂａｒｂａｒａ Ｒｏｔｈ， ｅｔ ａｌ．: '５-Ａｒｙｌｔｈｉｏｐｙｒｉｍｉｄｉｎｅｓ． Ｖ． Ｋｉｎｅｔｉｃｓ ｏｆ ｔｈｅ Ｃｙｃｌｉｚａｔｉｏｎ ｏｆ ４-Ｏｘｏ Ｄｅｒｉｖａｔｉｖｅｓ ｔｏ １０Ｈ- ａｎｄ １０-Ａｌｋｙｌｐｙｒｉｍ' Ｊ． Ａｍ． Ｃｈｅｍ． Ｓｏｃ． Ｖｏｌ．８７， Ｎｏ．２, 1965, ｐｐ．３４０-３４９ * |
| JPN6015015045; Ｂａｒｂａｒａ Ｒｏｔｈ， ｅｔ ａｌ．: '５-Ａｒｙｌｔｈｉｏｐｙｒｉｍｉｄｉｎｅｓ． ＩＶ． Ｓｐｅｃｔｒｏｐｈｏｔｏｍｅｔｒｉｃ Ｄｅｔｅｒｍｉｎａｔｉｏｎ ｏｆ Ｓｕｃｃｅｓｓｉｖｅ Ａｃｉｄ Ｄｉｓｓｏｃｉａｔｉｏｎ Ｃｏｎｓｔａｎｔ' Ｊ． Ａｍ． Ｃｈｅｍ． Ｓｏｃ． Ｖｏｌ．８７， Ｎｏ．２, 1965, ｐｐ．３３４-３３９ * |
| JPN6015015047; Ｂａｒｂａｒａ Ｒｏｔｈ， ｅｔ ａｌ．: '５-Ａｒｙｌｔｈｉｏｐｙｒｉｍｉｄｉｎｅｓ． ＩＩＩ． Ｃｙｃｌｉｚａｔｉｏｎ ｏｆ ４-Ｈｙｄｒｏｘｙ Ｄｅｒｉｖａｔｉｖｅｓ ｔｏ １０Ｈ-Ｐｙｒｉｍｉｄｏ［５，４-ｂ］［１，４］ｂｅｎｚｏｔｈｉ' Ｊ． Ｏｒｇ． Ｃｈｅｍ． Ｖｏｌ．２８， Ｎｏ．１０, 1963, ｐｐ．２６５９-２６７２ * |
| JPN6015015050; Ｗｉｌｌｉａｍ Ｔ． ｅｔ ａｌ．: 'Ｔｈｅ Ｐｒｅｐａｒａｔｉｏｎ ｏｆ ａ Ｐｙｒｉｍｉｄｉｎｅ Ａｎａｌｏｇ （Ｉｓｏｓｔｅｒｅ） ｏｆ Ｐｒｏｍｉｚｏｌｅ ａｎｄ Ｏｔｈｅｒ Ｓｕｂｓｔｉｔｕｔｅｄ Ｐｙｒｉｍｉｄｉｎｅｓ' Ｊ． Ａｍ． Ｃｈｅｍ． Ｓｏｃ． Ｖｏｌ．７４， Ｎｏ．１７, 1952, ｐｐ．４３１４-４３１７ * |
Cited By (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017502994A (ja) * | 2014-01-17 | 2017-01-26 | ノバルティス アーゲー | Ｓｈｐ２の活性を阻害するための１−（トリアジン−３−イル／ピリダジン−３−イル）−ピペリジン／ピペラジン誘導体およびその組成物 |
| JP2017515857A (ja) * | 2014-05-13 | 2017-06-15 | メモリアル スローン−ケタリング キャンサー センター | Ｈｓｐ７０モジュレーターならびにその作製および使用方法 |
| US10647683B2 (en) | 2014-05-13 | 2020-05-12 | Memorial Sloan Kettering Cancer Center | Hsp70 modulators and methods for making and using the same |
| WO2017111076A1 (ja) * | 2015-12-24 | 2017-06-29 | 協和発酵キリン株式会社 | α、β不飽和アミド化合物 |
| JPWO2017111076A1 (ja) * | 2015-12-24 | 2018-10-18 | 協和発酵キリン株式会社 | α、β不飽和アミド化合物 |
| US10787428B2 (en) * | 2015-12-24 | 2020-09-29 | Kyowa Kirin Co., Ltd. | α,β-unsaturated amide compound |
| US11332455B2 (en) | 2015-12-24 | 2022-05-17 | Kyowa Kirin Co., Ltd. | α,β-unsaturated amide compound |
| JP2021176870A (ja) * | 2016-07-12 | 2021-11-11 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としての２，５−二置換３−メチルピラジンおよび２，５，６−三置換３−メチルピラジン |
| JP7416740B2 (ja) | 2016-07-12 | 2024-01-17 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としての２，５－二置換３－メチルピラジンおよび２，５，６－三置換３－メチルピラジン |
| JP2019527728A (ja) * | 2016-07-12 | 2019-10-03 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としての２，５−二置換３−メチルピラジンおよび２，５，６−三置換３−メチルピラジン |
| JPWO2018235926A1 (ja) * | 2017-06-23 | 2020-05-21 | 協和キリン株式会社 | α、β不飽和アミド化合物 |
| WO2018235926A1 (ja) * | 2017-06-23 | 2018-12-27 | 協和発酵キリン株式会社 | α、β不飽和アミド化合物 |
| AU2018289759B2 (en) * | 2017-06-23 | 2022-03-10 | Kyowa Kirin Co., Ltd. | Alpha, beta-unsaturated amide compound |
| US11447471B2 (en) | 2017-06-23 | 2022-09-20 | Kyowa Kirin Co., Ltd. | α,β-unsaturated amide compound |
| JP7221202B2 (ja) | 2017-06-23 | 2023-02-13 | 協和キリン株式会社 | α、β不飽和アミド化合物 |
| JP2020536881A (ja) * | 2017-10-12 | 2020-12-17 | レヴォリューション・メディスンズ，インコーポレイテッド | アロステリックｓｈｐ２阻害剤としてのピリジン、ピラジンおよびトリアジン化合物 |
| US11702411B2 (en) | 2017-10-12 | 2023-07-18 | Revolution Medicines, Inc. | Pyridine, pyrazine, and triazine compounds as allosteric SHP2 inhibitors |
| US11673901B2 (en) | 2017-12-15 | 2023-06-13 | Revolution Medicines, Inc. | Polycyclic compounds as allosteric SHP2 inhibitors |
| JP2022017221A (ja) * | 2018-04-30 | 2022-01-25 | ライボン・セラピューティクス・インコーポレイテッド | Ｐａｒｐ７阻害剤としてのピリダジノン |
| JP2021523104A (ja) * | 2018-04-30 | 2021-09-02 | ライボン・セラピューティクス・インコーポレイテッドＲｉｂｏｎ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | Ｐａｒｐ７阻害剤としてのピリダジノン |
| US11566020B1 (en) | 2018-04-30 | 2023-01-31 | Ribon Therapeutics, Inc. | Pyridazinones as PARP7 inhibitors |
| JP7518049B2 (ja) | 2018-04-30 | 2024-07-17 | ライボン・セラピューティクス・インコーポレイテッド | Ｐａｒｐ７阻害剤としてのピリダジノン |
| US12371421B2 (en) | 2019-04-29 | 2025-07-29 | Ribon Therapeutics, Inc. | Solid forms of a PARP7 inhibitor |
| JP2022534788A (ja) * | 2019-06-07 | 2022-08-03 | レヴォリューション・メディスンズ，インコーポレイテッド | Ｓｈｐ２阻害物質である｛６－［（２－アミノ－３－クロロピリジン－４－イル）スルファニル］－３－［（３ｓ，４ｓ）－４－アミノ－３－メチル－２－オキサ－８－アザスピロ［４．５］デカン－８－イル］－５－メチルピラジン－２－イル｝メタノールの固体形態 |
| US11691969B2 (en) | 2019-10-30 | 2023-07-04 | Ribon Therapeutics, Inc. | Pyridazinones as PARP7 inhibtors |
| JP2023541992A (ja) * | 2020-09-18 | 2023-10-04 | ボロノイバイオ インコーポレイテッド | ヘテロアリール誘導体、そのヘテロアリール誘導体の調製方法、及びそのヘテロアリール誘導体を活性成分として含む医薬組成物 |
| JP7790746B2 (ja) | 2020-09-18 | 2025-12-23 | ボロノイ インコーポレイテッド | ヘテロアリール誘導体、そのヘテロアリール誘導体の調製方法、及びそのヘテロアリール誘導体を活性成分として含む医薬組成物 |
| WO2022191253A1 (ja) * | 2021-03-10 | 2022-09-15 | 住友ファーマ株式会社 | 融合タンパク質の製造方法 |
| US12617782B2 (en) | 2023-05-12 | 2026-05-05 | Ribon Therapeutics, Inc. | Pyridazinones as PARP7 inhibitors |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6465774B2 (ja) | 熱ショックタンパク質結合化合物、組成物、およびそれらを製造するための方法 | |
| Türe et al. | Design, synthesis, and anticancer activity of novel 4-thiazolidinone-phenylaminopyrimidine hybrids | |
| JP7015059B2 (ja) | 置換複素環式基を含む２－置換キナゾリン化合物およびその使用方法 | |
| KR101446742B1 (ko) | Ｎ2,ｎ4-비스(4-(피페라진-1-일)페닐)피리미딘-2,4-디아민 유도체 또는 이의 약학적으로 허용가능한 염 및 이를 유효성분으로 함유하는 암의 예방 또는 치료용 약학적 조성물 | |
| AU2020311337B2 (en) | Regimens of estrogen receptor antagonists | |
| EP2598508B1 (en) | Isoxazolo-quinazolines as modulators of protein kinase activity | |
| WO2014079150A1 (en) | Compounds and their methods of use | |
| EP2417125B1 (en) | N-aryl-2-(2-arylaminopyrimidin-4-yl)pyrrol-4-carboxamide derivatives as mps1 kinase inhibitors | |
| Lu et al. | Discovery of the first examples of threonine tyrosine kinase PROTAC degraders | |
| Zhou et al. | Design and optimization of hybrid of 2, 4-diaminopyrimidine and arylthiazole scaffold as anticancer cell proliferation and migration agents | |
| Tapera et al. | Design, synthesis, molecular docking and biological evaluation of 1, 2, 4-triazole derivatives possessing a hydrazone moiety as anti-breast cancer agents | |
| KR20070054205A (ko) | Ｃｈｋ1 억제에 유용한 화합물 | |
| KR100392468B1 (ko) | 사이클린 의존 키나아제의 저해제로서 유용한3-히드록시크로멘-4-온 유도체 | |
| Shao et al. | Beyond Acrylamide: A Structure-Guided Investigation of Covalent Warheads in the Development of CDK7 Inhibitors | |
| HK1241360A1 (en) | 2-(pyrimidin-5-yl)-thiopyrimidine derivatives as hsp70 and hsc70 modulators for the treatment of proliferative disorders | |
| HK1241360B (en) | 2-(pyrimidin-5-yl)-thiopyrimidine derivatives as hsp70 and hsc70 modulators for the treatment of proliferative disorders | |
| HK1175393B (en) | 2-(pyrimidin-5-yl)-thiopyrimidine derivatives as hsp70 and hsc70 modulators for the treatment of proliferative disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130816 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130816 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20140724 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140725 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141024 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141031 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141121 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141201 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141217 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20141225 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150126 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150415 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150817 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150824 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20151030 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161124 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170201 |
|
| A045 | Written measure of dismissal of application [lapsed due to lack of payment] |
Free format text: JAPANESE INTERMEDIATE CODE: A045 Effective date: 20170525 |