BRPI0710805A2 - métodos para tratar uma doença ou condição, e para evitar resistência a insulina, diabetes, fibrose pulmonar idiopática, mielofibrose, fibrose hepática, esteatofibrose ou esteatoepatite - Google Patents

Info

Publication number

BRPI0710805A2

BRPI0710805A2 BRPI0710805-2A BRPI0710805A BRPI0710805A2 BR PI0710805 A2 BRPI0710805 A2 BR PI0710805A2 BR PI0710805 A BRPI0710805 A BR PI0710805A BR PI0710805 A2 BRPI0710805 A2 BR PI0710805A2

Authority

BR

Brazil

Prior art keywords

substituted

unsubstituted

formula

mmol

kinase

Prior art date

2006-04-26

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 75
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 59
• 201000010099 disease Diseases 0.000 title claims abstract description 45
• 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 35
• 206010028537 myelofibrosis Diseases 0.000 title claims abstract description 7
• 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims description 14
• 206010022489 Insulin Resistance Diseases 0.000 title claims description 5
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 title abstract description 3
• 208000036971 interstitial lung disease 2 Diseases 0.000 title abstract description 3
• 208000019425 cirrhosis of liver Diseases 0.000 title description 2
• -1 Aminopurine compounds Chemical class 0.000 claims abstract description 269
• 150000001875 compounds Chemical class 0.000 claims abstract description 115
• 239000000203 mixture Substances 0.000 claims abstract description 78
• 206010019668 Hepatic fibrosis Diseases 0.000 claims abstract description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 36
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 33
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 26
• 125000000217 alkyl group Chemical group 0.000 claims description 25
• 150000003839 salts Chemical class 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
• 125000001072 heteroaryl group Chemical group 0.000 claims description 19
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
• 125000003545 alkoxy group Chemical group 0.000 claims description 16
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 15
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 14
• 125000004442 acylamino group Chemical group 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000002883 imidazolyl group Chemical group 0.000 claims description 13
• 125000001425 triazolyl group Chemical group 0.000 claims description 13
• 125000003282 alkyl amino group Chemical group 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 11
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 9
• 230000001419 dependent effect Effects 0.000 claims description 8
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 208000007976 Ketosis Diseases 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 102000004877 Insulin Human genes 0.000 claims description 3
• 108090001061 Insulin Proteins 0.000 claims description 3
• 208000002720 Malnutrition Diseases 0.000 claims description 3
• 229940125396 insulin Drugs 0.000 claims description 3
• 230000004140 ketosis Effects 0.000 claims description 3
• 230000001071 malnutrition Effects 0.000 claims description 3
• 235000000824 malnutrition Nutrition 0.000 claims description 3
• 208000015380 nutritional deficiency disease Diseases 0.000 claims description 3
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 2
• 208000001280 Prediabetic State Diseases 0.000 claims description 2
• 208000004104 gestational diabetes Diseases 0.000 claims description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
• 201000009104 prediabetes syndrome Diseases 0.000 claims description 2
• 206010068271 Cystic fibrosis related diabetes Diseases 0.000 claims 1
• 206010016654 Fibrosis Diseases 0.000 claims 1
• 230000004761 fibrosis Effects 0.000 claims 1
• 125000003107 substituted aryl group Chemical group 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 abstract description 69
• 201000011510 cancer Diseases 0.000 abstract description 34
• 150000005018 aminopurines Chemical class 0.000 abstract description 31
• 230000037361 pathway Effects 0.000 abstract description 17
• 208000002193 Pain Diseases 0.000 abstract description 16
• 230000036407 pain Effects 0.000 abstract description 16
• 208000011580 syndromic disease Diseases 0.000 abstract description 16
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 13
• 206010063837 Reperfusion injury Diseases 0.000 abstract description 10
• 208000002780 macular degeneration Diseases 0.000 abstract description 10
• 208000002815 pulmonary hypertension Diseases 0.000 abstract description 8
• 239000010425 asbestos Substances 0.000 abstract description 7
• 230000001363 autoimmune Effects 0.000 abstract description 7
• 230000004968 inflammatory condition Effects 0.000 abstract description 7
• 230000002401 inhibitory effect Effects 0.000 abstract description 7
• 208000012947 ischemia reperfusion injury Diseases 0.000 abstract description 7
• 208000017169 kidney disease Diseases 0.000 abstract description 7
• 229910052895 riebeckite Inorganic materials 0.000 abstract description 7
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 146
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
• 239000000243 solution Substances 0.000 description 122
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 101
• 238000006243 chemical reaction Methods 0.000 description 96
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
• 108091000080 Phosphotransferase Proteins 0.000 description 78
• 102000020233 phosphotransferase Human genes 0.000 description 78
• 239000002904 solvent Substances 0.000 description 74
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 73
• 239000011541 reaction mixture Substances 0.000 description 70
• 230000015572 biosynthetic process Effects 0.000 description 65
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
• 238000003786 synthesis reaction Methods 0.000 description 59
• 239000007787 solid Substances 0.000 description 53
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
• 239000000047 product Substances 0.000 description 52
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 51
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
• 235000019439 ethyl acetate Nutrition 0.000 description 49
• 102000001253 Protein Kinase Human genes 0.000 description 48
• 108060006633 protein kinase Proteins 0.000 description 46
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 45
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 45
• 210000004027 cell Anatomy 0.000 description 45
• 230000002829 reductive effect Effects 0.000 description 42
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 39
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
• 150000001412 amines Chemical class 0.000 description 25
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 24
• 239000011347 resin Substances 0.000 description 23
• 229920005989 resin Polymers 0.000 description 23
• 238000003756 stirring Methods 0.000 description 22
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 238000011282 treatment Methods 0.000 description 21
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 20
• 239000012043 crude product Substances 0.000 description 20
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
• 235000019341 magnesium sulphate Nutrition 0.000 description 19
• 238000003556 assay Methods 0.000 description 18
• 238000004440 column chromatography Methods 0.000 description 18
• 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 18
• 102000005962 receptors Human genes 0.000 description 18
• 108020003175 receptors Proteins 0.000 description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
• 235000019441 ethanol Nutrition 0.000 description 17
• 108700020796 Oncogene Proteins 0.000 description 16
• 150000001413 amino acids Chemical class 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• 239000000725 suspension Substances 0.000 description 16
• 102000043136 MAP kinase family Human genes 0.000 description 15
• 108091054455 MAP kinase family Proteins 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 239000012074 organic phase Substances 0.000 description 15
• 239000012071 phase Substances 0.000 description 15
• 230000001105 regulatory effect Effects 0.000 description 15
• 229920002472 Starch Polymers 0.000 description 14
• 210000003169 central nervous system Anatomy 0.000 description 14
• 230000000694 effects Effects 0.000 description 14
• 208000014674 injury Diseases 0.000 description 14
• 235000019698 starch Nutrition 0.000 description 14
• 239000003826 tablet Substances 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• 208000009956 adenocarcinoma Diseases 0.000 description 13
• 230000037396 body weight Effects 0.000 description 13
• 208000035475 disorder Diseases 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• 229910052757 nitrogen Inorganic materials 0.000 description 13
• 239000008107 starch Substances 0.000 description 13
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 12
• 201000009030 Carcinoma Diseases 0.000 description 12
• 239000007995 HEPES buffer Substances 0.000 description 12
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 12
• 102000019145 JUN kinase activity proteins Human genes 0.000 description 12
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 12
• 206010039491 Sarcoma Diseases 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 230000006378 damage Effects 0.000 description 12
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
• 239000002244 precipitate Substances 0.000 description 12
• 239000000651 prodrug Substances 0.000 description 12
• 229940002612 prodrug Drugs 0.000 description 12
• 102000004169 proteins and genes Human genes 0.000 description 12
• 108090000623 proteins and genes Proteins 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
• 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
• 208000027418 Wounds and injury Diseases 0.000 description 11
• 230000001154 acute effect Effects 0.000 description 11
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
• 239000000460 chlorine Substances 0.000 description 11
• 239000001257 hydrogen Substances 0.000 description 11
• 229910052739 hydrogen Inorganic materials 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 235000019198 oils Nutrition 0.000 description 11
• 210000000056 organ Anatomy 0.000 description 11
• 235000018102 proteins Nutrition 0.000 description 11
• 239000000741 silica gel Substances 0.000 description 11
• 229910002027 silica gel Inorganic materials 0.000 description 11
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
• 108091007914 CDKs Proteins 0.000 description 10
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 10
• 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• 239000003814 drug Substances 0.000 description 10
• YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 10
• 229910001629 magnesium chloride Inorganic materials 0.000 description 10
• 239000003226 mitogen Substances 0.000 description 10
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
• 101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 9
• 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 9
• 102100024192 Mitogen-activated protein kinase 3 Human genes 0.000 description 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 239000002775 capsule Substances 0.000 description 9
• 230000004663 cell proliferation Effects 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 238000004128 high performance liquid chromatography Methods 0.000 description 9
• 238000006366 phosphorylation reaction Methods 0.000 description 9
• 229910052938 sodium sulfate Inorganic materials 0.000 description 9
• 235000011152 sodium sulphate Nutrition 0.000 description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
• 238000002054 transplantation Methods 0.000 description 9
• 108010067499 Clk dual-specificity kinases Proteins 0.000 description 8
• 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 8
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 8
• 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• 239000004743 Polypropylene Substances 0.000 description 8
• 108700020978 Proto-Oncogene Proteins 0.000 description 8
• 102000052575 Proto-Oncogene Human genes 0.000 description 8
• 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 239000013078 crystal Substances 0.000 description 8
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
• 208000028867 ischemia Diseases 0.000 description 8
• 208000032839 leukemia Diseases 0.000 description 8
• 201000001441 melanoma Diseases 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 230000026731 phosphorylation Effects 0.000 description 8
• 229920001155 polypropylene Polymers 0.000 description 8
• 210000003491 skin Anatomy 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 239000012453 solvate Substances 0.000 description 8
• 206010041823 squamous cell carcinoma Diseases 0.000 description 8
• 239000000758 substrate Substances 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 7
• 102000016736 Cyclin Human genes 0.000 description 7
• 108050006400 Cyclin Proteins 0.000 description 7
• 102000003903 Cyclin-dependent kinases Human genes 0.000 description 7
• 108090000266 Cyclin-dependent kinases Proteins 0.000 description 7
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
• 101000976900 Homo sapiens Mitogen-activated protein kinase 14 Proteins 0.000 description 7
• 108700027649 Mitogen-Activated Protein Kinase 3 Proteins 0.000 description 7
• 102100026929 Mitogen-activated protein kinase 11 Human genes 0.000 description 7
• 102100024189 Mitogen-activated protein kinase 4 Human genes 0.000 description 7
• 102100037801 Mitogen-activated protein kinase 6 Human genes 0.000 description 7
• 102100037805 Mitogen-activated protein kinase 7 Human genes 0.000 description 7
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
• 235000011114 ammonium hydroxide Nutrition 0.000 description 7
• 210000000481 breast Anatomy 0.000 description 7
• 230000001684 chronic effect Effects 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• 208000015122 neurodegenerative disease Diseases 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 230000002265 prevention Effects 0.000 description 7
• 239000000523 sample Substances 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 238000001356 surgical procedure Methods 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• 229940086542 triethylamine Drugs 0.000 description 7
• 230000003612 virological effect Effects 0.000 description 7
• INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 6
• DRNGLYHKYPNTEA-UHFFFAOYSA-N 4-azaniumylcyclohexane-1-carboxylate Chemical compound NC1CCC(C(O)=O)CC1 DRNGLYHKYPNTEA-UHFFFAOYSA-N 0.000 description 6
• 206010006187 Breast cancer Diseases 0.000 description 6
• 208000026310 Breast neoplasm Diseases 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 6
• 101001064462 Homo sapiens Ephrin type-B receptor 2 Proteins 0.000 description 6
• 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 6
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 6
• 108700012928 MAPK14 Proteins 0.000 description 6
• 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 6
• 102000054819 Mitogen-activated protein kinase 14 Human genes 0.000 description 6
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 239000000908 ammonium hydroxide Substances 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 150000003857 carboxamides Chemical class 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 239000013024 dilution buffer Substances 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 229940080856 gleevec Drugs 0.000 description 6
• 150000004677 hydrates Chemical class 0.000 description 6
• 239000005457 ice water Substances 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• 210000003734 kidney Anatomy 0.000 description 6
• 210000004072 lung Anatomy 0.000 description 6
• 230000007257 malfunction Effects 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 210000000496 pancreas Anatomy 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 238000002953 preparative HPLC Methods 0.000 description 6
• 108090000765 processed proteins & peptides Proteins 0.000 description 6
• 230000019491 signal transduction Effects 0.000 description 6
• 239000000377 silicon dioxide Substances 0.000 description 6
• 229910052708 sodium Inorganic materials 0.000 description 6
• 229910052717 sulfur Inorganic materials 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
• 206010012422 Derealisation Diseases 0.000 description 5
• 206010019233 Headaches Diseases 0.000 description 5
• 101000950687 Homo sapiens Mitogen-activated protein kinase 7 Proteins 0.000 description 5
• 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 5
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 5
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
• 108700027654 Mitogen-Activated Protein Kinase 10 Proteins 0.000 description 5
• 238000005481 NMR spectroscopy Methods 0.000 description 5
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 5
• 229910004298 SiO 2 Inorganic materials 0.000 description 5
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
• 239000012346 acetyl chloride Substances 0.000 description 5
• 230000004913 activation Effects 0.000 description 5
• 230000033115 angiogenesis Effects 0.000 description 5
• 230000006907 apoptotic process Effects 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
• 230000024245 cell differentiation Effects 0.000 description 5
• 229910052801 chlorine Inorganic materials 0.000 description 5
• 229910052681 coesite Inorganic materials 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 229910052906 cristobalite Inorganic materials 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
• 238000004090 dissolution Methods 0.000 description 5
• 229910052731 fluorine Inorganic materials 0.000 description 5
• 125000001153 fluoro group Chemical group F* 0.000 description 5
• 239000003102 growth factor Substances 0.000 description 5
• 125000001475 halogen functional group Chemical group 0.000 description 5
• 238000011534 incubation Methods 0.000 description 5
• 239000012280 lithium aluminium hydride Substances 0.000 description 5
• 210000004185 liver Anatomy 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 229920001184 polypeptide Polymers 0.000 description 5
• 102000004196 processed proteins & peptides Human genes 0.000 description 5
• 238000004007 reversed phase HPLC Methods 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 229910052682 stishovite Inorganic materials 0.000 description 5
• 229940124530 sulfonamide Drugs 0.000 description 5
• 150000003456 sulfonamides Chemical class 0.000 description 5
• 230000004083 survival effect Effects 0.000 description 5
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 5
• 229910052905 tridymite Inorganic materials 0.000 description 5
• 238000005160 1H NMR spectroscopy Methods 0.000 description 4
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 4
• 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 4
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 4
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
• 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 4
• 102000001301 EGF receptor Human genes 0.000 description 4
• 108060006698 EGF receptor Proteins 0.000 description 4
• 201000008808 Fibrosarcoma Diseases 0.000 description 4
• 208000032612 Glial tumor Diseases 0.000 description 4
• 206010018338 Glioma Diseases 0.000 description 4
• 239000007821 HATU Substances 0.000 description 4
• 102100035108 High affinity nerve growth factor receptor Human genes 0.000 description 4
• 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 4
• 101000950710 Homo sapiens Mitogen-activated protein kinase 6 Proteins 0.000 description 4
• 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 4
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
• 108010000837 Janus Kinase 1 Proteins 0.000 description 4
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
• 206010025323 Lymphomas Diseases 0.000 description 4
• 229930195725 Mannitol Natural products 0.000 description 4
• 102000056243 Mitogen-activated protein kinase 12 Human genes 0.000 description 4
• 108700015929 Mitogen-activated protein kinase 12 Proteins 0.000 description 4
• 102000056248 Mitogen-activated protein kinase 13 Human genes 0.000 description 4
• 101710166114 Mitogen-activated protein kinase 4 Proteins 0.000 description 4
• 208000008589 Obesity Diseases 0.000 description 4
• 108091007960 PI3Ks Proteins 0.000 description 4
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 4
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 4
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 4
• 208000009527 Refractory anemia Diseases 0.000 description 4
• 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 description 4
• 108010034782 Ribosomal Protein S6 Kinases Proteins 0.000 description 4
• 102000009738 Ribosomal Protein S6 Kinases Human genes 0.000 description 4
• 201000010208 Seminoma Diseases 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
• 102100023132 Transcription factor Jun Human genes 0.000 description 4
• 229920004890 Triton X-100 Polymers 0.000 description 4
• 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 239000011230 binding agent Substances 0.000 description 4
• 230000033228 biological regulation Effects 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 230000006369 cell cycle progression Effects 0.000 description 4
• 235000010980 cellulose Nutrition 0.000 description 4
• 239000001913 cellulose Substances 0.000 description 4
• 229920002678 cellulose Polymers 0.000 description 4
• 210000001072 colon Anatomy 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 4
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 230000018109 developmental process Effects 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 239000007789 gas Substances 0.000 description 4
• 239000011521 glass Substances 0.000 description 4
• 230000012010 growth Effects 0.000 description 4
• 231100000869 headache Toxicity 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
• 229910052740 iodine Inorganic materials 0.000 description 4
• 208000002551 irritable bowel syndrome Diseases 0.000 description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• 230000003211 malignant effect Effects 0.000 description 4
• 239000000594 mannitol Substances 0.000 description 4
• 235000010355 mannitol Nutrition 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• 230000004060 metabolic process Effects 0.000 description 4
• 229920000609 methyl cellulose Polymers 0.000 description 4
• 239000001923 methylcellulose Substances 0.000 description 4
• 235000010981 methylcellulose Nutrition 0.000 description 4
• 239000002480 mineral oil Substances 0.000 description 4
• 235000010446 mineral oil Nutrition 0.000 description 4
• 201000001119 neuropathy Diseases 0.000 description 4
• 230000007823 neuropathy Effects 0.000 description 4
• 230000000508 neurotrophic effect Effects 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 235000020824 obesity Nutrition 0.000 description 4
• 201000008482 osteoarthritis Diseases 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 4
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 210000002307 prostate Anatomy 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 4
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 4
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 description 4
• 239000011435 rock Substances 0.000 description 4
• 238000011894 semi-preparative HPLC Methods 0.000 description 4
• 235000012239 silicon dioxide Nutrition 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 235000017550 sodium carbonate Nutrition 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 235000011150 stannous chloride Nutrition 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 239000000829 suppository Substances 0.000 description 4
• 230000009967 tasteless effect Effects 0.000 description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 229960002898 threonine Drugs 0.000 description 4
• GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 4
• 210000003932 urinary bladder Anatomy 0.000 description 4
• 239000001993 wax Substances 0.000 description 4
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
• VFLQQZCRHPIGJU-UHFFFAOYSA-N 1-(2-chloroethyl)piperidine;hydron;chloride Chemical compound Cl.ClCCN1CCCCC1 VFLQQZCRHPIGJU-UHFFFAOYSA-N 0.000 description 3
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
• VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 3
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 3
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 3
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 208000005623 Carcinogenesis Diseases 0.000 description 3
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
• 206010009900 Colitis ulcerative Diseases 0.000 description 3
• 208000011231 Crohn disease Diseases 0.000 description 3
• 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 3
• 102100033245 Cyclin-dependent kinase 16 Human genes 0.000 description 3
• 102100026810 Cyclin-dependent kinase 7 Human genes 0.000 description 3
• 101710106276 Cyclin-dependent kinase 7 Proteins 0.000 description 3
• NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 3
• 101100291385 Drosophila melanogaster p38a gene Proteins 0.000 description 3
• 108010091824 Focal Adhesion Kinase 1 Proteins 0.000 description 3
• 102100037813 Focal adhesion kinase 1 Human genes 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 3
• 101000628967 Homo sapiens Mitogen-activated protein kinase 11 Proteins 0.000 description 3
• 101001052477 Homo sapiens Mitogen-activated protein kinase 4 Proteins 0.000 description 3
• 101000727826 Homo sapiens Tyrosine-protein kinase RYK Proteins 0.000 description 3
• 206010061218 Inflammation Diseases 0.000 description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• 102100028905 Megakaryocyte-associated tyrosine-protein kinase Human genes 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
• 108700036166 Mitogen-Activated Protein Kinase 11 Proteins 0.000 description 3
• 108700027647 Mitogen-Activated Protein Kinase 6 Proteins 0.000 description 3
• 108700027653 Mitogen-Activated Protein Kinase 9 Proteins 0.000 description 3
• 208000034578 Multiple myelomas Diseases 0.000 description 3
• 241001529936 Murinae Species 0.000 description 3
• 206010029260 Neuroblastoma Diseases 0.000 description 3
• 206010061535 Ovarian neoplasm Diseases 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• 206010035600 Pleural fibrosis Diseases 0.000 description 3
• 102100031426 Ras GTPase-activating protein 1 Human genes 0.000 description 3
• 108050004017 Ras GTPase-activating protein 1 Proteins 0.000 description 3
• 102000038012 SFKs Human genes 0.000 description 3
• 108091008118 SFKs Proteins 0.000 description 3
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 108010010057 TYK2 Kinase Proteins 0.000 description 3
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
• 239000004473 Threonine Substances 0.000 description 3
• 102100027053 Tyrosine-protein kinase Blk Human genes 0.000 description 3
• 101710083476 Tyrosine-protein kinase Blk Proteins 0.000 description 3
• 102100024537 Tyrosine-protein kinase Fer Human genes 0.000 description 3
• 102100027389 Tyrosine-protein kinase HCK Human genes 0.000 description 3
• 101710090365 Tyrosine-protein kinase HCK Proteins 0.000 description 3
• 102100029759 Tyrosine-protein kinase RYK Human genes 0.000 description 3
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 description 3
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 235000010443 alginic acid Nutrition 0.000 description 3
• 229920000615 alginic acid Polymers 0.000 description 3
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 239000012131 assay buffer Substances 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 208000029028 brain injury Diseases 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 230000005587 bubbling Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 229910000389 calcium phosphate Inorganic materials 0.000 description 3
• 230000036952 cancer formation Effects 0.000 description 3
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
• 231100000504 carcinogenesis Toxicity 0.000 description 3
• 230000022131 cell cycle Effects 0.000 description 3
• 230000003915 cell function Effects 0.000 description 3
• 230000010261 cell growth Effects 0.000 description 3
• 210000003679 cervix uteri Anatomy 0.000 description 3
• 208000037976 chronic inflammation Diseases 0.000 description 3
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 3
• 230000034994 death Effects 0.000 description 3
• 231100000517 death Toxicity 0.000 description 3
• 230000003247 decreasing effect Effects 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 208000037765 diseases and disorders Diseases 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 238000004043 dyeing Methods 0.000 description 3
• 239000002158 endotoxin Substances 0.000 description 3
• 206010016256 fatigue Diseases 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 238000010438 heat treatment Methods 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 150000003840 hydrochlorides Chemical class 0.000 description 3
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
• 230000006303 immediate early viral mRNA transcription Effects 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 230000001965 increasing effect Effects 0.000 description 3
• 208000027866 inflammatory disease Diseases 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 230000000302 ischemic effect Effects 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 230000001613 neoplastic effect Effects 0.000 description 3
• 208000004296 neuralgia Diseases 0.000 description 3
• 238000006386 neutralization reaction Methods 0.000 description 3
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 3
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 3
• 201000008968 osteosarcoma Diseases 0.000 description 3
• 230000002611 ovarian Effects 0.000 description 3
• 210000001672 ovary Anatomy 0.000 description 3
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 208000033808 peripheral neuropathy Diseases 0.000 description 3
• 239000008194 pharmaceutical composition Substances 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 210000003800 pharynx Anatomy 0.000 description 3
• 230000000704 physical effect Effects 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 3
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
• 229910000105 potassium hydride Inorganic materials 0.000 description 3
• 238000004237 preparative chromatography Methods 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 230000002062 proliferating effect Effects 0.000 description 3
• 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 description 3
• 238000001959 radiotherapy Methods 0.000 description 3
• 230000022983 regulation of cell cycle Effects 0.000 description 3
• 230000010410 reperfusion Effects 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 208000037803 restenosis Diseases 0.000 description 3
• 239000002002 slurry Substances 0.000 description 3
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 230000003068 static effect Effects 0.000 description 3
• 210000002784 stomach Anatomy 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• PWQIGBOSLQHOBT-ZETCQYMHSA-N tert-butyl n-[(2s)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound CON(C)C(=O)[C@H](C)NC(=O)OC(C)(C)C PWQIGBOSLQHOBT-ZETCQYMHSA-N 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 210000001685 thyroid gland Anatomy 0.000 description 3
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
• 230000014616 translation Effects 0.000 description 3
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• KOQNTUSATKDXGQ-UHFFFAOYSA-N (4-aminopiperidin-1-yl)-pyrrolidin-1-ylmethanone Chemical compound C1CC(N)CCN1C(=O)N1CCCC1 KOQNTUSATKDXGQ-UHFFFAOYSA-N 0.000 description 2
• KFJLLOJCPFYWRV-WCCKRBBISA-N (5s)-5-aminopiperidin-2-one;hydrochloride Chemical compound Cl.N[C@H]1CCC(=O)NC1 KFJLLOJCPFYWRV-WCCKRBBISA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• 102100021408 14-3-3 protein beta/alpha Human genes 0.000 description 2
• 102100040685 14-3-3 protein zeta/delta Human genes 0.000 description 2
• ICWYDTHIPOOOJV-NSHDSACASA-N 2,2,2-trifluoro-n-(4-oxocyclohexyl)-n-[(1s)-1-phenylethyl]acetamide Chemical compound FC(F)(F)C(=O)N([C@@H](C)C=1C=CC=CC=1)C1CCC(=O)CC1 ICWYDTHIPOOOJV-NSHDSACASA-N 0.000 description 2
• ABGGPKIFVAIRGU-UHFFFAOYSA-N 2,4-difluoro-1-isothiocyanatobenzene Chemical compound FC1=CC=C(N=C=S)C(F)=C1 ABGGPKIFVAIRGU-UHFFFAOYSA-N 0.000 description 2
• WCBURNWVRFRXTK-UHFFFAOYSA-N 2-chloro-n-cyclopentyl-5-nitropyrimidin-4-amine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1NC1CCCC1 WCBURNWVRFRXTK-UHFFFAOYSA-N 0.000 description 2
• CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
• RWMDJQJCEISWRT-UHFFFAOYSA-N 4-(dibenzylamino)cyclohexan-1-ol Chemical compound C1CC(O)CCC1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 RWMDJQJCEISWRT-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• KXMRDHPZQHAXML-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1CCC(C(O)=O)CC1 KXMRDHPZQHAXML-UHFFFAOYSA-N 0.000 description 2
• DMXUHMLNPMIDJN-ROKHWSDSSA-N 4-[[9-[(3r)-thiolan-3-yl]-8-(2,4,6-trifluoroanilino)purin-2-yl]amino]cyclohexan-1-ol Chemical compound C1CC(O)CCC1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2F)F)N2[C@H]3CSCC3)C2=N1 DMXUHMLNPMIDJN-ROKHWSDSSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• XJLDYKIEURAVBW-UHFFFAOYSA-N Aethyl-heptyl-keton Natural products CCCCCCCC(=O)CC XJLDYKIEURAVBW-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• 102000003989 Aurora kinases Human genes 0.000 description 2
• 108090000433 Aurora kinases Proteins 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
• 206010004146 Basal cell carcinoma Diseases 0.000 description 2
• 102100021738 Beta-adrenergic receptor kinase 1 Human genes 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• 208000003174 Brain Neoplasms Diseases 0.000 description 2
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• GVUBZULXXACFAF-IYARVYRRSA-N C1C[C@@H](NC(=O)OC(C)(C)C)CC[C@@H]1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2)F)N2C3CCCC3)C2=N1 Chemical compound C1C[C@@H](NC(=O)OC(C)(C)C)CC[C@@H]1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2)F)N2C3CCCC3)C2=N1 GVUBZULXXACFAF-IYARVYRRSA-N 0.000 description 2
• 206010006895 Cachexia Diseases 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 201000000274 Carcinosarcoma Diseases 0.000 description 2
• 102100037402 Casein kinase I isoform delta Human genes 0.000 description 2
• 102100037398 Casein kinase I isoform epsilon Human genes 0.000 description 2
• 102100040751 Casein kinase II subunit alpha Human genes 0.000 description 2
• 102100027992 Casein kinase II subunit beta Human genes 0.000 description 2
• 208000001387 Causalgia Diseases 0.000 description 2
• 206010008479 Chest Pain Diseases 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
• 241000272194 Ciconiiformes Species 0.000 description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
• 201000003883 Cystic fibrosis Diseases 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
• 102000011107 Diacylglycerol Kinase Human genes 0.000 description 2
• 108010062677 Diacylglycerol Kinase Proteins 0.000 description 2
• 101001031598 Dictyostelium discoideum Probable serine/threonine-protein kinase fhkC Proteins 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• 102000010778 Dual Specificity Phosphatase 1 Human genes 0.000 description 2
• 108010038537 Dual Specificity Phosphatase 1 Proteins 0.000 description 2
• 102100040862 Dual specificity protein kinase CLK1 Human genes 0.000 description 2
• 102100040844 Dual specificity protein kinase CLK2 Human genes 0.000 description 2
• 102100040856 Dual specificity protein kinase CLK3 Human genes 0.000 description 2
• 102100040858 Dual specificity protein kinase CLK4 Human genes 0.000 description 2
• 102100030322 Ephrin type-A receptor 1 Human genes 0.000 description 2
• 102100021605 Ephrin type-A receptor 5 Human genes 0.000 description 2
• 101710116742 Ephrin type-A receptor 5 Proteins 0.000 description 2
• 102100030779 Ephrin type-B receptor 1 Human genes 0.000 description 2
• 102100023721 Ephrin-B2 Human genes 0.000 description 2
• 108010044090 Ephrin-B2 Proteins 0.000 description 2
• 101710190709 Eukaryotic translation initiation factor 4 gamma 2 Proteins 0.000 description 2
• 101710165576 Extracellular signal-regulated kinase 2 Proteins 0.000 description 2
• 241000282324 Felis Species 0.000 description 2
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
• 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 2
• 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 2
• 229930091371 Fructose Natural products 0.000 description 2
• 239000005715 Fructose Substances 0.000 description 2
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
• 108010056715 G-Protein-Coupled Receptor Kinase 2 Proteins 0.000 description 2
• 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 2
• 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 2
• 208000017604 Hodgkin disease Diseases 0.000 description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000818893 Homo sapiens 14-3-3 protein beta/alpha Proteins 0.000 description 2
• 101000964898 Homo sapiens 14-3-3 protein zeta/delta Proteins 0.000 description 2
• 101001026336 Homo sapiens Casein kinase I isoform delta Proteins 0.000 description 2
• 101001026376 Homo sapiens Casein kinase I isoform epsilon Proteins 0.000 description 2
• 101000892026 Homo sapiens Casein kinase II subunit alpha Proteins 0.000 description 2
• 101000858625 Homo sapiens Casein kinase II subunit beta Proteins 0.000 description 2
• 101000944357 Homo sapiens Cyclin-dependent kinase 16 Proteins 0.000 description 2
• 101000938354 Homo sapiens Ephrin type-A receptor 1 Proteins 0.000 description 2
• 101001064150 Homo sapiens Ephrin type-B receptor 1 Proteins 0.000 description 2
• 101001005128 Homo sapiens LIM domain kinase 1 Proteins 0.000 description 2
• 101100457333 Homo sapiens MAPK11 gene Proteins 0.000 description 2
• 101001052490 Homo sapiens Mitogen-activated protein kinase 3 Proteins 0.000 description 2
• 101000595531 Homo sapiens Serine/threonine-protein kinase pim-1 Proteins 0.000 description 2
• 101001052849 Homo sapiens Tyrosine-protein kinase Fer Proteins 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 102000003746 Insulin Receptor Human genes 0.000 description 2
• 108010001127 Insulin Receptor Proteins 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 108010019437 Janus Kinase 2 Proteins 0.000 description 2
• 108010019421 Janus Kinase 3 Proteins 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• 102100026023 LIM domain kinase 1 Human genes 0.000 description 2
• 208000018142 Leiomyosarcoma Diseases 0.000 description 2
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 108700027650 Mitogen-Activated Protein Kinase 7 Proteins 0.000 description 2
• 108700027648 Mitogen-Activated Protein Kinase 8 Proteins 0.000 description 2
• 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 2
• 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 2
• 102100026932 Mitogen-activated protein kinase 12 Human genes 0.000 description 2
• 208000010190 Monoclonal Gammopathy of Undetermined Significance Diseases 0.000 description 2
• 206010057269 Mucoepidermoid carcinoma Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• 208000014767 Myeloproliferative disease Diseases 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
• 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 2
• 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 2
• 102000043276 Oncogene Human genes 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• 208000010191 Osteitis Deformans Diseases 0.000 description 2
• 208000027868 Paget disease Diseases 0.000 description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
• 208000007641 Pinealoma Diseases 0.000 description 2
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
• 208000002151 Pleural effusion Diseases 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 208000007541 Preleukemia Diseases 0.000 description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
• 108090000315 Protein Kinase C Proteins 0.000 description 2
• 102000003923 Protein Kinase C Human genes 0.000 description 2
• 102000001892 Protein Kinase C-theta Human genes 0.000 description 2
• 108010015499 Protein Kinase C-theta Proteins 0.000 description 2
• 101710092490 Protein kinase 3 Proteins 0.000 description 2
• 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 2
• 101710106759 Protein-tyrosine kinase 2-beta Proteins 0.000 description 2
• 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
• 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
• 208000001647 Renal Insufficiency Diseases 0.000 description 2
• 208000006265 Renal cell carcinoma Diseases 0.000 description 2
• 206010039085 Rhinitis allergic Diseases 0.000 description 2
• 102100033643 Ribosomal protein S6 kinase alpha-3 Human genes 0.000 description 2
• 102100030571 STE20-like serine/threonine-protein kinase Human genes 0.000 description 2
• 101710157230 STE20-like serine/threonine-protein kinase Proteins 0.000 description 2
• 101710202841 Serine/threonine-protein kinase 2 Proteins 0.000 description 2
• 101710091457 Serine/threonine-protein kinase Nek4 Proteins 0.000 description 2
• 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 description 2
• 206010041067 Small cell lung cancer Diseases 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• 102100024519 Src-like-adapter Human genes 0.000 description 2
• 101710184766 Src-like-adapter Proteins 0.000 description 2
• 208000027073 Stargardt disease Diseases 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 210000001744 T-lymphocyte Anatomy 0.000 description 2
• 108010009978 Tec protein-tyrosine kinase Proteins 0.000 description 2
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
• 102100026145 Transitional endoplasmic reticulum ATPase Human genes 0.000 description 2
• 101710132062 Transitional endoplasmic reticulum ATPase Proteins 0.000 description 2
• 206010052779 Transplant rejections Diseases 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
• 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 2
• 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 2
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 2
• 102100040177 Tyrosine-protein kinase Tec Human genes 0.000 description 2
• 102100037236 Tyrosine-protein kinase receptor UFO Human genes 0.000 description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
• 108091008605 VEGF receptors Proteins 0.000 description 2
• 102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 description 2
• 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 2
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
• 208000036142 Viral infection Diseases 0.000 description 2
• 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 2
• 208000017733 acquired polycythemia vera Diseases 0.000 description 2
• 208000021841 acute erythroid leukemia Diseases 0.000 description 2
• 208000002517 adenoid cystic carcinoma Diseases 0.000 description 2
• 201000010105 allergic rhinitis Diseases 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 125000004103 aminoalkyl group Chemical group 0.000 description 2
• 238000002399 angioplasty Methods 0.000 description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 description 2
• 239000002260 anti-inflammatory agent Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 108010023337 axl receptor tyrosine kinase Proteins 0.000 description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
• 102000012740 beta Adrenergic Receptors Human genes 0.000 description 2
• 108010079452 beta Adrenergic Receptors Proteins 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• DHCLVCXQIBBOPH-UHFFFAOYSA-N beta-glycerol phosphate Natural products OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
• GHRQXJHBXKYCLZ-UHFFFAOYSA-L beta-glycerolphosphate Chemical compound [Na+].[Na+].CC(CO)OOP([O-])([O-])=O GHRQXJHBXKYCLZ-UHFFFAOYSA-L 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 210000000133 brain stem Anatomy 0.000 description 2
• 210000000621 bronchi Anatomy 0.000 description 2
• 206010006451 bronchitis Diseases 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 235000011089 carbon dioxide Nutrition 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 230000032823 cell division Effects 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 230000005754 cellular signaling Effects 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 210000000038 chest Anatomy 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
• 208000020832 chronic kidney disease Diseases 0.000 description 2
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
• 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
• 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 230000003436 cytoskeletal effect Effects 0.000 description 2
• 238000000354 decomposition reaction Methods 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
• 230000009977 dual effect Effects 0.000 description 2
• 230000008482 dysregulation Effects 0.000 description 2
• 210000003238 esophagus Anatomy 0.000 description 2
• 238000010931 ester hydrolysis Methods 0.000 description 2
• UPVSMFHQPMRMLP-UHFFFAOYSA-N ethyl 4-aminocyclohexane-1-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1CCC(N)CC1 UPVSMFHQPMRMLP-UHFFFAOYSA-N 0.000 description 2
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 210000003414 extremity Anatomy 0.000 description 2
• 210000001508 eye Anatomy 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 230000003325 follicular Effects 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 210000004907 gland Anatomy 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• DHCLVCXQIBBOPH-UHFFFAOYSA-L glycerol 2-phosphate(2-) Chemical compound OCC(CO)OP([O-])([O-])=O DHCLVCXQIBBOPH-UHFFFAOYSA-L 0.000 description 2
• 208000036670 glycogen storage disease IXa1 Diseases 0.000 description 2
• 201000004503 glycogen storage disease VIII Diseases 0.000 description 2
• 210000003128 head Anatomy 0.000 description 2
• 230000003463 hyperproliferative effect Effects 0.000 description 2
• 230000002977 hyperthermial effect Effects 0.000 description 2
• 229960002411 imatinib Drugs 0.000 description 2
• 229960003685 imatinib mesylate Drugs 0.000 description 2
• 230000036039 immunity Effects 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 210000000936 intestine Anatomy 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• 201000006370 kidney failure Diseases 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 229940043355 kinase inhibitor Drugs 0.000 description 2
• 210000000867 larynx Anatomy 0.000 description 2
• 210000000265 leukocyte Anatomy 0.000 description 2
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
• 108010052968 leupeptin Proteins 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 206010024627 liposarcoma Diseases 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• 206010025135 lupus erythematosus Diseases 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 208000027202 mammary Paget disease Diseases 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 235000012054 meals Nutrition 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• NVVWJSURGDRQLC-AWEZNQCLSA-N methyl (4s)-5-(4-methylphenyl)sulfonyloxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate Chemical compound COC(=O)CC[C@H](NC(=O)OC(C)(C)C)COS(=O)(=O)C1=CC=C(C)C=C1 NVVWJSURGDRQLC-AWEZNQCLSA-N 0.000 description 2
• JZPVPCDNNWQPCD-QMMMGPOBSA-N methyl (4s)-5-azido-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate Chemical compound COC(=O)CC[C@@H](CN=[N+]=[N-])NC(=O)OC(C)(C)C JZPVPCDNNWQPCD-QMMMGPOBSA-N 0.000 description 2
• JRSYYLJDKVSNJH-CZEYKFRCSA-N methyl (e,4s)-4-[(2-methylpropan-2-yl)oxycarbonylamino]pent-2-enoate Chemical compound COC(=O)\C=C\[C@H](C)NC(=O)OC(C)(C)C JRSYYLJDKVSNJH-CZEYKFRCSA-N 0.000 description 2
• XHNHAXPWQJFZQK-UUTQUOLZSA-N methyl (e,4s)-4-aminopent-2-enoate;hydrochloride Chemical compound Cl.COC(=O)\C=C\[C@H](C)N XHNHAXPWQJFZQK-UUTQUOLZSA-N 0.000 description 2
• HNIQUPSCUTXLMM-UHFFFAOYSA-N methyl 1-hydroxy-4-[2-(propan-2-ylamino)-8-(2,4,6-trifluoroanilino)purin-9-yl]cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OC)(O)CCC1N1C2=NC(NC(C)C)=NC=C2N=C1NC1=C(F)C=C(F)C=C1F HNIQUPSCUTXLMM-UHFFFAOYSA-N 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 201000005328 monoclonal gammopathy of uncertain significance Diseases 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 239000012452 mother liquor Substances 0.000 description 2
• 210000000214 mouth Anatomy 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• 210000003739 neck Anatomy 0.000 description 2
• 208000007538 neurilemmoma Diseases 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 239000000082 organ preservation Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
• 208000037244 polycythemia vera Diseases 0.000 description 2
• 108010036962 polypeptide 3 90kDa ribosomal protein S6 kinase Proteins 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 230000009822 protein phosphorylation Effects 0.000 description 2
• 125000004258 purin-2-yl group Chemical group [H]N1C2=NC(*)=NC([H])=C2N([H])C1([H])[H] 0.000 description 2
• 125000002755 pyrazolinyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 230000011514 reflex Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
• 210000003705 ribosome Anatomy 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 201000007416 salivary gland adenoid cystic carcinoma Diseases 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 208000000587 small cell lung carcinoma Diseases 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 210000000952 spleen Anatomy 0.000 description 2
• 230000007480 spreading Effects 0.000 description 2
• 238000003892 spreading Methods 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 125000000547 substituted alkyl group Chemical group 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 150000003457 sulfones Chemical class 0.000 description 2
• 206010042863 synovial sarcoma Diseases 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• PWQIGBOSLQHOBT-SSDOTTSWSA-N tert-butyl n-[(2r)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound CON(C)C(=O)[C@@H](C)NC(=O)OC(C)(C)C PWQIGBOSLQHOBT-SSDOTTSWSA-N 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• 230000008733 trauma Effects 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• 206010044652 trigeminal neuralgia Diseases 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 230000006433 tumor necrosis factor production Effects 0.000 description 2
• 210000004291 uterus Anatomy 0.000 description 2
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
• 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 238000009423 ventilation Methods 0.000 description 2
• 230000035899 viability Effects 0.000 description 2
• 230000009385 viral infection Effects 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• 229910000166 zirconium phosphate Inorganic materials 0.000 description 2
• GNLJBJNONOOOQC-UHFFFAOYSA-N $l^{3}-carbane;magnesium Chemical compound [Mg]C GNLJBJNONOOOQC-UHFFFAOYSA-N 0.000 description 1
• NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
• RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
• QVHJQCGUWFKTSE-RXMQYKEDSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-RXMQYKEDSA-N 0.000 description 1
• ZGEYCCHDTIDZAE-SCSAIBSYSA-N (2r)-2-amino-5-methoxy-5-oxopentanoic acid Chemical compound COC(=O)CC[C@@H](N)C(O)=O ZGEYCCHDTIDZAE-SCSAIBSYSA-N 0.000 description 1
• OHYMUFVCRVPMEY-ZETCQYMHSA-N (2s)-5-methoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid Chemical compound COC(=O)CC[C@@H](C(O)=O)NC(=O)OC(C)(C)C OHYMUFVCRVPMEY-ZETCQYMHSA-N 0.000 description 1
• YUXKOWPNKJSTPQ-AXWWPMSFSA-N (2s,3r)-2-amino-3-hydroxybutanoic acid;(2s)-2-amino-3-hydroxypropanoic acid Chemical compound OC[C@H](N)C(O)=O.C[C@@H](O)[C@H](N)C(O)=O YUXKOWPNKJSTPQ-AXWWPMSFSA-N 0.000 description 1
• SSTBQGZAWTYVKJ-SCSAIBSYSA-N (3r)-3-[(2-chloro-5-nitropyrimidin-4-yl)amino]butanamide Chemical compound NC(=O)C[C@@H](C)NC1=NC(Cl)=NC=C1[N+]([O-])=O SSTBQGZAWTYVKJ-SCSAIBSYSA-N 0.000 description 1
• OWALISXAXYPTJD-SECBINFHSA-N (3r)-3-[2-(propan-2-ylamino)-8-(2,4,6-trifluoroanilino)purin-9-yl]butanamide Chemical compound NC(=O)C[C@@H](C)N1C2=NC(NC(C)C)=NC=C2N=C1NC1=C(F)C=C(F)C=C1F OWALISXAXYPTJD-SECBINFHSA-N 0.000 description 1
• JFQQZOCKXIICPE-IAGOWNOFSA-N (3r)-3-[benzyl-[(1r)-1-phenylethyl]amino]butan-1-ol Chemical compound OCC[C@@H](C)N([C@H](C)C=1C=CC=CC=1)CC1=CC=CC=C1 JFQQZOCKXIICPE-IAGOWNOFSA-N 0.000 description 1
• AGMZSYQMSHMXLT-SCSAIBSYSA-N (3r)-3-aminobutan-1-ol Chemical compound C[C@@H](N)CCO AGMZSYQMSHMXLT-SCSAIBSYSA-N 0.000 description 1
• SSTBQGZAWTYVKJ-BYPYZUCNSA-N (3s)-3-[(2-chloro-5-nitropyrimidin-4-yl)amino]butanamide Chemical compound NC(=O)C[C@H](C)NC1=NC(Cl)=NC=C1[N+]([O-])=O SSTBQGZAWTYVKJ-BYPYZUCNSA-N 0.000 description 1
• OWALISXAXYPTJD-VIFPVBQESA-N (3s)-3-[2-(propan-2-ylamino)-8-(2,4,6-trifluoroanilino)purin-9-yl]butanamide Chemical compound NC(=O)C[C@H](C)N1C2=NC(NC(C)C)=NC=C2N=C1NC1=C(F)C=C(F)C=C1F OWALISXAXYPTJD-VIFPVBQESA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• GYVSFOHSVVNCKC-WCCKRBBISA-N (3s)-thiolan-3-amine;hydrochloride Chemical compound Cl.N[C@H]1CCSC1 GYVSFOHSVVNCKC-WCCKRBBISA-N 0.000 description 1
• HXZSYUOXTKQNNY-UHFFFAOYSA-N (4-carboxycyclohexyl)azanium;chloride Chemical compound Cl.NC1CCC(C(O)=O)CC1 HXZSYUOXTKQNNY-UHFFFAOYSA-N 0.000 description 1
• QJIMTLTYXBDJFC-UHFFFAOYSA-N (4-methylphenyl)-diphenylphosphane Chemical compound C1=CC(C)=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJIMTLTYXBDJFC-UHFFFAOYSA-N 0.000 description 1
• IOGISYQVOGVIEU-GSVOUGTGSA-N (4r)-4-hydroxypyrrolidin-2-one Chemical compound O[C@H]1CNC(=O)C1 IOGISYQVOGVIEU-GSVOUGTGSA-N 0.000 description 1
• HVIKCIPJUZAPNJ-VKHMYHEASA-N (4s)-4-azidopyrrolidin-2-one Chemical compound [N-]=[N+]=N[C@@H]1CNC(=O)C1 HVIKCIPJUZAPNJ-VKHMYHEASA-N 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
• 230000006269 (delayed) early viral mRNA transcription Effects 0.000 description 1
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• DBSXNGIBAKYMSS-UHFFFAOYSA-N 1,3-difluoro-2-isothiocyanatobenzene Chemical compound FC1=CC=CC(F)=C1N=C=S DBSXNGIBAKYMSS-UHFFFAOYSA-N 0.000 description 1
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• DCKAGEYBDDBZQB-UHFFFAOYSA-N 1-hydroxy-4-[2-(propan-2-ylamino)-8-(2,4,6-trifluoroanilino)purin-9-yl]cyclohexane-1-carboxylic acid Chemical compound C1CC(O)(C(O)=O)CCC1N1C2=NC(NC(C)C)=NC=C2N=C1NC1=C(F)C=C(F)C=C1F DCKAGEYBDDBZQB-UHFFFAOYSA-N 0.000 description 1
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
• 102100024682 14-3-3 protein eta Human genes 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
• DSEXMLJKJZQKFF-ZETCQYMHSA-N 2,2-dimethyl-n-[(3s)-pyrrolidin-3-yl]propanamide Chemical compound CC(C)(C)C(=O)N[C@H]1CCNC1 DSEXMLJKJZQKFF-ZETCQYMHSA-N 0.000 description 1
• CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 1
• UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
• FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
• QVHJQCGUWFKTSE-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)C(C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-UHFFFAOYSA-N 0.000 description 1
• HNLXNOZHXNSSPN-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCOCCOCCOCCO)C=C1 HNLXNOZHXNSSPN-UHFFFAOYSA-N 0.000 description 1
• UVQVYRPYXXBLQH-UHFFFAOYSA-N 2-[4-(dibenzylamino)cyclohexyl]propan-2-ol Chemical compound C1CC(C(C)(O)C)CCC1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 UVQVYRPYXXBLQH-UHFFFAOYSA-N 0.000 description 1
• ZJLAWMDJTMMTQB-UHFFFAOYSA-N 2-chloro-6-fluoroaniline Chemical compound NC1=C(F)C=CC=C1Cl ZJLAWMDJTMMTQB-UHFFFAOYSA-N 0.000 description 1
• ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 1
• 101150090724 3 gene Proteins 0.000 description 1
• 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 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• WWEINXQNCAWBPD-UHFFFAOYSA-N 3-fluoropyridin-2-amine Chemical compound NC1=NC=CC=C1F WWEINXQNCAWBPD-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 description 1
• DTGIKBNWABRUNB-UHFFFAOYSA-N 4-[[4-(cyclopentylamino)-5-nitropyrimidin-2-yl]amino]cyclohexan-1-ol Chemical compound C1CC(O)CCC1NC1=NC=C([N+]([O-])=O)C(NC2CCCC2)=N1 DTGIKBNWABRUNB-UHFFFAOYSA-N 0.000 description 1
• JIMSBKAHGYGPLD-UHFFFAOYSA-N 4-aminopyrrolidin-2-one Chemical compound NC1CNC(=O)C1 JIMSBKAHGYGPLD-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• SDMXLAZIFYYECU-UHFFFAOYSA-N 4-methoxycyclohexan-1-amine Chemical compound COC1CCC(N)CC1 SDMXLAZIFYYECU-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• XIWUIBSJTMITRL-UHFFFAOYSA-N 5-[[9-cyclopentyl-8-(2,4,6-trifluoroanilino)purin-2-yl]amino]-1h-pyridin-2-one Chemical compound C1=NC(O)=CC=C1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2F)F)N2C3CCCC3)C2=N1 XIWUIBSJTMITRL-UHFFFAOYSA-N 0.000 description 1
• KFJLLOJCPFYWRV-UHFFFAOYSA-N 5-aminopiperidin-2-one;hydrochloride Chemical compound Cl.NC1CCC(=O)NC1 KFJLLOJCPFYWRV-UHFFFAOYSA-N 0.000 description 1
• NOYDQGFVFOQSAJ-UHFFFAOYSA-N 5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=CN=C1 NOYDQGFVFOQSAJ-UHFFFAOYSA-N 0.000 description 1
• 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• KSGXQKOKMTXXOI-UHFFFAOYSA-N 9-cyclopentyl-2-n-(6-methoxypyridin-3-yl)-8-n-(2,4,6-trifluorophenyl)purine-2,8-diamine Chemical compound C1=NC(OC)=CC=C1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2F)F)N2C3CCCC3)C2=N1 KSGXQKOKMTXXOI-UHFFFAOYSA-N 0.000 description 1
• 102000019050 90-kDa Ribosomal Protein S6 Kinases Human genes 0.000 description 1
• 108010012196 90-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 206010000599 Acromegaly Diseases 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 102000007469 Actins Human genes 0.000 description 1
• 108010052946 Activin Receptors Proteins 0.000 description 1
• 102000018918 Activin Receptors Human genes 0.000 description 1
• 102000005606 Activins Human genes 0.000 description 1
• 108010059616 Activins Proteins 0.000 description 1
• 206010000830 Acute leukaemia Diseases 0.000 description 1
• 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
• 206010054196 Affect lability Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 208000001446 Anaplastic Thyroid Carcinoma Diseases 0.000 description 1
• 206010002240 Anaplastic thyroid cancer Diseases 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 201000003076 Angiosarcoma Diseases 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 206010002941 Apallic syndrome Diseases 0.000 description 1
• 101100110008 Arabidopsis thaliana ASD2 gene Proteins 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• 208000033116 Asbestos intoxication Diseases 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 102100032306 Aurora kinase B Human genes 0.000 description 1
• 206010003840 Autonomic nervous system imbalance Diseases 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• 208000035821 Benign schwannoma Diseases 0.000 description 1
• 206010058956 Bicytopenia Diseases 0.000 description 1
• 208000020925 Bipolar disease Diseases 0.000 description 1
• 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
• 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
• 206010068975 Bone atrophy Diseases 0.000 description 1
• 206010052346 Brain contusion Diseases 0.000 description 1
• 206010006491 Brown-Sequard syndrome Diseases 0.000 description 1
• LRNJOHNTOVHTQZ-UAPYVXQJSA-N C1C[C@@H](C(=O)OCC)CC[C@@H]1N1C2=NC(NC=3C=CC(OC)=CC=3)=NC=C2N=C1NC1=CC=CC=C1F Chemical compound C1C[C@@H](C(=O)OCC)CC[C@@H]1N1C2=NC(NC=3C=CC(OC)=CC=3)=NC=C2N=C1NC1=CC=CC=C1F LRNJOHNTOVHTQZ-UAPYVXQJSA-N 0.000 description 1
• SXZWHAMVECDDFO-JOCQHMNTSA-N C1C[C@@H](N)CC[C@@H]1OCCN1CCCCC1 Chemical compound C1C[C@@H](N)CC[C@@H]1OCCN1CCCCC1 SXZWHAMVECDDFO-JOCQHMNTSA-N 0.000 description 1
• KDKNNKOXOPJQLS-SAABIXHNSA-N C1C[C@@H](NC)CC[C@@H]1N1C2=NC(NC=3C=CC(OC)=CC=3)=NC=C2N=C1NC1=CC=CC=C1F Chemical compound C1C[C@@H](NC)CC[C@@H]1N1C2=NC(NC=3C=CC(OC)=CC=3)=NC=C2N=C1NC1=CC=CC=C1F KDKNNKOXOPJQLS-SAABIXHNSA-N 0.000 description 1
• RWMDJQJCEISWRT-MXVIHJGJSA-N C1C[C@@H](O)CC[C@@H]1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 Chemical compound C1C[C@@H](O)CC[C@@H]1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 RWMDJQJCEISWRT-MXVIHJGJSA-N 0.000 description 1
• ZLALGIQLWSBSDE-KOMQPUFPSA-N C1C[C@@H](O)CC[C@@H]1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2)F)N2C3CCSCC3)C2=N1 Chemical compound C1C[C@@H](O)CC[C@@H]1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2)F)N2C3CCSCC3)C2=N1 ZLALGIQLWSBSDE-KOMQPUFPSA-N 0.000 description 1
• YIIJKGPGWGFFCY-JCNLHEQBSA-N C1C[C@@H](OC(=O)CCC(=O)O)CC[C@@H]1NC1=NC=C(N=C(NC=2C(=CC=CC=2F)F)N2C3CCCC3)C2=N1 Chemical compound C1C[C@@H](OC(=O)CCC(=O)O)CC[C@@H]1NC1=NC=C(N=C(NC=2C(=CC=CC=2F)F)N2C3CCCC3)C2=N1 YIIJKGPGWGFFCY-JCNLHEQBSA-N 0.000 description 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
• 101150012716 CDK1 gene Proteins 0.000 description 1
• 101100397595 Caenorhabditis elegans jnk-1 gene Proteins 0.000 description 1
• 101100343342 Caenorhabditis elegans lin-11 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 101710132601 Capsid protein Proteins 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• 206010058039 Cardiac perforation Diseases 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 108010010919 Casein Kinase II Proteins 0.000 description 1
• 102000052052 Casein Kinase II Human genes 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 208000009043 Chemical Burns Diseases 0.000 description 1
• 208000018380 Chemical injury Diseases 0.000 description 1
• 206010008469 Chest discomfort Diseases 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• 208000005243 Chondrosarcoma Diseases 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 241000207199 Citrus Species 0.000 description 1
• 208000028698 Cognitive impairment Diseases 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
• 206010010254 Concussion Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 208000022540 Consciousness disease Diseases 0.000 description 1
• 208000034656 Contusions Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 108010068192 Cyclin A Proteins 0.000 description 1
• 108010060385 Cyclin B1 Proteins 0.000 description 1
• 108010060387 Cyclin B2 Proteins 0.000 description 1
• 108010058546 Cyclin D1 Proteins 0.000 description 1
• 108010058544 Cyclin D2 Proteins 0.000 description 1
• 108010058545 Cyclin D3 Proteins 0.000 description 1
• 102000003909 Cyclin E Human genes 0.000 description 1
• 108090000257 Cyclin E Proteins 0.000 description 1
• 102100025191 Cyclin-A2 Human genes 0.000 description 1
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
• 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 1
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 101710113614 DNA primase small subunit PriS Proteins 0.000 description 1
• 230000004543 DNA replication Effects 0.000 description 1
• 102100038587 Death-associated protein kinase 1 Human genes 0.000 description 1
• 208000021709 Delayed Graft Function Diseases 0.000 description 1
• 208000000202 Diffuse Axonal Injury Diseases 0.000 description 1
• 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
• 208000003164 Diplopia Diseases 0.000 description 1
• 102100036723 Discoidin domain-containing receptor 2 Human genes 0.000 description 1
• 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
• 101000827763 Drosophila melanogaster Fibroblast growth factor receptor homolog 1 Proteins 0.000 description 1
• 101001023124 Drosophila melanogaster Myosin heavy chain, non-muscle Proteins 0.000 description 1
• 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
• 102100028554 Dual specificity tyrosine-phosphorylation-regulated kinase 1A Human genes 0.000 description 1
• 101710129551 Dual specificity tyrosine-phosphorylation-regulated kinase 1A Proteins 0.000 description 1
• 102100033363 Dual specificity tyrosine-phosphorylation-regulated kinase 1B Human genes 0.000 description 1
• 102100023112 Dual specificity tyrosine-phosphorylation-regulated kinase 4 Human genes 0.000 description 1
• 206010058314 Dysplasia Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• 101150068276 ERT1 gene Proteins 0.000 description 1
• 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 1
• 101710199605 Endoribonuclease Proteins 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 102100030324 Ephrin type-A receptor 3 Human genes 0.000 description 1
• 102100031982 Ephrin type-B receptor 3 Human genes 0.000 description 1
• 102100040954 Ephrin-A1 Human genes 0.000 description 1
• 108010043945 Ephrin-A1 Proteins 0.000 description 1
• 102100033941 Ephrin-A5 Human genes 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 241000402754 Erythranthe moschata Species 0.000 description 1
• 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
• 208000036566 Erythroleukaemia Diseases 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
• 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
• 102100020903 Ezrin Human genes 0.000 description 1
• 208000004930 Fatty Liver Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000001640 Fibromyalgia Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010016935 Follicular thyroid cancer Diseases 0.000 description 1
• 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
• 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 description 1
• 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 1
• 102100032340 G2/mitotic-specific cyclin-B1 Human genes 0.000 description 1
• 102100033201 G2/mitotic-specific cyclin-B2 Human genes 0.000 description 1
• 102100022086 GRB2-related adapter protein 2 Human genes 0.000 description 1
• 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
• 108091006109 GTPases Proteins 0.000 description 1
• 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 208000034951 Genetic Translocation Diseases 0.000 description 1
• 208000032320 Germ cell tumor of testis Diseases 0.000 description 1
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 229920002527 Glycogen Polymers 0.000 description 1
• 102100022975 Glycogen synthase kinase-3 alpha Human genes 0.000 description 1
• 229920002683 Glycosaminoglycan Polymers 0.000 description 1
• 208000009329 Graft vs Host Disease Diseases 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 229920002907 Guar gum Polymers 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000023661 Haematological disease Diseases 0.000 description 1
• 206010018852 Haematoma Diseases 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 208000001258 Hemangiosarcoma Diseases 0.000 description 1
• 208000018565 Hemochromatosis Diseases 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 101000760084 Homo sapiens 14-3-3 protein eta Proteins 0.000 description 1
• 101000798306 Homo sapiens Aurora kinase B Proteins 0.000 description 1
• 101000956145 Homo sapiens Death-associated protein kinase 1 Proteins 0.000 description 1
• 101000929429 Homo sapiens Discoidin domain-containing receptor 2 Proteins 0.000 description 1
• 101001014196 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
• 101000926738 Homo sapiens Dual specificity tyrosine-phosphorylation-regulated kinase 1B Proteins 0.000 description 1
• 101001049983 Homo sapiens Dual specificity tyrosine-phosphorylation-regulated kinase 4 Proteins 0.000 description 1
• 101000938351 Homo sapiens Ephrin type-A receptor 3 Proteins 0.000 description 1
• 101001064458 Homo sapiens Ephrin type-B receptor 3 Proteins 0.000 description 1
• 101000925251 Homo sapiens Ephrin-A5 Proteins 0.000 description 1
• 101001043764 Homo sapiens Inhibitor of nuclear factor kappa-B kinase subunit alpha Proteins 0.000 description 1
• 101000926535 Homo sapiens Interferon-induced, double-stranded RNA-activated protein kinase Proteins 0.000 description 1
• 101001042360 Homo sapiens LIM domain kinase 2 Proteins 0.000 description 1
• 101000956807 Homo sapiens Leukocyte tyrosine kinase receptor Proteins 0.000 description 1
• 101100457336 Homo sapiens MAPK12 gene Proteins 0.000 description 1
• 101100291373 Homo sapiens MAPK14 gene Proteins 0.000 description 1
• 101001106413 Homo sapiens Macrophage-stimulating protein receptor Proteins 0.000 description 1
• 101000628954 Homo sapiens Mitogen-activated protein kinase 12 Proteins 0.000 description 1
• 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 1
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
• 101001051767 Homo sapiens Protein kinase C beta type Proteins 0.000 description 1
• 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 1
• 101001125116 Homo sapiens Putative serine/threonine-protein kinase PRKY Proteins 0.000 description 1
• 101000944909 Homo sapiens Ribosomal protein S6 kinase alpha-1 Proteins 0.000 description 1
• 101000771237 Homo sapiens Serine/threonine-protein kinase A-Raf Proteins 0.000 description 1
• 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 description 1
• 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 description 1
• 101001047681 Homo sapiens Tyrosine-protein kinase Lck Proteins 0.000 description 1
• 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 description 1
• 101001026573 Homo sapiens cAMP-dependent protein kinase type I-alpha regulatory subunit Proteins 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• 208000004454 Hyperalgesia Diseases 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 206010021450 Immunodeficiency congenital Diseases 0.000 description 1
• 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 description 1
• 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 description 1
• 102100021892 Inhibitor of nuclear factor kappa-B kinase subunit alpha Human genes 0.000 description 1
• 102100034170 Interferon-induced, double-stranded RNA-activated protein kinase Human genes 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 description 1
• 206010073086 Iris melanoma Diseases 0.000 description 1
• 206010022998 Irritability Diseases 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 239000012825 JNK inhibitor Substances 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• ZGEYCCHDTIDZAE-BYPYZUCNSA-N L-glutamic acid 5-methyl ester Chemical compound COC(=O)CC[C@H](N)C(O)=O ZGEYCCHDTIDZAE-BYPYZUCNSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• 102100021756 LIM domain kinase 2 Human genes 0.000 description 1
• 208000034693 Laceration Diseases 0.000 description 1
• 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 1
• 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
• 208000009625 Lesch-Nyhan syndrome Diseases 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 102100038420 Leukocyte tyrosine kinase receptor Human genes 0.000 description 1
• 229910010084 LiAlH4 Inorganic materials 0.000 description 1
• 208000000501 Lipidoses Diseases 0.000 description 1
• 206010024585 Lipidosis Diseases 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• 108010068342 MAP Kinase Kinase 1 Proteins 0.000 description 1
• 102000002576 MAP Kinase Kinase 1 Human genes 0.000 description 1
• 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
• 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
• 101150098805 MAPK6 gene Proteins 0.000 description 1
• 101150078127 MUSK gene Proteins 0.000 description 1
• 102100021435 Macrophage-stimulating protein receptor Human genes 0.000 description 1
• 206010025412 Macular dystrophy congenital Diseases 0.000 description 1
• 208000035719 Maculopathy Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 101150003567 Mapk12 gene Proteins 0.000 description 1
• 101150060694 Mapk13 gene Proteins 0.000 description 1
• 208000009018 Medullary thyroid cancer Diseases 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 101710170958 Megakaryocyte-associated tyrosine-protein kinase Proteins 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 208000001145 Metabolic Syndrome Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 101710166115 Mitogen-activated protein kinase 2 Proteins 0.000 description 1
• 101710166076 Mitogen-activated protein kinase 5 Proteins 0.000 description 1
• 102100027869 Moesin Human genes 0.000 description 1
• 208000003445 Mouth Neoplasms Diseases 0.000 description 1
• 208000034486 Multi-organ failure Diseases 0.000 description 1
• 208000010718 Multiple Organ Failure Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 102100038168 Muscle, skeletal receptor tyrosine-protein kinase Human genes 0.000 description 1
• 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
• 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 1
• 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 1
• 102000016349 Myosin Light Chains Human genes 0.000 description 1
• 108010067385 Myosin Light Chains Proteins 0.000 description 1
• 102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 description 1
• 108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• BBMSOUDUBZZOTM-HAQNSBGRSA-N N1=C(NC2CCCC2)C(N)=CN=C1N[C@H]1CC[C@H](O)CC1 Chemical compound N1=C(NC2CCCC2)C(N)=CN=C1N[C@H]1CC[C@H](O)CC1 BBMSOUDUBZZOTM-HAQNSBGRSA-N 0.000 description 1
• MQUPAUOPCOMFTM-UHFFFAOYSA-N N=C=S.FC1=CC=CC(Cl)=C1 Chemical compound N=C=S.FC1=CC=CC(Cl)=C1 MQUPAUOPCOMFTM-UHFFFAOYSA-N 0.000 description 1
• 229910004878 Na2S2O4 Inorganic materials 0.000 description 1
• 229910020700 Na3VO4 Inorganic materials 0.000 description 1
• 206010028813 Nausea Diseases 0.000 description 1
• 206010061309 Neoplasm progression Diseases 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 206010029216 Nervousness Diseases 0.000 description 1
• 206010058119 Neurogenic shock Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 208000001294 Nociceptive Pain Diseases 0.000 description 1
• 206010029488 Nodular melanoma Diseases 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• UEAQERZFMDWIMU-MCZWQBSQSA-N O([C@@H]1CC[C@H](CC1)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)CCN1CCCCC1 Chemical compound O([C@@H]1CC[C@H](CC1)N(CC=1C=CC=CC=1)CC=1C=CC=CC=1)CCN1CCCCC1 UEAQERZFMDWIMU-MCZWQBSQSA-N 0.000 description 1
• 208000011623 Obstructive Lung disease Diseases 0.000 description 1
• 206010030124 Oedema peripheral Diseases 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 206010030216 Oesophagitis Diseases 0.000 description 1
• 108010053291 Oncogene Protein v-akt Proteins 0.000 description 1
• 206010053159 Organ failure Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 101100202399 Oryza sativa subsp. japonica SAPK4 gene Proteins 0.000 description 1
• 101000822655 Oryza sativa subsp. japonica Serine/threonine-protein kinase SAPK2 Proteins 0.000 description 1
• 101000822645 Oryza sativa subsp. japonica Serine/threonine-protein kinase SAPK3 Proteins 0.000 description 1
• 101001092938 Oryza sativa subsp. japonica Serine/threonine-protein kinase SAPK4 Proteins 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 102100029181 PDZ and LIM domain protein 5 Human genes 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010053869 POEMS syndrome Diseases 0.000 description 1
• 206010033557 Palpitations Diseases 0.000 description 1
• 206010033661 Pancytopenia Diseases 0.000 description 1
• 206010033701 Papillary thyroid cancer Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• 208000004983 Phantom Limb Diseases 0.000 description 1
• 206010056238 Phantom pain Diseases 0.000 description 1
• 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
• 241000286209 Phasianidae Species 0.000 description 1
• 101710181935 Phosphate-binding protein PstS 1 Proteins 0.000 description 1
• 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 1
• 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
• 206010050487 Pinealoblastoma Diseases 0.000 description 1
• 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 1
• 208000007452 Plasmacytoma Diseases 0.000 description 1
• 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
• 206010035592 Pleural calcification Diseases 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 208000008348 Post-Concussion Syndrome Diseases 0.000 description 1
• 206010036312 Post-traumatic epilepsy Diseases 0.000 description 1
• 208000004550 Postoperative Pain Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102000003946 Prolactin Human genes 0.000 description 1
• 108010057464 Prolactin Proteins 0.000 description 1
• WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 102000005569 Protein Phosphatase 1 Human genes 0.000 description 1
• 108010059000 Protein Phosphatase 1 Proteins 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 101710092489 Protein kinase 2 Proteins 0.000 description 1
• 102100024923 Protein kinase C beta type Human genes 0.000 description 1
• 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 102100029403 Putative serine/threonine-protein kinase PRKY Human genes 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 101710108565 RAC serine/threonine-protein kinase Proteins 0.000 description 1
• 101150071831 RPS6KA1 gene Proteins 0.000 description 1
• 206010037779 Radiculopathy Diseases 0.000 description 1
• 102100022127 Radixin Human genes 0.000 description 1
• 108091005682 Receptor kinases Proteins 0.000 description 1
• 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
• 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 1
• 101710151245 Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
• 101710088411 Rho-associated protein kinase 1 Proteins 0.000 description 1
• 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 1
• 101710088493 Rho-associated protein kinase 2 Proteins 0.000 description 1
• 102000002278 Ribosomal Proteins Human genes 0.000 description 1
• 108010000605 Ribosomal Proteins Proteins 0.000 description 1
• 102100033536 Ribosomal protein S6 kinase alpha-1 Human genes 0.000 description 1
• 101150046814 SAPK2 gene Proteins 0.000 description 1
• 101150105578 SAPK3 gene Proteins 0.000 description 1
• 229910006074 SO2NH2 Inorganic materials 0.000 description 1
• 102000001332 SRC Human genes 0.000 description 1
• 108060006706 SRC Proteins 0.000 description 1
• 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• 101710116197 Serine/threonine kinase NLK Proteins 0.000 description 1
• 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
• 102100029437 Serine/threonine-protein kinase A-Raf Human genes 0.000 description 1
• 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 description 1
• 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 description 1
• 102100034447 Serine/threonine-protein kinase NLK Human genes 0.000 description 1
• 101710175706 Serine/threonine-protein kinase NLK Proteins 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 239000004141 Sodium laurylsulphate Substances 0.000 description 1
• 102000005157 Somatostatin Human genes 0.000 description 1
• 108010056088 Somatostatin Proteins 0.000 description 1
• 206010049679 Spinal shock Diseases 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 208000002667 Subdural Hematoma Diseases 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 206010042553 Superficial spreading melanoma stage unspecified Diseases 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 108010016672 Syk Kinase Proteins 0.000 description 1
• 102000000551 Syk Kinase Human genes 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 206010043276 Teratoma Diseases 0.000 description 1
• 206010053615 Thermal burn Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
• 108010092867 Transforming Growth Factor beta Receptors Proteins 0.000 description 1
• 206010060872 Transplant failure Diseases 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 102000004271 Tryptophan 5-monooxygenases Human genes 0.000 description 1
• 108090000885 Tryptophan 5-monooxygenases Proteins 0.000 description 1
• 206010073104 Tubular breast carcinoma Diseases 0.000 description 1
• 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
• 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 102100039094 Tyrosinase Human genes 0.000 description 1
• 108060008724 Tyrosinase Proteins 0.000 description 1
• 102100024036 Tyrosine-protein kinase Lck Human genes 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 201000005969 Uveal melanoma Diseases 0.000 description 1
• 208000009311 VIPoma Diseases 0.000 description 1
• 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 1
• 208000014070 Vestibular schwannoma Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 206010047513 Vision blurred Diseases 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 206010047741 Vulval cancer Diseases 0.000 description 1
• 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
• 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• 208000000260 Warts Diseases 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 1
• 208000012018 Yolk sac tumor Diseases 0.000 description 1
• XYZFHMPDCNIBGW-UHFFFAOYSA-N [4-(dibenzylamino)cyclohexyl]methanol Chemical compound C1CC(CO)CCC1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 XYZFHMPDCNIBGW-UHFFFAOYSA-N 0.000 description 1
• XQKRPEDJRVOOAA-UHFFFAOYSA-J [Mg+2].[Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O Chemical compound [Mg+2].[Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XQKRPEDJRVOOAA-UHFFFAOYSA-J 0.000 description 1
• WDZCJFZKULYAMW-UHFFFAOYSA-N [O-][N+](S)=O Chemical compound [O-][N+](S)=O WDZCJFZKULYAMW-UHFFFAOYSA-N 0.000 description 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 150000007960 acetonitrile Chemical class 0.000 description 1
• PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 208000004064 acoustic neuroma Diseases 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 239000000488 activin Substances 0.000 description 1
• 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
• 150000001263 acyl chlorides Chemical class 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
• 208000020990 adrenal cortex carcinoma Diseases 0.000 description 1
• 201000005188 adrenal gland cancer Diseases 0.000 description 1
• 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
• 208000007128 adrenocortical carcinoma Diseases 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 206010064930 age-related macular degeneration Diseases 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000002877 alkyl aryl group Chemical group 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 206010053552 allodynia Diseases 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• WFIZFOITSJXTSV-UHFFFAOYSA-N amino(cyclohexyl)methanol Chemical compound NC(O)C1CCCCC1 WFIZFOITSJXTSV-UHFFFAOYSA-N 0.000 description 1
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 208000036878 aneuploidy Diseases 0.000 description 1
• 231100001075 aneuploidy Toxicity 0.000 description 1
• 230000002491 angiogenic effect Effects 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
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 239000003146 anticoagulant agent Substances 0.000 description 1
• 229940127090 anticoagulant agent Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 239000004019 antithrombin Substances 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• 235000015197 apple juice Nutrition 0.000 description 1
• 101150039804 arsk gene Proteins 0.000 description 1
• 230000004872 arterial blood pressure Effects 0.000 description 1
• 208000011775 arteriosclerosis disease Diseases 0.000 description 1
• 238000006254 arylation reaction Methods 0.000 description 1
• 206010003441 asbestosis Diseases 0.000 description 1
• 230000000923 atherogenic effect Effects 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 208000003373 basosquamous carcinoma Diseases 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000005605 benzo group Chemical group 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• JUPOJLQLZYUENU-UHFFFAOYSA-N benzyl 4-(dibenzylamino)cyclohexane-1-carboxylate Chemical compound C1CC(N(CC=2C=CC=CC=2)CC=2C=CC=CC=2)CCC1C(=O)OCC1=CC=CC=C1 JUPOJLQLZYUENU-UHFFFAOYSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• BFAKENXZKHGIGE-UHFFFAOYSA-N bis(2,3,5,6-tetrafluoro-4-iodophenyl)diazene Chemical compound FC1=C(C(=C(C(=C1F)I)F)F)N=NC1=C(C(=C(C(=C1F)F)I)F)F BFAKENXZKHGIGE-UHFFFAOYSA-N 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 208000018420 bone fibrosarcoma Diseases 0.000 description 1
• 238000010322 bone marrow transplantation Methods 0.000 description 1
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
• 230000005978 brain dysfunction Effects 0.000 description 1
• 201000000135 breast papillary carcinoma Diseases 0.000 description 1
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
• 229940045348 brown mixture Drugs 0.000 description 1
• 208000034526 bruise Diseases 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 102100037490 cAMP-dependent protein kinase type I-alpha regulatory subunit Human genes 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 235000001465 calcium Nutrition 0.000 description 1
• YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
• 239000001354 calcium citrate Substances 0.000 description 1
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Inorganic materials [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 150000001722 carbon compounds Chemical class 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 208000002458 carcinoid tumor Diseases 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 239000003729 cation exchange resin Substances 0.000 description 1
• 229940023913 cation exchange resins Drugs 0.000 description 1
• 230000021164 cell adhesion Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000012292 cell migration Effects 0.000 description 1
• 230000009087 cell motility Effects 0.000 description 1
• 210000003855 cell nucleus Anatomy 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 210000003793 centrosome Anatomy 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 239000007910 chewable tablet Substances 0.000 description 1
• 238000003403 chloroformylation reaction Methods 0.000 description 1
• 125000000068 chlorophenyl group Chemical group 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 208000024207 chronic leukemia Diseases 0.000 description 1
• 235000020971 citrus fruits Nutrition 0.000 description 1
• 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 230000001149 cognitive effect Effects 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
• 239000002361 compost Substances 0.000 description 1
• 230000009514 concussion Effects 0.000 description 1
• 208000018631 connective tissue disease Diseases 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 239000002178 crystalline material Substances 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• NZNMSOFKMUBTKW-UHFFFAOYSA-M cyclohexanecarboxylate Chemical compound [O-]C(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-M 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
• 208000002445 cystadenocarcinoma Diseases 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 238000006264 debenzylation reaction Methods 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000003795 desorption Methods 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 201000010064 diabetes insipidus Diseases 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 125000004663 dialkyl amino group Chemical group 0.000 description 1
• 125000003963 dichloro group Chemical group Cl* 0.000 description 1
• KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 230000009521 diffuse axonal injury Effects 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 230000000245 dipsogenic effect Effects 0.000 description 1
• IKYOVSVBLHGFMA-UHFFFAOYSA-N dipyridin-2-yloxymethanethione Chemical compound C=1C=CC=NC=1OC(=S)OC1=CC=CC=N1 IKYOVSVBLHGFMA-UHFFFAOYSA-N 0.000 description 1
• 238000007907 direct compression Methods 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• XJCRCPKBJWRZAX-UHFFFAOYSA-L disodium;dibenzoate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1.[O-]C(=O)C1=CC=CC=C1 XJCRCPKBJWRZAX-UHFFFAOYSA-L 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 238000007908 dry granulation Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 1
• 210000005069 ears Anatomy 0.000 description 1
• 238000002592 echocardiography Methods 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 208000026500 emaciation Diseases 0.000 description 1
• 208000028208 end stage renal disease Diseases 0.000 description 1
• 201000000523 end stage renal failure Diseases 0.000 description 1
• 206010014665 endocarditis Diseases 0.000 description 1
• 208000001991 endodermal sinus tumor Diseases 0.000 description 1
• 230000002357 endometrial effect Effects 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
• 206010015037 epilepsy Diseases 0.000 description 1
• 208000037828 epithelial carcinoma Diseases 0.000 description 1
• 208000006881 esophagitis Diseases 0.000 description 1
• 230000023209 establishment of centrosome localization Effects 0.000 description 1
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 208000024519 eye neoplasm Diseases 0.000 description 1
• 108010055671 ezrin Proteins 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000003176 fibrotic effect Effects 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 210000001650 focal adhesion Anatomy 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
• 201000000052 gastrinoma Diseases 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
• 229940096919 glycogen Drugs 0.000 description 1
• 208000007345 glycogen storage disease Diseases 0.000 description 1
• 108010049611 glycogen synthase kinase 3 alpha Proteins 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000000122 growth hormone Substances 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 235000010417 guar gum Nutrition 0.000 description 1
• 239000000665 guar gum Substances 0.000 description 1
• 229960002154 guar gum Drugs 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 235000015220 hamburgers Nutrition 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 210000005003 heart tissue Anatomy 0.000 description 1
• 208000025750 heavy chain disease Diseases 0.000 description 1
• 201000002222 hemangioblastoma Diseases 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
• USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• IBUDOENFVGHGFQ-UHFFFAOYSA-N hydroxy propyl carbonate Chemical compound CCCOC(=O)OO IBUDOENFVGHGFQ-UHFFFAOYSA-N 0.000 description 1
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 208000022119 inability to concentrate Diseases 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 201000004653 inflammatory breast carcinoma Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 206010022498 insulinoma Diseases 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 230000004073 interleukin-2 production Effects 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 201000002696 invasive tubular breast carcinoma Diseases 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 210000004153 islets of langerhan Anatomy 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 150000002540 isothiocyanates Chemical class 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000000244 kidney pelvis Anatomy 0.000 description 1
• 230000002147 killing effect Effects 0.000 description 1
• 208000003849 large cell carcinoma Diseases 0.000 description 1
• 206010024217 lentigo Diseases 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 208000037829 lymphangioendotheliosarcoma Diseases 0.000 description 1
• 230000035168 lymphangiogenesis Effects 0.000 description 1
• 208000012804 lymphangiosarcoma Diseases 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 208000038015 macular disease Diseases 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000003760 magnetic stirring Methods 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 201000002350 malignant ciliary body melanoma Diseases 0.000 description 1
• 208000006178 malignant mesothelioma Diseases 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 101150016833 mec-3 gene Proteins 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• 206010027191 meningioma Diseases 0.000 description 1
• 229940041616 menthol Drugs 0.000 description 1
• 238000003328 mesylation reaction Methods 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal 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
• CGPUIOJUNVHKIC-NSHDSACASA-N methyl (4s)-4-[2-(propan-2-ylamino)-8-(2,4,6-trifluoroanilino)purin-9-yl]pentanoate Chemical compound N=1C2=CN=C(NC(C)C)N=C2N([C@@H](C)CCC(=O)OC)C=1NC1=C(F)C=C(F)C=C1F CGPUIOJUNVHKIC-NSHDSACASA-N 0.000 description 1
• LYEPLCBRYTXYIE-VIFPVBQESA-N methyl (4s)-4-[[5-amino-2-(propan-2-ylamino)pyrimidin-4-yl]amino]pentanoate Chemical compound COC(=O)CC[C@H](C)NC1=NC(NC(C)C)=NC=C1N LYEPLCBRYTXYIE-VIFPVBQESA-N 0.000 description 1
• JRSYYLJDKVSNJH-HYDMIIDASA-N methyl (e,4r)-4-[(2-methylpropan-2-yl)oxycarbonylamino]pent-2-enoate Chemical compound COC(=O)\C=C\[C@@H](C)NC(=O)OC(C)(C)C JRSYYLJDKVSNJH-HYDMIIDASA-N 0.000 description 1
• XHNHAXPWQJFZQK-NHVBXQNASA-N methyl (e,4r)-4-aminopent-2-enoate;hydrochloride Chemical compound Cl.COC(=O)\C=C\[C@@H](C)N XHNHAXPWQJFZQK-NHVBXQNASA-N 0.000 description 1
• SIGOIUCRXKUEIG-UHFFFAOYSA-N methyl 2-dimethoxyphosphorylacetate Chemical compound COC(=O)CP(=O)(OC)OC SIGOIUCRXKUEIG-UHFFFAOYSA-N 0.000 description 1
• MZXGHSDGSIEODB-UHFFFAOYSA-N methyl 4-amino-1-hydroxycyclohexane-1-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1(O)CCC(N)CC1 MZXGHSDGSIEODB-UHFFFAOYSA-N 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 238000001471 micro-filtration Methods 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 230000011278 mitosis Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 108010071525 moesin Proteins 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 235000019691 monocalcium phosphate Nutrition 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 208000030454 monosomy Diseases 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 208000001611 myxosarcoma Diseases 0.000 description 1
• KMHGMMRSDZEUMJ-ZDUSSCGKSA-N n-(1,4-dioxaspiro[4.5]decan-8-yl)-2,2,2-trifluoro-n-[(1s)-1-phenylethyl]acetamide Chemical compound FC(F)(F)C(=O)N([C@@H](C)C=1C=CC=CC=1)C(CC1)CCC21OCCO2 KMHGMMRSDZEUMJ-ZDUSSCGKSA-N 0.000 description 1
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
• DTFDUIVYVHCCQG-UHFFFAOYSA-N n-benzyl-4-(4-formyl-3-methoxyphenoxy)butanamide Chemical compound C1=C(C=O)C(OC)=CC(OCCCC(=O)NCC=2C=CC=CC=2)=C1 DTFDUIVYVHCCQG-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
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000008693 nausea Effects 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 230000002988 nephrogenic effect Effects 0.000 description 1
• 230000001272 neurogenic effect Effects 0.000 description 1
• 230000007971 neurological deficit Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000002981 neuropathic effect Effects 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 208000004235 neutropenia Diseases 0.000 description 1
• 150000002828 nitro derivatives Chemical class 0.000 description 1
• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 1
• 230000003040 nociceptive effect Effects 0.000 description 1
• 201000000032 nodular malignant melanoma Diseases 0.000 description 1
• 210000001331 nose Anatomy 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 201000002575 ocular melanoma Diseases 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000003305 oral gavage Methods 0.000 description 1
• 235000015205 orange juice Nutrition 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 230000000399 orthopedic effect Effects 0.000 description 1
• 201000009234 osteosclerotic myeloma Diseases 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 125000000466 oxiranyl group Chemical group 0.000 description 1
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 208000021255 pancreatic insulinoma Diseases 0.000 description 1
• 201000010198 papillary carcinoma Diseases 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• YIYBQIKDCADOSF-UHFFFAOYSA-N pent-2-enoic acid Chemical compound CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 description 1
• IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 230000003836 peripheral circulation Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 150000003906 phosphoinositides Chemical class 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 201000003113 pineoblastoma Diseases 0.000 description 1
• 206010035059 pineocytoma Diseases 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 208000031223 plasma cell leukemia Diseases 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229920003124 powdered cellulose Polymers 0.000 description 1
• 235000019814 powdered cellulose Nutrition 0.000 description 1
• 238000004321 preservation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
• 208000003476 primary myelofibrosis Diseases 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• 229940097325 prolactin Drugs 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 235000019833 protease Nutrition 0.000 description 1
• 239000011814 protection agent Substances 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 230000006920 protein precipitation Effects 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
• 210000001147 pulmonary artery Anatomy 0.000 description 1
• 125000004544 purin-8-yl group Chemical group N1=CN=C2N=C(NC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
• XACWJIQLDLUFSR-UHFFFAOYSA-N pyrrolidine-1-carbonyl chloride Chemical compound ClC(=O)N1CCCC1 XACWJIQLDLUFSR-UHFFFAOYSA-N 0.000 description 1
• 108010048484 radixin Proteins 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 210000003370 receptor cell Anatomy 0.000 description 1
• 108091008600 receptor tyrosine phosphatases Proteins 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 239000013643 reference control Substances 0.000 description 1
• 230000016515 regulation of signal transduction Effects 0.000 description 1
• 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000005488 sandblasting Methods 0.000 description 1
• 238000003118 sandwich ELISA Methods 0.000 description 1
• 230000037390 scarring Effects 0.000 description 1
• 206010039667 schwannoma Diseases 0.000 description 1
• 238000003345 scintillation counting Methods 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 239000013049 sediment Substances 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 201000010153 skin papilloma Diseases 0.000 description 1
• 208000019116 sleep disease Diseases 0.000 description 1
• 208000022925 sleep disturbance Diseases 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229940001607 sodium bisulfite Drugs 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 235000010268 sodium methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 238000003746 solid phase reaction Methods 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
• 229960000553 somatostatin Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 208000017572 squamous cell neoplasm Diseases 0.000 description 1
• 239000003381 stabilizer Substances 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
• 239000008117 stearic acid Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 210000003518 stress fiber Anatomy 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 229940014800 succinic anhydride Drugs 0.000 description 1
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 208000030457 superficial spreading melanoma Diseases 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 210000004243 sweat Anatomy 0.000 description 1
• 206010042772 syncope Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000007916 tablet composition Substances 0.000 description 1
• 239000007885 tablet disintegrant Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• QHSPZGZEUDEIQM-AATRIKPKSA-N tert-butyl (e)-but-2-enoate Chemical compound C\C=C\C(=O)OC(C)(C)C QHSPZGZEUDEIQM-AATRIKPKSA-N 0.000 description 1
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
• DQARDWKWPIRJEH-UHFFFAOYSA-N tert-butyl n-(4-hydroxycyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(O)CC1 DQARDWKWPIRJEH-UHFFFAOYSA-N 0.000 description 1
• ZYYXGYAWMJJYHY-UHFFFAOYSA-N tert-butyl n-(4-methoxycyclohexyl)carbamate Chemical compound COC1CCC(NC(=O)OC(C)(C)C)CC1 ZYYXGYAWMJJYHY-UHFFFAOYSA-N 0.000 description 1
• KBNSUMIBERIFIT-ZETCQYMHSA-N tert-butyl n-[(3s)-6-oxopiperidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCC(=O)NC1 KBNSUMIBERIFIT-ZETCQYMHSA-N 0.000 description 1
• VEADDTRQRUBZFU-UHFFFAOYSA-N tert-butyl n-[1-(pyrrolidine-1-carbonyl)piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C(=O)N1CCCC1 VEADDTRQRUBZFU-UHFFFAOYSA-N 0.000 description 1
• SGNKPJPMWHKOJO-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CO)CC1 SGNKPJPMWHKOJO-UHFFFAOYSA-N 0.000 description 1
• CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 208000002918 testicular germ cell tumor Diseases 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• 201000006361 tethered spinal cord syndrome Diseases 0.000 description 1
• 150000003527 tetrahydropyrans Chemical group 0.000 description 1
• 229960003433 thalidomide Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• RPIXOLUIHUFDOY-UHFFFAOYSA-N thian-4-amine Chemical compound NC1CCSCC1 RPIXOLUIHUFDOY-UHFFFAOYSA-N 0.000 description 1
• 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
• 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 1
• 208000019179 thyroid gland undifferentiated (anaplastic) carcinoma Diseases 0.000 description 1
• 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 230000017423 tissue regeneration Effects 0.000 description 1
• 231100000167 toxic agent Toxicity 0.000 description 1
• 239000003440 toxic substance Substances 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• 206010044412 transitional cell carcinoma Diseases 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• 230000000472 traumatic effect Effects 0.000 description 1
• 230000008736 traumatic injury Effects 0.000 description 1
• 235000013337 tricalcium citrate Nutrition 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 201000008827 tuberculosis Diseases 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 230000005751 tumor progression Effects 0.000 description 1
• 125000005289 uranyl group Chemical group 0.000 description 1
• 208000037965 uterine sarcoma Diseases 0.000 description 1
• 208000013139 vaginal neoplasm Diseases 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000005167 vascular cell Anatomy 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 230000004218 vascular function Effects 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 229940099039 velcade Drugs 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• 208000009935 visceral pain Diseases 0.000 description 1
• 201000007790 vitelliform macular dystrophy Diseases 0.000 description 1
• 201000005102 vulva cancer Diseases 0.000 description 1
• 239000002699 waste material Substances 0.000 description 1
• 208000016261 weight loss Diseases 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 238000005550 wet granulation Methods 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 239000002023 wood Substances 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 210000004340 zona pellucida Anatomy 0.000 description 1