CA2530589A1

CA2530589A1 - Arylmethyl triazolo and imidazopyrazines as c-met inhibitors

Arylmethyl triazolo and imidazopyrazines as c-met inhibitors Download PDF

Info

Publication number: CA2530589A1
Authority: CA; Canada
Prior art keywords: group; substituted; heteroalicyclic; lower alkyl; heteroaryl
Prior art date: 2003-07-02
Legal status : Abandoned

Application number

CA002530589A

Other languages

English (en)

French (fr)

Inventor

Jingrong Cui

Iriny Botrous

Current Assignee

Sugen LLC

Original Assignee

Individual

Priority date

2003-07-02

Filing date

2004-06-25

Publication date

2005-01-20

2004-06-25 Application filed by Individual filed Critical Individual

2005-01-20 Publication of CA2530589A1 publication Critical patent/CA2530589A1/en

Status Abandoned legal-status Critical Current

Links

239000003112 inhibitor Substances 0.000 title description 16
125000005002 aryl methyl group Chemical group 0.000 title 1
150000005235 imidazopyrazines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 140
206010028980 Neoplasm Diseases 0.000 claims abstract description 43
150000003839 salts Chemical class 0.000 claims abstract description 42
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
201000011510 cancer Diseases 0.000 claims abstract description 19
-1 heteroalicyclic Chemical group 0.000 claims description 61
125000000217 alkyl group Chemical group 0.000 claims description 54
238000000034 method Methods 0.000 claims description 51
125000003342 alkenyl group Chemical group 0.000 claims description 37
125000000304 alkynyl group Chemical group 0.000 claims description 35
125000001072 heteroaryl group Chemical group 0.000 claims description 35
125000000753 cycloalkyl group Chemical group 0.000 claims description 34
125000003118 aryl group Chemical group 0.000 claims description 33
125000004432 carbon atom Chemical group C* 0.000 claims description 28
150000002367 halogens Chemical class 0.000 claims description 26
229910052739 hydrogen Inorganic materials 0.000 claims description 26
229910052736 halogen Inorganic materials 0.000 claims description 25
239000001257 hydrogen Substances 0.000 claims description 22
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 22
125000004093 cyano group Chemical group *C#N 0.000 claims description 20
239000008194 pharmaceutical composition Substances 0.000 claims description 20
208000035475 disorder Diseases 0.000 claims description 18
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 17
229910052799 carbon Inorganic materials 0.000 claims description 16
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 16
239000000546 pharmaceutical excipient Substances 0.000 claims description 14
125000004429 atom Chemical group 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
125000004103 aminoalkyl group Chemical group 0.000 claims description 12
229910052801 chlorine Inorganic materials 0.000 claims description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
229910052731 fluorine Inorganic materials 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
208000005718 Stomach Neoplasms Diseases 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000004663 dialkyl amino group Chemical group 0.000 claims description 6
208000014829 head and neck neoplasm Diseases 0.000 claims description 6
208000032839 leukemia Diseases 0.000 claims description 6
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
206010039491 Sarcoma Diseases 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
201000002528 pancreatic cancer Diseases 0.000 claims description 5
208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
208000032612 Glial tumor Diseases 0.000 claims description 4
206010018338 Glioma Diseases 0.000 claims description 4
208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
206010017758 gastric cancer Diseases 0.000 claims description 4
208000020816 lung neoplasm Diseases 0.000 claims description 4
201000011549 stomach cancer Diseases 0.000 claims description 4
206010009944 Colon cancer Diseases 0.000 claims description 3
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
206010038389 Renal cancer Diseases 0.000 claims description 3
201000010982 kidney cancer Diseases 0.000 claims description 3
201000007270 liver cancer Diseases 0.000 claims description 3
208000014018 liver neoplasm Diseases 0.000 claims description 3
201000005202 lung cancer Diseases 0.000 claims description 3
201000001441 melanoma Diseases 0.000 claims description 3
201000000050 myeloid neoplasm Diseases 0.000 claims description 3
208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
206010060862 Prostate cancer Diseases 0.000 claims description 2
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
208000026037 malignant tumor of neck Diseases 0.000 claims description 2
230000000694 effects Effects 0.000 abstract description 39
238000011282 treatment Methods 0.000 abstract description 26
230000002265 prevention Effects 0.000 abstract description 4
239000000203 mixture Substances 0.000 description 46
210000004027 cell Anatomy 0.000 description 39
239000000243 solution Substances 0.000 description 23
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
230000003197 catalytic effect Effects 0.000 description 15
102000005962 receptors Human genes 0.000 description 15
108020003175 receptors Proteins 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
239000003814 drug Substances 0.000 description 14
238000003556 assay Methods 0.000 description 13
238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 13
238000012360 testing method Methods 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
238000002360 preparation method Methods 0.000 description 12
239000000126 substance Substances 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
241000282414 Homo sapiens Species 0.000 description 11
230000008859 change Effects 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
108090000623 proteins and genes Proteins 0.000 description 11
102000027426 receptor tyrosine kinases Human genes 0.000 description 11
108091008598 receptor tyrosine kinases Proteins 0.000 description 11
239000007787 solid Substances 0.000 description 11
102000003745 Hepatocyte Growth Factor Human genes 0.000 description 10
108090000100 Hepatocyte Growth Factor Proteins 0.000 description 10
108091000080 Phosphotransferase Proteins 0.000 description 10
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 10
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 10
238000009472 formulation Methods 0.000 description 10
102000020233 phosphotransferase Human genes 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
201000010099 disease Diseases 0.000 description 9
229940079593 drug Drugs 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
235000018102 proteins Nutrition 0.000 description 9
102000004169 proteins and genes Human genes 0.000 description 9
102000009465 Growth Factor Receptors Human genes 0.000 description 8
108010009202 Growth Factor Receptors Proteins 0.000 description 8
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 8
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
230000014509 gene expression Effects 0.000 description 8
239000003446 ligand Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 7
108010010803 Gelatin Proteins 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
239000002775 capsule Substances 0.000 description 7
239000000969 carrier Substances 0.000 description 7
230000001413 cellular effect Effects 0.000 description 7
239000006184 cosolvent Substances 0.000 description 7
229920000159 gelatin Polymers 0.000 description 7
239000008273 gelatin Substances 0.000 description 7
235000019322 gelatine Nutrition 0.000 description 7
235000011852 gelatine desserts Nutrition 0.000 description 7
239000000463 material Substances 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
229920001223 polyethylene glycol Polymers 0.000 description 7
229940002612 prodrug Drugs 0.000 description 7
239000000651 prodrug Substances 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
239000000725 suspension Substances 0.000 description 7
208000024891 symptom Diseases 0.000 description 7
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 7
KTNGGZUOYRVYGI-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-5-thiophen-2-ylimidazo[4,5-b]pyrazine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C=3SC=CC=3)=CN=C2N=C1 KTNGGZUOYRVYGI-UHFFFAOYSA-N 0.000 description 6
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
206010027476 Metastases Diseases 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 6
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 6
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000002246 antineoplastic agent Substances 0.000 description 6
239000000872 buffer Substances 0.000 description 6
230000024245 cell differentiation Effects 0.000 description 6
230000010261 cell growth Effects 0.000 description 6
230000004663 cell proliferation Effects 0.000 description 6
230000001086 cytosolic effect Effects 0.000 description 6
229940127089 cytotoxic agent Drugs 0.000 description 6
235000019439 ethyl acetate Nutrition 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 6
230000019491 signal transduction Effects 0.000 description 6
239000007858 starting material Substances 0.000 description 6
235000000346 sugar Nutrition 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
210000000481 breast Anatomy 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
150000001721 carbon Chemical group 0.000 description 5
238000004113 cell culture Methods 0.000 description 5
230000001419 dependent effect Effects 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000000499 gel Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
230000002209 hydrophobic effect Effects 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
230000003993 interaction Effects 0.000 description 5
230000003834 intracellular effect Effects 0.000 description 5
230000001404 mediated effect Effects 0.000 description 5
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 5
125000005010 perfluoroalkyl group Chemical group 0.000 description 5
239000012071 phase Substances 0.000 description 5
238000006366 phosphorylation reaction Methods 0.000 description 5
230000036470 plasma concentration Effects 0.000 description 5
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
239000001267 polyvinylpyrrolidone Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
239000000758 substrate Substances 0.000 description 5
150000008163 sugars Chemical class 0.000 description 5
RZSFFEADPCOCNQ-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-5-thiophen-2-yltriazolo[4,5-b]pyrazine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C=3SC=CC=3)=CN=C2N=N1 RZSFFEADPCOCNQ-UHFFFAOYSA-N 0.000 description 4
BZKMVPNSSFDJPN-UHFFFAOYSA-N 4-[(5-thiophen-2-ylimidazo[4,5-b]pyrazin-3-yl)methyl]phenol Chemical compound C1=CC(O)=CC=C1CN1C2=NC(C=3SC=CC=3)=CN=C2N=C1 BZKMVPNSSFDJPN-UHFFFAOYSA-N 0.000 description 4
MKJNRQGIMKMQPL-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-[(4-methoxyphenyl)methyl]imidazo[4,5-b]pyrazine Chemical compound C1=CC(OC)=CC=C1CN1C2=NC(C=3C=CC(F)=CC=3)=CN=C2N=C1 MKJNRQGIMKMQPL-UHFFFAOYSA-N 0.000 description 4
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 4
ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 4
ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
229910015845 BBr3 Inorganic materials 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
101001059535 Homo sapiens Megakaryocyte-associated tyrosine-protein kinase Proteins 0.000 description 4
101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 4
102100028905 Megakaryocyte-associated tyrosine-protein kinase Human genes 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 4
102000001253 Protein Kinase Human genes 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000006180 TBST buffer Substances 0.000 description 4
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 description 4
230000004071 biological effect Effects 0.000 description 4
239000011203 carbon fibre reinforced carbon Substances 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
239000000460 chlorine Substances 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
239000008298 dragée Substances 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
239000002502 liposome Substances 0.000 description 4
230000007246 mechanism Effects 0.000 description 4
239000002609 medium Substances 0.000 description 4
230000009401 metastasis Effects 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
230000035772 mutation Effects 0.000 description 4
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 4
230000026731 phosphorylation Effects 0.000 description 4
239000000843 powder Substances 0.000 description 4
238000002953 preparative HPLC Methods 0.000 description 4
108060006633 protein kinase Proteins 0.000 description 4
238000001959 radiotherapy Methods 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
239000008107 starch Substances 0.000 description 4
230000004083 survival effect Effects 0.000 description 4
238000013268 sustained release Methods 0.000 description 4
239000012730 sustained-release form Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
239000002525 vasculotropin inhibitor Substances 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
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 3
102100026802 72 kDa type IV collagenase Human genes 0.000 description 3
101710151806 72 kDa type IV collagenase Proteins 0.000 description 3
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
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 3
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 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 3
108010001127 Insulin Receptor Proteins 0.000 description 3
102000003746 Insulin Receptor Human genes 0.000 description 3
108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 3
102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 3
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 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
241000124008 Mammalia Species 0.000 description 3
102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 3
108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
102100033237 Pro-epidermal growth factor Human genes 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
230000002159 abnormal effect Effects 0.000 description 3
230000004913 activation Effects 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
150000001413 amino acids Chemical group 0.000 description 3
230000033115 angiogenesis Effects 0.000 description 3
125000004104 aryloxy group Chemical group 0.000 description 3
OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 3
239000002585 base Substances 0.000 description 3
229910000019 calcium carbonate Inorganic materials 0.000 description 3
239000001506 calcium phosphate Substances 0.000 description 3
229910000389 calcium phosphate Inorganic materials 0.000 description 3
235000011010 calcium phosphates Nutrition 0.000 description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
230000003247 decreasing effect Effects 0.000 description 3
239000013024 dilution buffer Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
230000002255 enzymatic effect Effects 0.000 description 3
229940088598 enzyme Drugs 0.000 description 3
230000012010 growth Effects 0.000 description 3
239000003102 growth factor Substances 0.000 description 3
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
210000004185 liver Anatomy 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
239000001630 malic acid Substances 0.000 description 3
238000012544 monitoring process Methods 0.000 description 3
239000013642 negative control Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
230000008569 process Effects 0.000 description 3
230000035755 proliferation Effects 0.000 description 3
230000001105 regulatory effect Effects 0.000 description 3
230000011664 signaling Effects 0.000 description 3
239000011734 sodium Substances 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
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 3
230000004614 tumor growth Effects 0.000 description 3
DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 3
GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
FPYJSJDOHRDAMT-KQWNVCNZSA-N 1h-indole-5-sulfonamide, n-(3-chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1h-pyrrol-2-yl]methylene]-2,3-dihydro-n-methyl-2-oxo-, (3z)- Chemical compound C=1C=C2NC(=O)\C(=C/C3=C(C(C(=O)N4CCN(C)CC4)=C(C)N3)C)C2=CC=1S(=O)(=O)N(C)C1=CC=CC(Cl)=C1 FPYJSJDOHRDAMT-KQWNVCNZSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
DTLBKXRFWUERQN-UHFFFAOYSA-N 3,5-dibromopyrazin-2-amine Chemical compound NC1=NC=C(Br)N=C1Br DTLBKXRFWUERQN-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
KMEDLVMTFCOGHW-UHFFFAOYSA-N 4-[(6-bromoimidazo[4,5-b]pyridin-1-yl)methyl]phenol Chemical compound C1=CC(O)=CC=C1CN1C2=CC(Br)=CN=C2N=C1 KMEDLVMTFCOGHW-UHFFFAOYSA-N 0.000 description 2
FENDUWDOKASCNR-UHFFFAOYSA-N 4-[2-[3-[3-[(4-fluorophenyl)methyl]imidazo[4,5-b]pyrazin-5-yl]phenoxy]ethyl]morpholine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C=3C=C(OCCN4CCOCC4)C=CC=3)=CN=C2N=C1 FENDUWDOKASCNR-UHFFFAOYSA-N 0.000 description 2
JQSXXAITNWGQAR-UHFFFAOYSA-N 4-[[(3-amino-6-thiophen-2-ylpyrazin-2-yl)amino]methyl]phenol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC1=NC=C(C=2SC=CC=2)N=C1NCC1=CC=C(O)C=C1 JQSXXAITNWGQAR-UHFFFAOYSA-N 0.000 description 2
XFSPUECBJISPDO-UHFFFAOYSA-N 4-[[5-(4-fluorophenyl)imidazo[4,5-b]pyrazin-3-yl]methyl]phenol Chemical compound C1=CC(O)=CC=C1CN1C2=NC(C=3C=CC(F)=CC=3)=CN=C2N=C1 XFSPUECBJISPDO-UHFFFAOYSA-N 0.000 description 2
DFYXIXOWAHRERH-UHFFFAOYSA-N 6-bromo-1-[(4-methoxyphenyl)methyl]imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1CN1C2=CC(Br)=CN=C2N=C1 DFYXIXOWAHRERH-UHFFFAOYSA-N 0.000 description 2
XPHWCAKVRKUXLK-UHFFFAOYSA-N 6-bromo-1h-imidazo[4,5-b]pyridine Chemical compound BrC1=CN=C2N=CNC2=C1 XPHWCAKVRKUXLK-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
108090000994 Catalytic RNA Proteins 0.000 description 2
102000053642 Catalytic RNA Human genes 0.000 description 2
241001227713 Chiron Species 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 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
102100039137 Insulin receptor-related protein Human genes 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
229910021380 Manganese Chloride Inorganic materials 0.000 description 2
GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 2
102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 2
108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 2
102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
206010033128 Ovarian cancer Diseases 0.000 description 2
206010061535 Ovarian neoplasm Diseases 0.000 description 2
239000004743 Polypropylene Substances 0.000 description 2
102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 2
102000052575 Proto-Oncogene Human genes 0.000 description 2
108700020978 Proto-Oncogene Proteins 0.000 description 2
108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
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 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
239000004037 angiogenesis inhibitor Substances 0.000 description 2
238000010171 animal model Methods 0.000 description 2
238000013459 approach Methods 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000008827 biological function Effects 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
239000011575 calcium Substances 0.000 description 2
235000013877 carbamide Nutrition 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
230000032823 cell division Effects 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
230000036755 cellular response Effects 0.000 description 2
238000000576 coating method Methods 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
238000002648 combination therapy Methods 0.000 description 2
MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
210000000172 cytosol Anatomy 0.000 description 2
239000008121 dextrose Substances 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
230000004069 differentiation Effects 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
229940121647 egfr inhibitor Drugs 0.000 description 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
239000010685 fatty oil Substances 0.000 description 2
239000000945 filler Substances 0.000 description 2
229960002949 fluorouracil Drugs 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
230000006870 function Effects 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
201000010536 head and neck cancer Diseases 0.000 description 2
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 description 2
108010054372 insulin receptor-related receptor Proteins 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
230000009545 invasion Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
238000002372 labelling Methods 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
231100000053 low toxicity Toxicity 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
239000000314 lubricant Substances 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
235000011090 malic acid Nutrition 0.000 description 2
239000011565 manganese chloride Substances 0.000 description 2
235000002867 manganese chloride Nutrition 0.000 description 2
229940099607 manganese chloride Drugs 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
229940068968 polysorbate 80 Drugs 0.000 description 2
229920000053 polysorbate 80 Polymers 0.000 description 2
238000012545 processing Methods 0.000 description 2
210000002307 prostate Anatomy 0.000 description 2
239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 2
125000001453 quaternary ammonium group Chemical group 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
108091092562 ribozyme Proteins 0.000 description 2
229960004889 salicylic acid Drugs 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
238000003419 tautomerization reaction Methods 0.000 description 2
WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
150000003626 triacylglycerols Chemical class 0.000 description 2
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
ZHCXOELPVFPGHI-PZJWPPBQSA-N (2r,3r)-1-[4-[(4-fluoro-2-methylphenyl)methoxy]phenyl]sulfonyl-n,3-dihydroxy-3-methylpiperidine-2-carboxamide Chemical compound CC1=CC(F)=CC=C1COC1=CC=C(S(=O)(=O)N2[C@H]([C@](C)(O)CCC2)C(=O)NO)C=C1 ZHCXOELPVFPGHI-PZJWPPBQSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
JJSAEDOMTCNEQL-GOSISDBHSA-N (3r)-3-[[4-(4-chlorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-3-carboxamide Chemical compound C=1C=C(OC=2C=CC(Cl)=CC=2)C=CC=1S(=O)(=O)N[C@]1(C(=O)NO)CCCOC1 JJSAEDOMTCNEQL-GOSISDBHSA-N 0.000 description 1
YZIGEYGKVJNXSU-QGZVFWFLSA-N (3r)-3-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxolane-3-carboxamide Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N[C@]1(C(=O)NO)CCOC1 YZIGEYGKVJNXSU-QGZVFWFLSA-N 0.000 description 1
IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 1
KMPLYESDOZJASB-PAHRJMAXSA-N (6s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-hydroxy-6-methoxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one;(z)-n-carbamoyl-2-ethylbut-2-enamide;6-ethoxy-1,3-benzothiazole-2-sulfonamide Chemical compound CC\C(=C\C)C(=O)NC(N)=O.CCOC1=CC=C2N=C(S(N)(=O)=O)SC2=C1.C([C@@]12C)CC(=O)C=C1[C@@H](OC)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 KMPLYESDOZJASB-PAHRJMAXSA-N 0.000 description 1
FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
CTRPRMNBTVRDFH-UHFFFAOYSA-N 2-n-methyl-1,3,5-triazine-2,4,6-triamine Chemical class CNC1=NC(N)=NC(N)=N1 CTRPRMNBTVRDFH-UHFFFAOYSA-N 0.000 description 1
CJGGKSPGRJHZNP-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyrazine Chemical compound C1=CN=C2NN=NC2=N1 CJGGKSPGRJHZNP-UHFFFAOYSA-N 0.000 description 1
NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
RYCSNJCJOVQGBC-UHFFFAOYSA-N 3-(1-cyclopropyl-2h-pyridin-4-yl)-1h-quinolin-2-one Chemical class O=C1NC2=CC=CC=C2C=C1C(C=C1)=CCN1C1CC1 RYCSNJCJOVQGBC-UHFFFAOYSA-N 0.000 description 1
ZPRHFNYJNTVNIR-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-5-(1h-indol-2-yl)triazolo[4,5-b]pyrazine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C=3NC4=CC=CC=C4C=3)=CN=C2N=N1 ZPRHFNYJNTVNIR-UHFFFAOYSA-N 0.000 description 1
NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 description 1
WARXYAHFCARUNH-UHFFFAOYSA-N 3-[[4-(4-fluorophenoxy)phenyl]sulfonyl-[4-(hydroxycarbamoyl)oxan-4-yl]amino]propanoic acid Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)N(CCC(O)=O)C1(C(=O)NO)CCOCC1 WARXYAHFCARUNH-UHFFFAOYSA-N 0.000 description 1
AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
LBRSJIRWKUSQCA-UHFFFAOYSA-N 4-[2-[3-[3-[(4-fluorophenyl)methyl]triazolo[4,5-b]pyrazin-5-yl]phenoxy]ethyl]morpholine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C=3C=C(OCCN4CCOCC4)C=CC=3)=CN=C2N=N1 LBRSJIRWKUSQCA-UHFFFAOYSA-N 0.000 description 1
KFLPSZZMBDJEJU-UHFFFAOYSA-N 4-[2-[4-[3-[(4-fluorophenyl)methyl]imidazo[4,5-b]pyrazin-5-yl]phenoxy]ethyl]morpholine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C=3C=CC(OCCN4CCOCC4)=CC=3)=CN=C2N=C1 KFLPSZZMBDJEJU-UHFFFAOYSA-N 0.000 description 1
WOGSCAOROCXHKX-UHFFFAOYSA-N 4-[[(3-amino-6-bromopyrazin-2-yl)amino]methyl]phenol Chemical compound NC1=NC=C(Br)N=C1NCC1=CC=C(O)C=C1 WOGSCAOROCXHKX-UHFFFAOYSA-N 0.000 description 1
ZFVBTSPPLNQCBX-UHFFFAOYSA-N 4-[[(3-amino-6-thiophen-2-ylpyrazin-2-yl)amino]methyl]phenol Chemical compound NC1=NC=C(C=2SC=CC=2)N=C1NCC1=CC=C(O)C=C1 ZFVBTSPPLNQCBX-UHFFFAOYSA-N 0.000 description 1
CYZMUIMLRBJSRO-UHFFFAOYSA-N 4-[[4-(4-chlorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-4-carboxamide Chemical compound C=1C=C(OC=2C=CC(Cl)=CC=2)C=CC=1S(=O)(=O)NC1(C(=O)NO)CCOCC1 CYZMUIMLRBJSRO-UHFFFAOYSA-N 0.000 description 1
ZBRHTUMWSDPCMI-UHFFFAOYSA-N 4-[[4-(4-fluorophenoxy)phenyl]sulfonylamino]-n-hydroxyoxane-4-carboxamide Chemical compound C=1C=C(OC=2C=CC(F)=CC=2)C=CC=1S(=O)(=O)NC1(C(=O)NO)CCOCC1 ZBRHTUMWSDPCMI-UHFFFAOYSA-N 0.000 description 1
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
AWGDWUISITYDTJ-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-[(4-fluorophenyl)methyl]imidazo[4,5-b]pyrazine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(C=3C=CC(F)=CC=3)=CN=C2N=C1 AWGDWUISITYDTJ-UHFFFAOYSA-N 0.000 description 1
IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
YFGWLHMBLIRISW-UHFFFAOYSA-N 5-bromo-3-[(4-fluorophenyl)methyl]triazolo[4,5-b]pyrazine Chemical compound C1=CC(F)=CC=C1CN1C2=NC(Br)=CN=C2N=N1 YFGWLHMBLIRISW-UHFFFAOYSA-N 0.000 description 1
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 1
KRRTXVSBTPCDOS-UHFFFAOYSA-N 5-bromopyrazin-2-amine Chemical compound NC1=CN=C(Br)C=N1 KRRTXVSBTPCDOS-UHFFFAOYSA-N 0.000 description 1
YRGMYJUKFJPNPD-UHFFFAOYSA-N 5-bromopyridine-2,3-diamine Chemical compound NC1=CC(Br)=CN=C1N YRGMYJUKFJPNPD-UHFFFAOYSA-N 0.000 description 1
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
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 1
108090000644 Angiozyme Proteins 0.000 description 1
108010024976 Asparaginase Proteins 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
OGBVRMYSNSKIEF-UHFFFAOYSA-N Benzylphosphonic acid Chemical class OP(O)(=O)CC1=CC=CC=C1 OGBVRMYSNSKIEF-UHFFFAOYSA-N 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
108010006654 Bleomycin Proteins 0.000 description 1
206010005949 Bone cancer Diseases 0.000 description 1
208000018084 Bone neoplasm Diseases 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
208000003174 Brain Neoplasms Diseases 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282465 Canis Species 0.000 description 1
GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
241000283707 Capra Species 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
SHHKQEUPHAENFK-UHFFFAOYSA-N Carboquone Chemical compound O=C1C(C)=C(N2CC2)C(=O)C(C(COC(N)=O)OC)=C1N1CC1 SHHKQEUPHAENFK-UHFFFAOYSA-N 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
229940123587 Cell cycle inhibitor Drugs 0.000 description 1
GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 1
208000006332 Choriocarcinoma Diseases 0.000 description 1
208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
102100027995 Collagenase 3 Human genes 0.000 description 1
108050005238 Collagenase 3 Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
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 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
230000004544 DNA amplification Effects 0.000 description 1
108010092160 Dactinomycin Proteins 0.000 description 1
240000006497 Dianthus caryophyllus Species 0.000 description 1
235000009355 Dianthus caryophyllus Nutrition 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
241000792859 Enema Species 0.000 description 1
101800003838 Epidermal growth factor Proteins 0.000 description 1
HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
208000032027 Essential Thrombocythemia Diseases 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
241000282324 Felis Species 0.000 description 1
102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
238000010268 HPLC based assay Methods 0.000 description 1
101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
DOMWKUIIPQCAJU-LJHIYBGHSA-N Hydroxyprogesterone caproate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)CCCCC)[C@@]1(C)CC2 DOMWKUIIPQCAJU-LJHIYBGHSA-N 0.000 description 1
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
108010031794 IGF Type 1 Receptor Proteins 0.000 description 1
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 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
208000007766 Kaposi sarcoma Diseases 0.000 description 1
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
239000004367 Lipase Substances 0.000 description 1
102000004882 Lipase Human genes 0.000 description 1
108090001060 Lipase Proteins 0.000 description 1
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
229940125895 MET kinase inhibitor Drugs 0.000 description 1
229940124761 MMP inhibitor Drugs 0.000 description 1
108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 description 1
102100027998 Macrophage metalloelastase Human genes 0.000 description 1
101710187853 Macrophage metalloelastase Proteins 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
102100030417 Matrilysin Human genes 0.000 description 1
108090000855 Matrilysin Proteins 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
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 1
FTFRZXFNZVCRSK-UHFFFAOYSA-N N4-(3-chloro-4-fluorophenyl)-N6-(1-methyl-4-piperidinyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FTFRZXFNZVCRSK-UHFFFAOYSA-N 0.000 description 1
208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
102100030411 Neutrophil collagenase Human genes 0.000 description 1
101710118230 Neutrophil collagenase Proteins 0.000 description 1
208000022873 Ocular disease Diseases 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
108091008606 PDGF receptors Proteins 0.000 description 1
229930012538 Paclitaxel Natural products 0.000 description 1
102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
229920002642 Polysorbate 65 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 1
241000288906 Primates Species 0.000 description 1
108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
108091005682 Receptor kinases Proteins 0.000 description 1
102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
241000220317 Rosa Species 0.000 description 1
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
208000021712 Soft tissue sarcoma Diseases 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
102100030416 Stromelysin-1 Human genes 0.000 description 1
101710108790 Stromelysin-1 Proteins 0.000 description 1
102100028848 Stromelysin-2 Human genes 0.000 description 1
101710108792 Stromelysin-2 Proteins 0.000 description 1
102100028847 Stromelysin-3 Human genes 0.000 description 1
108050005271 Stromelysin-3 Proteins 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
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 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
208000024313 Testicular Neoplasms Diseases 0.000 description 1
206010057644 Testis cancer Diseases 0.000 description 1
PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
FYAMXEPQQLNQDM-UHFFFAOYSA-N Tris(1-aziridinyl)phosphine oxide Chemical compound C1CN1P(N1CC1)(=O)N1CC1 FYAMXEPQQLNQDM-UHFFFAOYSA-N 0.000 description 1
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
241000863480 Vinca Species 0.000 description 1
208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
208000008383 Wilms tumor Diseases 0.000 description 1
USDJGQLNFPZEON-UHFFFAOYSA-N [[4,6-bis(hydroxymethylamino)-1,3,5-triazin-2-yl]amino]methanol Chemical compound OCNC1=NC(NCO)=NC(NCO)=N1 USDJGQLNFPZEON-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 1
229910001573 adamantine Inorganic materials 0.000 description 1
230000006978 adaptation Effects 0.000 description 1
229960001456 adenosine triphosphate Drugs 0.000 description 1
238000009098 adjuvant therapy Methods 0.000 description 1
230000001780 adrenocortical effect Effects 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
229940040563 agaric acid Drugs 0.000 description 1
150000001299 aldehydes Chemical group 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000002723 alicyclic group Chemical group 0.000 description 1
229910001413 alkali metal ion Inorganic materials 0.000 description 1
229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
150000008052 alkyl sulfonates Chemical class 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
230000004075 alteration Effects 0.000 description 1
229960000473 altretamine Drugs 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
229960003437 aminoglutethimide Drugs 0.000 description 1
ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 1
230000003321 amplification Effects 0.000 description 1
229960002932 anastrozole Drugs 0.000 description 1
YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
239000003098 androgen Substances 0.000 description 1
229940030486 androgens Drugs 0.000 description 1
239000002870 angiogenesis inducing agent Substances 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
229940046836 anti-estrogen Drugs 0.000 description 1
230000001833 anti-estrogenic effect Effects 0.000 description 1
230000003388 anti-hormonal effect Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
229940045713 antineoplastic alkylating drug ethylene imines Drugs 0.000 description 1
230000005975 antitumor immune response Effects 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
239000003886 aromatase inhibitor Substances 0.000 description 1
229940046844 aromatase inhibitors Drugs 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
150000001541 aziridines Chemical class 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
229950005567 benzodepa Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
VFIUCBTYGKMLCM-UHFFFAOYSA-N benzyl n-[bis(aziridin-1-yl)phosphoryl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NP(=O)(N1CC1)N1CC1 VFIUCBTYGKMLCM-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
229920000249 biocompatible polymer Polymers 0.000 description 1
230000003592 biomimetic effect Effects 0.000 description 1
230000001851 biosynthetic effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
229960001561 bleomycin Drugs 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000012267 brine Substances 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229950004398 broxuridine Drugs 0.000 description 1
229960002092 busulfan Drugs 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
230000009400 cancer invasion Effects 0.000 description 1
229960004117 capecitabine Drugs 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
229960002115 carboquone Drugs 0.000 description 1
150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
230000012292 cell migration Effects 0.000 description 1
230000033077 cellular process Effects 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
210000003679 cervix uteri Anatomy 0.000 description 1
208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
230000000875 corresponding effect Effects 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
239000006071 cream Substances 0.000 description 1
108010044165 crotoxin drug combination cardiotoxin Proteins 0.000 description 1
239000012043 crude product Substances 0.000 description 1
CHVJITGCYZJHLR-UHFFFAOYSA-N cyclohepta-1,3,5-triene Chemical compound C1C=CC=CC=C1 CHVJITGCYZJHLR-UHFFFAOYSA-N 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
229960000684 cytarabine Drugs 0.000 description 1
210000000805 cytoplasm Anatomy 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
229960003901 dacarbazine Drugs 0.000 description 1
229960000640 dactinomycin Drugs 0.000 description 1
229960000975 daunorubicin Drugs 0.000 description 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
230000007423 decrease Effects 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
235000021186 dishes Nutrition 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
229940116977 epidermal growth factor Drugs 0.000 description 1
229960001904 epirubicin Drugs 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
230000008472 epithelial growth Effects 0.000 description 1
210000003238 esophagus Anatomy 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
229960001842 estramustine Drugs 0.000 description 1
FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
210000003527 eukaryotic cell Anatomy 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
210000003754 fetus Anatomy 0.000 description 1
229940126864 fibroblast growth factor Drugs 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000011888 foil Substances 0.000 description 1
150000002224 folic acids Chemical class 0.000 description 1
230000037406 food intake Effects 0.000 description 1
239000012458 free base Substances 0.000 description 1
208000024386 fungal infectious disease Diseases 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
DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
229960005277 gemcitabine Drugs 0.000 description 1
SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
230000004077 genetic alteration Effects 0.000 description 1
231100000118 genetic alteration Toxicity 0.000 description 1
210000004602 germ cell Anatomy 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
208000005017 glioblastoma Diseases 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
238000000227 grinding Methods 0.000 description 1
208000037824 growth disorder Diseases 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
229940022353 herceptin Drugs 0.000 description 1
UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
239000003667 hormone antagonist Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
229920001600 hydrophobic polymer Polymers 0.000 description 1
229960001330 hydroxycarbamide Drugs 0.000 description 1
229950000801 hydroxyprogesterone caproate 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
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
229960001101 ifosfamide Drugs 0.000 description 1
HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
NVOITFNSLADCKT-UHFFFAOYSA-N imidazo[4,5-b]pyrazine Chemical compound C1=C[N]C2=NC=NC2=N1 NVOITFNSLADCKT-UHFFFAOYSA-N 0.000 description 1
208000026278 immune system disease Diseases 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
239000003547 immunosorbent Substances 0.000 description 1
238000002513 implantation Methods 0.000 description 1
DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 description 1
229950008097 improsulfan Drugs 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
230000007794 irritation Effects 0.000 description 1
229940045996 isethionic acid Drugs 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
229940043355 kinase inhibitor Drugs 0.000 description 1
239000004922 lacquer Substances 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
150000002605 large molecules Chemical class 0.000 description 1
108020001756 ligand binding domains Proteins 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
239000006210 lotion Substances 0.000 description 1
230000000527 lymphocytic effect Effects 0.000 description 1
239000006166 lysate Substances 0.000 description 1
201000000564 macroglobulinemia Diseases 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
229940049920 malate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
230000010311 mammalian development Effects 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
229960001428 mercaptopurine Drugs 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
239000003475 metalloproteinase inhibitor Substances 0.000 description 1
208000037819 metastatic cancer Diseases 0.000 description 1
208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
QTFKTBRIGWJQQL-UHFFFAOYSA-N meturedepa Chemical compound C1C(C)(C)N1P(=O)(NC(=O)OCC)N1CC1(C)C QTFKTBRIGWJQQL-UHFFFAOYSA-N 0.000 description 1
229950009847 meturedepa Drugs 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
238000000520 microinjection Methods 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
229960000350 mitotane Drugs 0.000 description 1
230000000394 mitotic effect Effects 0.000 description 1
229960001156 mitoxantrone Drugs 0.000 description 1
KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical class CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
230000000921 morphogenic effect Effects 0.000 description 1
230000004899 motility Effects 0.000 description 1
CXVAWFXMIUVTFT-UHFFFAOYSA-N n-[5-bromo-3-[(4-methoxyphenyl)methylamino]pyrazin-2-yl]formamide Chemical compound C1=CC(OC)=CC=C1CNC1=NC(Br)=CN=C1NC=O CXVAWFXMIUVTFT-UHFFFAOYSA-N 0.000 description 1
IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
230000014399 negative regulation of angiogenesis Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
229940074355 nitric acid Drugs 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
235000021231 nutrient uptake Nutrition 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000002674 ointment Substances 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
239000000668 oral spray Substances 0.000 description 1
210000003463 organelle Anatomy 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
229920000620 organic polymer Polymers 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
230000008520 organization Effects 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
229940045681 other alkylating agent in atc Drugs 0.000 description 1
229940127075 other antimetabolite Drugs 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
101710135378 pH 6 antigen Proteins 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
229940055726 pantothenic acid Drugs 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
201000010279 papillary renal cell carcinoma Diseases 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000005499 phosphonyl group Chemical group 0.000 description 1
229960004838 phosphoric acid Drugs 0.000 description 1
239000003757 phosphotransferase inhibitor Substances 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
NUKCGLDCWQXYOQ-UHFFFAOYSA-N piposulfan Chemical compound CS(=O)(=O)OCCC(=O)N1CCN(C(=O)CCOS(C)(=O)=O)CC1 NUKCGLDCWQXYOQ-UHFFFAOYSA-N 0.000 description 1
229950001100 piposulfan Drugs 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229960003171 plicamycin Drugs 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000008389 polyethoxylated castor oil Substances 0.000 description 1
229940068886 polyethylene glycol 300 Drugs 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
150000004804 polysaccharides Chemical class 0.000 description 1
229940099511 polysorbate 65 Drugs 0.000 description 1
238000010837 poor prognosis Methods 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
229960004694 prednimustine Drugs 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
239000000955 prescription drug Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
229960000624 procarbazine Drugs 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
230000009696 proliferative response Effects 0.000 description 1
230000001902 propagating effect Effects 0.000 description 1
239000003380 propellant Substances 0.000 description 1
230000029983 protein stabilization Effects 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical class 0.000 description 1
150000003230 pyrimidines Chemical class 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 1
238000009790 rate-determining step (RDS) Methods 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
201000009410 rhabdomyosarcoma Diseases 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
210000003705 ribosome Anatomy 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
229960000371 rofecoxib Drugs 0.000 description 1
RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
102200133318 rs782531869 Human genes 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
150000003346 selenoethers Chemical class 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
239000002002 slurry Substances 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
125000005504 styryl group Chemical group 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229940032330 sulfuric acid Drugs 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
229960004964 temozolomide Drugs 0.000 description 1
NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
229960001278 teniposide Drugs 0.000 description 1
201000003120 testicular cancer Diseases 0.000 description 1
229960001712 testosterone propionate Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
229960003087 tioguanine Drugs 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
102000027257 transmembrane receptors Human genes 0.000 description 1
108091008578 transmembrane receptors Proteins 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 1
229950001353 tretamine Drugs 0.000 description 1
150000003918 triazines Chemical class 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000005423 trihalomethanesulfonamido group Chemical group 0.000 description 1
125000005152 trihalomethanesulfonyl group Chemical group 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
230000005748 tumor development Effects 0.000 description 1
229960001055 uracil mustard Drugs 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
229950006929 uredepa Drugs 0.000 description 1
SPDZFJLQFWSJGA-UHFFFAOYSA-N uredepa Chemical compound C1CN1P(=O)(NC(=O)OCC)N1CC1 SPDZFJLQFWSJGA-UHFFFAOYSA-N 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
229960002004 valdecoxib Drugs 0.000 description 1
LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
230000004862 vasculogenesis Effects 0.000 description 1
JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
229960003048 vinblastine Drugs 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
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
229960004355 vindesine Drugs 0.000 description 1
UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1