RU2384331C2 - Способ лечения аномального роста клеток - Google Patents
Способ лечения аномального роста клеток Download PDFInfo
- Publication number
- RU2384331C2 RU2384331C2 RU2008122471/14A RU2008122471A RU2384331C2 RU 2384331 C2 RU2384331 C2 RU 2384331C2 RU 2008122471/14 A RU2008122471/14 A RU 2008122471/14A RU 2008122471 A RU2008122471 A RU 2008122471A RU 2384331 C2 RU2384331 C2 RU 2384331C2
- Authority
- RU
- Russia
- Prior art keywords
- cancer
- hgfr
- met
- carcinoma
- cells
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 38
- 230000010261 cell growth Effects 0.000 title claims abstract description 15
- 230000002159 abnormal effect Effects 0.000 title claims abstract description 13
- 210000004027 cell Anatomy 0.000 claims abstract description 153
- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 claims abstract description 108
- 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 claims abstract description 104
- 230000000694 effects Effects 0.000 claims abstract description 32
- 206010025323 Lymphomas Diseases 0.000 claims abstract description 16
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 147
- 150000001875 compounds Chemical class 0.000 claims description 52
- 102100033793 ALK tyrosine kinase receptor Human genes 0.000 claims description 41
- 101710168331 ALK tyrosine kinase receptor Proteins 0.000 claims description 41
- 201000011510 cancer Diseases 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 21
- 206010017758 gastric cancer Diseases 0.000 claims description 20
- 206010073478 Anaplastic large-cell lymphoma Diseases 0.000 claims description 19
- 208000032004 Large-Cell Anaplastic Lymphoma Diseases 0.000 claims description 19
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 16
- 208000010749 gastric carcinoma Diseases 0.000 claims description 15
- 201000000498 stomach carcinoma Diseases 0.000 claims description 15
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 15
- 206010038389 Renal cancer Diseases 0.000 claims description 13
- 206010009944 Colon cancer Diseases 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 10
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 10
- 201000010174 renal carcinoma Diseases 0.000 claims description 10
- 210000002919 epithelial cell Anatomy 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 8
- 210000003734 kidney Anatomy 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 6
- 201000011549 stomach cancer Diseases 0.000 claims description 6
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 claims description 5
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 5
- 201000005296 lung carcinoma Diseases 0.000 claims description 5
- 210000003606 umbilical vein Anatomy 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 208000025997 central nervous system neoplasm Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 claims description 3
- 102000001253 Protein Kinase Human genes 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 210000001985 kidney epithelial cell Anatomy 0.000 claims description 3
- 108060006633 protein kinase Proteins 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 208000017572 squamous cell neoplasm Diseases 0.000 claims description 3
- 206010000830 Acute leukaemia Diseases 0.000 claims description 2
- 206010061424 Anal cancer Diseases 0.000 claims description 2
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 206010061252 Intraocular melanoma Diseases 0.000 claims description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 2
- 208000032271 Malignant tumor of penis Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000000821 Parathyroid Neoplasms Diseases 0.000 claims description 2
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 2
- 206010034299 Penile cancer Diseases 0.000 claims description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 208000023915 Ureteral Neoplasms Diseases 0.000 claims description 2
- 206010046392 Ureteric cancer Diseases 0.000 claims description 2
- 206010046431 Urethral cancer Diseases 0.000 claims description 2
- 206010046458 Urethral neoplasms Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 201000005969 Uveal melanoma Diseases 0.000 claims description 2
- 201000003761 Vaginal carcinoma Diseases 0.000 claims description 2
- 201000005188 adrenal gland cancer Diseases 0.000 claims description 2
- 208000024447 adrenal gland neoplasm Diseases 0.000 claims description 2
- 201000011165 anus cancer Diseases 0.000 claims description 2
- 201000008275 breast carcinoma Diseases 0.000 claims description 2
- 208000019065 cervical carcinoma Diseases 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 208000024207 chronic leukemia Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 208000030381 cutaneous melanoma Diseases 0.000 claims description 2
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 201000001343 fallopian tube carcinoma Diseases 0.000 claims description 2
- 208000018821 hormone-resistant prostate carcinoma Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000029559 malignant endocrine neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 208000026037 malignant tumor of neck Diseases 0.000 claims description 2
- 208000026045 malignant tumor of parathyroid gland Diseases 0.000 claims description 2
- 201000002575 ocular melanoma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 201000010279 papillary renal cell carcinoma Diseases 0.000 claims description 2
- 206010038038 rectal cancer Diseases 0.000 claims description 2
- 201000001275 rectum cancer Diseases 0.000 claims description 2
- 201000007444 renal pelvis carcinoma Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 201000003708 skin melanoma Diseases 0.000 claims description 2
- 201000002314 small intestine cancer Diseases 0.000 claims description 2
- 208000037959 spinal tumor Diseases 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 210000001519 tissue Anatomy 0.000 claims description 2
- 201000011294 ureter cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 201000004916 vulva carcinoma Diseases 0.000 claims description 2
- 208000013013 vulvar carcinoma Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims 1
- 201000005746 Pituitary adenoma Diseases 0.000 claims 1
- 206010061538 Pituitary tumour benign Diseases 0.000 claims 1
- 210000000133 brain stem Anatomy 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 208000021310 pituitary gland adenoma Diseases 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 abstract description 110
- 230000005764 inhibitory process Effects 0.000 abstract description 75
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 33
- 102000020233 phosphotransferase Human genes 0.000 abstract description 33
- 230000004614 tumor growth Effects 0.000 abstract description 26
- 239000003814 drug Substances 0.000 abstract description 18
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 abstract description 8
- 108020003175 receptors Proteins 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 5
- 239000003102 growth factor Substances 0.000 abstract description 4
- 210000003494 hepatocyte Anatomy 0.000 abstract description 2
- 230000026731 phosphorylation Effects 0.000 description 58
- 238000006366 phosphorylation reaction Methods 0.000 description 58
- 239000000203 mixture Substances 0.000 description 48
- 239000000243 solution Substances 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
- 241000699670 Mus sp. Species 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 23
- -1 their polymorphs Chemical class 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 230000000259 anti-tumor effect Effects 0.000 description 22
- 230000035772 mutation Effects 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 239000003826 tablet Substances 0.000 description 19
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 18
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 18
- 101000868152 Homo sapiens Son of sevenless homolog 1 Proteins 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 230000001419 dependent effect Effects 0.000 description 16
- 229940079593 drug Drugs 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 15
- 238000009472 formulation Methods 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- 239000003981 vehicle Substances 0.000 description 14
- 238000003556 assay Methods 0.000 description 13
- 210000004881 tumor cell Anatomy 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 230000006907 apoptotic process Effects 0.000 description 11
- 210000002889 endothelial cell Anatomy 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 10
- 241000699660 Mus musculus Species 0.000 description 10
- 238000011161 development Methods 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 238000011580 nude mouse model Methods 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 9
- SCJNCDSAIRBRIA-DOFZRALJSA-N arachidonyl-2'-chloroethylamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCCl SCJNCDSAIRBRIA-DOFZRALJSA-N 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
- 229940088598 enzyme Drugs 0.000 description 9
- 239000012091 fetal bovine serum Substances 0.000 description 9
- 238000003119 immunoblot Methods 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 230000009545 invasion Effects 0.000 description 9
- 108010082117 matrigel Proteins 0.000 description 9
- 239000004017 serum-free culture medium Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 8
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 108700020796 Oncogene Proteins 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000003111 delayed effect Effects 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 7
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 7
- 230000002035 prolonged effect Effects 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- JAOYKRSASYNDGH-UHFFFAOYSA-N 1-(2,6-dichloro-3-fluorophenyl)ethanol Chemical compound CC(O)C1=C(Cl)C=CC(F)=C1Cl JAOYKRSASYNDGH-UHFFFAOYSA-N 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 101100262697 Mus musculus Axl gene Proteins 0.000 description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000013508 migration Methods 0.000 description 6
- 230000027405 negative regulation of phosphorylation Effects 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 102100021435 Macrophage-stimulating protein receptor Human genes 0.000 description 5
- 101150111783 NTRK1 gene Proteins 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 230000005754 cellular signaling Effects 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 230000005012 migration Effects 0.000 description 5
- 239000006199 nebulizer Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 231100000590 oncogenic Toxicity 0.000 description 5
- 230000002246 oncogenic effect Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- IZHRGJAQMNPACR-UHFFFAOYSA-N 1-(2,6-dichloro-3-fluorophenyl)ethyl acetate Chemical compound CC(=O)OC(C)C1=C(Cl)C=CC(F)=C1Cl IZHRGJAQMNPACR-UHFFFAOYSA-N 0.000 description 4
- 206010069754 Acquired gene mutation Diseases 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 208000034951 Genetic Translocation Diseases 0.000 description 4
- 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 4
- 206010027476 Metastases Diseases 0.000 description 4
- 101150056950 Ntrk2 gene Proteins 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 230000003321 amplification Effects 0.000 description 4
- 230000004709 cell invasion Effects 0.000 description 4
- 230000012292 cell migration Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 208000005017 glioblastoma Diseases 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 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 4
- 239000008101 lactose Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 210000004924 lung microvascular endothelial cell Anatomy 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 230000001394 metastastic effect Effects 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 238000003199 nucleic acid amplification method Methods 0.000 description 4
- 238000001543 one-way ANOVA Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 230000003285 pharmacodynamic effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 201000001514 prostate carcinoma Diseases 0.000 description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
- 230000037439 somatic mutation Effects 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 3
- SFHYNDMGZXWXBU-LIMNOBDPSA-N 6-amino-2-[[(e)-(3-formylphenyl)methylideneamino]carbamoylamino]-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1NC(=O)N\N=C\C1=CC=CC(C=O)=C1 SFHYNDMGZXWXBU-LIMNOBDPSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000012286 ELISA Assay Methods 0.000 description 3
- 102000009123 Fibrin Human genes 0.000 description 3
- 108010073385 Fibrin Proteins 0.000 description 3
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 3
- 101150022345 GAS6 gene Proteins 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000000423 cell based assay Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229950003499 fibrin Drugs 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 230000000771 oncological effect Effects 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000003531 protein hydrolysate Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- QSQWENQPOSRWLP-UHFFFAOYSA-N tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1N=CC(B2OC(C)(C)C(C)(C)O2)=C1 QSQWENQPOSRWLP-UHFFFAOYSA-N 0.000 description 3
- WOEQSXAIPTXOPY-UHFFFAOYSA-N tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1 WOEQSXAIPTXOPY-UHFFFAOYSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 239000012224 working solution Substances 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- JAOYKRSASYNDGH-BYPYZUCNSA-N (1s)-1-(2,6-dichloro-3-fluorophenyl)ethanol Chemical compound C[C@H](O)C1=C(Cl)C=CC(F)=C1Cl JAOYKRSASYNDGH-BYPYZUCNSA-N 0.000 description 2
- 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 2
- PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 description 2
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 2
- VJBFZHHRVCPAPZ-UHFFFAOYSA-N 1-(2,6-dichloro-3-fluorophenyl)ethanone Chemical compound CC(=O)C1=C(Cl)C=CC(F)=C1Cl VJBFZHHRVCPAPZ-UHFFFAOYSA-N 0.000 description 2
- YPYRKNZLHVLIFY-UHFFFAOYSA-N 3-[(2,6-dichloro-3-fluorophenyl)methoxy]-2-nitropyridine Chemical compound [O-][N+](=O)C1=NC=CC=C1OCC1=C(Cl)C=CC(F)=C1Cl YPYRKNZLHVLIFY-UHFFFAOYSA-N 0.000 description 2
- BFWIYZIYEXZHLJ-UHFFFAOYSA-N 3-[(2,6-dichloro-3-fluorophenyl)methoxy]pyridin-2-amine Chemical compound NC1=NC=CC=C1OCC1=C(Cl)C=CC(F)=C1Cl BFWIYZIYEXZHLJ-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241001133757 Carpentaria Species 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 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 2
- 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 2
- 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 2
- 102000053602 DNA Human genes 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
- 238000008157 ELISA kit Methods 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 102220553565 Hepatocyte growth factor receptor_H1094R_mutation Human genes 0.000 description 2
- 102220553480 Hepatocyte growth factor receptor_M1250T_mutation Human genes 0.000 description 2
- 102220553470 Hepatocyte growth factor receptor_Y1230C_mutation Human genes 0.000 description 2
- 101710086591 Hepatocyte growth factor-like protein Proteins 0.000 description 2
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007993 MOPS buffer Substances 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 101710201137 Photosystem II manganese-stabilizing polypeptide Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- 102000001712 STAT5 Transcription Factor Human genes 0.000 description 2
- 108010029477 STAT5 Transcription Factor Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 238000002835 absorbance Methods 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000002210 biocatalytic effect Effects 0.000 description 2
- 238000012742 biochemical analysis Methods 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000015916 branching morphogenesis of a tube Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical class [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000012578 cell culture reagent Substances 0.000 description 2
- 238000012832 cell culture technique Methods 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940112822 chewing gum Drugs 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000009650 gentamicin protection assay Methods 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 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 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 239000012133 immunoprecipitate Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229960001855 mannitol Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 230000004899 motility Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000003076 paracrine Effects 0.000 description 2
- 108010021753 peptide-Gly-Leu-amide Proteins 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 108091005981 phosphorylated proteins Proteins 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000006659 positive regulation of apoptotic process Effects 0.000 description 2
- 230000035409 positive regulation of cell proliferation Effects 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000013207 serial dilution Methods 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 229960002920 sorbitol Drugs 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 230000037351 starvation Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 150000003900 succinic acid esters Chemical class 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- IONGFFYQZADMPH-UHFFFAOYSA-N tert-butyl 4-(4-iodopyrazol-1-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1N=CC(I)=C1 IONGFFYQZADMPH-UHFFFAOYSA-N 0.000 description 2
- 230000036962 time dependent Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 230000006444 vascular growth Effects 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 1
- HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- GIXNNVOMGTZNCH-SNVBAGLBSA-N 3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1B1OC(C)(C)C(C)(C)O1 GIXNNVOMGTZNCH-SNVBAGLBSA-N 0.000 description 1
- QBPDSKPWYWIHGA-UHFFFAOYSA-N 3-hydroxy-2-nitropyridine Chemical compound OC1=CC=CN=C1[N+]([O-])=O QBPDSKPWYWIHGA-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- LLNQWPTUJJYTTE-UHFFFAOYSA-N 4-iodopyrazole Chemical compound IC=1C=NNC=1 LLNQWPTUJJYTTE-UHFFFAOYSA-N 0.000 description 1
- SGVSTYFVBPJDRH-UHFFFAOYSA-N 4-methylsulfonyloxypiperidine-1-carboxylic acid Chemical compound CS(=O)(=O)OC1CCN(C(O)=O)CC1 SGVSTYFVBPJDRH-UHFFFAOYSA-N 0.000 description 1
- URFUZAZEKBBCEY-ZCFIWIBFSA-N 5-bromo-3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C1=CC(Br)=CN=C1N URFUZAZEKBBCEY-ZCFIWIBFSA-N 0.000 description 1
- KFBVKSXSXBYYBA-UHFFFAOYSA-N 5-bromo-3-[(2,6-dichloro-3-fluorophenyl)methoxy]pyridin-2-amine Chemical compound NC1=NC=C(Br)C=C1OCC1=C(Cl)C=CC(F)=C1Cl KFBVKSXSXBYYBA-UHFFFAOYSA-N 0.000 description 1
- URFUZAZEKBBCEY-UHFFFAOYSA-N 5-bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC1=CC(Br)=CN=C1N URFUZAZEKBBCEY-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- RFRMMZAKBNXNHE-UHFFFAOYSA-N 6-[4,6-dihydroxy-5-(2-hydroxyethoxy)-2-(hydroxymethyl)oxan-3-yl]oxy-2-(hydroxymethyl)-5-(2-hydroxypropoxy)oxane-3,4-diol Chemical compound CC(O)COC1C(O)C(O)C(CO)OC1OC1C(O)C(OCCO)C(O)OC1CO RFRMMZAKBNXNHE-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102000003736 ATP Synthetase Complexes Human genes 0.000 description 1
- 108010082072 ATP Synthetase Complexes Proteins 0.000 description 1
- 241001502050 Acis Species 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010006143 Brain stem glioma Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 108010051152 Carboxylesterase Proteins 0.000 description 1
- 102000013392 Carboxylesterase Human genes 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 206010052358 Colorectal cancer metastatic Diseases 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108010040476 FITC-annexin A5 Proteins 0.000 description 1
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 1
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 102100033295 Glial cell line-derived neurotrophic factor Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108091008603 HGF receptors Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102220553570 Hepatocyte growth factor receptor_V1092I_mutation Human genes 0.000 description 1
- 206010067943 Hereditary papillary renal carcinoma Diseases 0.000 description 1
- 208000027927 Hereditary papillary renal cell carcinoma Diseases 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 description 1
- 101000827688 Homo sapiens Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
- 101000731000 Homo sapiens Membrane-associated progesterone receptor component 1 Proteins 0.000 description 1
- 101000823316 Homo sapiens Tyrosine-protein kinase ABL1 Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-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
- 108090001060 Lipase Proteins 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 206010052178 Lymphocytic lymphoma Diseases 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 101150100676 Map2k1 gene Proteins 0.000 description 1
- 238000007807 Matrigel invasion assay Methods 0.000 description 1
- 102100032399 Membrane-associated progesterone receptor component 1 Human genes 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100230981 Mus musculus Hgf gene Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 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
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000013009 Pyruvate Kinase Human genes 0.000 description 1
- 108020005115 Pyruvate Kinase Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 102100022596 Tyrosine-protein kinase ABL1 Human genes 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 206010047741 Vulval cancer Diseases 0.000 description 1
- 102100023038 WD and tetratricopeptide repeats protein 1 Human genes 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 108010058834 acylcarnitine hydrolase Proteins 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 238000000627 alternating current impedance spectroscopy Methods 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 210000002403 aortic endothelial cell Anatomy 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 108010046910 brain-derived growth factor Proteins 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229940077731 carbohydrate nutrients Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000037011 constitutive activity Effects 0.000 description 1
- 230000030944 contact inhibition Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000002435 cytoreductive effect Effects 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229950010286 diolamine Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000005520 electrodynamics Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000029578 entry into host Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000006277 exogenous ligand Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 201000005306 familial renal papillary carcinoma Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 201000003911 head and neck carcinoma Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 102000057308 human HGF Human genes 0.000 description 1
- 102000055590 human KDR Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007915 intraurethral administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 238000003674 kinase activity assay Methods 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 150000003903 lactic acid esters Chemical class 0.000 description 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 229960004873 levomenthol Drugs 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 235000019626 lipase activity Nutrition 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000003232 mucoadhesive effect Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 239000000025 natural resin Substances 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000002353 niosome Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229950004864 olamine Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003300 oropharynx Anatomy 0.000 description 1
- 150000003901 oxalic acid esters Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 108700009251 p80(NPM-ALK) Proteins 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 230000011340 peptidyl-tyrosine autophosphorylation Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 1
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 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 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000034918 positive regulation of cell growth Effects 0.000 description 1
- 230000013155 positive regulation of cell migration Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- IYNZAVDBHAQODX-UHFFFAOYSA-N tert-butyl 4-(4-bromopyrazol-1-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1N=CC(Br)=C1 IYNZAVDBHAQODX-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940074410 trehalose Drugs 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 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 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74276605P | 2005-12-05 | 2005-12-05 | |
| US60/742,766 | 2005-12-05 | ||
| US86463706P | 2006-11-07 | 2006-11-07 | |
| US60/864,637 | 2006-11-07 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2008122471A RU2008122471A (ru) | 2009-12-10 |
| RU2384331C2 true RU2384331C2 (ru) | 2010-03-20 |
Family
ID=38123250
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2008122471/14A RU2384331C2 (ru) | 2005-12-05 | 2006-11-23 | Способ лечения аномального роста клеток |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US7825137B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1959955B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP4619346B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR101026676B1 (cg-RX-API-DMAC7.html) |
| AR (1) | AR056832A1 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE488237T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2006323027B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0619424B1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2632286C (cg-RX-API-DMAC7.html) |
| CY (1) | CY1110931T1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE602006018354D1 (cg-RX-API-DMAC7.html) |
| DK (1) | DK1959955T3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL191471A (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ568654A (cg-RX-API-DMAC7.html) |
| PL (1) | PL1959955T3 (cg-RX-API-DMAC7.html) |
| PT (1) | PT1959955E (cg-RX-API-DMAC7.html) |
| RU (1) | RU2384331C2 (cg-RX-API-DMAC7.html) |
| SI (1) | SI1959955T1 (cg-RX-API-DMAC7.html) |
| TW (1) | TWI321050B (cg-RX-API-DMAC7.html) |
| WO (1) | WO2007066187A2 (cg-RX-API-DMAC7.html) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014104924A1 (ru) * | 2012-12-28 | 2014-07-03 | Lobko Vladimir Pavlovich | Противоопухолевое средство (варианты) |
| RU2675850C2 (ru) * | 2012-11-06 | 2018-12-25 | Шанхай Фокон Фармасьютикал Ко Лтд | Ингибиторы alk-киназы |
| RU2788606C2 (ru) * | 2018-03-22 | 2023-01-23 | Вертикаль Био АГ | Комбинация антитела против hgfr и hegfr для лечения опухоли и/или метастаза |
| US11814433B2 (en) | 2018-03-22 | 2023-11-14 | Vertical Bio Ag | Combination of anti-HGFR antibody and HEGFR for the treatment of a tumor and/or metastasis |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100859891B1 (ko) | 2004-08-26 | 2008-09-23 | 화이자 인코포레이티드 | 단백질 키나제 억제제로서 거울상이성질체적으로 순수한아미노헤테로아릴 화합물 |
| TWI377198B (en) * | 2005-08-24 | 2012-11-21 | Eisai R&D Man Co Ltd | Novel pyridine derivatives and pyrimidine derivatives (3) |
| US8217057B2 (en) * | 2005-12-05 | 2012-07-10 | Pfizer Inc. | Polymorphs of a c-MET/HGFR inhibitor |
| US20120208824A1 (en) | 2006-01-20 | 2012-08-16 | Cell Signaling Technology, Inc. | ROS Kinase in Lung Cancer |
| EP2447360A1 (en) | 2006-04-14 | 2012-05-02 | Cell Signaling Technology, Inc. | Gene defects and mutant ALK kinase in human solid tumors |
| US8168383B2 (en) | 2006-04-14 | 2012-05-01 | Cell Signaling Technology, Inc. | Gene defects and mutant ALK kinase in human solid tumors |
| ATE535520T1 (de) * | 2006-08-23 | 2011-12-15 | Eisai R&D Man Co Ltd | Salz eines phenoxypyridinderivats oder kristall davon und verfahren zu dessen herstellung |
| US7790885B2 (en) | 2006-08-31 | 2010-09-07 | Eisai R&D Management Co., Ltd. | Process for preparing phenoxypyridine derivatives |
| JP2009132660A (ja) * | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
| DE102007061963A1 (de) | 2007-12-21 | 2009-06-25 | Merck Patent Gmbh | Pyridazinonderivate |
| JP2009203226A (ja) * | 2008-01-31 | 2009-09-10 | Eisai R & D Management Co Ltd | ピリジン誘導体およびピリミジン誘導体を含有するレセプターチロシンキナーゼ阻害剤 |
| US20110206691A1 (en) | 2008-02-15 | 2011-08-25 | Mosse Yael P | Methods and Compositions for Treating Neuroblastoma |
| WO2009103061A2 (en) * | 2008-02-15 | 2009-08-20 | The Children's Hospital Of Philadelphia | Methods and compositions for identifying, diagnosing, and treating neuroblastoma |
| EP2248810A4 (en) * | 2008-02-18 | 2011-05-25 | Eisai R&D Man Co Ltd | METHOD FOR PRODUCING A PHENOXYPYRIDINE DERIVATIVE |
| EP2143441A1 (en) * | 2008-07-08 | 2010-01-13 | Pierre Fabre Medicament | Combination of a c-Met antagonist and an aminoheteroaryl compound for the treatment of cancer |
| CN101653607B (zh) * | 2008-08-19 | 2013-02-13 | 鼎泓国际投资（香港）有限公司 | 含有肝细胞生长因子受体抑制剂和丝裂原细胞外激酶抑制剂的药物组合物及其用途 |
| WO2010064300A1 (ja) * | 2008-12-02 | 2010-06-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 食道癌治療用組成物 |
| DE102009003954A1 (de) | 2009-01-07 | 2010-07-08 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102009004061A1 (de) | 2009-01-08 | 2010-07-15 | Merck Patent Gmbh | Pyridazinonderivate |
| JP5675850B2 (ja) | 2010-02-05 | 2015-02-25 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | ヘタリール−［１，８］ナフチリジン誘導体 |
| EP2534156A1 (en) * | 2010-02-11 | 2012-12-19 | OSI Pharmaceuticals, LLC | 7-aminofuropyridine derivatives |
| CA2796967C (en) | 2010-05-04 | 2015-12-01 | Pfizer Inc. | Heterocyclic derivatives as alk inhibitors |
| AU2011270165B2 (en) | 2010-06-25 | 2015-12-24 | Eisai R&D Management Co., Ltd. | Antitumor agent using compounds having kinase inhibitory effect in combination |
| CA2804285C (en) | 2010-07-05 | 2019-05-14 | Merck Patent Gmbh | Bipyridyl derivatives useful for the treatment of kinase - induced diseases |
| WO2012019132A2 (en) | 2010-08-06 | 2012-02-09 | Cell Signaling Technology, Inc. | Anaplastic lymphoma kinase in kidney cancer |
| US9145390B2 (en) | 2011-03-03 | 2015-09-29 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
| MX2013010067A (es) * | 2011-03-03 | 2014-01-31 | Concert Pharmaceuticals Inc | Derivados de compuestos de amino-heteroarilo sustituidos con pirazol. |
| WO2012119690A1 (en) | 2011-03-09 | 2012-09-13 | Merck Patent Gmbh | Pyrido [2, 3 - b] pyrazine derivatives and their therapeutical uses |
| EP2758387A4 (en) * | 2011-09-21 | 2015-03-11 | Teligene Ltd | Pyridine compounds as kinase inhibitors |
| SI2810937T1 (sl) | 2012-01-31 | 2017-01-31 | Daiichi Sankyo Company, Limited | Derivat piridona |
| AP2014007881A0 (en) | 2012-03-06 | 2014-08-31 | Pfizer | Macrocyclic derivatives for the treatment of proliferative diseases |
| WO2013148537A1 (en) * | 2012-03-29 | 2013-10-03 | Ning Xi | Substituted spirobicyclic compounds and methods of use |
| PL2838998T3 (pl) | 2012-04-18 | 2018-04-30 | Cell Signaling Technology, Inc. | EGFR i ROS1 w nowotworze |
| CN103509008A (zh) * | 2012-06-22 | 2014-01-15 | 康瑟特制药公司 | 吡唑取代的氨基-杂芳基化合物的衍生物 |
| WO2014020467A2 (en) | 2012-07-30 | 2014-02-06 | Fresenius Kabi Oncology Ltd | Process for the preparation of pyrazole substituted aminoheteroaryl compounds |
| CN104603620B (zh) | 2012-09-24 | 2018-02-23 | 文塔纳医疗系统公司 | 使用间变性淋巴瘤激酶(alk)作为标志物鉴定治疗响应性非小细胞肺癌的方法 |
| JPWO2014098176A1 (ja) | 2012-12-21 | 2017-01-12 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キノリン誘導体のアモルファス及びその製造方法 |
| WO2014115169A2 (en) * | 2013-01-24 | 2014-07-31 | Hetero Research Foundation | Crizotinib solid dispersion |
| HK1211235A1 (en) | 2013-02-22 | 2016-05-20 | 霍夫曼-拉罗奇有限公司 | Methods of treating cancer and preventing drug resistance |
| US20160022661A1 (en) * | 2013-03-13 | 2016-01-28 | Ratiopharm Gmbh | Dosage Form Comprising Crizotinib |
| CN105264380B (zh) | 2013-05-14 | 2017-09-05 | 卫材R&D管理有限公司 | 用于预测和评价子宫内膜癌受试者对乐伐替尼化合物响应性的生物标志 |
| JP6291179B2 (ja) * | 2013-07-26 | 2018-03-14 | 関東化學株式会社 | 光学活性２級アルコールの製造方法 |
| WO2015036898A2 (en) * | 2013-09-10 | 2015-03-19 | Shilpa Medicare Limited | Novel salts of crizotinib and their preparation |
| RU2550346C2 (ru) | 2013-09-26 | 2015-05-10 | Общество с ограниченной ответственностью "Отечественные Фармацевтические Технологии" ООО"ФармТех" | Новые химические соединения (варианты) и их применение для лечения онкологических заболеваний |
| WO2015069922A2 (en) | 2013-11-06 | 2015-05-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Alk antibodies, conjugates, and chimeric antigen receptors, and their use |
| TWI723572B (zh) | 2014-07-07 | 2021-04-01 | 日商第一三共股份有限公司 | 具有四氫吡喃基甲基之吡啶酮衍生物及其用途 |
| EP3185866A1 (en) | 2014-08-25 | 2017-07-05 | Pfizer Inc. | Combination of a pd-1 antagonist and an alk inhibitor for treating cancer |
| SMT202200367T1 (it) | 2014-08-28 | 2022-11-18 | Eisai R&D Man Co Ltd | Derivato di chinolina a elevata purezza e metodo per la produzione dello stesso |
| CA2976325C (en) | 2015-02-25 | 2023-07-04 | Eisai R&D Management Co., Ltd. | Method for suppressing bitterness of quinoline derivative |
| KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| CN107801379B (zh) | 2015-06-16 | 2021-05-25 | 卫材R&D管理有限公司 | 抗癌剂 |
| AU2016309356B2 (en) | 2015-08-20 | 2021-06-24 | Eisai R&D Management Co., Ltd. | Tumor therapeutic agent |
| US20180282415A1 (en) | 2015-09-30 | 2018-10-04 | Merck Patent Gmbh | Combination of a PD-1 Axis Binding Antagonist and an ALK Inhibitor for Treating ALK-Negative Cancer |
| US12066428B2 (en) * | 2015-11-20 | 2024-08-20 | Agilent Technologies, Inc. | Cell-substrate impedance monitoring of cancer cells |
| JP7169195B2 (ja) | 2016-05-20 | 2022-11-10 | バイオヘイブン・ファーマシューティカル・ホールディング・カンパニー・リミテッド | 癌を処置するためのリルゾール、リルゾールプロドラッグまたはリルゾール類似体と免疫療法との併用 |
| GB201616116D0 (en) * | 2016-09-22 | 2016-11-09 | Astrazeneca Ab | Use of c-Met inhibitors to treat cancers harbouring MET mutations |
| ES2971448T3 (es) | 2017-02-08 | 2024-06-05 | Eisai R&D Man Co Ltd | Composición farmacéutica para el tratamiento de tumores |
| CA3061888A1 (en) | 2017-05-16 | 2018-11-22 | Eisai R&D Management Co., Ltd. | Treatment of hepatocellular carcinoma |
| CN108047231B (zh) * | 2018-01-02 | 2020-02-11 | 江苏医药职业学院 | [1,2,4]三嗪并[6,1-a]异吲哚化合物的盐酸盐及其应用 |
| CA3149796A1 (en) | 2019-08-02 | 2021-02-11 | Onehealthcompany, Inc. | Anti-cancer agents for the treatment of canine cancers |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2174977C2 (ru) * | 1995-03-30 | 2001-10-20 | Пфайзер Инк. | Производные 4-(замещенного фениламино)хиназолина или их фармацевтически приемлемые соли, способ ингибирования рецепторной тирозинкиназы и фармацевтическая композиция |
| US20050009840A1 (en) * | 2003-02-26 | 2005-01-13 | Sugen, Inc. | Aminoheteroaryl compounds as protein kinase inhibitors |
| WO2005026129A1 (en) * | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| RU2260592C2 (ru) * | 1999-04-15 | 2005-09-20 | Бристол-Маерс Сквибб Ко. | Циклические ингибиторы протеинтирозинкиназ |
| WO2005112918A1 (en) * | 2004-05-05 | 2005-12-01 | Celgene Corporation | Methods and compositions using selective cytokine inhibitory drugs for treatment and management of cancers and other diseases |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4725601A (en) | 1985-06-04 | 1988-02-16 | Fujisawa Pharmaceutical Co., Ltd. | Certain imidazo[1,2-a]pyridines useful in the treatment of ulcers |
| GB9201693D0 (en) | 1992-01-27 | 1992-03-11 | Smithkline Beecham Intercredit | Compounds |
| JPH07109260A (ja) | 1993-10-12 | 1995-04-25 | Fuji Photo Film Co Ltd | ５−アミノ−２−ニトロピリジン誘導体及び２，５−ジアミノ−３−ヒドロキシピリジン誘導体の製造方法 |
| SE9700661D0 (sv) | 1997-02-25 | 1997-02-25 | Astra Ab | New compounds |
| SE9801526D0 (sv) * | 1998-04-29 | 1998-04-29 | Astra Ab | New compounds |
| GB9908410D0 (en) | 1999-04-13 | 1999-06-09 | Pfizer Ltd | Pyridines |
| WO2001000213A1 (en) * | 1999-06-30 | 2001-01-04 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| KR20030031886A (ko) * | 2000-02-16 | 2003-04-23 | 뉴로젠 코포레이션 | 치환된 아릴피라진 |
| GB0101577D0 (en) * | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| US6825198B2 (en) * | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
| US6992087B2 (en) * | 2001-11-21 | 2006-01-31 | Pfizer Inc | Substituted aryl 1,4-pyrazine derivatives |
| KR100859891B1 (ko) * | 2004-08-26 | 2008-09-23 | 화이자 인코포레이티드 | 단백질 키나제 억제제로서 거울상이성질체적으로 순수한아미노헤테로아릴 화합물 |
| ES2355923T3 (es) * | 2004-08-26 | 2011-04-01 | Pfizer, Inc. | Compuestos de aminoheteroarilo sustituidos con pirazol como inhibidores de proteina quinasa. |
| JP2008510792A (ja) * | 2004-08-26 | 2008-04-10 | ファイザー・インク | タンパク質チロシンキナーゼ阻害剤としてのアミノヘテロアリール化合物 |
| US8217057B2 (en) * | 2005-12-05 | 2012-07-10 | Pfizer Inc. | Polymorphs of a c-MET/HGFR inhibitor |
-
2006
- 2006-11-23 NZ NZ568654A patent/NZ568654A/en unknown
- 2006-11-23 BR BRPI0619424-9A patent/BRPI0619424B1/pt active IP Right Grant
- 2006-11-23 CA CA2632286A patent/CA2632286C/en active Active
- 2006-11-23 RU RU2008122471/14A patent/RU2384331C2/ru active
- 2006-11-23 US US12/095,114 patent/US7825137B2/en active Active
- 2006-11-23 DK DK06820997.2T patent/DK1959955T3/da active
- 2006-11-23 AU AU2006323027A patent/AU2006323027B2/en active Active
- 2006-11-23 DE DE602006018354T patent/DE602006018354D1/de active Active
- 2006-11-23 AT AT06820997T patent/ATE488237T1/de active
- 2006-11-23 SI SI200630864T patent/SI1959955T1/sl unknown
- 2006-11-23 EP EP06820997A patent/EP1959955B1/en active Active
- 2006-11-23 PT PT06820997T patent/PT1959955E/pt unknown
- 2006-11-23 KR KR20087016376A patent/KR101026676B1/ko active Active
- 2006-11-23 WO PCT/IB2006/003397 patent/WO2007066187A2/en not_active Ceased
- 2006-11-23 PL PL06820997T patent/PL1959955T3/pl unknown
- 2006-12-04 TW TW095145034A patent/TWI321050B/zh active
- 2006-12-04 JP JP2006327355A patent/JP4619346B2/ja active Active
- 2006-12-05 AR ARP060105369A patent/AR056832A1/es not_active Application Discontinuation
-
2008
- 2008-05-15 IL IL191471A patent/IL191471A/en active IP Right Grant
-
2010
- 2010-11-24 CY CY20101101055T patent/CY1110931T1/el unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2174977C2 (ru) * | 1995-03-30 | 2001-10-20 | Пфайзер Инк. | Производные 4-(замещенного фениламино)хиназолина или их фармацевтически приемлемые соли, способ ингибирования рецепторной тирозинкиназы и фармацевтическая композиция |
| RU2260592C2 (ru) * | 1999-04-15 | 2005-09-20 | Бристол-Маерс Сквибб Ко. | Циклические ингибиторы протеинтирозинкиназ |
| US20050009840A1 (en) * | 2003-02-26 | 2005-01-13 | Sugen, Inc. | Aminoheteroaryl compounds as protein kinase inhibitors |
| WO2005026129A1 (en) * | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| WO2005112918A1 (en) * | 2004-05-05 | 2005-12-01 | Celgene Corporation | Methods and compositions using selective cytokine inhibitory drugs for treatment and management of cancers and other diseases |
Non-Patent Citations (1)
| Title |
|---|
| BACKLUND M et al. Regulation of aryl hydrocarbon receptor signal transduction by protein tyrosine kinases // Cell Signal. 2005 Jan; 17(1): 39-48 - реферат, он-лайн [Найдено в Интернет на www.pubmed.com 08.05.2009], PMID: 15451023 [PubMed - indexed for MEDLINE. MA PC et al. A selective small molecule c-MET Inhibitor, PHA665752, cooperates with rapamycin // Clin Cancer Res. 2005 Mar 15;11(6):2312-9. реферат, он-лайн [Найдено в Интернет на www.pubmed.com 08.05.2009], PMID: 15788682 [PubMed - indexed for MEDLINE. * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2675850C2 (ru) * | 2012-11-06 | 2018-12-25 | Шанхай Фокон Фармасьютикал Ко Лтд | Ингибиторы alk-киназы |
| WO2014104924A1 (ru) * | 2012-12-28 | 2014-07-03 | Lobko Vladimir Pavlovich | Противоопухолевое средство (варианты) |
| RU2788606C2 (ru) * | 2018-03-22 | 2023-01-23 | Вертикаль Био АГ | Комбинация антитела против hgfr и hegfr для лечения опухоли и/или метастаза |
| US11814433B2 (en) | 2018-03-22 | 2023-11-14 | Vertical Bio Ag | Combination of anti-HGFR antibody and HEGFR for the treatment of a tumor and/or metastasis |
Also Published As
| Publication number | Publication date |
|---|---|
| AR056832A1 (es) | 2007-10-24 |
| US7825137B2 (en) | 2010-11-02 |
| IL191471A (en) | 2013-03-24 |
| WO2007066187A2 (en) | 2007-06-14 |
| BRPI0619424A2 (pt) | 2011-10-04 |
| PT1959955E (pt) | 2011-01-04 |
| JP4619346B2 (ja) | 2011-01-26 |
| JP2007153894A (ja) | 2007-06-21 |
| CA2632286A1 (en) | 2007-06-14 |
| DE602006018354D1 (de) | 2010-12-30 |
| AU2006323027B2 (en) | 2012-08-02 |
| US20080300273A1 (en) | 2008-12-04 |
| EP1959955B1 (en) | 2010-11-17 |
| SI1959955T1 (sl) | 2011-02-28 |
| NZ568654A (en) | 2012-02-24 |
| KR20080072965A (ko) | 2008-08-07 |
| ATE488237T1 (de) | 2010-12-15 |
| CA2632286C (en) | 2011-11-15 |
| PL1959955T3 (pl) | 2011-04-29 |
| AU2006323027A1 (en) | 2007-06-14 |
| HK1126121A1 (en) | 2009-08-28 |
| BRPI0619424B1 (pt) | 2022-02-08 |
| TWI321050B (en) | 2010-03-01 |
| WO2007066187A3 (en) | 2008-01-17 |
| KR101026676B1 (ko) | 2011-04-04 |
| TW200727899A (en) | 2007-08-01 |
| DK1959955T3 (da) | 2011-02-07 |
| IL191471A0 (en) | 2009-08-03 |
| CY1110931T1 (el) | 2015-06-10 |
| EP1959955A2 (en) | 2008-08-27 |
| RU2008122471A (ru) | 2009-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2384331C2 (ru) | Способ лечения аномального роста клеток | |
| EP2651403B1 (en) | Use of lp-pla2 inhibitors in the treatment and prevention of eye diseases | |
| EA002600B1 (ru) | ХИНОЛИНОВЫЕ И ХИНОКСАЛИНОВЫЕ СОЕДИНЕНИЯ, ИНГИБИРУЮЩИЕ ТИРОЗИНКИНАЗЫ ТРОМБОЦИТАРНОГО ФАКТОРА РОСТА И/ИЛИ р56 | |
| EP3677266B1 (en) | Exon 18 and/or exon 21 mutant egfr selective inhibitor | |
| KR20160079792A (ko) | 암 치료를 위한 raf 억제제로서의 1-(5-tert-부틸-2-아릴-피라졸-3-일)-3-[2-플루오로-4-[(3-옥소-4h-피리도[2,3-b]피라진-8-일)옥시]페닐]우레아 유도체 | |
| JP2020522569A (ja) | 線維症の処置のための組成物 | |
| US10464939B2 (en) | Deuterated triazolopyridazine as a kinase modulator | |
| JP2012072140A (ja) | 異常な細胞増殖を処置する方法 | |
| CA3241856A1 (en) | Crystalline form of n-(2-chloro-3-((5-chloro-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)-4-fluorophenyl)-3-fluoroazetidine-1-sulfonamide | |
| CN101321527B (zh) | 治疗不正常细胞生长的方法 | |
| EP4154890A1 (en) | Pharmaceutical composition for preventing or treating pancreatic cancer associated with ron mutation and method using same | |
| HK1126121B (en) | Method of treating abnormal cell growth | |
| TWI698238B (zh) | Ｅｚｈ２抑制劑組合治療 | |
| US20250339412A1 (en) | Methods of treating solid tumor using (19r)-5-chloro-3-ethyl-16-fluoro-10,19-dimethyl-20-oxa-3,4,10,11,23-pentaazapentacyclo[19.3.1.02,6.08,12.013,18]pentacosa-1(24),2(6),4,8,11,13,15,17,21(25),22-decaen-22-amine | |
| Faller | Targeting N-RAS as a Therapeutic Approach for Melanoma | |
| HK40033085B (en) | Exon 18 and/or exon 21 mutant egfr selective inhibitor |