KR20080018908A

KR20080018908A - 암 치료용 디아릴 우레아 화합물 및 ｐｉ３, ａｋｔ 키나제또는 ｍｔｏｒ 억제제 (라파마이신)를 포함하는 병용요법

암 치료용 디아릴 우레아 화합물 및 ｐｉ３, ａｋｔ 키나제또는 ｍｔｏｒ 억제제 (라파마이신)를 포함하는 병용요법 Download PDF

Info

Publication number: KR20080018908A
Authority: KR; South Korea
Prior art keywords: formula; cancer; compound; combination; akt
Prior art date: 2005-05-27
Legal status : Withdrawn

Application number

KR1020077030272A

Other languages

English (en)

Korean (ko)

Inventor

우르반 쉐우링그

인고 베르나르트

Original Assignee

바이엘 헬스케어 아게

Priority date

2005-05-27

Filing date

2006-05-13

Publication date

2008-02-28

2006-05-13 Application filed by 바이엘 헬스케어 아게 filed Critical 바이엘 헬스케어 아게

2008-02-28 Publication of KR20080018908A publication Critical patent/KR20080018908A/ko

Status Withdrawn legal-status Critical Current

Links

206010028980 Neoplasm Diseases 0.000 title claims abstract description 65
201000011510 cancer Diseases 0.000 title claims abstract description 35
-1 diaryl urea compounds Chemical class 0.000 title claims abstract description 32
229940124302 mTOR inhibitor Drugs 0.000 title claims abstract description 4
239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title claims abstract description 4
229940043355 kinase inhibitor Drugs 0.000 title claims abstract 3
239000003757 phosphotransferase inhibitor Substances 0.000 title claims abstract 3
229960002930 sirolimus Drugs 0.000 title claims description 13
QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title claims description 10
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 title claims description 9
108091000080 Phosphotransferase Proteins 0.000 title description 9
102000020233 phosphotransferase Human genes 0.000 title description 9
238000002648 combination therapy Methods 0.000 title 1
239000003112 inhibitor Substances 0.000 claims abstract description 31
230000007730 Akt signaling Effects 0.000 claims abstract description 21
CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 claims abstract description 5
229960000235 temsirolimus Drugs 0.000 claims abstract description 5
SZFPYBIJACMNJV-UHFFFAOYSA-N perifosine Chemical compound CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1 SZFPYBIJACMNJV-UHFFFAOYSA-N 0.000 claims abstract description 4
229950010632 perifosine Drugs 0.000 claims abstract description 4
QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 105
238000000034 method Methods 0.000 claims description 32
150000003839 salts Chemical class 0.000 claims description 25
QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 claims description 11
QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 claims description 10
206010006187 Breast cancer Diseases 0.000 claims description 9
208000026310 Breast neoplasm Diseases 0.000 claims description 9
201000001441 melanoma Diseases 0.000 claims description 9
206010073071 hepatocellular carcinoma Diseases 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
239000000651 prodrug Substances 0.000 claims description 7
229940002612 prodrug Drugs 0.000 claims description 7
206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
206010060862 Prostate cancer Diseases 0.000 claims description 6
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
206010033128 Ovarian cancer Diseases 0.000 claims description 5
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 5
239000002207 metabolite Substances 0.000 claims description 5
208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
201000002528 pancreatic cancer Diseases 0.000 claims description 5
208000008443 pancreatic carcinoma Diseases 0.000 claims description 5
239000012453 solvate Substances 0.000 claims description 5
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
BUROJSBIWGDYCN-GAUTUEMISA-N AP 23573 Chemical compound C1C[C@@H](OP(C)(C)=O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 BUROJSBIWGDYCN-GAUTUEMISA-N 0.000 claims description 4
206010009944 Colon cancer Diseases 0.000 claims description 4
208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 4
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
229960005167 everolimus Drugs 0.000 claims description 4
208000014018 liver neoplasm Diseases 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
229960001302 ridaforolimus Drugs 0.000 claims description 4
102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 claims description 3
208000006265 Renal cell carcinoma Diseases 0.000 claims description 3
108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 claims description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 3
UCOYIUOEXIYJFD-UHFFFAOYSA-N 2-[4-[5-phenanthren-2-yl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]guanidine Chemical compound C1=CC(NC(=N)N)=CC=C1N1C(C=2C=C3C(C4=CC=CC=C4C=C3)=CC=2)=CC(C(F)(F)F)=N1 UCOYIUOEXIYJFD-UHFFFAOYSA-N 0.000 claims description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
YULUCECVQOCQFQ-UHFFFAOYSA-N OSU-03012 Chemical compound C1=CC(NC(=O)CN)=CC=C1N1C(C=2C=C3C(C4=CC=CC=C4C=C3)=CC=2)=CC(C(F)(F)F)=N1 YULUCECVQOCQFQ-UHFFFAOYSA-N 0.000 claims description 2
QIUASFSNWYMDFS-NILGECQDSA-N PX-866 Chemical class CC(=O)O[C@@H]1C[C@]2(C)C(=O)CC[C@H]2C2=C1[C@@]1(C)[C@@H](COC)OC(=O)\C(=C\N(CC=C)CC=C)C1=C(O)C2=O QIUASFSNWYMDFS-NILGECQDSA-N 0.000 claims description 2
GJZGRYXGQBWBEB-AVMFAVRISA-N [(2r)-2-methoxy-3-octadecoxypropyl] [(1r,2r,3s,4r,6r)-2,3,4,6-tetrahydroxycyclohexyl] hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCCCOC[C@@H](OC)COP(O)(=O)O[C@@H]1[C@H](O)C[C@@H](O)[C@H](O)[C@H]1O GJZGRYXGQBWBEB-AVMFAVRISA-N 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
150000004802 benzothiophens Chemical class 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
229960000590 celecoxib Drugs 0.000 claims description 2
RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
239000003623 enhancer Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
208000015347 renal cell adenocarcinoma Diseases 0.000 claims 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
239000004480 active ingredient Substances 0.000 claims 1
230000002195 synergetic effect Effects 0.000 claims 1
108091008611 Protein Kinase B Proteins 0.000 abstract description 21
102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 abstract description 16
108091007960 PI3Ks Proteins 0.000 abstract description 14
230000019491 signal transduction Effects 0.000 abstract description 8
239000004202 carbamide Substances 0.000 abstract description 2
HOGVTUZUJGHKPL-HTVVRFAVSA-N triciribine Chemical compound C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HOGVTUZUJGHKPL-HTVVRFAVSA-N 0.000 abstract description 2
102000038030 PI3Ks Human genes 0.000 abstract 1
239000008194 pharmaceutical composition Substances 0.000 abstract 1
FNHKPVJBJVTLMP-UHFFFAOYSA-N regorafenib Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 FNHKPVJBJVTLMP-UHFFFAOYSA-N 0.000 abstract 1
229950003873 triciribine Drugs 0.000 abstract 1
210000004027 cell Anatomy 0.000 description 43
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 39
238000012360 testing method Methods 0.000 description 32
201000010099 disease Diseases 0.000 description 29
230000000694 effects Effects 0.000 description 24
230000033115 angiogenesis Effects 0.000 description 23
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
239000000890 drug combination Substances 0.000 description 14
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 13
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 13
239000000758 substrate Substances 0.000 description 13
230000001225 therapeutic effect Effects 0.000 description 13
102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 9
239000000872 buffer Substances 0.000 description 9
208000035475 disorder Diseases 0.000 description 9
208000015181 infectious disease Diseases 0.000 description 9
239000000203 mixture Substances 0.000 description 9
230000037361 pathway Effects 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
101100342473 Drosophila melanogaster Raf gene Proteins 0.000 description 8
101100523543 Rattus norvegicus Raf1 gene Proteins 0.000 description 8
101100523549 Xenopus laevis raf1 gene Proteins 0.000 description 8
101150037250 Zhx2 gene Proteins 0.000 description 8
239000013543 active substance Substances 0.000 description 8
239000003795 chemical substances by application Substances 0.000 description 8
230000035755 proliferation Effects 0.000 description 8
102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 7
239000011324 bead Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
239000002552 dosage form Substances 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000003814 drug Substances 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
239000007995 HEPES buffer Substances 0.000 description 6
102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 6
210000002889 endothelial cell Anatomy 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
238000004020 luminiscence type Methods 0.000 description 6
230000035772 mutation Effects 0.000 description 6
101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 5
206010061218 Inflammation Diseases 0.000 description 5
108010011536 PTEN Phosphohydrolase Proteins 0.000 description 5
102000014160 PTEN Phosphohydrolase Human genes 0.000 description 5
108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 5
239000002585 base Substances 0.000 description 5
210000004204 blood vessel Anatomy 0.000 description 5
230000004663 cell proliferation Effects 0.000 description 5
239000003102 growth factor Substances 0.000 description 5
239000001963 growth medium Substances 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
230000004054 inflammatory process Effects 0.000 description 5
239000011159 matrix material Substances 0.000 description 5
210000000056 organ Anatomy 0.000 description 5
230000026731 phosphorylation Effects 0.000 description 5
238000006366 phosphorylation reaction Methods 0.000 description 5
108090000765 processed proteins & peptides Proteins 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
208000037803 restenosis Diseases 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
201000001320 Atherosclerosis Diseases 0.000 description 4
208000017604 Hodgkin disease Diseases 0.000 description 4
208000010747 Hodgkins lymphoma Diseases 0.000 description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
201000004681 Psoriasis Diseases 0.000 description 4
208000017442 Retinal disease Diseases 0.000 description 4
206010038923 Retinopathy Diseases 0.000 description 4
206010039491 Sarcoma Diseases 0.000 description 4
229920004890 Triton X-100 Polymers 0.000 description 4
239000013504 Triton X-100 Substances 0.000 description 4
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 4
230000002491 angiogenic effect Effects 0.000 description 4
230000010261 cell growth Effects 0.000 description 4
210000003711 chorioallantoic membrane Anatomy 0.000 description 4
230000001419 dependent effect Effects 0.000 description 4
230000003511 endothelial effect Effects 0.000 description 4
230000012010 growth Effects 0.000 description 4
231100000844 hepatocellular carcinoma Toxicity 0.000 description 4
230000002519 immonomodulatory effect Effects 0.000 description 4
208000032839 leukemia Diseases 0.000 description 4
150000007522 mineralic acids Chemical class 0.000 description 4
201000006417 multiple sclerosis Diseases 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
206010039073 rheumatoid arthritis Diseases 0.000 description 4
239000011550 stock solution Substances 0.000 description 4
230000004083 survival effect Effects 0.000 description 4
208000011580 syndromic disease Diseases 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
206010012689 Diabetic retinopathy Diseases 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
206010016654 Fibrosis Diseases 0.000 description 3
206010018364 Glomerulonephritis Diseases 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
241000238631 Hexapoda Species 0.000 description 3
241000725303 Human immunodeficiency virus Species 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
206010025323 Lymphomas Diseases 0.000 description 3
206010027476 Metastases Diseases 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
102000001253 Protein Kinase Human genes 0.000 description 3
208000034189 Sclerosis Diseases 0.000 description 3
206010040047 Sepsis Diseases 0.000 description 3
206010040070 Septic Shock Diseases 0.000 description 3
239000007983 Tris buffer Substances 0.000 description 3
239000002253 acid Substances 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
238000012054 celltiter-glo Methods 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
206010012601 diabetes mellitus Diseases 0.000 description 3
208000014829 head and neck neoplasm Diseases 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
238000003018 immunoassay Methods 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
230000000302 ischemic effect Effects 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
210000004185 liver Anatomy 0.000 description 3
239000012139 lysis buffer Substances 0.000 description 3
230000010534 mechanism of action Effects 0.000 description 3
210000004379 membrane Anatomy 0.000 description 3
239000012528 membrane Substances 0.000 description 3
230000009401 metastasis Effects 0.000 description 3
210000000496 pancreas Anatomy 0.000 description 3
230000008569 process Effects 0.000 description 3
230000002062 proliferating effect Effects 0.000 description 3
210000002307 prostate Anatomy 0.000 description 3
108060006633 protein kinase Proteins 0.000 description 3
208000005069 pulmonary fibrosis Diseases 0.000 description 3
230000002285 radioactive effect Effects 0.000 description 3
108010014186 ras Proteins Proteins 0.000 description 3
239000000523 sample Substances 0.000 description 3
210000003491 skin Anatomy 0.000 description 3
239000000243 solution Substances 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
241000701447 unidentified baculovirus Species 0.000 description 3
230000002792 vascular Effects 0.000 description 3
230000029663 wound healing Effects 0.000 description 3
YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
DHKIKHKEDYKSJJ-UHFFFAOYSA-N 3-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-3-fluorophenoxy]-n-methylpyridine-2-carboxamide Chemical class CNC(=O)C1=NC=CC=C1OC(C=C1F)=CC=C1NC(=O)NC1=CC=C(Cl)C(C(F)(F)F)=C1 DHKIKHKEDYKSJJ-UHFFFAOYSA-N 0.000 description 2
206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
206010001935 American trypanosomiasis Diseases 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
206010003571 Astrocytoma Diseases 0.000 description 2
208000023275 Autoimmune disease Diseases 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
208000003174 Brain Neoplasms Diseases 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
208000024699 Chagas disease Diseases 0.000 description 2
208000011231 Crohn disease Diseases 0.000 description 2
102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 2
101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 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
206010014759 Endometrial neoplasm Diseases 0.000 description 2
201000009273 Endometriosis Diseases 0.000 description 2
206010015150 Erythema Diseases 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
241000287828 Gallus gallus Species 0.000 description 2
208000010412 Glaucoma Diseases 0.000 description 2
206010018338 Glioma Diseases 0.000 description 2
208000007766 Kaposi sarcoma Diseases 0.000 description 2
208000008839 Kidney Neoplasms Diseases 0.000 description 2
102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 2
101100335081 Mus musculus Flt3 gene Proteins 0.000 description 2
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
206010030113 Oedema Diseases 0.000 description 2
208000031481 Pathologic Constriction Diseases 0.000 description 2
108010089430 Phosphoproteins Proteins 0.000 description 2
102000007982 Phosphoproteins Human genes 0.000 description 2
102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
208000000453 Skin Neoplasms Diseases 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
206010052779 Transplant rejections Diseases 0.000 description 2
108091008605 VEGF receptors Proteins 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
239000000654 additive Substances 0.000 description 2
208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
101150045355 akt1 gene Proteins 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
230000001028 anti-proliverative effect Effects 0.000 description 2
230000001640 apoptogenic effect Effects 0.000 description 2
238000003556 assay Methods 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
230000031018 biological processes and functions Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000011575 calcium Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
230000002490 cerebral effect Effects 0.000 description 2
230000008859 change Effects 0.000 description 2
235000013330 chicken meat Nutrition 0.000 description 2
208000006990 cholangiocarcinoma Diseases 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
230000006378 damage Effects 0.000 description 2
230000004069 differentiation Effects 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
239000012636 effector Substances 0.000 description 2
208000030533 eye disease Diseases 0.000 description 2
230000004761 fibrosis Effects 0.000 description 2
230000001434 glomerular Effects 0.000 description 2
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
230000009036 growth inhibition Effects 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
239000007943 implant Substances 0.000 description 2
208000027866 inflammatory disease Diseases 0.000 description 2
230000002757 inflammatory effect Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000000977 initiatory effect Effects 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
208000002780 macular degeneration Diseases 0.000 description 2
201000004792 malaria Diseases 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000000463 material Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
201000008968 osteosarcoma Diseases 0.000 description 2
230000002611 ovarian Effects 0.000 description 2
108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 2
238000003566 phosphorylation assay Methods 0.000 description 2
238000007747 plating Methods 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000002028 premature Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
230000001850 reproductive effect Effects 0.000 description 2
201000009410 rhabdomyosarcoma Diseases 0.000 description 2
230000011664 signaling Effects 0.000 description 2
239000002904 solvent Substances 0.000 description 2
206010041823 squamous cell carcinoma Diseases 0.000 description 2
208000037804 stenosis Diseases 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
238000010998 test method Methods 0.000 description 2
238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
238000012546 transfer Methods 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
210000004291 uterus Anatomy 0.000 description 2
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 1
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical compound CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
UHFMDUIMUVSXJC-UHFFFAOYSA-N 1-hydroxy-2h-pyridine Chemical compound ON1CC=CC=C1 UHFMDUIMUVSXJC-UHFFFAOYSA-N 0.000 description 1
QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical class C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 1
WNJSKZBEWNVKGU-UHFFFAOYSA-N 2,2-dimethoxyethylbenzene Chemical compound COC(OC)CC1=CC=CC=C1 WNJSKZBEWNVKGU-UHFFFAOYSA-N 0.000 description 1
229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
PBCZSGKMGDDXIJ-HQCWYSJUSA-N 7-hydroxystaurosporine Chemical compound N([C@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@H]1C[C@@H](NC)[C@@H](OC)[C@]3(C)O1 PBCZSGKMGDDXIJ-HQCWYSJUSA-N 0.000 description 1
PBCZSGKMGDDXIJ-UHFFFAOYSA-N 7beta-hydroxystaurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3C(O)NC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 PBCZSGKMGDDXIJ-UHFFFAOYSA-N 0.000 description 1
208000002008 AIDS-Related Lymphoma Diseases 0.000 description 1
101150107888 AKT2 gene Proteins 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
101150051155 Akt3 gene Proteins 0.000 description 1
101001015038 Albizia kalkora Kunitz-type trypsin inhibitor alpha chain Proteins 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
102000009840 Angiopoietins Human genes 0.000 description 1
108010009906 Angiopoietins Proteins 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
206010003445 Ascites Diseases 0.000 description 1
206010060971 Astrocytoma malignant Diseases 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
239000002028 Biomass Substances 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
208000006386 Bone Resorption Diseases 0.000 description 1
241000589969 Borreliella burgdorferi Species 0.000 description 1
206010048962 Brain oedema Diseases 0.000 description 1
206010006448 Bronchiolitis Diseases 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
101100322915 Caenorhabditis elegans akt-1 gene Proteins 0.000 description 1
208000005623 Carcinogenesis Diseases 0.000 description 1
206010007559 Cardiac failure congestive Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
239000004381 Choline salt Substances 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
208000003322 Coinfection Diseases 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
208000035473 Communicable disease Diseases 0.000 description 1
201000000054 Coronary Restenosis Diseases 0.000 description 1
206010056489 Coronary artery restenosis Diseases 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
241000701022 Cytomegalovirus Species 0.000 description 1
101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
206010012441 Dermatitis bullous Diseases 0.000 description 1
208000007342 Diabetic Nephropathies Diseases 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
206010014733 Endometrial cancer Diseases 0.000 description 1
101710146739 Enterotoxin Proteins 0.000 description 1
229910052693 Europium Inorganic materials 0.000 description 1
208000006168 Ewing Sarcoma Diseases 0.000 description 1
208000002476 Falciparum Malaria Diseases 0.000 description 1
206010017076 Fracture Diseases 0.000 description 1
108091006057 GST-tagged proteins Proteins 0.000 description 1
206010017982 Gastrointestinal necrosis Diseases 0.000 description 1
208000032612 Glial tumor Diseases 0.000 description 1
YSWHPLCDIMUKFE-QWRGUYRKSA-N Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 YSWHPLCDIMUKFE-QWRGUYRKSA-N 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
206010018498 Goitre Diseases 0.000 description 1
206010018852 Haematoma Diseases 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
241000589989 Helicobacter Species 0.000 description 1
206010019375 Helicobacter infections Diseases 0.000 description 1
102000001554 Hemoglobins Human genes 0.000 description 1
108010054147 Hemoglobins Proteins 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical group 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
206010019663 Hepatic failure Diseases 0.000 description 1
206010019728 Hepatitis alcoholic Diseases 0.000 description 1
208000009889 Herpes Simplex Diseases 0.000 description 1
206010062639 Herpes dermatitis Diseases 0.000 description 1
208000007514 Herpes zoster Diseases 0.000 description 1
208000017605 Hodgkin disease nodular sclerosis Diseases 0.000 description 1
208000021519 Hodgkin lymphoma Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
101000798015 Homo sapiens RAC-beta serine/threonine-protein kinase Proteins 0.000 description 1
101000798007 Homo sapiens RAC-gamma serine/threonine-protein kinase Proteins 0.000 description 1
101000623857 Homo sapiens Serine/threonine-protein kinase mTOR Proteins 0.000 description 1
101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010021143 Hypoxia Diseases 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
IVYPNXXAYMYVSP-UHFFFAOYSA-N Indole-3-carbinol Natural products C1=CC=C2C(CO)=CNC2=C1 IVYPNXXAYMYVSP-UHFFFAOYSA-N 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
208000002979 Influenza in Birds Diseases 0.000 description 1
206010061252 Intraocular melanoma Diseases 0.000 description 1
206010023125 Jarisch-Herxheimer reaction Diseases 0.000 description 1
208000002260 Keloid Diseases 0.000 description 1
206010023330 Keloid scar Diseases 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
241001313288 Labia Species 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
208000018142 Leiomyosarcoma Diseases 0.000 description 1
208000019693 Lung disease Diseases 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
208000016604 Lyme disease Diseases 0.000 description 1
102000036243 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Human genes 0.000 description 1
108010002481 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Proteins 0.000 description 1
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
239000007993 MOPS buffer Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
208000000172 Medulloblastoma Diseases 0.000 description 1
208000034762 Meningococcal Infections Diseases 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
206010027761 Mixed hepatocellular cholangiocarcinoma Diseases 0.000 description 1
208000003445 Mouth Neoplasms Diseases 0.000 description 1
101150097381 Mtor gene Proteins 0.000 description 1
208000034578 Multiple myelomas Diseases 0.000 description 1
101100481410 Mus musculus Tek gene Proteins 0.000 description 1
101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 0.000 description 1
208000022873 Ocular disease Diseases 0.000 description 1
208000010191 Osteitis Deformans Diseases 0.000 description 1
206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 description 1
101150044441 PECAM1 gene Proteins 0.000 description 1
229940116355 PI3 kinase inhibitor Drugs 0.000 description 1
101150037263 PIP2 gene Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000027868 Paget disease Diseases 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
241000700639 Parapoxvirus Species 0.000 description 1
240000007711 Peperomia pellucida Species 0.000 description 1
208000008469 Peptic Ulcer Diseases 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
208000007641 Pinealoma Diseases 0.000 description 1
206010035226 Plasma cell myeloma Diseases 0.000 description 1
201000011336 Plasmodium falciparum malaria Diseases 0.000 description 1
108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
101710182846 Polyhedrin Proteins 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
208000037062 Polyps Diseases 0.000 description 1
208000006994 Precancerous Conditions Diseases 0.000 description 1
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
108010091528 Proto-Oncogene Proteins B-raf Proteins 0.000 description 1
206010037423 Pulmonary oedema Diseases 0.000 description 1
206010037660 Pyrexia Diseases 0.000 description 1
239000012614 Q-Sepharose Substances 0.000 description 1
102100032315 RAC-beta serine/threonine-protein kinase Human genes 0.000 description 1
102100032314 RAC-gamma serine/threonine-protein kinase Human genes 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
206010038486 Renal neoplasms Diseases 0.000 description 1
206010063837 Reperfusion injury Diseases 0.000 description 1
201000000582 Retinoblastoma Diseases 0.000 description 1
101100262439 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UBA2 gene Proteins 0.000 description 1
229920002684 Sepharose Polymers 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
101710142052 Serine/threonine-protein kinase mTOR Proteins 0.000 description 1
108010017898 Shiga Toxins Proteins 0.000 description 1
201000010001 Silicosis Diseases 0.000 description 1
206010041067 Small cell lung cancer Diseases 0.000 description 1
208000021712 Soft tissue sarcoma Diseases 0.000 description 1
241000191940 Staphylococcus Species 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
239000012505 Superdex™ Substances 0.000 description 1
206010042674 Swelling Diseases 0.000 description 1
208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
208000024313 Testicular Neoplasms Diseases 0.000 description 1
206010057644 Testis cancer Diseases 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
208000024770 Thyroid neoplasm Diseases 0.000 description 1
206010044248 Toxic shock syndrome Diseases 0.000 description 1
231100000650 Toxic shock syndrome Toxicity 0.000 description 1
201000005485 Toxoplasmosis Diseases 0.000 description 1
241000589884 Treponema pallidum Species 0.000 description 1
208000026911 Tuberous sclerosis complex Diseases 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
206010046788 Uterine haemorrhage Diseases 0.000 description 1
201000005969 Uveal melanoma Diseases 0.000 description 1
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
206010049060 Vascular Graft Occlusion Diseases 0.000 description 1
102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
241000700605 Viruses Species 0.000 description 1
208000004354 Vulvar Neoplasms Diseases 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000006022 acute inflammation Effects 0.000 description 1
208000038016 acute inflammation Diseases 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
206010064930 age-related macular degeneration Diseases 0.000 description 1
208000002353 alcoholic hepatitis Diseases 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
230000009285 allergic inflammation Effects 0.000 description 1
208000028004 allergic respiratory disease Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
230000004075 alteration Effects 0.000 description 1
230000008382 alveolar damage Effects 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000004037 angiogenesis inhibitor Substances 0.000 description 1
230000006481 angiogenic pathway Effects 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
229940034982 antineoplastic agent Drugs 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
210000000436 anus Anatomy 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
238000013096 assay test Methods 0.000 description 1
238000000376 autoradiography Methods 0.000 description 1
206010064097 avian influenza Diseases 0.000 description 1
210000002469 basement membrane Anatomy 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
238000010876 biochemical test Methods 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
201000000053 blastoma Diseases 0.000 description 1
210000000601 blood cell Anatomy 0.000 description 1
230000036770 blood supply Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
230000024279 bone resorption Effects 0.000 description 1
206010006007 bone sarcoma Diseases 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
230000006931 brain damage Effects 0.000 description 1
231100000874 brain damage Toxicity 0.000 description 1
208000006752 brain edema Diseases 0.000 description 1
208000029028 brain injury Diseases 0.000 description 1
210000000133 brain stem Anatomy 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
201000002143 bronchus adenoma Diseases 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
230000009702 cancer cell proliferation Effects 0.000 description 1
230000036952 cancer formation Effects 0.000 description 1
210000001043 capillary endothelial cell Anatomy 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
231100000504 carcinogenesis Toxicity 0.000 description 1
208000003295 carpal tunnel syndrome Diseases 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000006727 cell loss Effects 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
239000008004 cell lysis buffer Substances 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000009087 cell motility Effects 0.000 description 1
230000017455 cell-cell adhesion Effects 0.000 description 1
230000004640 cellular pathway Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
201000007335 cerebellar astrocytoma Diseases 0.000 description 1
208000030239 cerebral astrocytoma Diseases 0.000 description 1
239000013522 chelant Substances 0.000 description 1
235000019417 choline salt Nutrition 0.000 description 1
210000004252 chorionic villi Anatomy 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
150000004777 chromones Chemical class 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
230000006020 chronic inflammation Effects 0.000 description 1
208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
229940114081 cinnamate Drugs 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
239000003245 coal Substances 0.000 description 1
208000011588 combined hepatocellular carcinoma and cholangiocarcinoma Diseases 0.000 description 1
239000000306 component Substances 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
208000021921 corneal disease Diseases 0.000 description 1
201000000159 corneal neovascularization Diseases 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
BALGDZWGNCXXES-UHFFFAOYSA-N cyclopentane;propanoic acid Chemical compound CCC(O)=O.C1CCCC1 BALGDZWGNCXXES-UHFFFAOYSA-N 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
208000031513 cyst Diseases 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000004443 dendritic cell Anatomy 0.000 description 1
238000001514 detection method Methods 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
229950006137 dexfosfoserine Drugs 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
LMEDOLJKVASKTP-UHFFFAOYSA-N dibutyl sulfate Chemical compound CCCCOS(=O)(=O)OCCCC LMEDOLJKVASKTP-UHFFFAOYSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
210000002249 digestive system Anatomy 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical compound CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
238000009826 distribution Methods 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940043264 dodecyl sulfate Drugs 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
230000005014 ectopic expression Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
201000008184 embryoma Diseases 0.000 description 1
206010014599 encephalitis Diseases 0.000 description 1
201000002491 encephalomyelitis Diseases 0.000 description 1
230000002357 endometrial effect Effects 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
239000000147 enterotoxin Substances 0.000 description 1
231100000655 enterotoxin Toxicity 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
231100000321 erythema Toxicity 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
210000003238 esophagus Anatomy 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
208000024519 eye neoplasm Diseases 0.000 description 1
229960000556 fingolimod Drugs 0.000 description 1
KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 1
238000000684 flow cytometry Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000002875 fluorescence polarization Methods 0.000 description 1
238000002376 fluorescence recovery after photobleaching Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
210000000232 gallbladder Anatomy 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
210000002816 gill Anatomy 0.000 description 1
208000005017 glioblastoma Diseases 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
208000024908 graft versus host disease Diseases 0.000 description 1
230000003394 haemopoietic effect Effects 0.000 description 1
210000003128 head Anatomy 0.000 description 1
201000010536 head and neck cancer Diseases 0.000 description 1
230000036541 health Effects 0.000 description 1
210000002216 heart Anatomy 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
201000011066 hemangioma Diseases 0.000 description 1
230000011132 hemopoiesis Effects 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
208000029824 high grade glioma Diseases 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000000521 hyperimmunizing effect Effects 0.000 description 1
230000002267 hypothalamic effect Effects 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
238000012151 immunohistochemical method Methods 0.000 description 1
238000012744 immunostaining Methods 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
RUMVKBSXRDGBGO-UHFFFAOYSA-N indole-3-carbinol Chemical compound C1=CC=C[C]2C(CO)=CN=C21 RUMVKBSXRDGBGO-UHFFFAOYSA-N 0.000 description 1
235000002279 indole-3-carbinol Nutrition 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
208000014674 injury Diseases 0.000 description 1
210000002570 interstitial cell Anatomy 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
208000014899 intrahepatic bile duct cancer Diseases 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
201000008893 intraocular retinoblastoma Diseases 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical compound OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
210000001117 keloid Anatomy 0.000 description 1
201000010982 kidney cancer Diseases 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
210000000244 kidney pelvis Anatomy 0.000 description 1
238000000021 kinase assay Methods 0.000 description 1
210000000867 larynx Anatomy 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
206010024627 liposarcoma Diseases 0.000 description 1
239000007788 liquid Substances 0.000 description 1
208000019423 liver disease Diseases 0.000 description 1
231100000835 liver failure Toxicity 0.000 description 1
208000007903 liver failure Diseases 0.000 description 1
230000004807 localization Effects 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
210000002751 lymph Anatomy 0.000 description 1
230000035168 lymphangiogenesis Effects 0.000 description 1
208000019420 lymphoid neoplasm Diseases 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
208000030883 malignant astrocytoma Diseases 0.000 description 1
201000011614 malignant glioma Diseases 0.000 description 1
208000026037 malignant tumor of neck Diseases 0.000 description 1
208000027202 mammary Paget disease Diseases 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
210000000716 merkel cell Anatomy 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
208000037819 metastatic cancer Diseases 0.000 description 1
208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
238000010232 migration assay Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
210000000214 mouth Anatomy 0.000 description 1
230000023105 myelination Effects 0.000 description 1
210000003914 myeloid leukocyte Anatomy 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
210000001989 nasopharynx Anatomy 0.000 description 1
210000003739 neck Anatomy 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
230000000414 obstructive effect Effects 0.000 description 1
201000002575 ocular melanoma Diseases 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
208000003154 papilloma Diseases 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
210000003899 penis Anatomy 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
208000011906 peptic ulcer disease Diseases 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
239000006187 pill Substances 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
206010035653 pneumoconiosis Diseases 0.000 description 1
208000030761 polycystic kidney disease Diseases 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
208000001685 postmenopausal osteoporosis Diseases 0.000 description 1
201000011461 pre-eclampsia Diseases 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000000047 product Substances 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
108010043671 prostatic acid phosphatase Proteins 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
230000005855 radiation Effects 0.000 description 1
102000009929 raf Kinases Human genes 0.000 description 1
108010077182 raf Kinases Proteins 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
208000004644 retinal vein occlusion Diseases 0.000 description 1
201000003068 rheumatic fever Diseases 0.000 description 1
210000003079 salivary gland Anatomy 0.000 description 1
201000000306 sarcoidosis Diseases 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
201000008261 skin carcinoma Diseases 0.000 description 1
201000010106 skin squamous cell carcinoma Diseases 0.000 description 1
208000000587 small cell lung carcinoma Diseases 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
201000005671 spondyloarthropathy Diseases 0.000 description 1
208000017572 squamous cell neoplasm Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
201000004595 synovitis Diseases 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
229940095064 tartrate Drugs 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
201000003120 testicular cancer Diseases 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
206010043778 thyroiditis Diseases 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011541 total hip replacement Methods 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
230000008733 trauma Effects 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
201000008827 tuberculosis Diseases 0.000 description 1
208000009999 tuberous sclerosis Diseases 0.000 description 1
230000004565 tumor cell growth Effects 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
210000003954 umbilical cord Anatomy 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
241000712461 unidentified influenza virus Species 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
210000000626 ureter Anatomy 0.000 description 1
210000003708 urethra Anatomy 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
208000013139 vaginal neoplasm Diseases 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
YEIGUXGHHKAURB-UHFFFAOYSA-N viridine Natural products O=C1C2=C3CCC(=O)C3=CC=C2C2(C)C(O)C(OC)C(=O)C3=COC1=C23 YEIGUXGHHKAURB-UHFFFAOYSA-N 0.000 description 1
208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
238000001262 western blot Methods 0.000 description 1
CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
229950009819 zotarolimus Drugs 0.000 description 1