RU2609208C2 - МОРФОЛИНО-ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ БИЦИКЛИЧЕСКИХ ПИРИМИДИНМОЧЕВИНЫ ИЛИ КАРБАМАТА В КАЧЕСТВЕ ИНГИБИТОРОВ mTOR - Google Patents

Info

Publication number

RU2609208C2

RU2609208C2 RU2014109748A RU2014109748A RU2609208C2 RU 2609208 C2 RU2609208 C2 RU 2609208C2 RU 2014109748 A RU2014109748 A RU 2014109748A RU 2014109748 A RU2014109748 A RU 2014109748A RU 2609208 C2 RU2609208 C2 RU 2609208C2

Authority

RU

Russia

Prior art keywords

dioxo

phenyl

dihydrothieno

pyrimidin

urea

Prior art date

2011-10-07

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title abstract description 31
• 229940124302 mTOR inhibitor Drugs 0.000 title abstract description 26
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 title 1
• 125000002619 bicyclic group Chemical class 0.000 title 1
• ZENDWEPAVHORFD-UHFFFAOYSA-N pyrimidine;urea Chemical compound NC(N)=O.C1=CN=CN=C1 ZENDWEPAVHORFD-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 150
• 238000000034 method Methods 0.000 claims abstract description 89
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims abstract description 80
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims abstract description 80
• -1 8-oxa-3-azabicyclo[3.2.1]octane-3-yl Chemical group 0.000 claims abstract description 65
• 150000003839 salts Chemical class 0.000 claims abstract description 58
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 45
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 34
• 239000003814 drug Substances 0.000 claims abstract description 31
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
• 150000002367 halogens Chemical class 0.000 claims abstract description 15
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 10
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 5
• 125000003566 oxetanyl group Chemical group 0.000 claims abstract description 5
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 73
• 125000000217 alkyl group Chemical group 0.000 claims description 60
• 201000010099 disease Diseases 0.000 claims description 54
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 30
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
• 206010028980 Neoplasm Diseases 0.000 claims description 22
• 230000004900 autophagic degradation Effects 0.000 claims description 21
• 201000011510 cancer Diseases 0.000 claims description 19
• 239000004202 carbamide Substances 0.000 claims description 19
• 208000035475 disorder Diseases 0.000 claims description 19
• 239000010802 sludge Substances 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 238000004519 manufacturing process Methods 0.000 claims description 13
• 230000004770 neurodegeneration Effects 0.000 claims description 13
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 13
• 230000002757 inflammatory effect Effects 0.000 claims description 12
• 230000002062 proliferating effect Effects 0.000 claims description 12
• 206010052779 Transplant rejections Diseases 0.000 claims description 10
• 230000001900 immune effect Effects 0.000 claims description 10
• 208000030159 metabolic disease Diseases 0.000 claims description 10
• 241000124008 Mammalia Species 0.000 claims description 9
• 208000023275 Autoimmune disease Diseases 0.000 claims description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 8
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• 208000027866 inflammatory disease Diseases 0.000 claims description 8
• 230000009385 viral infection Effects 0.000 claims description 8
• 208000036142 Viral infection Diseases 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 6
• 208000016097 disease of metabolism Diseases 0.000 claims description 6
• 208000024908 graft versus host disease Diseases 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 208000026278 immune system disease Diseases 0.000 claims description 5
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
• PTZJHIUMDDFCMD-UONOGXRCSA-N 1-cyclopropyl-3-[4-[(5r)-5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1([C@H](S(C2)(=O)=O)C)=C2N=C(C=2C=CC(NC(=O)NC3CC3)=CC=2)N=C1N1CCOC[C@@H]1C PTZJHIUMDDFCMD-UONOGXRCSA-N 0.000 claims description 3
• PTZJHIUMDDFCMD-KBPBESRZSA-N 1-cyclopropyl-3-[4-[(5s)-5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1([C@@H](S(C2)(=O)=O)C)=C2N=C(C=2C=CC(NC(=O)NC3CC3)=CC=2)N=C1N1CCOC[C@@H]1C PTZJHIUMDDFCMD-KBPBESRZSA-N 0.000 claims description 3
• LPSHTXQPFSXJOB-ZDUSSCGKSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2 LPSHTXQPFSXJOB-ZDUSSCGKSA-N 0.000 claims description 3
• WKRMKFLEXUWZBH-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)CC2 WKRMKFLEXUWZBH-AWEZNQCLSA-N 0.000 claims description 3
• PRXDSNWIGMXHEB-JHAYDQECSA-N 1-cyclopropyl-3-[4-[7-fluoro-7-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2(C)F PRXDSNWIGMXHEB-JHAYDQECSA-N 0.000 claims description 3
• NXJSNBXHECGNMG-LSLKUGRBSA-N 1-cyclopropyl-3-[4-[7-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C=12CS(=O)(=O)C(C)C2=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC=1N1CCOC[C@@H]1C NXJSNBXHECGNMG-LSLKUGRBSA-N 0.000 claims description 3
• SLYBINBFUIDZMB-MLCCFXAWSA-N 1-ethyl-3-[4-[5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2(C)C SLYBINBFUIDZMB-MLCCFXAWSA-N 0.000 claims description 3
• LGLAILBRUKQLGF-UHFFFAOYSA-N 1-(2-fluoroethyl)-3-[4-(5,7,7-trimethyl-4-morpholin-4-yl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl)phenyl]urea Chemical compound CC1(C)S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NCCF)=CC=1)N=C2N1CCOCC1 LGLAILBRUKQLGF-UHFFFAOYSA-N 0.000 claims description 2
• GKMBYWKXCDKMRS-ZDUSSCGKSA-N 1-(2-fluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=NC2=C1CS(=O)(=O)C2 GKMBYWKXCDKMRS-ZDUSSCGKSA-N 0.000 claims description 2
• OBOYUQKGYQANBL-MLCCFXAWSA-N 1-(2-fluoroethyl)-3-[4-[5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound CC1(C)S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NCCF)=CC=1)N=C2N1CCOC[C@@H]1C OBOYUQKGYQANBL-MLCCFXAWSA-N 0.000 claims description 2
• SDUIYXKCZZSAEF-ZDUSSCGKSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=NC2=C1CS(=O)(=O)C2 SDUIYXKCZZSAEF-ZDUSSCGKSA-N 0.000 claims description 2
• JSOHXGJSEVULKJ-AWEZNQCLSA-N 1-(3-fluoropropyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCCF)=CC=2)=NC2=C1CS(=O)(=O)C2 JSOHXGJSEVULKJ-AWEZNQCLSA-N 0.000 claims description 2
• ZVRSXMXKIYBKHA-UEWDXFNNSA-N 1-[3-fluoro-4-[5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-methylurea Chemical compound FC1=CC(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2(C)C ZVRSXMXKIYBKHA-UEWDXFNNSA-N 0.000 claims description 2
• DPPZUXQNNUIBRE-UHFFFAOYSA-N 1-[4-(7,7-dimethyl-4-morpholin-4-yl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl)phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2CCOCC2)=NC2=C1CS(=O)(=O)C2(C)C DPPZUXQNNUIBRE-UHFFFAOYSA-N 0.000 claims description 2
• RCXLSGUTNHTFPV-WUJWULDRSA-N 1-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-5,7,7-trimethyl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]-3-fluorophenyl]-3-methylurea Chemical compound CC[C@H]1COCCN1C1=NC(C=2C(=CC(NC(=O)NC)=CC=2)F)=NC2=C1C(C)S(=O)(=O)C2(C)C RCXLSGUTNHTFPV-WUJWULDRSA-N 0.000 claims description 2
• MOIZYEFKOUCQHA-JRZJBTRGSA-N 1-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-5,7,7-trimethyl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-methylurea Chemical compound CC[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC)=CC=2)=NC2=C1C(C)S(=O)(=O)C2(C)C MOIZYEFKOUCQHA-JRZJBTRGSA-N 0.000 claims description 2
• RWTYATHCQVHGGM-AWEZNQCLSA-N 1-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-7,7-dimethyl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]-2-fluorophenyl]-3-methylurea Chemical compound CC[C@H]1COCCN1C1=NC(C=2C=C(F)C(NC(=O)NC)=CC=2)=NC2=C1CS(=O)(=O)C2(C)C RWTYATHCQVHGGM-AWEZNQCLSA-N 0.000 claims description 2
• KKOZUFFILMRGQH-AWEZNQCLSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]-3-propan-2-ylurea Chemical compound C1=CC(NC(=O)NC(C)C)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2 KKOZUFFILMRGQH-AWEZNQCLSA-N 0.000 claims description 2
• SRKUSFHOYIWTOR-HNNXBMFYSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC=3C=NC=CC=3)=CC=2)=NC2=C1CS(=O)(=O)C2 SRKUSFHOYIWTOR-HNNXBMFYSA-N 0.000 claims description 2
• QFXPMKTXPYFQSO-MLCCFXAWSA-N 1-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]-3-propylurea Chemical compound C1=CC(NC(=O)NCCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2 QFXPMKTXPYFQSO-MLCCFXAWSA-N 0.000 claims description 2
• OJDMFKGHYSDHOC-UHFFFAOYSA-N 1-[4-[7,7-dimethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2C3CCC2COC3)=NC2=C1CS(=O)(=O)C2(C)C OJDMFKGHYSDHOC-UHFFFAOYSA-N 0.000 claims description 2
• IZLPVLBNRGPOHA-CQSZACIVSA-N 1-[4-[7,7-dimethyl-4-[(3r)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@@H](COCC2)C)=NC2=C1CS(=O)(=O)C2(C)C IZLPVLBNRGPOHA-CQSZACIVSA-N 0.000 claims description 2
• JXOGJIGWPPCUHU-LBPRGKRZSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]-2-fluorophenyl]-3-methylurea Chemical compound C1=C(F)C(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2(C)C JXOGJIGWPPCUHU-LBPRGKRZSA-N 0.000 claims description 2
• IBCNZLNGLTVWAW-ZDUSSCGKSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]-3-fluorophenyl]-3-ethylurea Chemical compound FC1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2(C)C IBCNZLNGLTVWAW-ZDUSSCGKSA-N 0.000 claims description 2
• AMKGDMBHTOCQEL-LBPRGKRZSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]-3-fluorophenyl]-3-methylurea Chemical compound FC1=CC(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2(C)C AMKGDMBHTOCQEL-LBPRGKRZSA-N 0.000 claims description 2
• PTQAIEPKJUMVJP-AWEZNQCLSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-(2-fluoroethyl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=NC2=C1CS(=O)(=O)C2(C)C PTQAIEPKJUMVJP-AWEZNQCLSA-N 0.000 claims description 2
• IWUJBGZAQUIFSP-AWEZNQCLSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-(oxetan-3-yl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3COC3)=CC=2)=NC2=C1CS(=O)(=O)C2(C)C IWUJBGZAQUIFSP-AWEZNQCLSA-N 0.000 claims description 2
• IZLPVLBNRGPOHA-AWEZNQCLSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2(C)C IZLPVLBNRGPOHA-AWEZNQCLSA-N 0.000 claims description 2
• GIGYEYKNBDPIRS-ZDUSSCGKSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2(C)C GIGYEYKNBDPIRS-ZDUSSCGKSA-N 0.000 claims description 2
• ABEVJNWPAYMKNG-UHFFFAOYSA-N 1-cyclopropyl-3-[4-(4-morpholin-4-yl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl)phenyl]urea Chemical compound C=1C=C(C=2N=C(C=3CS(=O)(=O)CC=3N=2)N2CCOCC2)C=CC=1NC(=O)NC1CC1 ABEVJNWPAYMKNG-UHFFFAOYSA-N 0.000 claims description 2
• IFXAEMKDFWJOJW-UHFFFAOYSA-N 1-cyclopropyl-3-[4-(5-methyl-4-morpholin-4-yl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl)phenyl]urea Chemical compound C1S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NC3CC3)=CC=1)N=C2N1CCOCC1 IFXAEMKDFWJOJW-UHFFFAOYSA-N 0.000 claims description 2
• FOQLLQAMHWSGFN-LSDHHAIUSA-N 1-cyclopropyl-3-[4-[(5r)-5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1([C@H](S(C2(C)C)(=O)=O)C)=C2N=C(C=2C=CC(NC(=O)NC3CC3)=CC=2)N=C1N1CCOC[C@@H]1C FOQLLQAMHWSGFN-LSDHHAIUSA-N 0.000 claims description 2
• PTZJHIUMDDFCMD-KGLIPLIRSA-N 1-cyclopropyl-3-[4-[(5s)-5-methyl-4-[(3r)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1([C@@H](S(C2)(=O)=O)C)=C2N=C(C=2C=CC(NC(=O)NC3CC3)=CC=2)N=C1N1CCOC[C@H]1C PTZJHIUMDDFCMD-KGLIPLIRSA-N 0.000 claims description 2
• NIMRYHVGEYTTLW-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(3-ethylmorpholin-4-yl)-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound CCC1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2 NIMRYHVGEYTTLW-UHFFFAOYSA-N 0.000 claims description 2
• MTHDMBXVDMTBNP-OKILXGFUSA-N 1-cyclopropyl-3-[4-[4-[(2s,6r)-2,6-dimethylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1[C@@H](C)O[C@@H](C)CN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2 MTHDMBXVDMTBNP-OKILXGFUSA-N 0.000 claims description 2
• LPSHTXQPFSXJOB-CYBMUJFWSA-N 1-cyclopropyl-3-[4-[4-[(3r)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2 LPSHTXQPFSXJOB-CYBMUJFWSA-N 0.000 claims description 2
• XZUZIENJVIHTTD-IBYPIGCZSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-5-methyl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound CC[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1C(C)S(=O)(=O)C2 XZUZIENJVIHTTD-IBYPIGCZSA-N 0.000 claims description 2
• XYUAGXOXDFFZRI-FHERZECASA-N 1-cyclopropyl-3-[4-[5,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1C(C)S(=O)(=O)C(C)C2 XYUAGXOXDFFZRI-FHERZECASA-N 0.000 claims description 2
• FGDZUNGMYHIJSV-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[5-methyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1S(=O)(=O)C(C)C(C(=N2)N3C4CCC3COC4)=C1N=C2C(C=C1)=CC=C1NC(=O)NC1CC1 FGDZUNGMYHIJSV-UHFFFAOYSA-N 0.000 claims description 2
• CJCKEVOQMKGKGT-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[5-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1S(=O)(=O)C(C)C(C(=N2)N3CC4CCC(O4)C3)=C1N=C2C(C=C1)=CC=C1NC(=O)NC1CC1 CJCKEVOQMKGKGT-UHFFFAOYSA-N 0.000 claims description 2
• PTZJHIUMDDFCMD-KWCCSABGSA-N 1-cyclopropyl-3-[4-[5-methyl-4-[(3r)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NC3CC3)=CC=1)N=C2N1CCOC[C@H]1C PTZJHIUMDDFCMD-KWCCSABGSA-N 0.000 claims description 2
• SASGGXUCBYHSDM-MLCCFXAWSA-N 1-cyclopropyl-3-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1C(C)S(=O)(=O)CC2 SASGGXUCBYHSDM-MLCCFXAWSA-N 0.000 claims description 2
• NRGBYJVUETZWNN-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[7,7-dimethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound N=1C(N2C3CCC2COC3)=C2CS(=O)(=O)C(C)(C)C2=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 NRGBYJVUETZWNN-UHFFFAOYSA-N 0.000 claims description 2
• WPUSYXXXRWVUEH-HNNXBMFYSA-N 1-cyclopropyl-3-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,8-dihydrothiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C(C)(C)C2 WPUSYXXXRWVUEH-HNNXBMFYSA-N 0.000 claims description 2
• HQADXOKORBKKGD-MLCCFXAWSA-N 1-cyclopropyl-3-[4-[7-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C(C)C2 HQADXOKORBKKGD-MLCCFXAWSA-N 0.000 claims description 2
• MWVPVSMZQXQKFK-UEWDXFNNSA-N 1-ethyl-3-[2-fluoro-4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=C(F)C(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2 MWVPVSMZQXQKFK-UEWDXFNNSA-N 0.000 claims description 2
• CWYGFUYGCDCLPR-PBHICJAKSA-N 1-ethyl-3-[4-[(5r)-4-[(3s)-3-ethylmorpholin-4-yl]-5-methyl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)CC)=NC2=C1[C@@H](C)S(=O)(=O)C2 CWYGFUYGCDCLPR-PBHICJAKSA-N 0.000 claims description 2
• XBBPNIZKDLRPDM-UONOGXRCSA-N 1-ethyl-3-[4-[(5r)-5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1[C@@H](C)S(=O)(=O)C2 XBBPNIZKDLRPDM-UONOGXRCSA-N 0.000 claims description 2
• CWYGFUYGCDCLPR-YOEHRIQHSA-N 1-ethyl-3-[4-[(5s)-4-[(3s)-3-ethylmorpholin-4-yl]-5-methyl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)CC)=NC2=C1[C@H](C)S(=O)(=O)C2 CWYGFUYGCDCLPR-YOEHRIQHSA-N 0.000 claims description 2
• XBBPNIZKDLRPDM-KBPBESRZSA-N 1-ethyl-3-[4-[(5s)-5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1[C@H](C)S(=O)(=O)C2 XBBPNIZKDLRPDM-KBPBESRZSA-N 0.000 claims description 2
• IYGRPQSJSHUJLP-ZDUSSCGKSA-N 1-ethyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2 IYGRPQSJSHUJLP-ZDUSSCGKSA-N 0.000 claims description 2
• XFMLDRCZRQHGLK-PIVQAISJSA-N 1-ethyl-3-[4-[5-ethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(CC)S(=O)(=O)C2 XFMLDRCZRQHGLK-PIVQAISJSA-N 0.000 claims description 2
• XBBPNIZKDLRPDM-LSLKUGRBSA-N 1-ethyl-3-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2 XBBPNIZKDLRPDM-LSLKUGRBSA-N 0.000 claims description 2
• JHPHVOVQKZFJPF-LBPRGKRZSA-N 1-methyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2 JHPHVOVQKZFJPF-LBPRGKRZSA-N 0.000 claims description 2
• BKHHPUYBBKIPBW-LSLKUGRBSA-N 1-methyl-3-[4-[5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2(C)C BKHHPUYBBKIPBW-LSLKUGRBSA-N 0.000 claims description 2
• AMYQUFZFTUNUHG-UEWDXFNNSA-N 1-methyl-3-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2 AMYQUFZFTUNUHG-UEWDXFNNSA-N 0.000 claims description 2
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000006001 difluoroethyl group Chemical group 0.000 claims description 2
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
• 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 claims description 2
• 230000002526 effect on cardiovascular system Effects 0.000 claims 3
• 230000002503 metabolic effect Effects 0.000 claims 3
• KJAYNLZEOIBUQM-HNNXBMFYSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC=3C=CN=CC=3)=CC=2)=NC2=C1CS(=O)(=O)C2 KJAYNLZEOIBUQM-HNNXBMFYSA-N 0.000 claims 1
• NATFTUNGWCUINW-KTQQKIMGSA-N 1-cyclopropyl-3-[4-[5-ethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1S(=O)(=O)C(CC)C2=C1N=C(C=1C=CC(NC(=O)NC3CC3)=CC=1)N=C2N1CCOC[C@@H]1C NATFTUNGWCUINW-KTQQKIMGSA-N 0.000 claims 1
• LCJULVNUJFKFRC-JRZJBTRGSA-N 1-ethyl-3-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-7-methyl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)CC)=NC2=C1CS(=O)(=O)C2C LCJULVNUJFKFRC-JRZJBTRGSA-N 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 22
• 229940079593 drug Drugs 0.000 abstract description 17
• 125000005843 halogen group Chemical group 0.000 abstract description 15
• 208000037765 diseases and disorders Diseases 0.000 abstract description 8
• 239000000126 substance Substances 0.000 abstract description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 4
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
• 239000000203 mixture Substances 0.000 description 107
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 63
• 239000007787 solid Substances 0.000 description 63
• 239000000243 solution Substances 0.000 description 58
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 55
• 235000019439 ethyl acetate Nutrition 0.000 description 53
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
• 239000011734 sodium Substances 0.000 description 49
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 44
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 43
• 210000004027 cell Anatomy 0.000 description 42
• 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 description 35
• 239000012044 organic layer Substances 0.000 description 33
• 108090000623 proteins and genes Proteins 0.000 description 33
• 229960002930 sirolimus Drugs 0.000 description 33
• 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 description 31
• 239000012043 crude product Substances 0.000 description 30
• 239000011541 reaction mixture Substances 0.000 description 30
• 102000004169 proteins and genes Human genes 0.000 description 29
• 239000002904 solvent Substances 0.000 description 28
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
• 239000012267 brine Substances 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• 238000011282 treatment Methods 0.000 description 23
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
• 238000005481 NMR spectroscopy Methods 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• 239000000872 buffer Substances 0.000 description 21
• 239000000047 product Substances 0.000 description 20
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 19
• 239000003208 petroleum Substances 0.000 description 19
• 108091000080 Phosphotransferase Proteins 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 239000003480 eluent Substances 0.000 description 18
• 239000003112 inhibitor Substances 0.000 description 18
• 102000020233 phosphotransferase Human genes 0.000 description 18
• 239000000725 suspension Substances 0.000 description 18
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 17
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 17
• 238000004458 analytical method Methods 0.000 description 17
• 229910052757 nitrogen Inorganic materials 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• 239000001257 hydrogen Substances 0.000 description 16
• 238000010898 silica gel chromatography Methods 0.000 description 16
• 108091007960 PI3Ks Proteins 0.000 description 15
• 238000000746 purification Methods 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 15
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• 230000003595 spectral effect Effects 0.000 description 14
• 229960005419 nitrogen Drugs 0.000 description 13
• 238000002360 preparation method Methods 0.000 description 13
• 125000001424 substituent group Chemical group 0.000 description 13
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• 239000000460 chlorine Substances 0.000 description 12
• 238000001914 filtration Methods 0.000 description 12
• 125000000623 heterocyclic group Chemical group 0.000 description 12
• 238000012746 preparative thin layer chromatography Methods 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
• 229910052799 carbon Inorganic materials 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• 206010039073 rheumatoid arthritis Diseases 0.000 description 11
• 239000003826 tablet Substances 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 238000013459 approach Methods 0.000 description 10
• 210000004369 blood Anatomy 0.000 description 10
• 239000008280 blood Substances 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• 238000001514 detection method Methods 0.000 description 10
• 238000007876 drug discovery Methods 0.000 description 10
• 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 10
• 230000011664 signaling Effects 0.000 description 10
• SFWWGMKXCYLZEG-YFKPBYRVSA-N (3s)-3-methylmorpholine Chemical compound C[C@H]1COCCN1 SFWWGMKXCYLZEG-YFKPBYRVSA-N 0.000 description 9
• TUHNHHNBHVOYFR-UHFFFAOYSA-N 1-cyclopropyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea Chemical compound O1C(C)(C)C(C)(C)OB1C(C=C1)=CC=C1NC(=O)NC1CC1 TUHNHHNBHVOYFR-UHFFFAOYSA-N 0.000 description 9
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 239000013592 cell lysate Substances 0.000 description 9
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
• 238000011534 incubation Methods 0.000 description 9
• 239000012528 membrane Substances 0.000 description 9
• 201000006417 multiple sclerosis Diseases 0.000 description 9
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
• 241001465754 Metazoa Species 0.000 description 8
• BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 8
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 230000001363 autoimmune Effects 0.000 description 8
• 230000000903 blocking effect Effects 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 238000005516 engineering process Methods 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
• 210000004379 membrane Anatomy 0.000 description 8
• 230000002265 prevention Effects 0.000 description 8
• 125000006413 ring segment Chemical group 0.000 description 8
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 7
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
• 208000006029 Cardiomegaly Diseases 0.000 description 7
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 7
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 239000011324 bead Substances 0.000 description 7
• 235000019441 ethanol Nutrition 0.000 description 7
• 235000019253 formic acid Nutrition 0.000 description 7
• 235000011187 glycerol Nutrition 0.000 description 7
• 239000003102 growth factor Substances 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 7
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 6
• 102000000588 Interleukin-2 Human genes 0.000 description 6
• 108010002350 Interleukin-2 Proteins 0.000 description 6
• 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 6
• 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 6
• 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 6
• 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 6
• 101150003085 Pdcl gene Proteins 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 108091008611 Protein Kinase B Proteins 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• 230000000172 allergic effect Effects 0.000 description 6
• 208000010668 atopic eczema Diseases 0.000 description 6
• 230000010261 cell growth Effects 0.000 description 6
• 230000004663 cell proliferation Effects 0.000 description 6
• 230000001413 cellular effect Effects 0.000 description 6
• 230000001276 controlling effect Effects 0.000 description 6
• 239000005457 ice water Substances 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 238000001990 intravenous administration Methods 0.000 description 6
• DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 6
• 230000007246 mechanism Effects 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• 239000002953 phosphate buffered saline Substances 0.000 description 6
• 229910000029 sodium carbonate Inorganic materials 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• RZKSDXFIMOOBNI-JAMMHHFISA-N (3S)-4-(2-chloro-7-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound CC1SCC2=C1N=C(Cl)N=C2N1CCOC[C@@H]1C RZKSDXFIMOOBNI-JAMMHHFISA-N 0.000 description 5
• YSADLUWHNVZEJK-UHFFFAOYSA-N 2,4-dichloro-5,7-dihydrothieno[3,4-d]pyrimidine Chemical compound ClC1=NC(Cl)=NC2=C1CSC2 YSADLUWHNVZEJK-UHFFFAOYSA-N 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• 206010009900 Colitis ulcerative Diseases 0.000 description 5
• 208000011231 Crohn disease Diseases 0.000 description 5
• 102000004127 Cytokines Human genes 0.000 description 5
• 108090000695 Cytokines Proteins 0.000 description 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• 102000004877 Insulin Human genes 0.000 description 5
• 108090001061 Insulin Proteins 0.000 description 5
• 102000001253 Protein Kinase Human genes 0.000 description 5
• 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 description 5
• 239000007983 Tris buffer Substances 0.000 description 5
• 201000006704 Ulcerative Colitis Diseases 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 150000001413 amino acids Chemical class 0.000 description 5
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 239000012230 colorless oil Substances 0.000 description 5
• 239000006185 dispersion Substances 0.000 description 5
• 239000011737 fluorine Substances 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 150000002431 hydrogen Chemical class 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 229940125396 insulin Drugs 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 239000011159 matrix material Substances 0.000 description 5
• 230000001404 mediated effect Effects 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• 230000026731 phosphorylation Effects 0.000 description 5
• 238000006366 phosphorylation reaction Methods 0.000 description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• 108060006633 protein kinase Proteins 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 229960000235 temsirolimus Drugs 0.000 description 5
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 5
• 239000011534 wash buffer Substances 0.000 description 5
• UHIBZNWODXKZRU-ZETCQYMHSA-N (3s)-4-(2-chloro-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound C[C@H]1COCCN1C1=NC(Cl)=NC2=C1SCC2 UHIBZNWODXKZRU-ZETCQYMHSA-N 0.000 description 4
• VSWOUPGJRIRGLM-QMMMGPOBSA-N (3s)-4-(2-chloro-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound C[C@H]1COCCN1C1=NC(Cl)=NC2=C1CSCC2 VSWOUPGJRIRGLM-QMMMGPOBSA-N 0.000 description 4
• SWXXKWPYNMZFTE-UHFFFAOYSA-N (c-ethylsulfanylcarbonimidoyl)azanium;bromide Chemical compound Br.CCSC(N)=N SWXXKWPYNMZFTE-UHFFFAOYSA-N 0.000 description 4
• CELWEVMHFJQSAE-UHFFFAOYSA-N 2,4-dichloro-7-methyl-5,7-dihydrothieno[3,4-d]pyrimidine Chemical compound N1=C(Cl)N=C(Cl)C2=C1C(C)SC2 CELWEVMHFJQSAE-UHFFFAOYSA-N 0.000 description 4
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 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 description 4
• 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 4
• 241000282412 Homo Species 0.000 description 4
• 208000018737 Parkinson disease Diseases 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
• 208000006265 Renal cell carcinoma Diseases 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
• 239000000556 agonist Substances 0.000 description 4
• 230000033115 angiogenesis Effects 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 230000015556 catabolic process Effects 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 230000001684 chronic effect Effects 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 238000006731 degradation reaction Methods 0.000 description 4
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 239000012894 fetal calf serum Substances 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 230000014509 gene expression Effects 0.000 description 4
• 125000005842 heteroatom Chemical group 0.000 description 4
• 230000003993 interaction Effects 0.000 description 4
• 150000002632 lipids Chemical class 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• XNDKLLFGXIEGKL-UHFFFAOYSA-N methyl 3-(2-methoxy-2-oxoethyl)sulfanylpropanoate Chemical compound COC(=O)CCSCC(=O)OC XNDKLLFGXIEGKL-UHFFFAOYSA-N 0.000 description 4
• 125000004043 oxo group Chemical group O=* 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 230000003389 potentiating effect Effects 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 208000011580 syndromic disease Diseases 0.000 description 4
• 102000013498 tau Proteins Human genes 0.000 description 4
• 108010026424 tau Proteins Proteins 0.000 description 4
• 230000014616 translation Effects 0.000 description 4
• 208000009999 tuberous sclerosis Diseases 0.000 description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 4
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 4
• DXEKQAABYLNBCU-ZETCQYMHSA-N (3s)-4-(2-chloro-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound C[C@H]1COCCN1C1=NC(Cl)=NC2=C1CSC2 DXEKQAABYLNBCU-ZETCQYMHSA-N 0.000 description 3
• PTZJHIUMDDFCMD-LSLKUGRBSA-N 1-cyclopropyl-3-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NC3CC3)=CC=1)N=C2N1CCOC[C@@H]1C PTZJHIUMDDFCMD-LSLKUGRBSA-N 0.000 description 3
• QYPYZSRTCKTHKP-UHFFFAOYSA-N 2,4-dichloro-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidine Chemical compound ClC1=NC(Cl)=C2C(C)SCC2=N1 QYPYZSRTCKTHKP-UHFFFAOYSA-N 0.000 description 3
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical class N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 108010006124 DNA-Activated Protein Kinase Proteins 0.000 description 3
• 102000005768 DNA-Activated Protein Kinase Human genes 0.000 description 3
• 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 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 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 3
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 3
• 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 3
• 229920001213 Polysorbate 20 Polymers 0.000 description 3
• 201000004681 Psoriasis Diseases 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 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 3
• 229930006000 Sucrose Natural products 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 3
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
• 230000001594 aberrant effect Effects 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 238000009825 accumulation Methods 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 210000001789 adipocyte Anatomy 0.000 description 3
• 230000000259 anti-tumor effect Effects 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 125000004432 carbon atom Chemical group C* 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
• 210000001072 colon Anatomy 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• IBDMRHDXAQZJAP-UHFFFAOYSA-N dichlorophosphorylbenzene Chemical compound ClP(Cl)(=O)C1=CC=CC=C1 IBDMRHDXAQZJAP-UHFFFAOYSA-N 0.000 description 3
• 231100000673 dose–response relationship Toxicity 0.000 description 3
• 229940088598 enzyme Drugs 0.000 description 3
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 3
• 229960005167 everolimus Drugs 0.000 description 3
• 210000001035 gastrointestinal tract Anatomy 0.000 description 3
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
• 230000001506 immunosuppresive effect Effects 0.000 description 3
• 230000001939 inductive effect Effects 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 230000003834 intracellular effect Effects 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 238000004811 liquid chromatography Methods 0.000 description 3
• 229910052744 lithium Inorganic materials 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 239000012139 lysis buffer Substances 0.000 description 3
• 108020004999 messenger RNA Proteins 0.000 description 3
• 239000002207 metabolite Substances 0.000 description 3
• MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 3
• TUSSXVYKOOVOID-UHFFFAOYSA-N methyl 3-oxothiolane-2-carboxylate Chemical compound COC(=O)C1SCCC1=O TUSSXVYKOOVOID-UHFFFAOYSA-N 0.000 description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 description 3
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
• 230000035699 permeability Effects 0.000 description 3
• 208000030761 polycystic kidney disease Diseases 0.000 description 3
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 230000035755 proliferation Effects 0.000 description 3
• 210000000664 rectum Anatomy 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 208000037803 restenosis Diseases 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 229940083542 sodium Drugs 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• 229910052717 sulfur Inorganic materials 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 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 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 239000000225 tumor suppressor protein Substances 0.000 description 3
• 239000003643 water by type Substances 0.000 description 3
• MZODXBRBMSZTCW-IENPIDJESA-N (3S)-4-(2-chloro-5,7,7-trimethyl-5H-thieno[3,4-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound ClC=1N=C(C2=C(N=1)C(SC2C)(C)C)N1[C@H](COCC1)C MZODXBRBMSZTCW-IENPIDJESA-N 0.000 description 2
• BYTWXPJPRFZJRG-UEJVZZJDSA-N (3S)-4-(2-chloro-5,7-dimethyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound ClC=1N=C(C2=C(N=1)C(SC2C)C)N1[C@H](COCC1)C BYTWXPJPRFZJRG-UEJVZZJDSA-N 0.000 description 2
• PTWPPOAECQDNQG-QMMMGPOBSA-N (3S)-4-(2-chloro-7,7-dimethyl-5H-thieno[3,4-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound C[C@H]1COCCN1c1nc(Cl)nc2c1CSC2(C)C PTWPPOAECQDNQG-QMMMGPOBSA-N 0.000 description 2
• RGHNPICJCLJJAV-KAJCPDDVSA-N (3S)-4-(2-chloro-7-fluoro-7-methyl-5H-thieno[3,4-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound C[C@H]1COCCN1c1nc(Cl)nc2c1CSC2(C)F RGHNPICJCLJJAV-KAJCPDDVSA-N 0.000 description 2
• PNOZHZOPAHDWHU-QMMMGPOBSA-N (3s)-4-(2-chloro-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-4-yl)-3-methylmorpholine Chemical compound C[C@H]1COCCN1C1=NC(Cl)=NC2=C1SCCC2 PNOZHZOPAHDWHU-QMMMGPOBSA-N 0.000 description 2
• HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• JGSFAQOCIXEFQL-ZDUSSCGKSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-5,5-dioxo-6,7-dihydrothieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1S(=O)(=O)CC2 JGSFAQOCIXEFQL-ZDUSSCGKSA-N 0.000 description 2
• CBOPGLRBWYFSAV-ZDUSSCGKSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CSC2 CBOPGLRBWYFSAV-ZDUSSCGKSA-N 0.000 description 2
• OWRMWXQMGOZNPC-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CSCC2 OWRMWXQMGOZNPC-AWEZNQCLSA-N 0.000 description 2
• DTRRFSMNAUOSAH-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1SCCC2 DTRRFSMNAUOSAH-AWEZNQCLSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• CUVQFHMQHBMFCI-UHFFFAOYSA-N 2,4-dichloro-6,7-dihydrothieno[3,2-d]pyrimidine Chemical compound ClC1=NC(Cl)=NC2=C1SCC2 CUVQFHMQHBMFCI-UHFFFAOYSA-N 0.000 description 2
• IHJDGIDSEZWIQT-UHFFFAOYSA-N 2,4-dichloro-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidine Chemical compound C1SCCC2=NC(Cl)=NC(Cl)=C21 IHJDGIDSEZWIQT-UHFFFAOYSA-N 0.000 description 2
• HIKOVOQFJFSCLL-UHFFFAOYSA-N 2,4-dichloro-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidine Chemical compound S1CCCC2=NC(Cl)=NC(Cl)=C21 HIKOVOQFJFSCLL-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
• IKZZIXLWWGDBDW-UHFFFAOYSA-N 2-ethylsulfanyl-1,6,7,8-tetrahydrothiopyrano[3,2-d]pyrimidin-4-one Chemical compound C1CCSC2=C1N=C(SCC)NC2=O IKZZIXLWWGDBDW-UHFFFAOYSA-N 0.000 description 2
• LYRFRAGJINNJEF-UHFFFAOYSA-N 2-ethylsulfanyl-5,7-dihydro-1h-thieno[3,4-d]pyrimidin-4-one Chemical compound O=C1NC(SCC)=NC2=C1CSC2 LYRFRAGJINNJEF-UHFFFAOYSA-N 0.000 description 2
• PZMPSMFQNROOBG-UHFFFAOYSA-N 2-ethylsulfanyl-5-methyl-5,7-dihydro-1h-thieno[3,4-d]pyrimidin-4-one Chemical compound O=C1NC(SCC)=NC2=C1C(C)SC2 PZMPSMFQNROOBG-UHFFFAOYSA-N 0.000 description 2
• NKXZQPOEBJNDKL-UHFFFAOYSA-N 2-ethylsulfanyl-6,7-dihydro-1h-thieno[3,2-d]pyrimidin-4-one Chemical compound OC1=NC(SCC)=NC2=C1SCC2 NKXZQPOEBJNDKL-UHFFFAOYSA-N 0.000 description 2
• SOXJPKLYDSRGKF-UHFFFAOYSA-N 2-ethylsulfanyl-7-methyl-5,7-dihydro-1h-thieno[3,4-d]pyrimidin-4-one Chemical compound O=C1NC(SCC)=NC2=C1CSC2C SOXJPKLYDSRGKF-UHFFFAOYSA-N 0.000 description 2
• ZGNMHODMGHFTBY-UHFFFAOYSA-N 2H-chromene 4-phenylmorpholine Chemical compound O1CC=CC2=CC=CC=C12.C1(=CC=CC=C1)N1CCOCC1 ZGNMHODMGHFTBY-UHFFFAOYSA-N 0.000 description 2
• XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 2
• OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
• IJPJTZKMCHONTH-UHFFFAOYSA-N 6,7-dihydro-1h-thieno[3,2-d]pyrimidine-2,4-dione Chemical compound OC1=NC(O)=NC2=C1SCC2 IJPJTZKMCHONTH-UHFFFAOYSA-N 0.000 description 2
• UITKTMAKCLVHMR-UHFFFAOYSA-N 7-methyl-5,7-dihydro-1h-thieno[3,4-d]pyrimidine-2,4-dione Chemical compound N1C(=O)NC(=O)C2=C1C(C)SC2 UITKTMAKCLVHMR-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 201000007815 Bannayan-Riley-Ruvalcaba syndrome Diseases 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
• XRLUXDBFVNBOKA-JAMMHHFISA-N C[C@H]1COCCN1C2=NC(=NC3=C2C(SC3)C)Cl Chemical compound C[C@H]1COCCN1C2=NC(=NC3=C2C(SC3)C)Cl XRLUXDBFVNBOKA-JAMMHHFISA-N 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
• 108010036949 Cyclosporine Proteins 0.000 description 2
• RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 2
• 206010014733 Endometrial cancer Diseases 0.000 description 2
• 206010014759 Endometrial neoplasm Diseases 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 230000005526 G1 to G0 transition Effects 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 208000023105 Huntington disease Diseases 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 206010022489 Insulin Resistance Diseases 0.000 description 2
• 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 2
• 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
• 102000046985 LST8 Homolog mTOR Associated Human genes 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 102000007474 Multiprotein Complexes Human genes 0.000 description 2
• 108010085220 Multiprotein Complexes Proteins 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• 208000003019 Neurofibromatosis 1 Diseases 0.000 description 2
• 239000000020 Nitrocellulose Substances 0.000 description 2
• 208000008589 Obesity Diseases 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 2
• 101710093328 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 108010034782 Ribosomal Protein S6 Kinases Proteins 0.000 description 2
• 102000009738 Ribosomal Protein S6 Kinases Human genes 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• 101710115678 Target of rapamycin complex subunit LST8 Proteins 0.000 description 2
• 208000026911 Tuberous sclerosis complex Diseases 0.000 description 2
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
• 235000011054 acetic acid Nutrition 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• 230000002776 aggregation Effects 0.000 description 2
• 238000004220 aggregation Methods 0.000 description 2
• 229960004238 anakinra Drugs 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 230000000692 anti-sense effect Effects 0.000 description 2
• 239000003146 anticoagulant agent Substances 0.000 description 2
• 229940127219 anticoagulant drug Drugs 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 210000004957 autophagosome Anatomy 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 210000001715 carotid artery Anatomy 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 229960001265 ciclosporin Drugs 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 229940125782 compound 2 Drugs 0.000 description 2
• 229940126214 compound 3 Drugs 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 238000007405 data analysis Methods 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 125000003963 dichloro group Chemical group Cl* 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
• 238000004821 distillation Methods 0.000 description 2
• 238000009509 drug development Methods 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 229960001433 erlotinib Drugs 0.000 description 2
• 239000003797 essential amino acid Substances 0.000 description 2
• 235000020776 essential amino acid Nutrition 0.000 description 2
• QPDMNTQYPRWOES-UHFFFAOYSA-N ethyl 2-(3-methoxy-3-oxopropyl)sulfanylpropanoate Chemical compound CCOC(=O)C(C)SCCC(=O)OC QPDMNTQYPRWOES-UHFFFAOYSA-N 0.000 description 2
• VCOKLWJRNMSWPY-UHFFFAOYSA-N ethyl 3-oxothiane-2-carboxylate Chemical compound CCOC(=O)C1SCCCC1=O VCOKLWJRNMSWPY-UHFFFAOYSA-N 0.000 description 2
• QAUACNHILIEKFW-UHFFFAOYSA-N ethyl 4-(2-ethoxy-2-oxoethyl)sulfanylbutanoate Chemical compound CCOC(=O)CCCSCC(=O)OCC QAUACNHILIEKFW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 238000002474 experimental method Methods 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 235000013305 food Nutrition 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 229960002584 gefitinib Drugs 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 238000001415 gene therapy Methods 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 208000035474 group of disease Diseases 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 229960002897 heparin Drugs 0.000 description 2
• 229920000669 heparin Polymers 0.000 description 2
• 208000024697 human cytomegalovirus infection Diseases 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• 230000001969 hypertrophic effect Effects 0.000 description 2
• 210000002865 immune cell Anatomy 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 230000004054 inflammatory process 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
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 229940043355 kinase inhibitor Drugs 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 238000012417 linear regression Methods 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 210000003712 lysosome Anatomy 0.000 description 2
• 230000001868 lysosomic effect Effects 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• 230000037353 metabolic pathway Effects 0.000 description 2
• 229960000485 methotrexate Drugs 0.000 description 2
• MCVVUJPXSBQTRZ-ONEGZZNKSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C MCVVUJPXSBQTRZ-ONEGZZNKSA-N 0.000 description 2
• LSVMAPATPCAFTF-UHFFFAOYSA-N methyl 2-methyl-4-oxothiolane-3-carboxylate Chemical compound COC(=O)C1C(C)SCC1=O LSVMAPATPCAFTF-UHFFFAOYSA-N 0.000 description 2
• DJTWZCMETVXNSK-UHFFFAOYSA-N methyl 3-(2-methoxy-2-oxoethyl)sulfanylbutanoate Chemical compound COC(=O)CSC(C)CC(=O)OC DJTWZCMETVXNSK-UHFFFAOYSA-N 0.000 description 2
• OBJGTGYIKSEYBA-UHFFFAOYSA-N methyl 3-oxothiane-4-carboxylate Chemical compound COC(=O)C1CCSCC1=O OBJGTGYIKSEYBA-UHFFFAOYSA-N 0.000 description 2
• LEAKUJFYXNILRB-UHFFFAOYSA-N methyl 4-oxothiolane-3-carboxylate Chemical compound COC(=O)C1CSCC1=O LEAKUJFYXNILRB-UHFFFAOYSA-N 0.000 description 2
• HLNPATHSTGXZRT-UHFFFAOYSA-N methyl 5-methyl-4-oxothiolane-3-carboxylate Chemical compound COC(=O)C1CSC(C)C1=O HLNPATHSTGXZRT-UHFFFAOYSA-N 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 229920001220 nitrocellulos Polymers 0.000 description 2
• 125000006574 non-aromatic ring group Chemical group 0.000 description 2
• 235000015097 nutrients Nutrition 0.000 description 2
• 235000020824 obesity Nutrition 0.000 description 2
• 210000003463 organelle Anatomy 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 239000008177 pharmaceutical agent Substances 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
• 230000036470 plasma concentration Effects 0.000 description 2
• 229920001993 poloxamer 188 Polymers 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 229920000136 polysorbate Polymers 0.000 description 2
• 238000000634 powder X-ray diffraction Methods 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
• 230000004224 protection Effects 0.000 description 2
• 238000001243 protein synthesis Methods 0.000 description 2
• 238000011002 quantification Methods 0.000 description 2
• 238000001959 radiotherapy Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 238000005070 sampling Methods 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 238000003419 tautomerization reaction Methods 0.000 description 2
• 238000002411 thermogravimetry Methods 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• AKCRNFFTGXBONI-UHFFFAOYSA-N torin 1 Chemical compound C1CN(C(=O)CC)CCN1C1=CC=C(N2C(C=CC3=C2C2=CC(=CC=C2N=C3)C=2C=C3C=CC=CC3=NC=2)=O)C=C1C(F)(F)F AKCRNFFTGXBONI-UHFFFAOYSA-N 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
• UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 229950000578 vatalanib Drugs 0.000 description 2
• YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 229960003048 vinblastine Drugs 0.000 description 2
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
• RJNRORZRFGUAKL-ADMBVFOFSA-N (1r)-1-[(3ar,5r,6s,6ar)-6-[3-(dimethylamino)propoxy]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethane-1,2-diol;hydrochloride Chemical compound Cl.O1C(C)(C)O[C@@H]2[C@@H](OCCCN(C)C)[C@@H]([C@H](O)CO)O[C@@H]21 RJNRORZRFGUAKL-ADMBVFOFSA-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
• LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• NENLYAQPNATJSU-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline Chemical compound C1NCCC2CCCCC21 NENLYAQPNATJSU-UHFFFAOYSA-N 0.000 description 1
• POTIYWUALSJREP-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a-decahydroquinoline Chemical compound N1CCCC2CCCCC21 POTIYWUALSJREP-UHFFFAOYSA-N 0.000 description 1
• UUZJJNBYJDFQHL-UHFFFAOYSA-N 1,2,3-triazolidine Chemical compound C1CNNN1 UUZJJNBYJDFQHL-UHFFFAOYSA-N 0.000 description 1
• CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
• KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
• IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 1
• IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
• KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 1
• DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 1
• ZDQYTKONHYFZQR-NFOMZHRRSA-N 1-cyclopropyl-3-[4-[5,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C=12C(C)S(=O)(=O)C(C)C2=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC=1N1CCOC[C@@H]1C ZDQYTKONHYFZQR-NFOMZHRRSA-N 0.000 description 1
• BYHDTZHNPIWVOP-UHFFFAOYSA-N 1-ethyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1B1OC(C)(C)C(C)(C)O1 BYHDTZHNPIWVOP-UHFFFAOYSA-N 0.000 description 1
• ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• GOSBUVMCOAWATC-UHFFFAOYSA-N 2-(sulfanylmethyl)butanoic acid Chemical compound CCC(CS)C(O)=O GOSBUVMCOAWATC-UHFFFAOYSA-N 0.000 description 1
• OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
• YMZZPMVKABUEBL-UHFFFAOYSA-N 2-methylthiolan-3-one Chemical compound CC1SCCC1=O YMZZPMVKABUEBL-UHFFFAOYSA-N 0.000 description 1
• WYKHSBAVLOPISI-UHFFFAOYSA-N 2-phenyl-1,3-thiazole Chemical compound C1=CSC(C=2C=CC=CC=2)=N1 WYKHSBAVLOPISI-UHFFFAOYSA-N 0.000 description 1
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
• WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
• SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 description 1
• 102100033714 40S ribosomal protein S6 Human genes 0.000 description 1
• KYMPMRNVUJEWSV-UHFFFAOYSA-N 5-methyl-5,7-dihydro-1h-thieno[3,4-d]pyrimidine-2,4-dione Chemical compound N1C(=O)NC(=O)C2=C1CSC2C KYMPMRNVUJEWSV-UHFFFAOYSA-N 0.000 description 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
• 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 1
• DGGKXQQCVPAUEA-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCC1N2 DGGKXQQCVPAUEA-UHFFFAOYSA-N 0.000 description 1
• 230000035502 ADME Effects 0.000 description 1
• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 102000007469 Actins Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 1
• 230000007730 Akt signaling Effects 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
• 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
• 102000009075 Angiopoietin-2 Human genes 0.000 description 1
• 108010048036 Angiopoietin-2 Proteins 0.000 description 1
• 102000012936 Angiostatins Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• 102000006306 Antigen Receptors Human genes 0.000 description 1
• 108010083359 Antigen Receptors Proteins 0.000 description 1
• BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• XHVAWZZCDCWGBK-WYRLRVFGSA-M Aurothioglucose Chemical compound OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O XHVAWZZCDCWGBK-WYRLRVFGSA-M 0.000 description 1
• 230000003844 B-cell-activation Effects 0.000 description 1
• 102000052609 BRCA2 Human genes 0.000 description 1
• 108700020462 BRCA2 Proteins 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 101150008921 Brca2 gene Proteins 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• 208000026310 Breast neoplasm Diseases 0.000 description 1
• 108010037003 Buserelin Proteins 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• PAFLVJCKYINXRV-JAMMHHFISA-N C[C@H]1COCCN1C2=NC3=C(C(SC3)C)C(=N2)Cl Chemical compound C[C@H]1COCCN1C2=NC3=C(C(SC3)C)C(=N2)Cl PAFLVJCKYINXRV-JAMMHHFISA-N 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 description 1
• 208000012609 Cowden disease Diseases 0.000 description 1
• 201000002847 Cowden syndrome Diseases 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• 102000000311 Cytosine Deaminase Human genes 0.000 description 1
• 108010080611 Cytosine Deaminase Proteins 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 108010092160 Dactinomycin Proteins 0.000 description 1
• WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 208000016192 Demyelinating disease Diseases 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• 206010048768 Dermatosis Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• NTURVSFTOYPGON-UHFFFAOYSA-N Dihydroquinazoline Chemical compound C1=CC=C2C=NCNC2=C1 NTURVSFTOYPGON-UHFFFAOYSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
• 102000013138 Drug Receptors Human genes 0.000 description 1
• 108010065556 Drug Receptors Proteins 0.000 description 1
• 102000001301 EGF receptor Human genes 0.000 description 1
• 108060006698 EGF receptor Proteins 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 238000012286 ELISA Assay Methods 0.000 description 1
• 241000305071 Enterobacterales Species 0.000 description 1
• 102400001368 Epidermal growth factor Human genes 0.000 description 1
• 101800003838 Epidermal growth factor Proteins 0.000 description 1
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
• 108010008165 Etanercept Proteins 0.000 description 1
• CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
• 102100022466 Eukaryotic translation initiation factor 4E-binding protein 1 Human genes 0.000 description 1
• 108050000946 Eukaryotic translation initiation factor 4E-binding protein 1 Proteins 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 208000031448 Genomic Instability Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
• 108010069236 Goserelin Proteins 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 102100031561 Hamartin Human genes 0.000 description 1
• 208000002927 Hamartoma Diseases 0.000 description 1
• 239000012981 Hank's balanced salt solution Substances 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 101000656896 Homo sapiens 40S ribosomal protein S6 Proteins 0.000 description 1
• 101000795643 Homo sapiens Hamartin Proteins 0.000 description 1
• 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 101000623857 Homo sapiens Serine/threonine-protein kinase mTOR Proteins 0.000 description 1
• 101000795659 Homo sapiens Tuberin Proteins 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 102000016252 Huntingtin Human genes 0.000 description 1
• 108050004784 Huntingtin Proteins 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 1
• 108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 1
• 101150106931 IFNG gene Proteins 0.000 description 1
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
• JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 102000003746 Insulin Receptor Human genes 0.000 description 1
• 108010001127 Insulin Receptor Proteins 0.000 description 1
• 108010047852 Integrin alphaVbeta3 Proteins 0.000 description 1
• 102000003996 Interferon-beta Human genes 0.000 description 1
• 108090000467 Interferon-beta Proteins 0.000 description 1
• 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
• 102000003815 Interleukin-11 Human genes 0.000 description 1
• 108090000177 Interleukin-11 Proteins 0.000 description 1
• 102100030694 Interleukin-11 Human genes 0.000 description 1
• 102000004388 Interleukin-4 Human genes 0.000 description 1
• 108090000978 Interleukin-4 Proteins 0.000 description 1
• 241000764238 Isis Species 0.000 description 1
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
• 102000001399 Kallikrein Human genes 0.000 description 1
• 108060005987 Kallikrein Proteins 0.000 description 1
• 206010023439 Kidney transplant rejection Diseases 0.000 description 1
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
• 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
• 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
• DAQAKHDKYAWHCG-UHFFFAOYSA-N Lactacystin Natural products CC(=O)NC(C(O)=O)CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O DAQAKHDKYAWHCG-UHFFFAOYSA-N 0.000 description 1
• 108010000817 Leuprolide Proteins 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 108700041567 MDR Genes Proteins 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
• 101150097381 Mtor gene Proteins 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 101100087591 Mus musculus Rictor gene Proteins 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 102000008300 Mutant Proteins Human genes 0.000 description 1
• 108010021466 Mutant Proteins Proteins 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
• 208000009905 Neurofibromatoses Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 102000004459 Nitroreductase Human genes 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 101710111747 Peptidyl-prolyl cis-trans isomerase FKBP12 Proteins 0.000 description 1
• 102100036056 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Human genes 0.000 description 1
• 101710204747 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Proteins 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
• 208000012287 Prolapse Diseases 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
• 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
• 229940079156 Proteasome inhibitor Drugs 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 241000588769 Proteus <enterobacteria> Species 0.000 description 1
• 208000007531 Proteus syndrome Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 238000001237 Raman spectrum Methods 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 208000025747 Rheumatic disease Diseases 0.000 description 1
• 102000002278 Ribosomal Proteins Human genes 0.000 description 1
• 108010000605 Ribosomal Proteins Proteins 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 102000001332 SRC Human genes 0.000 description 1
• 108060006706 SRC Proteins 0.000 description 1
• WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 101710181599 Serine/threonine-protein kinase STK11 Proteins 0.000 description 1
• 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 101150044628 Sin1 gene Proteins 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 230000017274 T cell anergy Effects 0.000 description 1
• 230000006052 T cell proliferation Effects 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 102000006601 Thymidine Kinase Human genes 0.000 description 1
• 108020004440 Thymidine kinase Proteins 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 102100031638 Tuberin Human genes 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000044159 Ubiquitin Human genes 0.000 description 1
• 108090000848 Ubiquitin Proteins 0.000 description 1
• 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
• 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• JOOSFXXMIOXKAZ-UHFFFAOYSA-H [Au+3].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O Chemical compound [Au+3].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O JOOSFXXMIOXKAZ-UHFFFAOYSA-H 0.000 description 1
• 229960003697 abatacept Drugs 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 229960002964 adalimumab Drugs 0.000 description 1
• TTWYZDPBDWHJOR-IDIVVRGQSA-L adenosine triphosphate disodium Chemical compound [Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O TTWYZDPBDWHJOR-IDIVVRGQSA-L 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 230000011759 adipose tissue development Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 229940009456 adriamycin Drugs 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000004931 aggregating effect Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
• 229960001220 amsacrine Drugs 0.000 description 1
• 229960002932 anastrozole Drugs 0.000 description 1
• YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 230000003466 anti-cipated effect Effects 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 230000003432 anti-folate effect Effects 0.000 description 1
• 230000002942 anti-growth Effects 0.000 description 1
• 230000001740 anti-invasion Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 230000003356 anti-rheumatic effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940127074 antifolate Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 239000003435 antirheumatic agent Substances 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000003886 aromatase inhibitor Substances 0.000 description 1
• 229940046844 aromatase inhibitors Drugs 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
• AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 1
• 229960005207 auranofin Drugs 0.000 description 1
• 229960001799 aurothioglucose Drugs 0.000 description 1
• 229940120638 avastin Drugs 0.000 description 1
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• 229960000397 bevacizumab Drugs 0.000 description 1
• 229960000997 bicalutamide Drugs 0.000 description 1
• 230000002457 bidirectional effect Effects 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 238000009534 blood test Methods 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 238000010322 bone marrow transplantation Methods 0.000 description 1
• 230000008993 bowel inflammation Effects 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
• CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 1
• 229960002719 buserelin Drugs 0.000 description 1
• 229960002092 busulfan Drugs 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 229950002826 canertinib Drugs 0.000 description 1
• 229960000623 carbamazepine Drugs 0.000 description 1
• FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 229960002412 cediranib Drugs 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000005779 cell damage Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000032823 cell division Effects 0.000 description 1
• 208000037887 cell injury Diseases 0.000 description 1
• 230000006037 cell lysis Effects 0.000 description 1
• 230000009087 cell motility Effects 0.000 description 1
• 230000019522 cellular metabolic process Effects 0.000 description 1
• 230000007541 cellular toxicity Effects 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 229960005395 cetuximab Drugs 0.000 description 1
• OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 1
• DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 235000019693 cherries Nutrition 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 238000011284 combination treatment Methods 0.000 description 1
• 229940046044 combinations of antineoplastic agent Drugs 0.000 description 1
• 229960005537 combretastatin A-4 Drugs 0.000 description 1
• HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 description 1
• 230000000536 complexating effect Effects 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 230000006552 constitutive activation Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 238000007887 coronary angioplasty Methods 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 239000002254 cytotoxic agent Substances 0.000 description 1
• 231100000599 cytotoxic agent Toxicity 0.000 description 1
• 229960000640 dactinomycin Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 230000008021 deposition Effects 0.000 description 1
• 210000004207 dermis Anatomy 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• 238000000113 differential scanning calorimetry Methods 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 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
• 230000006806 disease prevention Effects 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000002612 dispersion medium Substances 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 230000006739 dopaminergic cell death Effects 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 229950004203 droloxifene Drugs 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 210000001513 elbow Anatomy 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
• 201000003914 endometrial carcinoma Diseases 0.000 description 1
• 150000002085 enols Chemical group 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229940116977 epidermal growth factor Drugs 0.000 description 1
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 230000008995 epigenetic change Effects 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• 102000015694 estrogen receptors Human genes 0.000 description 1
• 108010038795 estrogen receptors Proteins 0.000 description 1
• 229960000403 etanercept Drugs 0.000 description 1
• HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 1
• ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
• PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 description 1
• OPXNFHAILOHHFO-UHFFFAOYSA-N ethyl 4-chlorobutanoate Chemical compound CCOC(=O)CCCCl OPXNFHAILOHHFO-UHFFFAOYSA-N 0.000 description 1
• OIVSLWMZGJLGKG-UHFFFAOYSA-N ethylthiourea;hydrobromide Chemical compound Br.CCNC(S)=N OIVSLWMZGJLGKG-UHFFFAOYSA-N 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 229960000255 exemestane Drugs 0.000 description 1
• 239000010685 fatty oil Substances 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
• 229960004039 finasteride Drugs 0.000 description 1
• 235000013312 flour Nutrition 0.000 description 1
• 238000002376 fluorescence recovery after photobleaching Methods 0.000 description 1
• 150000005699 fluoropyrimidines Chemical class 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
• 229960002074 flutamide Drugs 0.000 description 1
• 239000004052 folic acid antagonist Substances 0.000 description 1
• 229960002258 fulvestrant Drugs 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 239000000174 gluconic acid Substances 0.000 description 1
• 235000012208 gluconic acid Nutrition 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
• XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
• 229960002913 goserelin Drugs 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 239000000122 growth hormone Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• 229940022353 herceptin Drugs 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 230000001697 htt accumulation Effects 0.000 description 1
• 210000003917 human chromosome Anatomy 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 229960001330 hydroxycarbamide Drugs 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 229960000908 idarubicin Drugs 0.000 description 1
• 210000003405 ileum Anatomy 0.000 description 1
• 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
• 229960002411 imatinib Drugs 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 239000012133 immunoprecipitate Substances 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 230000001024 immunotherapeutic effect Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 229940060367 inert ingredients Drugs 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 229960000598 infliximab Drugs 0.000 description 1
• 238000003331 infrared imaging Methods 0.000 description 1
• 238000012739 integrated shape imaging system Methods 0.000 description 1
• 229940074383 interleukin-11 Drugs 0.000 description 1
• 229940028885 interleukin-4 Drugs 0.000 description 1
• 239000000543 intermediate Substances 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• 210000004731 jugular vein Anatomy 0.000 description 1
• 210000002510 keratinocyte Anatomy 0.000 description 1
• 206010023332 keratitis Diseases 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 210000003127 knee Anatomy 0.000 description 1
• DAQAKHDKYAWHCG-RWTHQLGUSA-N lactacystin Chemical compound CC(=O)N[C@H](C(O)=O)CSC(=O)[C@]1([C@@H](O)C(C)C)NC(=O)[C@H](C)[C@@H]1O DAQAKHDKYAWHCG-RWTHQLGUSA-N 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960004891 lapatinib Drugs 0.000 description 1
• BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
• 210000002414 leg Anatomy 0.000 description 1
• 229960003881 letrozole Drugs 0.000 description 1
• HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
• 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
• GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
• 229960004338 leuprorelin Drugs 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical class 0.000 description 1
• 210000005229 liver cell Anatomy 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 229940123729 mTOR kinase inhibitor Drugs 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 235000014380 magnesium carbonate Nutrition 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 101150010039 mapkap1 gene Proteins 0.000 description 1
• 229950008959 marimastat Drugs 0.000 description 1
• OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
• 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229960004296 megestrol acetate Drugs 0.000 description 1
• RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 230000006679 metabolic signaling pathway Effects 0.000 description 1
• 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 229950000844 mizoribine Drugs 0.000 description 1
• 230000003020 moisturizing effect Effects 0.000 description 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000004400 mucous membrane Anatomy 0.000 description 1
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 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
• JTSLALYXYSRPGW-UHFFFAOYSA-N n-[5-(4-cyanophenyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=C(C#N)C=C1 JTSLALYXYSRPGW-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
• 201000004931 neurofibromatosis Diseases 0.000 description 1
• 239000000712 neurohormone Substances 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 108020001162 nitroreductase Proteins 0.000 description 1
• 239000002777 nucleoside Substances 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 108010046821 oprelvekin Proteins 0.000 description 1
• 229960001840 oprelvekin Drugs 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
• 239000006179 pH buffering agent Substances 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 230000000865 phosphorylative effect Effects 0.000 description 1
• USRGIUJOYOXOQJ-GBXIJSLDSA-N phosphothreonine Chemical compound OP(=O)(O)O[C@H](C)[C@H](N)C(O)=O USRGIUJOYOXOQJ-GBXIJSLDSA-N 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 229940044519 poloxamer 188 Drugs 0.000 description 1
• 208000030428 polyarticular arthritis Diseases 0.000 description 1
• 239000004417 polycarbonate Substances 0.000 description 1
• 229920000515 polycarbonate Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 210000000229 preadipocyte Anatomy 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 239000000583 progesterone congener Substances 0.000 description 1
• 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 229960003712 propranolol Drugs 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 239000003207 proteasome inhibitor Substances 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 229940076372 protein antagonist Drugs 0.000 description 1
• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
• 239000003531 protein hydrolysate Substances 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
• 229960004432 raltitrexed Drugs 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 238000004064 recycling Methods 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 230000003362 replicative effect Effects 0.000 description 1
• MYFATKRONKHHQL-UHFFFAOYSA-N rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C2C=CC(=[NH2+])C=C2OC2=CC(N)=CC=C21 MYFATKRONKHHQL-UHFFFAOYSA-N 0.000 description 1
• 210000003705 ribosome Anatomy 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• 229960003522 roquinimex Drugs 0.000 description 1
• 102220197955 rs1057519777 Human genes 0.000 description 1
• 102200163423 rs587777894 Human genes 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
• 229960004889 salicylic acid Drugs 0.000 description 1
• 239000012723 sample buffer Substances 0.000 description 1
• OUKYUETWWIPKQR-UHFFFAOYSA-N saracatinib Chemical compound C1CN(C)CCN1CCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 OUKYUETWWIPKQR-UHFFFAOYSA-N 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 210000004761 scalp Anatomy 0.000 description 1
• 230000007017 scission Effects 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
• 238000000926 separation method Methods 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 230000008054 signal transmission Effects 0.000 description 1
• 230000007781 signaling event Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 210000002363 skeletal muscle cell Anatomy 0.000 description 1
• 235000020183 skimmed milk Nutrition 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• IVDHYUQIDRJSTI-UHFFFAOYSA-N sorafenib tosylate Chemical compound [H+].CC1=CC=C(S([O-])(=O)=O)C=C1.C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 IVDHYUQIDRJSTI-UHFFFAOYSA-N 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 238000012453 sprague-dawley rat model Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
• HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
• 229960001796 sunitinib Drugs 0.000 description 1
• WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 210000001258 synovial membrane Anatomy 0.000 description 1
• 238000003786 synthesis reaction Methods 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
• 229960001603 tamoxifen Drugs 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 229940063683 taxotere Drugs 0.000 description 1
• WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
• 229960001674 tegafur Drugs 0.000 description 1
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• ZYXWYDDFNXBTFO-UHFFFAOYSA-N tetrazolidine Chemical compound C1NNNN1 ZYXWYDDFNXBTFO-UHFFFAOYSA-N 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• KQWHKLZRDFJOCN-UHFFFAOYSA-N thieno[3,4-d]pyrimidine Chemical compound N1=CN=CC2=CSC=C21 KQWHKLZRDFJOCN-UHFFFAOYSA-N 0.000 description 1
• XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• 229960005026 toremifene Drugs 0.000 description 1
• XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 229960000575 trastuzumab Drugs 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 150000003918 triazines Chemical class 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 102000003390 tumor necrosis factor Human genes 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
• 230000004222 uncontrolled growth Effects 0.000 description 1
• 208000025086 undetermined colitis Diseases 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
• 229960000241 vandetanib Drugs 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
• 229960004355 vindesine Drugs 0.000 description 1
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 229910000166 zirconium phosphate Inorganic materials 0.000 description 1