ES2925450T3 - Compuestos de isofuranona útiles como inhibidores de HPK1 - Google Patents

Info

Publication number

ES2925450T3

ES2925450T3 ES18808167T ES18808167T ES2925450T3 ES 2925450 T3 ES2925450 T3 ES 2925450T3 ES 18808167 T ES18808167 T ES 18808167T ES 18808167 T ES18808167 T ES 18808167T ES 2925450 T3 ES2925450 T3 ES 2925450T3

Authority

ES

Spain

Prior art keywords

amino

hydroxy

dimethyl

dihydro

benzofuran

Prior art date

2017-11-06

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 271
• 102100028199 Mitogen-activated protein kinase kinase kinase kinase 1 Human genes 0.000 title abstract description 48
• 239000003112 inhibitor Substances 0.000 title description 18
• 101001059991 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 1 Proteins 0.000 title 1
• 150000003839 salts Chemical class 0.000 claims abstract description 81
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 38
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 201000011510 cancer Diseases 0.000 claims abstract description 20
• 208000036142 Viral infection Diseases 0.000 claims abstract description 11
• 230000009385 viral infection Effects 0.000 claims abstract description 11
• -1 1,8-dioxa-3-azaspiro[4.5]decenyl Chemical group 0.000 claims description 293
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 157
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 77
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 59
• 125000004076 pyridyl group Chemical group 0.000 claims description 48
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
• 125000002757 morpholinyl group Chemical group 0.000 claims description 38
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 26
• YAPIPGOLZSTISM-HXUWFJFHSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 YAPIPGOLZSTISM-HXUWFJFHSA-N 0.000 claims description 25
• 125000000217 alkyl group Chemical group 0.000 claims description 22
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
• 239000003937 drug carrier Substances 0.000 claims description 18
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 18
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 14
• 125000000335 thiazolyl group Chemical group 0.000 claims description 14
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
• NHZPDPUNWKMEOR-GOSISDBHSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carbohydrazide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NN)C=C12 NHZPDPUNWKMEOR-GOSISDBHSA-N 0.000 claims description 13
• 125000004432 carbon atom Chemical group C* 0.000 claims description 13
• 125000004122 cyclic group Chemical group 0.000 claims description 13
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 13
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 229910052731 fluorine Inorganic materials 0.000 claims description 12
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 11
• 125000002883 imidazolyl group Chemical group 0.000 claims description 11
• 201000001441 melanoma Diseases 0.000 claims description 11
• 125000003386 piperidinyl group Chemical group 0.000 claims description 11
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 11
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 11
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
• 125000000623 heterocyclic group Chemical group 0.000 claims description 10
• RQIPJVOZKMTHHP-HSZRJFAPSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N'-(pyridine-3-carbonyl)pyrimidine-5-carbohydrazide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NNC(=O)C3=CC=CN=C3)C=C12 RQIPJVOZKMTHHP-HSZRJFAPSA-N 0.000 claims description 9
• VEGNUCOGHZSZJO-HSZRJFAPSA-N 2-[[5-[3-(1-azabicyclo[2.2.2]octan-4-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridin-2-yl]amino]-7,7-dimethylfuro[3,4-b]pyridin-5-one Chemical compound C1(C2=NC(=CC=C2C(=O)O1)NC1=CC(=C(C=N1)C=1ON=C(N=1)C12CCN(CC1)CC2)N[C@@H](C1=CC=CC=C1)CO)(C)C VEGNUCOGHZSZJO-HSZRJFAPSA-N 0.000 claims description 9
• 239000002246 antineoplastic agent Substances 0.000 claims description 9
• 229940127089 cytotoxic agent Drugs 0.000 claims description 9
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 8
• HFTLJZNCUOJIMQ-GOSISDBHSA-N 5-[2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-5-yl]-3H-1,3,4-oxadiazol-2-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NNC(=O)O3)C=C12 HFTLJZNCUOJIMQ-GOSISDBHSA-N 0.000 claims description 8
• 239000002253 acid Substances 0.000 claims description 8
• 239000003443 antiviral agent Substances 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 8
• 125000006399 methylpyrazinyl group Chemical group 0.000 claims description 8
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
• 125000003944 tolyl group Chemical group 0.000 claims description 8
• OSVNBQOEGZKTGJ-ICCFGIFFSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N'-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl)pyrimidine-5-carbohydrazide Chemical compound CC1(OC(C2=C1C=C(C=C2)NC1=NC=C(C(=N1)N[C@H](CO)C1=CC=CC=C1)C(=O)NNC(C(C(F)(F)F)(C)O)=O)=O)C OSVNBQOEGZKTGJ-ICCFGIFFSA-N 0.000 claims description 7
• HZOALEGJSTVQMD-COTLDPOVSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-(1-phenylethyl)pyrimidine-5-carboxamide Chemical compound C1(=CC2=C(C=C1)C(=O)OC2(C)C)NC1=NC(=C(C(=O)NC(C2=CC=CC=C2)C)C=N1)N[C@@H](C1=CC=CC=C1)CO HZOALEGJSTVQMD-COTLDPOVSA-N 0.000 claims description 7
• IXUJZIJFNHWYOH-OAQYLSRUSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-(2-methoxyethyl)pyrimidine-5-carboxamide Chemical compound COCCNC(=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 IXUJZIJFNHWYOH-OAQYLSRUSA-N 0.000 claims description 7
• MBSIHNFLFBUXKU-JOCHJYFZSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-(2-methylpropyl)pyrimidine-5-carboxamide Chemical compound C1(C2=CC(NC3=NC(=C(C=N3)C(=O)NCC(C)C)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C MBSIHNFLFBUXKU-JOCHJYFZSA-N 0.000 claims description 7
• ZEKJGMBDVLBKHB-XMMPIXPASA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-(3-imidazol-1-ylpropyl)pyrimidine-5-carboxamide Chemical compound C1(C2=CC(NC3=NC(=C(C(=O)NCCCN4C=CN=C4)C=N3)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C ZEKJGMBDVLBKHB-XMMPIXPASA-N 0.000 claims description 7
• ZPBZQVPSDFGNPX-XMMPIXPASA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-[(5-methylpyrazin-2-yl)methyl]pyrimidine-5-carboxamide Chemical compound C1(=CC2=C(C=C1)C(=O)OC2(C)C)NC1=NC(=C(C=N1)C(=O)NCC1=NC=C(C)N=C1)N[C@@H](C1=CC=CC=C1)CO ZPBZQVPSDFGNPX-XMMPIXPASA-N 0.000 claims description 7
• LQECULGJNPIMIR-OAQYLSRUSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-prop-2-ynylpyrimidine-5-carboxamide Chemical compound C1=2C(OC(=O)C=2C=CC(=C1)NC1=NC(=C(C(=O)NCC#C)C=N1)N[C@@H](C1=CC=CC=C1)CO)(C)C LQECULGJNPIMIR-OAQYLSRUSA-N 0.000 claims description 7
• JBGWDRMZKMTPOT-OAQYLSRUSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-propylpyrimidine-5-carboxamide Chemical compound CC1(OC(C2=C1C=C(C=C2)NC1=NC=C(C(=N1)N[C@H](CO)C1=CC=CC=C1)C(=O)NCCC)=O)C JBGWDRMZKMTPOT-OAQYLSRUSA-N 0.000 claims description 7
• MIKDINVGJQDSKP-OOWIMERYSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-N-[[(3R)-3-hydroxy-1-azabicyclo[2.2.2]octan-3-yl]methyl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound C1(C2=C(C=CC(NC3=NC(=C(C=N3)C(=O)NC[C@@]3(C4CCN(CC4)C3)O)N[C@@H](C3=CC=CC=C3)CO)=C2)C(=O)O1)(C)C MIKDINVGJQDSKP-OOWIMERYSA-N 0.000 claims description 7
• DZIXRHJRLCGYPK-HXUWFJFHSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-N-ethyl-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound CCNC(=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 DZIXRHJRLCGYPK-HXUWFJFHSA-N 0.000 claims description 7
• PMLBTWFXEOLUGL-UHFFFAOYSA-N 2-[[5-[3-(1-azabicyclo[2.2.2]octan-4-yl)-1,2,4-oxadiazol-5-yl]-4-(1,3-thiazol-2-ylmethylamino)pyridin-2-yl]amino]-7,7-dimethylfuro[3,4-b]pyridin-5-one Chemical compound N12CCC(CC1)(CC2)C1=NOC(=N1)C=1C(=CC(=NC=1)NC1=CC=C2C(=N1)C(OC2=O)(C)C)NCC=1SC=CN=1 PMLBTWFXEOLUGL-UHFFFAOYSA-N 0.000 claims description 7
• MMLAKENCIOFVTM-HSZRJFAPSA-N 2-[[5-[3-(1-azabicyclo[2.2.2]octan-4-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-1-(4-fluorophenyl)-2-hydroxyethyl]amino]pyridin-2-yl]amino]-7,7-dimethylfuro[3,4-b]pyridin-5-one Chemical compound N1=C2C(=CC=C1NC1=NC=C(C=3ON=C(N=3)C34CCN(CC3)CC4)C(N[C@@H](C3=CC=C(F)C=C3)CO)=C1)C(=O)OC2(C)C MMLAKENCIOFVTM-HSZRJFAPSA-N 0.000 claims description 7
• CXAXWJKEINZFDM-JFGZAKSSSA-N 2-[[5-[3-(4-fluoro-1-azabicyclo[2.2.2]octan-3-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridin-2-yl]amino]-7,7-dimethylfuro[3,4-b]pyridin-5-one Chemical compound FC12C(CN(CC1)CC2)C1=NOC(=N1)C=1C(=CC(=NC=1)NC1=CC=C2C(=N1)C(OC2=O)(C)C)N[C@H](CO)C1=CC=CC=C1 CXAXWJKEINZFDM-JFGZAKSSSA-N 0.000 claims description 7
• RVSSNRBUPQUIEG-LJQANCHMSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NN=CO3)C=C12 RVSSNRBUPQUIEG-LJQANCHMSA-N 0.000 claims description 7
• WASOUQNAOUGKDE-HSZRJFAPSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3=NC=CC=C3)C=C12 WASOUQNAOUGKDE-HSZRJFAPSA-N 0.000 claims description 7
• DTHDBWPUQXSBEE-HXUWFJFHSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(5-methyl-1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1=NN=C(O1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 DTHDBWPUQXSBEE-HXUWFJFHSA-N 0.000 claims description 7
• ALUASDZMWAZLHB-ICCFGIFFSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-[5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3,4-oxadiazol-2-yl]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound OC[C@H](C1=CC=CC=C1)NC1=NC(=NC=C1C=1OC(=NN=1)C(C(F)(F)F)(C)O)NC1=CC2=C(C(OC2(C)C)=O)C=C1 ALUASDZMWAZLHB-ICCFGIFFSA-N 0.000 claims description 7
• OTCPKWAMZMECHW-HXUWFJFHSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-pyrimidin-2-ylpyrimidin-2-yl]amino]-3H-2-benzofuran-1-one Chemical compound OC[C@@H](NC1=C(C=NC(NC2=CC=C3C(=O)OCC3=C2)=N1)C1=NC=CC=N1)C1=CC=CC=C1 OTCPKWAMZMECHW-HXUWFJFHSA-N 0.000 claims description 7
• GLJGQOCKPYEXEC-JOCHJYFZSA-N 5-[[5-(3-butyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CCCCC1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 GLJGQOCKPYEXEC-JOCHJYFZSA-N 0.000 claims description 7
• LRINILBKXCVIMV-OAQYLSRUSA-N 5-[[5-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound C12=CC(NC3=NC(=C(C=N3)C3=NN=C(O3)C3CC3)N[C@@H](C3=CC=CC=C3)CO)=CC=C1C(=O)OC2(C)C LRINILBKXCVIMV-OAQYLSRUSA-N 0.000 claims description 7
• IASNYPXBJWFRFI-XMMPIXPASA-N 5-[[5-[3-(6-hydroxy-2-methylhexan-2-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC(C)(CCCCO)C1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 IASNYPXBJWFRFI-XMMPIXPASA-N 0.000 claims description 7
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 7
• KPXNVJDRNBAYLW-OAQYLSRUSA-N N'-(cyclopropanecarbonyl)-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carbohydrazide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NNC(=O)C3CC3)C=C12 KPXNVJDRNBAYLW-OAQYLSRUSA-N 0.000 claims description 7
• MPEKFPPMYFPECW-JOCHJYFZSA-N N-[(3,3-difluorocyclobutyl)methyl]-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NCC3CC(F)(F)C3)C=C12 MPEKFPPMYFPECW-JOCHJYFZSA-N 0.000 claims description 7
• QOGREAGLGXUPTP-JOCHJYFZSA-N N-[2-(dimethylamino)ethyl]-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound CN(C)CCNC(=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 QOGREAGLGXUPTP-JOCHJYFZSA-N 0.000 claims description 7
• RWUQSCPXTQZCIS-HSZRJFAPSA-N N-[3-(dimethylamino)propyl]-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound CN(C)CCCNC(=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 RWUQSCPXTQZCIS-HSZRJFAPSA-N 0.000 claims description 7
• RXPCYHHWLZWYGC-RUZDIDTESA-N N-benzyl-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound C1(C2=CC(NC3=NC(=C(C=N3)C(=O)NCC3=CC=CC=C3)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C RXPCYHHWLZWYGC-RUZDIDTESA-N 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 7
• LIDOMNKOZKYOKU-RUZDIDTESA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-(3-morpholin-4-ylpropyl)pyrimidine-5-carboxamide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NCCCN3CCOCC3)C=C12 LIDOMNKOZKYOKU-RUZDIDTESA-N 0.000 claims description 6
• ZXFHMIREGALVLU-XMMPIXPASA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-(pyridin-2-ylmethyl)pyrimidine-5-carboxamide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NCC3=NC=CC=C3)C=C12 ZXFHMIREGALVLU-XMMPIXPASA-N 0.000 claims description 6
• YJYIDHIHAOTJRD-HXUWFJFHSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-N'-(2-hydroxy-2-methylpropanoyl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carbohydrazide Chemical compound CC(C)(O)C(=O)NNC(=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 YJYIDHIHAOTJRD-HXUWFJFHSA-N 0.000 claims description 6
• RCFHZRPZNAZURB-HXUWFJFHSA-N 5-[2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-5-yl]-3-ethyl-1,3,4-oxadiazol-2-one Chemical compound CCN1N=C(OC1=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 RCFHZRPZNAZURB-HXUWFJFHSA-N 0.000 claims description 6
• NOQLRDRQOPJFFA-UHFFFAOYSA-N 5-[[4-[(3-amino-2,2-dimethylpropyl)amino]-5-[3-(oxan-4-yl)-1,2,4-oxadiazol-5-yl]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC(C)(CN)CNC1=C(C=NC(NC2=CC=C3C(=O)OC(C)(C)C3=C2)=N1)C1=NC(=NO1)C1CCOCC1 NOQLRDRQOPJFFA-UHFFFAOYSA-N 0.000 claims description 6
• FLIGDDITJRPVMG-HSZRJFAPSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(5-pyridin-2-yl-1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NN=C(O3)C3=NC=CC=C3)C=C12 FLIGDDITJRPVMG-HSZRJFAPSA-N 0.000 claims description 6
• PKUNLWSYEWDQNN-HXUWFJFHSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-[5-(2-hydroxypropan-2-yl)-1,3,4-oxadiazol-2-yl]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC(C)(O)C1=NN=C(O1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 PKUNLWSYEWDQNN-HXUWFJFHSA-N 0.000 claims description 6
• MAOYZOCGDSXKGJ-UHFFFAOYSA-N 5-[[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-(1H-indazol-5-ylamino)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(NC4=CC5=C(NN=C5)C=C4)=C(C=N3)C3=NC(=NO3)C3CC3)C=C12 MAOYZOCGDSXKGJ-UHFFFAOYSA-N 0.000 claims description 6
• QIHSWWKNUUFDTI-RUZDIDTESA-N CC1(OC(C2=C1C=C(C=C2)NC1=NC=C(C(=N1)N[C@H](CO)C1=CC=CC=C1)C(=O)NNC(NCCCN(C)C)=NCC)=O)C Chemical compound CC1(OC(C2=C1C=C(C=C2)NC1=NC=C(C(=N1)N[C@H](CO)C1=CC=CC=C1)C(=O)NNC(NCCCN(C)C)=NCC)=O)C QIHSWWKNUUFDTI-RUZDIDTESA-N 0.000 claims description 6
• 102000004127 Cytokines Human genes 0.000 claims description 6
• 108090000695 Cytokines Proteins 0.000 claims description 6
• 150000001602 bicycloalkyls Chemical group 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 125000003566 oxetanyl group Chemical group 0.000 claims description 6
• QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
• AFVWZAHAUPRCOI-UHFFFAOYSA-N 5-[[4-(1H-indazol-5-ylamino)-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1=NOC(=N1)C1=C(NC2=CC3=C(NN=C3)C=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 AFVWZAHAUPRCOI-UHFFFAOYSA-N 0.000 claims description 5
• UOGBCNGJNCDZGW-UHFFFAOYSA-N 5-[[4-[[2-(2-hydroxypropan-2-yl)phenyl]methylamino]-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1=NOC(=N1)C1=C(NCC2=C(C=CC=C2)C(C)(C)O)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 UOGBCNGJNCDZGW-UHFFFAOYSA-N 0.000 claims description 5
• XPTBFHPHUGOQQO-HSZRJFAPSA-N 5-[[5-(1,8-dioxa-3-azaspiro[4.5]dec-2-en-2-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound C1(C2=CC(NC3=NC(=C(C=N3)C3=NCC4(O3)CCOCC4)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C XPTBFHPHUGOQQO-HSZRJFAPSA-N 0.000 claims description 5
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 5
• PLYPGNJLNMXCEB-OAQYLSRUSA-N N-tert-butyl-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound CC(C)(C)NC(=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 PLYPGNJLNMXCEB-OAQYLSRUSA-N 0.000 claims description 5
• 230000000259 anti-tumor effect Effects 0.000 claims description 5
• 125000002393 azetidinyl group Chemical group 0.000 claims description 5
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
• LVNVONQWVPXZTD-JOCHJYFZSA-N 2'-[[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridin-2-yl]amino]spiro[cyclopentane-1,7'-furo[3,4-b]pyridine]-5'-one Chemical compound OC[C@@H](NC1=CC(NC2=CC=C3C(=O)OC4(CCCC4)C3=N2)=NC=C1C1=NC(=NO1)C1CC1)C1=CC=CC=C1 LVNVONQWVPXZTD-JOCHJYFZSA-N 0.000 claims description 4
• VJQKLYLOFOYNBU-DURWQBQJSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-[(1S,2R)-2-phenylcyclopropyl]pyrimidine-5-carboxamide Chemical compound C1(C2=CC(NC3=NC(=C(C=N3)C(=O)N[C@@H]3[C@@H](C4=CC=CC=C4)C3)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C VJQKLYLOFOYNBU-DURWQBQJSA-N 0.000 claims description 4
• ZFLWKTUDBCDFTD-AREMUKBSSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-[(2-methylphenyl)methyl]pyrimidine-5-carboxamide Chemical compound CC1=C(CNC(=O)C2=C(N[C@H](CO)C3=CC=CC=C3)N=C(NC3=CC=C4C(=O)OC(C)(C)C4=C3)N=C2)C=CC=C1 ZFLWKTUDBCDFTD-AREMUKBSSA-N 0.000 claims description 4
• CYJPFBCHYRZAJL-OAQYLSRUSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-propan-2-ylpyrimidine-5-carboxamide Chemical compound CC(C)NC(=O)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 CYJPFBCHYRZAJL-OAQYLSRUSA-N 0.000 claims description 4
• HLCCRSRQLPEAHO-HXUWFJFHSA-N 2-[[5-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridin-2-yl]amino]-7,7-dimethylfuro[3,4-b]pyridin-5-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC=C(C4=NN=C(O4)C4CC4)C(N[C@H](CO)C4=CC=CC=C4)=C3)N=C12 HLCCRSRQLPEAHO-HXUWFJFHSA-N 0.000 claims description 4
• DZCRAVOBEJDBAB-UHFFFAOYSA-N 2-[[5-[3-(1-azabicyclo[2.2.2]octan-4-yl)-1,2,4-oxadiazol-5-yl]-4-(pyridin-3-ylmethylamino)pyridin-2-yl]amino]-7,7-dimethylfuro[3,4-b]pyridin-5-one Chemical compound N1=C2C(=CC=C1NC1=CC(=C(C=N1)C=1ON=C(N=1)C13CCN(CC1)CC3)NCC1=CC=CN=C1)C(=O)OC2(C)C DZCRAVOBEJDBAB-UHFFFAOYSA-N 0.000 claims description 4
• PQYSJQAPEPEKPX-HXUWFJFHSA-N 5-[[4-[[(1S)-1-cyclopropyl-2-hydroxyethyl]amino]-5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)pyridin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC=C(C4=NC(=NO4)C4CC4)C(N[C@H](CO)C4CC4)=C3)C=C12 PQYSJQAPEPEKPX-HXUWFJFHSA-N 0.000 claims description 4
• YRVXATDCJUAJGN-JOCHJYFZSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(5-pyridazin-3-yl-1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NN=C(O3)C3=CC=CN=N3)C=C12 YRVXATDCJUAJGN-JOCHJYFZSA-N 0.000 claims description 4
• IEIGXEPRQHYZAD-HXUWFJFHSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NN=C(O3)C3(CC3)C(F)(F)F)C=C12 IEIGXEPRQHYZAD-HXUWFJFHSA-N 0.000 claims description 4
• HTSNSNPDGSLYOH-HSZRJFAPSA-N 5-[[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC=C(C4=NC(=NO4)C4CC4)C(N[C@H](CO)C4=CC=CC=C4)=C3)C=C12 HTSNSNPDGSLYOH-HSZRJFAPSA-N 0.000 claims description 4
• DHMUJZGINJTRCL-UHFFFAOYSA-N 5-[[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[[2-(2-hydroxypropan-2-yl)phenyl]methylamino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC(C)(O)C1=C(CNC2=C(C=NC(NC3=CC=C4C(=O)OC(C)(C)C4=C3)=N2)C2=NC(=NO2)C2CC2)C=CC=C1 DHMUJZGINJTRCL-UHFFFAOYSA-N 0.000 claims description 4
• RMYZEICXBRZXFD-HXUWFJFHSA-N 5-[[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CCC1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 RMYZEICXBRZXFD-HXUWFJFHSA-N 0.000 claims description 4
• NZYHUDMTKSMEGB-HSZRJFAPSA-N 5-[[5-[5-(1,1-dioxothian-4-yl)-1,3,4-oxadiazol-2-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NN=C(O3)C3CCS(=O)(=O)CC3)C=C12 NZYHUDMTKSMEGB-HSZRJFAPSA-N 0.000 claims description 4
• ACYOTBQBXQTWHI-ZTDHTWSHSA-N N-(1-azabicyclo[2.2.2]octan-3-ylmethyl)-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound C1(C2=C(C=CC(NC3=NC(=C(C=N3)C(=O)NCC3C4CCN(CC4)C3)N[C@@H](C3=CC=CC=C3)CO)=C2)C(=O)O1)(C)C ACYOTBQBXQTWHI-ZTDHTWSHSA-N 0.000 claims description 4
• FNICMCXCTJKCQI-SNSSHHSLSA-N N-(1-benzylpyrrolidin-3-yl)-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxamide Chemical compound C1=CC=CC=C1CN1CCC(NC(=O)C2=C(N[C@@H](C3=CC=CC=C3)CO)N=C(NC3=CC=4C(OC(=O)C=4C=C3)(C)C)N=C2)C1 FNICMCXCTJKCQI-SNSSHHSLSA-N 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
• 229960005486 vaccine Drugs 0.000 claims description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
• RVFYCRCCTDEQQD-XMMPIXPASA-N 5-[[5-[3-(1-azabicyclo[2.2.2]octan-4-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound C1(=CC2=C(C=C1)C(=O)OC2(C)C)NC1=NC(=C(C=N1)C=1ON=C(N=1)C12CCN(CC1)CC2)N[C@@H](C1=CC=CC=C1)CO RVFYCRCCTDEQQD-XMMPIXPASA-N 0.000 claims description 3
• 206010006187 Breast cancer Diseases 0.000 claims description 3
• 208000026310 Breast neoplasm Diseases 0.000 claims description 3
• 206010038389 Renal cancer Diseases 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 125000005050 dihydrooxazolyl group Chemical group O1C(NC=C1)* 0.000 claims description 3
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 claims description 3
• 125000001425 triazolyl group Chemical group 0.000 claims description 3
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
• BZNUWUBAPANEMZ-HXUWFJFHSA-N 1-[5-[6-[(7,7-dimethyl-5-oxofuro[3,4-b]pyridin-2-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridin-3-yl]-1,3,4-oxadiazol-2-yl]cyclopropane-1-carbonitrile Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=CC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NN=C(O3)C3(CC3)C#N)N=C12 BZNUWUBAPANEMZ-HXUWFJFHSA-N 0.000 claims description 2
• 206010009944 Colon cancer Diseases 0.000 claims description 2
• 206010025323 Lymphomas Diseases 0.000 claims description 2
• 206010033128 Ovarian cancer Diseases 0.000 claims description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
• 206010060862 Prostate cancer Diseases 0.000 claims description 2
• 208000029742 colonic neoplasm Diseases 0.000 claims description 2
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
• 208000020816 lung neoplasm Diseases 0.000 claims description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
• 230000005855 radiation Effects 0.000 claims description 2
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 2
• 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 2
• 229960004854 viral vaccine Drugs 0.000 claims description 2
• 206010008342 Cervix carcinoma Diseases 0.000 claims 1
• 101000983970 Conus catus Alpha-conotoxin CIB Proteins 0.000 claims 1
• 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
• 201000010881 cervical cancer Diseases 0.000 claims 1
• 238000002651 drug therapy Methods 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 201000010536 head and neck cancer Diseases 0.000 claims 1
• 208000014829 head and neck neoplasm Diseases 0.000 claims 1
• 201000010982 kidney cancer Diseases 0.000 claims 1
• 208000032839 leukemia Diseases 0.000 claims 1
• 201000005202 lung cancer Diseases 0.000 claims 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
• 201000002528 pancreatic cancer Diseases 0.000 claims 1
• 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 70
• 108010002838 hematopoietic progenitor kinase 1 Proteins 0.000 abstract description 47
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 33
• 230000002062 proliferating effect Effects 0.000 abstract description 6
• 230000002255 enzymatic effect Effects 0.000 abstract 1
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 603
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 220
• 239000012071 phase Substances 0.000 description 200
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 186
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 170
• 239000005695 Ammonium acetate Substances 0.000 description 170
• 235000019257 ammonium acetate Nutrition 0.000 description 170
• 229940043376 ammonium acetate Drugs 0.000 description 170
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 98
• 238000005160 1H NMR spectroscopy Methods 0.000 description 97
• 239000002245 particle Substances 0.000 description 95
• 238000002360 preparation method Methods 0.000 description 87
• 239000000243 solution Substances 0.000 description 82
• 238000004128 high performance liquid chromatography Methods 0.000 description 81
• 239000011541 reaction mixture Substances 0.000 description 77
• 239000000203 mixture Substances 0.000 description 75
• 235000002639 sodium chloride Nutrition 0.000 description 72
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 70
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
• YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
• 235000019439 ethyl acetate Nutrition 0.000 description 50
• 239000000047 product Substances 0.000 description 48
• 239000003814 drug Substances 0.000 description 43
• 238000001023 centrifugal evaporation Methods 0.000 description 42
• 239000013058 crude material Substances 0.000 description 42
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 40
• 229940124597 therapeutic agent Drugs 0.000 description 36
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
• 239000003795 chemical substances by application Substances 0.000 description 29
• 239000007787 solid Substances 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 28
• 239000012267 brine Substances 0.000 description 25
• 238000006243 chemical reaction Methods 0.000 description 25
• 239000000463 material Substances 0.000 description 25
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
• BUVXADKKXYLSTP-UHFFFAOYSA-N (3,3-difluorocyclobutyl)methanamine Chemical compound NCC1CC(F)(F)C1 BUVXADKKXYLSTP-UHFFFAOYSA-N 0.000 description 22
• 201000010099 disease Diseases 0.000 description 22
• 230000000694 effects Effects 0.000 description 22
• 229910052757 nitrogen Inorganic materials 0.000 description 22
• 229940045207 immuno-oncology agent Drugs 0.000 description 21
• 239000002584 immunological anticancer agent Substances 0.000 description 21
• 238000003756 stirring Methods 0.000 description 20
• 210000001744 T-lymphocyte Anatomy 0.000 description 19
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
• 235000019341 magnesium sulphate Nutrition 0.000 description 16
• 238000010898 silica gel chromatography Methods 0.000 description 16
• 239000000725 suspension Substances 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical class CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
• 239000004480 active ingredient Substances 0.000 description 15
• 239000005557 antagonist Substances 0.000 description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
• 210000004027 cell Anatomy 0.000 description 13
• 229910052760 oxygen Inorganic materials 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
• 239000002671 adjuvant Substances 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• 239000002552 dosage form Substances 0.000 description 11
• 125000005842 heteroatom Chemical group 0.000 description 11
• YYROPELSRYBVMQ-UHFFFAOYSA-N p-toluenesulfonyl chloride Substances CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 11
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
• 239000012298 atmosphere Substances 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 230000002829 reductive effect Effects 0.000 description 10
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 239000000556 agonist Substances 0.000 description 9
• 239000003085 diluting agent Substances 0.000 description 9
• 239000003995 emulsifying agent Substances 0.000 description 9
• 239000002808 molecular sieve Substances 0.000 description 9
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 9
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 9
• 241000124008 Mammalia Species 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 238000002648 combination therapy Methods 0.000 description 8
• 238000010438 heat treatment Methods 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 238000011457 non-pharmacological treatment Methods 0.000 description 8
• 239000001301 oxygen Substances 0.000 description 8
• 239000003755 preservative agent Substances 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• 239000012453 solvate Substances 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• 239000003981 vehicle Substances 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 235000014113 dietary fatty acids Nutrition 0.000 description 7
• 235000019441 ethanol Nutrition 0.000 description 7
• 239000000194 fatty acid Substances 0.000 description 7
• 229930195729 fatty acid Natural products 0.000 description 7
• 150000004665 fatty acids Chemical class 0.000 description 7
• 239000000796 flavoring agent Substances 0.000 description 7
• 229910052739 hydrogen Inorganic materials 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• 239000003765 sweetening agent Substances 0.000 description 7
• 239000003039 volatile agent Substances 0.000 description 7
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• GTUMWCCEYLGOMO-UHFFFAOYSA-N 5-amino-3,3-dimethyl-2-benzofuran-1-one Chemical compound C1=C(N)C=C2C(C)(C)OC(=O)C2=C1 GTUMWCCEYLGOMO-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 6
• 108090000790 Enzymes Proteins 0.000 description 6
• 241000282414 Homo sapiens Species 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 102100040678 Programmed cell death protein 1 Human genes 0.000 description 6
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• 239000000839 emulsion Substances 0.000 description 6
• 229940088598 enzyme Drugs 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 235000013355 food flavoring agent Nutrition 0.000 description 6
• 235000003599 food sweetener Nutrition 0.000 description 6
• 125000001072 heteroaryl group Chemical group 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 238000002156 mixing Methods 0.000 description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 description 6
• 231100000252 nontoxic Toxicity 0.000 description 6
• 230000003000 nontoxic effect Effects 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• UOYSTPYCLSTYPU-UHFFFAOYSA-N pyrimidine-5-carbohydrazide Chemical compound NNC(=O)C1=CN=CN=C1 UOYSTPYCLSTYPU-UHFFFAOYSA-N 0.000 description 6
• 239000003643 water by type Substances 0.000 description 6
• 239000000080 wetting agent Substances 0.000 description 6
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 5
• JHUVOBBZRYHQMZ-JOCHJYFZSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N'-(pyrazine-2-carbonyl)pyrimidine-5-carbohydrazide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NNC(=O)C3=CN=CC=N3)C=C12 JHUVOBBZRYHQMZ-JOCHJYFZSA-N 0.000 description 5
• RAZWUHJFDPYUGJ-JOCHJYFZSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-[(3-methyloxetan-3-yl)methyl]pyrimidine-5-carboxamide Chemical compound CC1(OC(C2=C1C=C(C=C2)NC1=NC=C(C(=N1)N[C@H](CO)C1=CC=CC=C1)C(=O)NCC1(COC1)C)=O)C RAZWUHJFDPYUGJ-JOCHJYFZSA-N 0.000 description 5
• DUWBAMYVSALGDH-AREMUKBSSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N-[[1-(morpholin-4-ylmethyl)cyclopropyl]methyl]pyrimidine-5-carboxamide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NCC3(CN4CCOCC4)CC3)C=C12 DUWBAMYVSALGDH-AREMUKBSSA-N 0.000 description 5
• SLYRPTJABQNLGM-JOCHJYFZSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-morpholin-4-yl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound C1=2C(OC(=O)C=2C=CC(=C1)NC1=NC(=C(C=N1)C=1ON=C(N=1)N1CCOCC1)N[C@@H](C1=CC=CC=C1)CO)(C)C SLYRPTJABQNLGM-JOCHJYFZSA-N 0.000 description 5
• HFCOFXJWXXUQAZ-HSZRJFAPSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3=CC=CN=C3)C=C12 HFCOFXJWXXUQAZ-HSZRJFAPSA-N 0.000 description 5
• FJULRKZZAYOJRW-HSZRJFAPSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(5-pyridin-3-yl-1,3,4-oxadiazol-2-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NN=C(O3)C3=CC=CN=C3)C=C12 FJULRKZZAYOJRW-HSZRJFAPSA-N 0.000 description 5
• CJEDRQLHKUFXRG-HSZRJFAPSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-[3-(oxan-4-yl)-1,2,4-oxadiazol-5-yl]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3CCOCC3)C=C12 CJEDRQLHKUFXRG-HSZRJFAPSA-N 0.000 description 5
• NHLRQGPSAURBBL-OAQYLSRUSA-N 5-[[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3CC3)C=C12 NHLRQGPSAURBBL-OAQYLSRUSA-N 0.000 description 5
• VIFIYUJKYORJAS-OAQYLSRUSA-N 5-[[5-[3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3CC(F)(F)C3)C=C12 VIFIYUJKYORJAS-OAQYLSRUSA-N 0.000 description 5
• ICBGBIAVCGLHPM-OAQYLSRUSA-N 5-[[5-[3-[1-(hydroxymethyl)cyclopropyl]-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3(CO)CC3)C=C12 ICBGBIAVCGLHPM-OAQYLSRUSA-N 0.000 description 5
• 229940045513 CTLA4 antagonist Drugs 0.000 description 5
• 201000009030 Carcinoma Diseases 0.000 description 5
• 229920000858 Cyclodextrin Polymers 0.000 description 5
• 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 5
• 239000007832 Na2SO4 Substances 0.000 description 5
• 108091000080 Phosphotransferase Proteins 0.000 description 5
• 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 5
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 5
• 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 5
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 5
• 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 5
• 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 5
• MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 239000007900 aqueous suspension Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 238000001514 detection method Methods 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• SRJBDGLSCPDXBL-UHFFFAOYSA-N ethyl 2,4-dichloropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)N=C1Cl SRJBDGLSCPDXBL-UHFFFAOYSA-N 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 239000008187 granular material Substances 0.000 description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
• 210000000987 immune system Anatomy 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 230000036961 partial effect Effects 0.000 description 5
• 102000020233 phosphotransferase Human genes 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
• 229910052717 sulfur Inorganic materials 0.000 description 5
• 239000000375 suspending agent Substances 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• 229940062627 tribasic potassium phosphate Drugs 0.000 description 5
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• NTTPVLDIJOHTEV-GOSISDBHSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxylic acid Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(O)=O)C=C12 NTTPVLDIJOHTEV-GOSISDBHSA-N 0.000 description 4
• CBBSCTLFVLWGEZ-OAQYLSRUSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-propyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CCCC1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 CBBSCTLFVLWGEZ-OAQYLSRUSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 108010074708 B7-H1 Antigen Proteins 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 4
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
• 229940125962 HPK1 kinase inhibitor Drugs 0.000 description 4
• 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 4
• 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 4
• 108010002350 Interleukin-2 Proteins 0.000 description 4
• 102000017578 LAG3 Human genes 0.000 description 4
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
• 241000699670 Mus sp. Species 0.000 description 4
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
• 235000019483 Peanut oil Nutrition 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
• 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 4
• 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 239000000427 antigen Substances 0.000 description 4
• 102000036639 antigens Human genes 0.000 description 4
• 108091007433 antigens Proteins 0.000 description 4
• 239000003963 antioxidant agent Substances 0.000 description 4
• 235000006708 antioxidants Nutrition 0.000 description 4
• 230000009286 beneficial effect Effects 0.000 description 4
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 4
• 229960004316 cisplatin Drugs 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 235000019197 fats Nutrition 0.000 description 4
• 239000007903 gelatin capsule Substances 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 238000001990 intravenous administration Methods 0.000 description 4
• 238000010253 intravenous injection Methods 0.000 description 4
• 229940043355 kinase inhibitor Drugs 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 4
• 235000001968 nicotinic acid Nutrition 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 229960003552 other antineoplastic agent in atc Drugs 0.000 description 4
• 230000007170 pathology Effects 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• 239000000312 peanut oil Substances 0.000 description 4
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 230000002335 preservative effect Effects 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 125000004434 sulfur atom Chemical group 0.000 description 4
• 239000006188 syrup Substances 0.000 description 4
• 235000020357 syrup Nutrition 0.000 description 4
• IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 3
• JFJXUVXSIUJJNC-LWTKGLMZSA-N (Z)-5-hydroxy-2,2,6,6-tetramethylhept-4-en-3-one manganese Chemical compound [Mn].CC(C)(C)C(\O)=C\C(=O)C(C)(C)C.CC(C)(C)C(\O)=C\C(=O)C(C)(C)C.CC(C)(C)C(\O)=C\C(=O)C(C)(C)C JFJXUVXSIUJJNC-LWTKGLMZSA-N 0.000 description 3
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
• SCJYOOFDWYHCNB-UHFFFAOYSA-N 2-amino-7,7-dimethylfuro[3,4-b]pyridin-5-one Chemical compound NC1=CC=C2C(=N1)C(OC2=O)(C)C SCJYOOFDWYHCNB-UHFFFAOYSA-N 0.000 description 3
• YXNKVVQNDPHXDG-UHFFFAOYSA-N 4-amino-2-(2-hydroxypropan-2-yl)benzonitrile Chemical compound NC1=CC(=C(C#N)C=C1)C(C)(C)O YXNKVVQNDPHXDG-UHFFFAOYSA-N 0.000 description 3
• FQIPCNISFYSYFW-UHFFFAOYSA-N 4-amino-2-prop-1-en-2-ylbenzonitrile Chemical compound NC1=CC(=C(C#N)C=C1)C(=C)C FQIPCNISFYSYFW-UHFFFAOYSA-N 0.000 description 3
• MKZJMEQFYSBMLR-PQLMJIFMSA-N 5-[[5-[3-(3-amino-1-bicyclo[1.1.1]pentanyl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound C1=C2C(=CC=C1NC1=NC(=C(C=N1)C=1ON=C(N=1)C13CC(N)(C1)C3)N[C@@H](C1=CC=CC=C1)CO)C(=O)OC2(C)C MKZJMEQFYSBMLR-PQLMJIFMSA-N 0.000 description 3
• DQTBPANHSUIJIF-UHFFFAOYSA-N 6-amino-2-chloropyridine-3-carbonitrile Chemical compound NC1=CC=C(C#N)C(Cl)=N1 DQTBPANHSUIJIF-UHFFFAOYSA-N 0.000 description 3
• WTVIUBNJFNYVIC-UHFFFAOYSA-N 6-amino-2-prop-1-en-2-ylpyridine-3-carbonitrile Chemical compound NC1=NC(=C(C#N)C=C1)C(=C)C WTVIUBNJFNYVIC-UHFFFAOYSA-N 0.000 description 3
• 244000215068 Acacia senegal Species 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
• 101150013553 CD40 gene Proteins 0.000 description 3
• 102100025221 CD70 antigen Human genes 0.000 description 3
• 108010021064 CTLA-4 Antigen Proteins 0.000 description 3
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 229920000084 Gum arabic Polymers 0.000 description 3
• 239000007821 HATU Substances 0.000 description 3
• 101001090688 Homo sapiens Lymphocyte cytosolic protein 2 Proteins 0.000 description 3
• 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
• 102000037982 Immune checkpoint proteins Human genes 0.000 description 3
• 108091008036 Immune checkpoint proteins Proteins 0.000 description 3
• 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 3
• 102000000588 Interleukin-2 Human genes 0.000 description 3
• 101150030213 Lag3 gene Proteins 0.000 description 3
• 102100034709 Lymphocyte cytosolic protein 2 Human genes 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• 102000004473 OX40 Ligand Human genes 0.000 description 3
• 108010042215 OX40 Ligand Proteins 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 3
• 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 3
• 235000010489 acacia gum Nutrition 0.000 description 3
• 239000000205 acacia gum Substances 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 235000010443 alginic acid Nutrition 0.000 description 3
• 229920000615 alginic acid Polymers 0.000 description 3
• 229940034982 antineoplastic agent Drugs 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 229910052786 argon Inorganic materials 0.000 description 3
• 125000003118 aryl group Chemical group 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 230000000973 chemotherapeutic effect Effects 0.000 description 3
• 230000001684 chronic effect Effects 0.000 description 3
• 239000003086 colorant Substances 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• VNTPMRVWQMYOMF-UHFFFAOYSA-N ethyl 2-chloro-4-[(2-prop-1-en-2-ylphenyl)methylamino]pyrimidine-5-carboxylate Chemical compound ClC1=NC=C(C(=N1)NCC1=C(C=CC=C1)C(=C)C)C(=O)OCC VNTPMRVWQMYOMF-UHFFFAOYSA-N 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 125000001153 fluoro group Chemical group F* 0.000 description 3
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
• 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 3
• 239000005457 ice water Substances 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 108091008042 inhibitory receptors Proteins 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 235000010445 lecithin Nutrition 0.000 description 3
• 239000000787 lecithin Substances 0.000 description 3
• 229940067606 lecithin Drugs 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• 210000004379 membrane Anatomy 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• JFAYYFKDMBXHHT-UHFFFAOYSA-N methyl 6-chloro-4-(1,3-thiazol-2-ylmethylamino)pyridine-3-carboxylate Chemical compound ClC1=NC=C(C(=O)OC)C(=C1)NCC=1SC=CN=1 JFAYYFKDMBXHHT-UHFFFAOYSA-N 0.000 description 3
• 239000004530 micro-emulsion Substances 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• 239000011664 nicotinic acid Substances 0.000 description 3
• 239000000346 nonvolatile oil Substances 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
• PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 230000004936 stimulating effect Effects 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 239000000454 talc Substances 0.000 description 3
• 229910052623 talc Inorganic materials 0.000 description 3
• 235000012222 talc Nutrition 0.000 description 3
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 239000001993 wax Substances 0.000 description 3
• NIDRYBLTWYFCFV-FMTVUPSXSA-N (+)-calanolide A Chemical compound C1=CC(C)(C)OC2=C1C(O[C@H](C)[C@@H](C)[C@@H]1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-FMTVUPSXSA-N 0.000 description 2
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 2
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• GKYXUYBMJPOLGN-JOCHJYFZSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-N'-(pyridazine-3-carbonyl)pyrimidine-5-carbohydrazide Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C(=O)NNC(=O)C3=CC=CN=N3)C=C12 GKYXUYBMJPOLGN-JOCHJYFZSA-N 0.000 description 2
• GWFOVSGRNGAGDL-FSDSQADBSA-N 2-amino-9-[(1r,2r,3s)-2,3-bis(hydroxymethyl)cyclobutyl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1C[C@H](CO)[C@H]1CO GWFOVSGRNGAGDL-FSDSQADBSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 description 2
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
• SVSUYEJKNSMKKW-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-prop-1-en-2-yl-1,3,2-dioxaborolane Chemical compound CC(=C)B1OC(C)(C)C(C)(C)O1 SVSUYEJKNSMKKW-UHFFFAOYSA-N 0.000 description 2
• 102000002627 4-1BB Ligand Human genes 0.000 description 2
• 108010082808 4-1BB Ligand Proteins 0.000 description 2
• VQYASORGHMGXQV-OAQYLSRUSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC(C)C1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 VQYASORGHMGXQV-OAQYLSRUSA-N 0.000 description 2
• SMMHXXKVBRERRD-HSZRJFAPSA-N 5-[[4-[[(1S)-2-hydroxy-1-phenylethyl]amino]-5-[3-(morpholin-4-ylmethyl)-1,2,4-oxadiazol-5-yl]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(CN4CCOCC4)=NO3)C=C12 SMMHXXKVBRERRD-HSZRJFAPSA-N 0.000 description 2
• YPUUKVINJSRXQN-OAQYLSRUSA-N 5-[[5-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC(C)(C)C1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 YPUUKVINJSRXQN-OAQYLSRUSA-N 0.000 description 2
• URWLNMNDZAEYMS-AREMUKBSSA-N 5-[[5-[3-(1-azabicyclo[2.2.2]octan-4-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound C1(C2=C(C=CC(NC3=NC=C(C=4ON=C(N=4)C45CCN(CC4)CC5)C(N[C@@H](C4=CC=CC=C4)CO)=C3)=C2)C(=O)O1)(C)C URWLNMNDZAEYMS-AREMUKBSSA-N 0.000 description 2
• CSPMMGWEBVVESH-XMMPIXPASA-N 5-[[5-[3-(3-fluorophenyl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3=CC(F)=CC=C3)C=C12 CSPMMGWEBVVESH-XMMPIXPASA-N 0.000 description 2
• KBDKZFILRCQRGO-XMMPIXPASA-N 5-[[5-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC1(C)OC(=O)C2=CC=C(NC3=NC(N[C@H](CO)C4=CC=CC=C4)=C(C=N3)C3=NC(=NO3)C3=CC=C(F)C=C3)C=C12 KBDKZFILRCQRGO-XMMPIXPASA-N 0.000 description 2
• RGCIZSRRAOCQJI-QYLBLJEFSA-N 5-[[5-[3-[3-(dimethylamino)-1-bicyclo[1.1.1]pentanyl]-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound C1(C2=CC(NC3=NC(=C(C=4ON=C(N=4)C45CC(N(C)C)(C4)C5)C=N3)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C RGCIZSRRAOCQJI-QYLBLJEFSA-N 0.000 description 2
• ZUFIFULMTGIWNN-UHFFFAOYSA-N 6-amino-2-(2-hydroxypropan-2-yl)pyridine-3-carbonitrile Chemical compound NC1=NC(=C(C#N)C=C1)C(C)(C)O ZUFIFULMTGIWNN-UHFFFAOYSA-N 0.000 description 2
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-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
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 208000003174 Brain Neoplasms Diseases 0.000 description 2
• 229940121697 CD27 agonist Drugs 0.000 description 2
• 102100027207 CD27 antigen Human genes 0.000 description 2
• 102100038078 CD276 antigen Human genes 0.000 description 2
• 229940123189 CD40 agonist Drugs 0.000 description 2
• 229940122551 CD40 antagonist Drugs 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 241000701022 Cytomegalovirus Species 0.000 description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
• 102100037354 Ectodysplasin-A Human genes 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 241000711549 Hepacivirus C Species 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
• 101000934356 Homo sapiens CD70 antigen Proteins 0.000 description 2
• 101000880080 Homo sapiens Ectodysplasin-A Proteins 0.000 description 2
• 101001019455 Homo sapiens ICOS ligand Proteins 0.000 description 2
• 101000610605 Homo sapiens Tumor necrosis factor receptor superfamily member 10A Proteins 0.000 description 2
• 101000610604 Homo sapiens Tumor necrosis factor receptor superfamily member 10B Proteins 0.000 description 2
• 101000679903 Homo sapiens Tumor necrosis factor receptor superfamily member 25 Proteins 0.000 description 2
• 101000679907 Homo sapiens Tumor necrosis factor receptor superfamily member 27 Proteins 0.000 description 2
• 101000920026 Homo sapiens Tumor necrosis factor receptor superfamily member EDAR Proteins 0.000 description 2
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
• 241000725303 Human immunodeficiency virus Species 0.000 description 2
• 241000701806 Human papillomavirus Species 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 102100034980 ICOS ligand Human genes 0.000 description 2
• 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 2
• 108060003951 Immunoglobulin Proteins 0.000 description 2
• 101710199010 Interleukin-1 receptor-associated kinase 4 Proteins 0.000 description 2
• 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 description 2
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 2
• 102000004083 Lymphotoxin-alpha Human genes 0.000 description 2
• 108090000542 Lymphotoxin-alpha Proteins 0.000 description 2
• 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 2
• 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 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
• UQEDOJNBGRNRTK-UHFFFAOYSA-N N'-hydroxy-1-azabicyclo[2.2.2]octane-4-carboximidamide Chemical compound ONC(=N)C12CCN(CC1)CC2 UQEDOJNBGRNRTK-UHFFFAOYSA-N 0.000 description 2
• FGLJAYDPJJKJLL-GOSISDBHSA-N N-[(1S)-2-[tert-butyl(dimethyl)silyl]oxy-1-phenylethyl]-2-chloro-5-pyrimidin-2-ylpyrimidin-4-amine Chemical compound [Si](C)(C)(C(C)(C)C)OC[C@H](C1=CC=CC=C1)NC1=NC(=NC=C1C1=NC=CC=N1)Cl FGLJAYDPJJKJLL-GOSISDBHSA-N 0.000 description 2
• GDQLMYLNPAONGN-QYLBLJEFSA-N N-[3-[5-[2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-5-yl]-1,2,4-oxadiazol-3-yl]-1-bicyclo[1.1.1]pentanyl]acetamide Chemical compound C1(C2=CC(NC3=NC(=C(C=4ON=C(N=4)C45CC(NC(=O)C)(C4)C5)C=N3)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C GDQLMYLNPAONGN-QYLBLJEFSA-N 0.000 description 2
• 239000005642 Oleic acid Substances 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• 229940124060 PD-1 antagonist Drugs 0.000 description 2
• 229940123751 PD-L1 antagonist Drugs 0.000 description 2
• 108091008611 Protein Kinase B Proteins 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 230000006044 T cell activation Effects 0.000 description 2
• 230000005867 T cell response Effects 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
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 102100024587 Tumor necrosis factor ligand superfamily member 15 Human genes 0.000 description 2
• 102100040113 Tumor necrosis factor receptor superfamily member 10A Human genes 0.000 description 2
• 102100040112 Tumor necrosis factor receptor superfamily member 10B Human genes 0.000 description 2
• 102100022203 Tumor necrosis factor receptor superfamily member 25 Human genes 0.000 description 2
• 102100022202 Tumor necrosis factor receptor superfamily member 27 Human genes 0.000 description 2
• 102100030810 Tumor necrosis factor receptor superfamily member EDAR Human genes 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
• 241000700605 Viruses Species 0.000 description 2
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 2
• 229960004748 abacavir Drugs 0.000 description 2
• 230000002159 abnormal effect Effects 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
• 230000004913 activation Effects 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 210000005006 adaptive immune system Anatomy 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 150000001447 alkali salts Chemical class 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 125000004103 aminoalkyl group Chemical group 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 230000000118 anti-neoplastic effect Effects 0.000 description 2
• 230000003078 antioxidant effect Effects 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
• 229960004853 betadex Drugs 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 235000019437 butane-1,3-diol Nutrition 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 229940022399 cancer vaccine Drugs 0.000 description 2
• 238000009566 cancer vaccine Methods 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 229960005243 carmustine Drugs 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 230000022131 cell cycle Effects 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 229940044683 chemotherapy drug Drugs 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 229940097362 cyclodextrins Drugs 0.000 description 2
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
• 239000002254 cytotoxic agent Substances 0.000 description 2
• 231100000599 cytotoxic agent Toxicity 0.000 description 2
• 229960003901 dacarbazine Drugs 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 229950009791 durvalumab Drugs 0.000 description 2
• XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 2
• MLILORUFDVLTSP-UHFFFAOYSA-N emivirine Chemical compound O=C1NC(=O)N(COCC)C(CC=2C=CC=CC=2)=C1C(C)C MLILORUFDVLTSP-UHFFFAOYSA-N 0.000 description 2
• GKNBJULHKLUKKZ-UHFFFAOYSA-N ethyl 2-chloro-4-(1H-indazol-5-ylamino)pyrimidine-5-carboxylate Chemical compound N1N=CC2=CC(=CC=C12)NC1=NC(=NC=C1C(=O)OCC)Cl GKNBJULHKLUKKZ-UHFFFAOYSA-N 0.000 description 2
• MIHIWARWUSAOLZ-GFCCVEGCSA-N ethyl 2-chloro-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidine-5-carboxylate Chemical compound N1=C(N=C(C(=C1)C(=O)OCC)N[C@@H](C1=CC=CC=C1)CO)Cl MIHIWARWUSAOLZ-GFCCVEGCSA-N 0.000 description 2
• VVPXHBWESYMVKB-UHFFFAOYSA-N ethyl 2-chloro-4-[[2-(2-hydroxypropan-2-yl)phenyl]methylamino]pyrimidine-5-carboxylate Chemical compound ClC1=NC=C(C(=N1)NCC1=C(C=CC=C1)C(C)(C)O)C(=O)OCC VVPXHBWESYMVKB-UHFFFAOYSA-N 0.000 description 2
• AAPXRTXPSBODGO-UHFFFAOYSA-N ethyl 2-chloro-4-[[3-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]butyl]amino]pyrimidine-5-carboxylate Chemical compound N1=C(N=C(C(=C1)C(=O)OCC)NCCC(C)(C)NC(=O)OC(C)(C)C)Cl AAPXRTXPSBODGO-UHFFFAOYSA-N 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 2
• 238000004108 freeze drying Methods 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 125000000524 functional group Chemical group 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
• 230000014509 gene expression Effects 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
• 102000018358 immunoglobulin Human genes 0.000 description 2
• 238000009169 immunotherapy Methods 0.000 description 2
• CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 230000002427 irreversible effect Effects 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• 230000009916 joint effect Effects 0.000 description 2
• JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• KBEMFSMODRNJHE-JFWOZONXSA-N lodenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)C[C@@H]1F KBEMFSMODRNJHE-JFWOZONXSA-N 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 229960001924 melphalan Drugs 0.000 description 2
• 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 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• JEJMDUMJSZTJTI-UHFFFAOYSA-N methyl 4,6-dichloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C=C1Cl JEJMDUMJSZTJTI-UHFFFAOYSA-N 0.000 description 2
• NOHNSWRBULAUSY-CYBMUJFWSA-N methyl 6-chloro-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridine-3-carboxylate Chemical compound N1=C(C=C(C(=C1)C(=O)OC)N[C@@H](C1=CC=CC=C1)CO)Cl NOHNSWRBULAUSY-CYBMUJFWSA-N 0.000 description 2
• YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 210000004400 mucous membrane Anatomy 0.000 description 2
• 210000000822 natural killer cell Anatomy 0.000 description 2
• 150000002823 nitrates Chemical class 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 229960003301 nivolumab Drugs 0.000 description 2
• 239000002777 nucleoside Substances 0.000 description 2
• 150000003833 nucleoside derivatives Chemical class 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• 229960002621 pembrolizumab Drugs 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 239000002304 perfume Substances 0.000 description 2
• 238000011422 pharmacological therapy Methods 0.000 description 2
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 239000008389 polyethoxylated castor oil Substances 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 125000002755 pyrazolinyl group Chemical group 0.000 description 2
• 201000010174 renal carcinoma Diseases 0.000 description 2
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 2
• 229960000311 ritonavir Drugs 0.000 description 2
• QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 2
• 238000007789 sealing Methods 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 235000015424 sodium Nutrition 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
• 235000019345 sodium thiosulphate Nutrition 0.000 description 2
• 230000007928 solubilization Effects 0.000 description 2
• 238000005063 solubilization Methods 0.000 description 2
• 235000011069 sorbitan monooleate Nutrition 0.000 description 2
• 239000001593 sorbitan monooleate Substances 0.000 description 2
• 229940035049 sorbitan monooleate Drugs 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• 229960004964 temozolomide Drugs 0.000 description 2
• 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 2
• BEUUJDAEPJZWHM-COROXYKFSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s)-1-(2-methoxyethylamino)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenyl-5-[(2,3,4-trimethoxyphenyl)methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@H](C(=O)NCCOC)C(C)C)CC=1C(=C(OC)C(OC)=CC=1)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 BEUUJDAEPJZWHM-COROXYKFSA-N 0.000 description 2
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
• HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
• AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 2
• 229960000984 tocofersolan Drugs 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 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
• 229960002555 zidovudine Drugs 0.000 description 2
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
• 239000002076 α-tocopherol Substances 0.000 description 2
• 235000004835 α-tocopherol Nutrition 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• XFQNWPYGEGCIMF-HCUGAJCMSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].[Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 XFQNWPYGEGCIMF-HCUGAJCMSA-N 0.000 description 1
• RMLOPQZAASLABO-CYBMUJFWSA-N (1s)-2-[tert-butyl(dimethyl)silyl]oxy-1-phenylethanamine Chemical compound CC(C)(C)[Si](C)(C)OC[C@@H](N)C1=CC=CC=C1 RMLOPQZAASLABO-CYBMUJFWSA-N 0.000 description 1
• CJAAPVQEZPAQNI-UHFFFAOYSA-N (2-methylphenyl)methanamine Chemical compound CC1=CC=CC=C1CN CJAAPVQEZPAQNI-UHFFFAOYSA-N 0.000 description 1
• URRMTIZKFFFZJM-UHFFFAOYSA-N (2-prop-1-en-2-ylphenyl)methanamine hydrochloride Chemical compound Cl.C=C(C)C1=C(C=CC=C1)CN URRMTIZKFFFZJM-UHFFFAOYSA-N 0.000 description 1
• ZADWXFSZEAPBJS-SNVBAGLBSA-N (2r)-2-amino-3-(1-methylindol-3-yl)propanoic acid Chemical compound C1=CC=C2N(C)C=C(C[C@@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-SNVBAGLBSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• LLCCGHDKJXAQLS-RXMQYKEDSA-N (2s)-2-amino-2-cyclopropylethanol Chemical compound OC[C@@H](N)C1CC1 LLCCGHDKJXAQLS-RXMQYKEDSA-N 0.000 description 1
• JPSHPWJJSVEEAX-OWPBQMJCSA-N (2s)-2-amino-4-fluoranylpentanedioic acid Chemical compound OC(=O)[C@@H](N)CC([18F])C(O)=O JPSHPWJJSVEEAX-OWPBQMJCSA-N 0.000 description 1
• MCPRXSXYXHMCKF-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanamine Chemical compound NCC1(C)COC1 MCPRXSXYXHMCKF-UHFFFAOYSA-N 0.000 description 1
• ONKCBKDTKZIWHZ-MRWFHJSOSA-N (4r)-4-[[(2r)-6-amino-2-[[(2r)-2-[[4-(aminocarbamothioylamino)benzoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-5-[[(2r)-1-amino-6-[bis[2-[[4-[2-(1h-imidazol-5-yl)ethylamino]-4-oxobutanoyl]amino]acetyl]amino]-1-oxohexan-2-yl]amino]-5-oxope Chemical compound C([C@H](C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN(C(=O)CNC(=O)CCC(=O)NCCC=1NC=NC=1)C(=O)CNC(=O)CCC(=O)NCCC=1NC=NC=1)C(N)=O)NC(=O)C=1C=CC(NC(=S)NN)=CC=1)C1=CC=C(O)C=C1 ONKCBKDTKZIWHZ-MRWFHJSOSA-N 0.000 description 1
• HINZVVDZPLARRP-YSVIXOAZSA-N (4r,5s,6s,7r)-1,3-bis[(3-aminophenyl)methyl]-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepan-2-one;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.NC1=CC=CC(CN2C(N(CC=3C=C(N)C=CC=3)[C@H](CC=3C=CC=CC=3)[C@H](O)[C@@H](O)[C@H]2CC=2C=CC=CC=2)=O)=C1 HINZVVDZPLARRP-YSVIXOAZSA-N 0.000 description 1
• KZEDPVFJLQLDIZ-UHFFFAOYSA-N (5-diphenylphosphanyl-9,9-dimethylxanthen-4-yl)-diphenylphosphane Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1.C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZEDPVFJLQLDIZ-UHFFFAOYSA-N 0.000 description 1
• MPBCUCGKHDEUDD-UHFFFAOYSA-N (5-methylpyrazin-2-yl)methanamine Chemical compound CC1=CN=C(CN)C=N1 MPBCUCGKHDEUDD-UHFFFAOYSA-N 0.000 description 1
• FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 description 1
• RPJRJUVGGDVVDF-UHFFFAOYSA-N 1,1-dioxothiane-4-carboxylic acid Chemical compound OC(=O)C1CCS(=O)(=O)CC1 RPJRJUVGGDVVDF-UHFFFAOYSA-N 0.000 description 1
• JOZSYOPADROCMP-UHFFFAOYSA-N 1,3-thiazol-2-ylmethanamine Chemical compound NCC1=NC=CS1 JOZSYOPADROCMP-UHFFFAOYSA-N 0.000 description 1
• YAHJSNOAOQAQKT-UHFFFAOYSA-N 1-(3,3-difluoroazetidine-1-carbonyl)oxycyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(CC1)OC(=O)N1CC(F)(F)C1 YAHJSNOAOQAQKT-UHFFFAOYSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• SKCBKBCACWDALV-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(C(F)(F)F)CC1 SKCBKBCACWDALV-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
• XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical group N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 1
• JVCBVWTTXCNJBJ-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCN1C2 JVCBVWTTXCNJBJ-UHFFFAOYSA-N 0.000 description 1
• HBVNLKQGRZPGRP-UHFFFAOYSA-N 1-benzylpyrrolidin-3-amine Chemical compound C1C(N)CCN1CC1=CC=CC=C1 HBVNLKQGRZPGRP-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
• XNHNRKQPBQOUPH-UHFFFAOYSA-N 1-hydroxyaziridine-2,3-dione Chemical compound ON1C(=O)C1=O XNHNRKQPBQOUPH-UHFFFAOYSA-N 0.000 description 1
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
• RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
• XBTOSRUBOXQWBO-UHFFFAOYSA-N 1h-indazol-5-amine Chemical compound NC1=CC=C2NN=CC2=C1 XBTOSRUBOXQWBO-UHFFFAOYSA-N 0.000 description 1
• ASOMNDIOOKDVDC-UHFFFAOYSA-N 1h-indol-2-yl-[4-[3-(propan-2-ylamino)pyridin-2-yl]piperazin-1-yl]methanone Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=CC=C3C=2)CC1 ASOMNDIOOKDVDC-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• RGJNPJRAXMSHKN-UHFFFAOYSA-N 2,4-dichloro-5-iodopyrimidine Chemical compound ClC1=NC=C(I)C(Cl)=N1 RGJNPJRAXMSHKN-UHFFFAOYSA-N 0.000 description 1
• LFCADBSUDWERJT-UHFFFAOYSA-N 2,6-dichloropyridine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)C(Cl)=N1 LFCADBSUDWERJT-UHFFFAOYSA-N 0.000 description 1
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
• NTTPVLDIJOHTEV-UHFFFAOYSA-N 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[(2-hydroxy-1-phenylethyl)amino]pyrimidine-5-carboxylic acid Chemical compound CC1(C2=C(C=CC(=C2)NC3=NC=C(C(=N3)NC(CO)C4=CC=CC=C4)C(=O)O)C(=O)O1)C NTTPVLDIJOHTEV-UHFFFAOYSA-N 0.000 description 1
• BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-n-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-n,1-n-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 description 1
• FHJNZIWBDMYSAP-UHFFFAOYSA-N 2-chloro-6-[(4-methoxyphenyl)methylamino]pyridine-3-carbonitrile Chemical compound ClC1=C(C#N)C=CC(=N1)NCC1=CC=C(C=C1)OC FHJNZIWBDMYSAP-UHFFFAOYSA-N 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• CTGJACFEVDCYMC-UHFFFAOYSA-N 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid Chemical compound OC(=O)C(O)(C)C(F)(F)F CTGJACFEVDCYMC-UHFFFAOYSA-N 0.000 description 1
• ZUULZQRRLIBGJY-UHFFFAOYSA-N 3,3-difluoroazetidine-1-carboxylic acid Chemical compound OC(=O)N1CC(F)(F)C1 ZUULZQRRLIBGJY-UHFFFAOYSA-N 0.000 description 1
• IMXNSPFBSCZEBW-UHFFFAOYSA-N 3,3-dimethyl-1H-2-benzofuran-5-amine Chemical compound O1CC2=C(C1(C)C)C=C(N)C=C2 IMXNSPFBSCZEBW-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
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical class OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• MBLKRNFDDBETRQ-UHFFFAOYSA-N 3-hydroxy-4-methylbenzenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1O MBLKRNFDDBETRQ-UHFFFAOYSA-N 0.000 description 1
• KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical class 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
• CGPIFQOTBHKPNM-UHFFFAOYSA-N 4-(aminomethyl)oxan-4-ol Chemical compound NCC1(O)CCOCC1 CGPIFQOTBHKPNM-UHFFFAOYSA-N 0.000 description 1
• OSYGPHDNNWRFJO-UHFFFAOYSA-N 4-amino-2-bromobenzonitrile Chemical compound NC1=CC=C(C#N)C(Br)=C1 OSYGPHDNNWRFJO-UHFFFAOYSA-N 0.000 description 1
• QVEOVDLRUMWCCO-OAQYLSRUSA-N 5-[[5-[3-(1-hydroxy-2-methylpropan-2-yl)-1,2,4-oxadiazol-5-yl]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyrimidin-2-yl]amino]-3,3-dimethyl-2-benzofuran-1-one Chemical compound CC(C)(CO)C1=NOC(=N1)C1=C(N[C@H](CO)C2=CC=CC=C2)N=C(NC2=CC=C3C(=O)OC(C)(C)C3=C2)N=C1 QVEOVDLRUMWCCO-OAQYLSRUSA-N 0.000 description 1
• IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 description 1
• ISMUWQMUWFPFBZ-UHFFFAOYSA-N 5-amino-3h-2-benzofuran-1-one Chemical compound NC1=CC=C2C(=O)OCC2=C1 ISMUWQMUWFPFBZ-UHFFFAOYSA-N 0.000 description 1
• ATCRIOJPQXDFNY-ZETCQYMHSA-N 6-chloro-2-(1-furo[2,3-c]pyridin-5-yl-ethylsulfanyl)-pyrimidin-4-ylamine Chemical compound S([C@@H](C)C=1N=CC=2OC=CC=2C=1)C1=NC(N)=CC(Cl)=N1 ATCRIOJPQXDFNY-ZETCQYMHSA-N 0.000 description 1
• VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-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
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
• 102100031934 Adhesion G-protein coupled receptor G1 Human genes 0.000 description 1
• 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
• 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 108010024976 Asparaginase Proteins 0.000 description 1
• 108010011485 Aspartame Proteins 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical class C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
• 102000006942 B-Cell Maturation Antigen Human genes 0.000 description 1
• 108010008014 B-Cell Maturation Antigen Proteins 0.000 description 1
• 229940125565 BMS-986016 Drugs 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 101000964894 Bos taurus 14-3-3 protein zeta/delta Proteins 0.000 description 1
• 206010006417 Bronchial carcinoma Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
• 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
• 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
• 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
• 102100032976 CCR4-NOT transcription complex subunit 6 Human genes 0.000 description 1
• 229940116741 CD137 agonist Drugs 0.000 description 1
• 108010046080 CD27 Ligand Proteins 0.000 description 1
• 101710185679 CD276 antigen Proteins 0.000 description 1
• 108010029697 CD40 Ligand Proteins 0.000 description 1
• 102100032937 CD40 ligand Human genes 0.000 description 1
• 102100036008 CD48 antigen Human genes 0.000 description 1
• 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
• 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
• 108050000299 Chemokine receptor Proteins 0.000 description 1
• 102000009410 Chemokine receptor Human genes 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 208000005243 Chondrosarcoma Diseases 0.000 description 1
• 208000006332 Choriocarcinoma Diseases 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000709687 Coxsackievirus Species 0.000 description 1
• 208000009798 Craniopharyngioma Diseases 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 101710093674 Cyclic nucleotide-gated cation channel beta-1 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
• 108010041986 DNA Vaccines Proteins 0.000 description 1
• 229940021995 DNA vaccine Drugs 0.000 description 1
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
• 108010092160 Dactinomycin Proteins 0.000 description 1
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
• 206010013911 Dysgeusia Diseases 0.000 description 1
• 102100025137 Early activation antigen CD69 Human genes 0.000 description 1
• XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
• XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 108010032976 Enfuvirtide 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
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 101150089023 FASLG gene Proteins 0.000 description 1
• 201000006107 Familial adenomatous polyposis Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 108010001498 Galectin 1 Proteins 0.000 description 1
• 102100021736 Galectin-1 Human genes 0.000 description 1
• 102100031351 Galectin-9 Human genes 0.000 description 1
• 101710121810 Galectin-9 Proteins 0.000 description 1
• 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
• 206010017964 Gastrointestinal infection Diseases 0.000 description 1
• 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 1
• 239000004471 Glycine Substances 0.000 description 1
• 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 108010007712 Hepatitis A Virus Cellular Receptor 1 Proteins 0.000 description 1
• 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 description 1
• 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
• 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 208000008051 Hereditary Nonpolyposis Colorectal Neoplasms Diseases 0.000 description 1
• 208000017095 Hereditary nonpolyposis colon cancer Diseases 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101000824278 Homo sapiens Acyl-[acyl-carrier-protein] hydrolase Proteins 0.000 description 1
• 101000775042 Homo sapiens Adhesion G-protein coupled receptor G1 Proteins 0.000 description 1
• 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
• 101000884279 Homo sapiens CD276 antigen Proteins 0.000 description 1
• 101000716130 Homo sapiens CD48 antigen Proteins 0.000 description 1
• 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 1
• 101001021491 Homo sapiens HERV-H LTR-associating protein 2 Proteins 0.000 description 1
• 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 1
• 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 1
• 101001023712 Homo sapiens Nectin-3 Proteins 0.000 description 1
• 101000628647 Homo sapiens Serine/threonine-protein kinase 24 Proteins 0.000 description 1
• 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 1
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
• 101100207070 Homo sapiens TNFSF8 gene Proteins 0.000 description 1
• 101000764622 Homo sapiens Transmembrane and immunoglobulin domain-containing protein 2 Proteins 0.000 description 1
• 101000830596 Homo sapiens Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 description 1
• 101000764263 Homo sapiens Tumor necrosis factor ligand superfamily member 4 Proteins 0.000 description 1
• 101000610602 Homo sapiens Tumor necrosis factor receptor superfamily member 10C Proteins 0.000 description 1
• 101000610609 Homo sapiens Tumor necrosis factor receptor superfamily member 10D Proteins 0.000 description 1
• 101000798130 Homo sapiens Tumor necrosis factor receptor superfamily member 11B Proteins 0.000 description 1
• 101000795167 Homo sapiens Tumor necrosis factor receptor superfamily member 13B Proteins 0.000 description 1
• 101000795169 Homo sapiens Tumor necrosis factor receptor superfamily member 13C Proteins 0.000 description 1
• 101000801227 Homo sapiens Tumor necrosis factor receptor superfamily member 19 Proteins 0.000 description 1
• 101000679921 Homo sapiens Tumor necrosis factor receptor superfamily member 21 Proteins 0.000 description 1
• 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 1
• 101000597785 Homo sapiens Tumor necrosis factor receptor superfamily member 6B Proteins 0.000 description 1
• 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 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
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000006992 Interferon-alpha Human genes 0.000 description 1
• 108010047761 Interferon-alpha Proteins 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 108010065805 Interleukin-12 Proteins 0.000 description 1
• KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
• PGOKBMWPBDRDGN-SIPQYZPLSA-N L-744,832 Chemical compound SC[C@H](N)CN[C@@H]([C@@H](C)CC)COC(C(=O)N[C@@H](CCS(C)(=O)=O)C(=O)OC(C)C)CC1=CC=CC=C1 PGOKBMWPBDRDGN-SIPQYZPLSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
• 239000004166 Lanolin Substances 0.000 description 1
• 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 1
• 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
• 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
• 102000008072 Lymphokines Human genes 0.000 description 1
• 108010074338 Lymphokines Proteins 0.000 description 1
• 201000005027 Lynch syndrome Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 101150024075 Mapk1 gene Proteins 0.000 description 1
• 201000005505 Measles Diseases 0.000 description 1
• 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 208000005647 Mumps Diseases 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 101100046559 Mus musculus Tnfrsf12a gene Proteins 0.000 description 1
• 101100207071 Mus musculus Tnfsf8 gene Proteins 0.000 description 1
• 101000597780 Mus musculus Tumor necrosis factor ligand superfamily member 18 Proteins 0.000 description 1
• 208000005927 Myosarcoma Diseases 0.000 description 1
• FBKMWOJEPMPVTQ-UHFFFAOYSA-N N'-(3-bromo-4-fluorophenyl)-N-hydroxy-4-[2-(sulfamoylamino)ethylamino]-1,2,5-oxadiazole-3-carboximidamide Chemical compound NS(=O)(=O)NCCNC1=NON=C1C(=NO)NC1=CC=C(F)C(Br)=C1 FBKMWOJEPMPVTQ-UHFFFAOYSA-N 0.000 description 1
• ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• FOYDGXFMUNECEM-OAHLLOKOSA-N N-[(1S)-2-[tert-butyl(dimethyl)silyl]oxy-1-phenylethyl]-2-chloro-5-iodopyrimidin-4-amine Chemical compound [Si](C)(C)(C(C)(C)C)OC[C@H](C1=CC=CC=C1)NC1=NC(=NC=C1I)Cl FOYDGXFMUNECEM-OAHLLOKOSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• 102100035487 Nectin-3 Human genes 0.000 description 1
• 108010032605 Nerve Growth Factor Receptors Proteins 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• YGACXVRLDHEXKY-WXRXAMBDSA-N O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 Chemical compound O[C@H](C[C@H]1c2c(cccc2F)-c2cncn12)[C@H]1CC[C@H](O)CC1 YGACXVRLDHEXKY-WXRXAMBDSA-N 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 206010033701 Papillary thyroid cancer Diseases 0.000 description 1
• 208000030852 Parasitic disease Diseases 0.000 description 1
• 229910002666 PdCl2 Inorganic materials 0.000 description 1
• 102000017343 Phosphatidylinositol kinases Human genes 0.000 description 1
• 108050005377 Phosphatidylinositol kinases Proteins 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 208000007452 Plasmacytoma Diseases 0.000 description 1
• 208000000474 Poliomyelitis Diseases 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 208000037276 Primitive Peripheral Neuroectodermal Tumors Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 102000014128 RANK Ligand Human genes 0.000 description 1
• 108010025832 RANK Ligand Proteins 0.000 description 1
• 102000018795 RELT Human genes 0.000 description 1
• 108010052562 RELT Proteins 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
• 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
• 206010061934 Salivary gland cancer Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 102100026764 Serine/threonine-protein kinase 24 Human genes 0.000 description 1
• 241000700584 Simplexvirus Species 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
• XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 230000017274 T cell anergy Effects 0.000 description 1
• 230000006052 T cell proliferation Effects 0.000 description 1
• 102100039367 T-cell immunoglobulin and mucin domain-containing protein 4 Human genes 0.000 description 1
• 101710174757 T-cell immunoglobulin and mucin domain-containing protein 4 Proteins 0.000 description 1
• 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 1
• 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 1
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
• 108700012920 TNF Proteins 0.000 description 1
• 102000016946 TWEAK Receptor Human genes 0.000 description 1
• 108010014401 TWEAK Receptor Proteins 0.000 description 1
• 206010043276 Teratoma Diseases 0.000 description 1
• 102100025946 Transforming growth factor beta activator LRRC32 Human genes 0.000 description 1
• 101710169732 Transforming growth factor beta activator LRRC32 Proteins 0.000 description 1
• 102100026224 Transmembrane and immunoglobulin domain-containing protein 2 Human genes 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
• 102100024584 Tumor necrosis factor ligand superfamily member 12 Human genes 0.000 description 1
• 101710097155 Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 1
• 108090000138 Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 description 1
• 102100035283 Tumor necrosis factor ligand superfamily member 18 Human genes 0.000 description 1
• 102100026890 Tumor necrosis factor ligand superfamily member 4 Human genes 0.000 description 1
• 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
• 102100032100 Tumor necrosis factor ligand superfamily member 8 Human genes 0.000 description 1
• 102100040115 Tumor necrosis factor receptor superfamily member 10C Human genes 0.000 description 1
• 102100040110 Tumor necrosis factor receptor superfamily member 10D Human genes 0.000 description 1
• 102100032236 Tumor necrosis factor receptor superfamily member 11B Human genes 0.000 description 1
• 102100029675 Tumor necrosis factor receptor superfamily member 13B Human genes 0.000 description 1
• 102100029690 Tumor necrosis factor receptor superfamily member 13C Human genes 0.000 description 1
• 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
• 102100033725 Tumor necrosis factor receptor superfamily member 16 Human genes 0.000 description 1
• 102100033760 Tumor necrosis factor receptor superfamily member 19 Human genes 0.000 description 1
• 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 1
• 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
• 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 description 1
• 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 1
• 102100022205 Tumor necrosis factor receptor superfamily member 21 Human genes 0.000 description 1
• 102100035284 Tumor necrosis factor receptor superfamily member 6B Human genes 0.000 description 1
• 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 description 1
• 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
• RLAHNGKRJJEIJL-RFZPGFLSSA-N [(2r,4r)-4-(2,6-diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@H]1CO[C@@H](CO)O1 RLAHNGKRJJEIJL-RFZPGFLSSA-N 0.000 description 1
• WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
• HDJXERCXTSMRGS-UHFFFAOYSA-N [1-(morpholin-4-ylmethyl)cyclopropyl]methanamine;dihydrochloride Chemical compound Cl.Cl.C1COCCN1CC1(CN)CC1 HDJXERCXTSMRGS-UHFFFAOYSA-N 0.000 description 1
• MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
• WMHSRBZIJNQHKT-FFKFEZPRSA-N abacavir sulfate Chemical compound OS(O)(=O)=O.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1.C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 WMHSRBZIJNQHKT-FFKFEZPRSA-N 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 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
• 230000003213 activating effect Effects 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 230000033289 adaptive immune response Effects 0.000 description 1
• 229960003205 adefovir dipivoxil Drugs 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 239000002487 adenosine deaminase inhibitor Substances 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
• 201000006966 adult T-cell leukemia Diseases 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
• 150000008052 alkyl sulfonates Chemical class 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 229940087168 alpha tocopherol Drugs 0.000 description 1
• HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
• 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 1
• 229950010817 alvocidib Drugs 0.000 description 1
• 230000001668 ameliorated effect Effects 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 229960001830 amprenavir Drugs 0.000 description 1
• 238000004458 analytical method Methods 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
• 150000008064 anhydrides Chemical class 0.000 description 1
• 230000003388 anti-hormonal effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 230000005809 anti-tumor immunity Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940124691 antibody therapeutics Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
• 239000000605 aspartame Substances 0.000 description 1
• IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
• 235000010357 aspartame Nutrition 0.000 description 1
• 229960003438 aspartame Drugs 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
• 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
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 229910052788 barium Inorganic materials 0.000 description 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 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 1
• JSMRMEYFZHIPJV-UHFFFAOYSA-N bicyclo[2.1.1]hexane Chemical compound C1C2CC1CC2 JSMRMEYFZHIPJV-UHFFFAOYSA-N 0.000 description 1
• 230000004071 biological effect 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
• 239000002981 blocking agent Substances 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 201000008275 breast carcinoma Diseases 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 229960002092 busulfan Drugs 0.000 description 1
• 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
• 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• NIDRYBLTWYFCFV-UHFFFAOYSA-N calanolide F Natural products C1=CC(C)(C)OC2=C1C(OC(C)C(C)C1O)=C1C1=C2C(CCC)=CC(=O)O1 NIDRYBLTWYFCFV-UHFFFAOYSA-N 0.000 description 1
• KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 230000003185 calcium uptake Effects 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 238000002619 cancer immunotherapy Methods 0.000 description 1
• 229960004117 capecitabine Drugs 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000012292 cell migration Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
• 208000019065 cervical carcinoma Diseases 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• XKXCGXSHUNVFCT-UHFFFAOYSA-N chembl3263490 Chemical compound ON=C(N)C1=CC=CC=N1 XKXCGXSHUNVFCT-UHFFFAOYSA-N 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
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 230000000139 costimulatory effect Effects 0.000 description 1
• 108091008034 costimulatory receptors Proteins 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• FXFPOKGPAPEJNE-UHFFFAOYSA-N cyclopropanecarboximidamide Chemical compound NC(=N)C1CC1 FXFPOKGPAPEJNE-UHFFFAOYSA-N 0.000 description 1
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
• 229950007409 dacetuzumab Drugs 0.000 description 1
• 229960002806 daclizumab Drugs 0.000 description 1
• 229960000640 dactinomycin Drugs 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 229960002656 didanosine Drugs 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
• 229960002986 dinoprostone Drugs 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 229960003804 efavirenz Drugs 0.000 description 1
• 229940056913 eftilagimod alfa Drugs 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 201000003914 endometrial carcinoma Diseases 0.000 description 1
• PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 1
• 229960002062 enfuvirtide Drugs 0.000 description 1
• 239000002662 enteric coated tablet Substances 0.000 description 1
• 230000004076 epigenetic alteration Effects 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• 201000005619 esophageal carcinoma Diseases 0.000 description 1
• XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• BBNCPWYGTPKOER-UHFFFAOYSA-N ethyl 2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-(1H-indazol-5-ylamino)pyrimidine-5-carboxylate Chemical compound C1(C2=CC(NC3=NC(=C(C=N3)C(=O)OCC)NC3=CC=C4C(C=NN4)=C3)=CC=C2C(=O)O1)(C)C BBNCPWYGTPKOER-UHFFFAOYSA-N 0.000 description 1
• KMKPMZUSRHIKRV-UHFFFAOYSA-N ethyl 2-chloro-4-[[2,2-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]pyrimidine-5-carboxylate Chemical compound N1=C(N=C(C(=C1)C(=O)OCC)NCC(C)(C)CNC(=O)OC(C)(C)C)Cl KMKPMZUSRHIKRV-UHFFFAOYSA-N 0.000 description 1
• IEMKQRSOAOPKRJ-UHFFFAOYSA-N ethyl 2-chloropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)N=C1 IEMKQRSOAOPKRJ-UHFFFAOYSA-N 0.000 description 1
• GAYPZQTWRMZHRT-UHFFFAOYSA-N ethyl 4-[[2,2-dimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]-2-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]pyrimidine-5-carboxylate Chemical compound C(C)(C)(C)OC(=O)NCC(CNC1=NC(=NC=C1C(=O)OCC)NC=1C=C2C(OC(C2=CC=1)=O)(C)C)(C)C GAYPZQTWRMZHRT-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-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
• 230000029142 excretion Effects 0.000 description 1
• 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
• 229960000961 floxuridine Drugs 0.000 description 1
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
• 229960005304 fludarabine phosphate Drugs 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• 239000004052 folic acid antagonist Substances 0.000 description 1
• 235000008191 folinic acid Nutrition 0.000 description 1
• 239000011672 folinic acid Substances 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 201000010175 gallbladder cancer Diseases 0.000 description 1
• 201000007487 gallbladder carcinoma Diseases 0.000 description 1
• GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
• 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 208000010749 gastric carcinoma Diseases 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 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 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
• 230000004077 genetic alteration Effects 0.000 description 1
• 229940080856 gleevec Drugs 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 238000003881 globally optimized alternating phase rectangular pulse Methods 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 150000002315 glycerophosphates Chemical class 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 239000003966 growth inhibitor Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 210000000777 hematopoietic system Anatomy 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 229940022353 herceptin Drugs 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 230000002977 hyperthermial effect Effects 0.000 description 1
• 208000013010 hypopharyngeal carcinoma Diseases 0.000 description 1
• 229960000908 idarubicin Drugs 0.000 description 1
• 229960001101 ifosfamide Drugs 0.000 description 1
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
• 229960002411 imatinib Drugs 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 230000005934 immune activation Effects 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000006028 immune-suppresssive effect Effects 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 229960001936 indinavir Drugs 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 229950009034 indoximod Drugs 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229960005386 ipilimumab Drugs 0.000 description 1
• 229940084651 iressa Drugs 0.000 description 1
• KLEAIHJJLUAXIQ-JDRGBKBRSA-N irinotecan hydrochloride hydrate Chemical compound O.O.O.Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 KLEAIHJJLUAXIQ-JDRGBKBRSA-N 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000003971 isoxazolinyl group Chemical group 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 150000003893 lactate salts Chemical class 0.000 description 1
• 229960001627 lamivudine Drugs 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• 201000005264 laryngeal carcinoma Diseases 0.000 description 1
• 229950004697 lasinavir Drugs 0.000 description 1
• 229960001691 leucovorin Drugs 0.000 description 1
• 230000021633 leukocyte mediated immunity Effects 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• 229950011263 lirilumab Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 229950005339 lobucavir Drugs 0.000 description 1
• 229950003557 lodenosine Drugs 0.000 description 1
• 229960002247 lomustine Drugs 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 229950004563 lucatumumab Drugs 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 235000012245 magnesium oxide Nutrition 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 201000004792 malaria Diseases 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
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
• 206010027191 meningioma Diseases 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• XJZKXKJVDBTQFP-OAQYLSRUSA-N methyl 6-[(3,3-dimethyl-1-oxo-2-benzofuran-5-yl)amino]-4-[[(1S)-2-hydroxy-1-phenylethyl]amino]pyridine-3-carboxylate Chemical compound C1(C2=CC(NC3=CC(=C(C=N3)C(=O)OC)N[C@@H](C3=CC=CC=C3)CO)=CC=C2C(=O)O1)(C)C XJZKXKJVDBTQFP-OAQYLSRUSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 229960001238 methylnicotinate Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 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
• 229960001156 mitoxantrone Drugs 0.000 description 1
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 208000010805 mumps infectious disease Diseases 0.000 description 1
• 201000002077 muscle cancer Diseases 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 229940043348 myristyl alcohol Drugs 0.000 description 1
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• CVOGFMYWFRFWEQ-UHFFFAOYSA-N n'-hydroxy-2,2-dimethylpropanimidamide Chemical compound CC(C)(C)C(N)=NO CVOGFMYWFRFWEQ-UHFFFAOYSA-N 0.000 description 1
• AQBMQGDKWIPBRF-UHFFFAOYSA-N n'-hydroxypyridine-3-carboximidamide Chemical compound ON=C(N)C1=CC=CN=C1 AQBMQGDKWIPBRF-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000006070 nanosuspension Substances 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• NQHXCOAXSHGTIA-SKXNDZRYSA-N nelfinavir mesylate Chemical compound CS(O)(=O)=O.CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 NQHXCOAXSHGTIA-SKXNDZRYSA-N 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 229960000689 nevirapine Drugs 0.000 description 1
• 150000002814 niacins Chemical class 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 229940042404 nucleoside and nucleotide reverse transcriptase inhibitor Drugs 0.000 description 1
• GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 239000007935 oral tablet Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 229940127084 other anti-cancer agent Drugs 0.000 description 1
• 150000003891 oxalate salts Chemical class 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 229960001972 panitumumab Drugs 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000003071 parasitic effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
• 229960002340 pentostatin Drugs 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 229940081066 picolinic acid Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
• 229950010773 pidilizumab Drugs 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• NJBFOOCLYDNZJN-UHFFFAOYSA-N pipobroman Chemical compound BrCCC(=O)N1CCN(C(=O)CCBr)CC1 NJBFOOCLYDNZJN-UHFFFAOYSA-N 0.000 description 1
• 229960000952 pipobroman Drugs 0.000 description 1
• 125000005547 pivalate group Chemical group 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
• 235000015497 potassium bicarbonate Nutrition 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
• 229960000624 procarbazine Drugs 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 201000001514 prostate carcinoma Diseases 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
• RUUOPSRRIKJHNH-UHFFFAOYSA-N pyridazine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=N1 RUUOPSRRIKJHNH-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 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 1
• 230000035484 reaction time Effects 0.000 description 1
• 108091006082 receptor inhibitors Proteins 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 230000000979 retarding effect Effects 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 229960000329 ribavirin Drugs 0.000 description 1
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 125000006413 ring segment Chemical group 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
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 201000003804 salivary gland carcinoma Diseases 0.000 description 1
• 229960001852 saquinavir Drugs 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 239000008299 semisolid dosage form Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 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 1
• 229960002930 sirolimus Drugs 0.000 description 1
• 206010040872 skin infection Diseases 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 229940126586 small molecule drug Drugs 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• JAYHOLAWADPIFN-UHFFFAOYSA-M sodium;pyrimidine-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1=NC=CC=N1 JAYHOLAWADPIFN-UHFFFAOYSA-M 0.000 description 1
• WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 238000007614 solvation Methods 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 239000008347 soybean phospholipid Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 201000000498 stomach carcinoma Diseases 0.000 description 1
• 229960001052 streptozocin Drugs 0.000 description 1
• ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000003900 succinic acid esters Chemical class 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 229960001674 tegafur 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
• 229960001278 teniposide Drugs 0.000 description 1
• QLPCQDZWRXWROH-UHFFFAOYSA-N tert-butyl n-(3-amino-2,2-dimethylpropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC(C)(C)CN QLPCQDZWRXWROH-UHFFFAOYSA-N 0.000 description 1
• HQZCKDWAFDGVHG-UHFFFAOYSA-N tert-butyl n-(4-amino-2-methylbutan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)(C)CCN HQZCKDWAFDGVHG-UHFFFAOYSA-N 0.000 description 1
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 230000004797 therapeutic response Effects 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 150000003567 thiocyanates Chemical class 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 1
• 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
• 125000005490 tosylate group Chemical group 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 229960000575 trastuzumab Drugs 0.000 description 1
• 238000011277 treatment modality Methods 0.000 description 1
• 229950007217 tremelimumab Drugs 0.000 description 1
• 229950001353 tretamine Drugs 0.000 description 1
• IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• 150000004654 triazenes Chemical class 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• WTFFOOAJSDVASL-UHFFFAOYSA-N tributyl(pyrimidin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CC=N1 WTFFOOAJSDVASL-UHFFFAOYSA-N 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 229960001055 uracil mustard Drugs 0.000 description 1
• 229950005972 urelumab Drugs 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 208000019206 urinary tract infection Diseases 0.000 description 1
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 229950001067 varlilumab Drugs 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
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 229940055760 yervoy Drugs 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1
• 229960000523 zalcitabine Drugs 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1