JP2011529904A - 加速された療法 - Google Patents

Info

Publication number

JP2011529904A

JP2011529904A JP2011521327A JP2011521327A JP2011529904A JP 2011529904 A JP2011529904 A JP 2011529904A JP 2011521327 A JP2011521327 A JP 2011521327A JP 2011521327 A JP2011521327 A JP 2011521327A JP 2011529904 A JP2011529904 A JP 2011529904A

Authority

JP

Japan

Prior art keywords

romidepsin

cancer

leu

period

administering

Prior art date

2008-07-30

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• 238000002560 therapeutic procedure Methods 0.000 title description 32
• OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 claims abstract description 159
• OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 claims abstract description 156
• 229960003452 romidepsin Drugs 0.000 claims abstract description 155
• 108010091666 romidepsin Proteins 0.000 claims abstract description 155
• 238000000034 method Methods 0.000 claims description 79
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 44
• 206010028980 Neoplasm Diseases 0.000 claims description 35
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
• 201000010099 disease Diseases 0.000 claims description 27
• 201000011510 cancer Diseases 0.000 claims description 26
• 229960000890 hydrocortisone Drugs 0.000 claims description 22
• 230000002411 adverse Effects 0.000 claims description 19
• 230000001988 toxicity Effects 0.000 claims description 18
• 231100000419 toxicity Toxicity 0.000 claims description 18
• -1 Medrizone Chemical compound 0.000 claims description 17
• 239000003792 electrolyte Substances 0.000 claims description 17
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 239000011734 sodium Substances 0.000 claims description 10
• 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 claims description 9
• 208000027190 Peripheral T-cell lymphomas Diseases 0.000 claims description 9
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 claims description 9
• 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 claims description 9
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 claims description 9
• 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 claims description 9
• 201000005962 mycosis fungoides Diseases 0.000 claims description 9
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 9
• 229910052708 sodium Inorganic materials 0.000 claims description 9
• 230000002062 proliferating effect Effects 0.000 claims description 8
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 7
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 7
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 7
• 206010048610 Cardiotoxicity Diseases 0.000 claims description 7
• 208000034578 Multiple myelomas Diseases 0.000 claims description 7
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
• 239000002253 acid Substances 0.000 claims description 7
• 231100000259 cardiotoxicity Toxicity 0.000 claims description 7
• 229940083542 sodium Drugs 0.000 claims description 7
• 206010025323 Lymphomas Diseases 0.000 claims description 6
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 6
• 201000005787 hematologic cancer Diseases 0.000 claims description 6
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 6
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 5
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 5
• 206010060862 Prostate cancer Diseases 0.000 claims description 5
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
• 239000002246 antineoplastic agent Substances 0.000 claims description 5
• 208000032839 leukemia Diseases 0.000 claims description 5
• 230000002336 repolarization Effects 0.000 claims description 5
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 4
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
• 208000017604 Hodgkin disease Diseases 0.000 claims description 4
• 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 4
• FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 claims description 4
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
• 229940079156 Proteasome inhibitor Drugs 0.000 claims description 4
• FMYKJLXRRQTBOR-BZSNNMDCSA-N acetylleucyl-leucyl-norleucinal Chemical compound CCCC[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(C)=O FMYKJLXRRQTBOR-BZSNNMDCSA-N 0.000 claims description 4
• 108010091545 acetylleucyl-leucyl-norleucinal Proteins 0.000 claims description 4
• 229960001467 bortezomib Drugs 0.000 claims description 4
• 229940127089 cytotoxic agent Drugs 0.000 claims description 4
• 229950002736 marizomib Drugs 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 4
• 239000003207 proteasome inhibitor Substances 0.000 claims description 4
• NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 claims description 4
• WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 claims description 3
• WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 claims description 3
• 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 3
• TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 claims description 3
• 208000007888 Sinus Tachycardia Diseases 0.000 claims description 3
• 229960005354 betamethasone sodium phosphate Drugs 0.000 claims description 3
• PLCQGRYPOISRTQ-LWCNAHDDSA-L betamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-LWCNAHDDSA-L 0.000 claims description 3
• 239000002254 cytotoxic agent Substances 0.000 claims description 3
• 231100000599 cytotoxic agent Toxicity 0.000 claims description 3
• 229960003957 dexamethasone Drugs 0.000 claims description 3
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 3
• 239000003276 histone deacetylase inhibitor Substances 0.000 claims description 3
• 229960005205 prednisolone Drugs 0.000 claims description 3
• OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 3
• 229960004786 prednisolone phosphate Drugs 0.000 claims description 3
• JDOZJEUDSLGTLU-VWUMJDOOSA-N prednisolone phosphate Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 JDOZJEUDSLGTLU-VWUMJDOOSA-N 0.000 claims description 3
• 150000003431 steroids Chemical class 0.000 claims description 3
• 230000009469 supplementation Effects 0.000 claims description 3
• FWPWHHUJACGNMZ-NBBQQVJHSA-N (1s,2r,5r)-5-[(1s)-1-hydroxy-2-methylpropyl]-2-methyl-7-oxa-4-azabicyclo[3.2.0]heptane-3,6-dione Chemical compound N1C(=O)[C@H](C)[C@@H]2OC(=O)[C@@]21[C@@H](O)C(C)C FWPWHHUJACGNMZ-NBBQQVJHSA-N 0.000 claims description 2
• SUGXUUGGLDCZKB-UHFFFAOYSA-N 3,4-dichloroisocoumarin Chemical compound C1=CC=C2C(Cl)=C(Cl)OC(=O)C2=C1 SUGXUUGGLDCZKB-UHFFFAOYSA-N 0.000 claims description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
• PITHJRRCEANNKJ-UHFFFAOYSA-N Aclacinomycin A Natural products C12=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C=C2C(C(=O)OC)C(CC)(O)CC1OC(OC1C)CC(N(C)C)C1OC(OC1C)CC(O)C1OC1CCC(=O)C(C)O1 PITHJRRCEANNKJ-UHFFFAOYSA-N 0.000 claims description 2
• 206010003130 Arrhythmia supraventricular Diseases 0.000 claims description 2
• KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 claims description 2
• 108010004877 CEP 1612 Proteins 0.000 claims description 2
• ITRJWOMZKQRYTA-RFZYENFJSA-N Cortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O ITRJWOMZKQRYTA-RFZYENFJSA-N 0.000 claims description 2
• ZPLVYYNMRMBNGE-UHFFFAOYSA-N Eponemycin Natural products CC(C)CCCCC(=O)NC(CO)C(=O)NC(CC(C)=C)C(=O)C1(CO)CO1 ZPLVYYNMRMBNGE-UHFFFAOYSA-N 0.000 claims description 2
• WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 claims description 2
• 206010059024 Gastrointestinal toxicity Diseases 0.000 claims description 2
• MUQNGPZZQDCDFT-JNQJZLCISA-N Halcinonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]1(C)C[C@@H]2O MUQNGPZZQDCDFT-JNQJZLCISA-N 0.000 claims description 2
• DAQAKHDKYAWHCG-UHFFFAOYSA-N Lactacystin Natural products CC(=O)NC(C(O)=O)CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O DAQAKHDKYAWHCG-UHFFFAOYSA-N 0.000 claims description 2
• KMXHEXRPYSXLRN-JDVQERKKSA-N PS-519 Chemical compound N1C(=O)[C@H](CCC)[C@@H]2OC(=O)[C@@]21[C@@H](O)C(C)C KMXHEXRPYSXLRN-JDVQERKKSA-N 0.000 claims description 2
• LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 claims description 2
• ZIAXNZCTODBCKW-UHFFFAOYSA-N TMC-95 C Natural products C12=CC=CC3=C2NC(=O)C3(O)C(O)C(C(=O)NC=CC)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(=O)C(C)CC)CC2=CC=C(O)C1=C2 ZIAXNZCTODBCKW-UHFFFAOYSA-N 0.000 claims description 2
• 108010065317 TMC-95A Proteins 0.000 claims description 2
• ZIAXNZCTODBCKW-BOYGTWLISA-N TMC-95A Chemical compound O[C@@H]([C@]1(O)C(=O)NC2=C1C=CC=C21)[C@@H](C(=O)N\C=C/C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)C(=O)[C@@H](C)CC)CC2=CC=C(O)C1=C2 ZIAXNZCTODBCKW-BOYGTWLISA-N 0.000 claims description 2
• 229940123237 Taxane Drugs 0.000 claims description 2
• XGMPVBXKDAHORN-RBWIMXSLSA-N Triamcinolone diacetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](OC(C)=O)[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O XGMPVBXKDAHORN-RBWIMXSLSA-N 0.000 claims description 2
• TZIZWYVVGLXXFV-FLRHRWPCSA-N Triamcinolone hexacetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)CC(C)(C)C)[C@@]1(C)C[C@@H]2O TZIZWYVVGLXXFV-FLRHRWPCSA-N 0.000 claims description 2
• 206010047281 Ventricular arrhythmia Diseases 0.000 claims description 2
• USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 claims description 2
• 229960004176 aclarubicin Drugs 0.000 claims description 2
• MGSKVZWGBWPBTF-UHFFFAOYSA-N aebsf Chemical compound NCCC1=CC=C(S(F)(=O)=O)C=C1 MGSKVZWGBWPBTF-UHFFFAOYSA-N 0.000 claims description 2
• FIVPIPIDMRVLAY-UHFFFAOYSA-N aspergillin Natural products C1C2=CC=CC(O)C2N2C1(SS1)C(=O)N(C)C1(CO)C2=O FIVPIPIDMRVLAY-UHFFFAOYSA-N 0.000 claims description 2
• 229950000210 beclometasone dipropionate Drugs 0.000 claims description 2
• 108010002974 benzyloxycarbonylleucyl-leucyl-leucine aldehyde Proteins 0.000 claims description 2
• 229960002537 betamethasone Drugs 0.000 claims description 2
• UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims description 2
• 229960004648 betamethasone acetate Drugs 0.000 claims description 2
• AKUJBENLRBOFTD-QZIXMDIESA-N betamethasone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(C)=O)(O)[C@@]1(C)C[C@@H]2O AKUJBENLRBOFTD-QZIXMDIESA-N 0.000 claims description 2
• 229960000870 betamethasone benzoate Drugs 0.000 claims description 2
• SOQJPQZCPBDOMF-YCUXZELOSA-N betamethasone benzoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@@H]1C)C(=O)CO)C(=O)C1=CC=CC=C1 SOQJPQZCPBDOMF-YCUXZELOSA-N 0.000 claims description 2
• 229960001102 betamethasone dipropionate Drugs 0.000 claims description 2
• CIWBQSYVNNPZIQ-XYWKZLDCSA-N betamethasone dipropionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CIWBQSYVNNPZIQ-XYWKZLDCSA-N 0.000 claims description 2
• 229960004311 betamethasone valerate Drugs 0.000 claims description 2
• SNHRLVCMMWUAJD-SUYDQAKGSA-N betamethasone valerate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O SNHRLVCMMWUAJD-SUYDQAKGSA-N 0.000 claims description 2
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
• BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 claims description 2
• 229960004703 clobetasol propionate Drugs 0.000 claims description 2
• CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 claims description 2
• ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 claims description 2
• BGSOJVFOEQLVMH-VWUMJDOOSA-N cortisol phosphate Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 BGSOJVFOEQLVMH-VWUMJDOOSA-N 0.000 claims description 2
• 229960002425 cortisol succinate Drugs 0.000 claims description 2
• 229960003290 cortisone acetate Drugs 0.000 claims description 2
• 229960003662 desonide Drugs 0.000 claims description 2
• WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 claims description 2
• PLCQGRYPOISRTQ-FCJDYXGNSA-L dexamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-FCJDYXGNSA-L 0.000 claims description 2
• ZPLVYYNMRMBNGE-TWOQFEAHSA-N eponemycin Chemical compound CC(C)CCCCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)=C)C(=O)[C@@]1(CO)CO1 ZPLVYYNMRMBNGE-TWOQFEAHSA-N 0.000 claims description 2
• SYWHXTATXSMDSB-GSLJADNHSA-N fludrocortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O SYWHXTATXSMDSB-GSLJADNHSA-N 0.000 claims description 2
• 229960000676 flunisolide Drugs 0.000 claims description 2
• 229960001347 fluocinolone acetonide Drugs 0.000 claims description 2
• FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 claims description 2
• 229960000785 fluocinonide Drugs 0.000 claims description 2
• 229960003336 fluorocortisol acetate Drugs 0.000 claims description 2
• 231100000414 gastrointestinal toxicity Toxicity 0.000 claims description 2
• 229960005277 gemcitabine Drugs 0.000 claims description 2
• 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 claims description 2
• FIVPIPIDMRVLAY-RBJBARPLSA-N gliotoxin Chemical compound C1C2=CC=C[C@H](O)[C@H]2N2[C@]1(SS1)C(=O)N(C)[C@@]1(CO)C2=O FIVPIPIDMRVLAY-RBJBARPLSA-N 0.000 claims description 2
• 229940103893 gliotoxin Drugs 0.000 claims description 2
• 229930190252 gliotoxin Natural products 0.000 claims description 2
• 231100000226 haematotoxicity Toxicity 0.000 claims description 2
• 229960002383 halcinonide Drugs 0.000 claims description 2
• 229940121372 histone deacetylase inhibitor Drugs 0.000 claims description 2
• 229960001067 hydrocortisone acetate Drugs 0.000 claims description 2
• VWQWXZAWFPZJDA-CGVGKPPMSA-N hydrocortisone succinate Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC(O)=O)[C@@H]4[C@@H]3CCC2=C1 VWQWXZAWFPZJDA-CGVGKPPMSA-N 0.000 claims description 2
• DAQAKHDKYAWHCG-RWTHQLGUSA-N lactacystin Chemical compound CC(=O)N[C@H](C(O)=O)CSC(=O)[C@]1([C@@H](O)C(C)C)NC(=O)[C@H](C)[C@@H]1O DAQAKHDKYAWHCG-RWTHQLGUSA-N 0.000 claims description 2
• 229960004584 methylprednisolone Drugs 0.000 claims description 2
• 229960001293 methylprednisolone acetate Drugs 0.000 claims description 2
• IUDBVFIQSSOIDB-TWOQFEAHSA-N n-[(2s)-3-hydroxy-1-[[(2s)-1-[(2r)-2-(hydroxymethyl)oxiran-2-yl]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]-6-methylheptanamide Chemical compound CC(C)CCCCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(CO)CO1 IUDBVFIQSSOIDB-TWOQFEAHSA-N 0.000 claims description 2
• OOEXUWDNTCTJMI-ZJHKYUCMSA-N n-[(2s)-5-[[amino(nitramido)methylidene]amino]-1-[[(2s)-4-methyl-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]-2-cyclopentyl-10-(1,3-dioxoisoindol-2-yl)decanamide Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCCCCCCCC(C(=O)N[C@@H](CCCN\C(N)=N\[N+]([O-])=O)C(=O)N[C@@H](CC(C)C)C=O)C1CCCC1 OOEXUWDNTCTJMI-ZJHKYUCMSA-N 0.000 claims description 2
• 229960002800 prednisolone acetate Drugs 0.000 claims description 2
• 229960004618 prednisone Drugs 0.000 claims description 2
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 2
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
• MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 claims description 2
• NGWSFRIPKNWYAO-UHFFFAOYSA-N salinosporamide A Natural products N1C(=O)C(CCCl)C2(C)OC(=O)C21C(O)C1CCCC=C1 NGWSFRIPKNWYAO-UHFFFAOYSA-N 0.000 claims description 2
• 230000003637 steroidlike Effects 0.000 claims description 2
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 229960005294 triamcinolone Drugs 0.000 claims description 2
• GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 claims description 2
• YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 claims description 2
• 229960002117 triamcinolone acetonide Drugs 0.000 claims description 2
• 229960004320 triamcinolone diacetate Drugs 0.000 claims description 2
• 229960004221 triamcinolone hexacetonide Drugs 0.000 claims description 2
• 229940070710 valerate Drugs 0.000 claims description 2
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
• 229940099039 velcade Drugs 0.000 claims description 2
• PFAGPIFFRLDBRN-AFKBWYBQSA-N (8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carboxylic acid Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(O)=O)(O)[C@@]1(C)C[C@@H]2O PFAGPIFFRLDBRN-AFKBWYBQSA-N 0.000 claims 1
• 206010060999 Benign neoplasm Diseases 0.000 claims 1
• HUMXXHTVHHLNRO-KAJVQRHHSA-N Prednisolone tebutate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)CC(C)(C)C)(O)[C@@]1(C)C[C@@H]2O HUMXXHTVHHLNRO-KAJVQRHHSA-N 0.000 claims 1
• 206010070308 Refractory cancer Diseases 0.000 claims 1
• 229940022663 acetate Drugs 0.000 claims 1
• 229940034982 antineoplastic agent Drugs 0.000 claims 1
• 229950006991 betamethasone phosphate Drugs 0.000 claims 1
• VQODGRNSFPNSQE-DVTGEIKXSA-N betamethasone phosphate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP(O)(O)=O)(O)[C@@]1(C)C[C@@H]2O VQODGRNSFPNSQE-DVTGEIKXSA-N 0.000 claims 1
• 229960002593 desoximetasone Drugs 0.000 claims 1
• VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 claims 1
• 229960002344 dexamethasone sodium phosphate Drugs 0.000 claims 1
• 230000001589 lymphoproliferative effect Effects 0.000 claims 1
• 230000036210 malignancy Effects 0.000 claims 1
• PLBHSZGDDKCEHR-LFYFAGGJSA-N methylprednisolone acetate Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(C)=O)CC[C@H]21 PLBHSZGDDKCEHR-LFYFAGGJSA-N 0.000 claims 1
• 229950009831 methylprednisolone succinate Drugs 0.000 claims 1
• 229960002744 mometasone furoate Drugs 0.000 claims 1
• WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 claims 1
• 210000004180 plasmocyte Anatomy 0.000 claims 1
• 229960004259 prednisolone tebutate Drugs 0.000 claims 1
• 208000016691 refractory malignant neoplasm Diseases 0.000 claims 1
• DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 32
• 239000011591 potassium Substances 0.000 description 32
• 229960003975 potassium Drugs 0.000 description 32
• 229910052700 potassium Inorganic materials 0.000 description 32
• 229940091250 magnesium supplement Drugs 0.000 description 28
• 239000011777 magnesium Substances 0.000 description 26
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 25
• 229910052749 magnesium Inorganic materials 0.000 description 25
• 210000002966 serum Anatomy 0.000 description 25
• 239000003814 drug Substances 0.000 description 20
• 150000003839 salts Chemical class 0.000 description 18
• 229940079593 drug Drugs 0.000 description 17
• XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 13
• 239000003112 inhibitor Substances 0.000 description 13
• 239000000203 mixture Substances 0.000 description 13
• 229940002612 prodrug Drugs 0.000 description 13
• 239000000651 prodrug Substances 0.000 description 13
• 210000004027 cell Anatomy 0.000 description 12
• 230000000694 effects Effects 0.000 description 10
• 238000001802 infusion Methods 0.000 description 10
• 208000011580 syndromic disease Diseases 0.000 description 9
• 230000005856 abnormality Effects 0.000 description 8
• 150000001875 compounds Chemical class 0.000 description 8
• 208000035475 disorder Diseases 0.000 description 8
• 230000000750 progressive effect Effects 0.000 description 8
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 7
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 7
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 7
• 238000001990 intravenous administration Methods 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 206010033661 Pancytopenia Diseases 0.000 description 6
• 230000002159 abnormal effect Effects 0.000 description 6
• 239000011575 calcium Substances 0.000 description 6
• 208000024389 cytopenia Diseases 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
• 208000009329 Graft vs Host Disease Diseases 0.000 description 5
• 229910052791 calcium Inorganic materials 0.000 description 5
• 208000024908 graft versus host disease Diseases 0.000 description 5
• 208000004235 neutropenia Diseases 0.000 description 5
• 229940070017 potassium supplement Drugs 0.000 description 5
• 206010043554 thrombocytopenia Diseases 0.000 description 5
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 4
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 4
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
• 206010028813 Nausea Diseases 0.000 description 4
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 206010039491 Sarcoma Diseases 0.000 description 4
• 206010047700 Vomiting Diseases 0.000 description 4
• 150000007513 acids Chemical class 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 230000000747 cardiac effect Effects 0.000 description 4
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 4
• 238000002648 combination therapy Methods 0.000 description 4
• 230000034994 death Effects 0.000 description 4
• 231100000517 death Toxicity 0.000 description 4
• 230000002496 gastric effect Effects 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
• 230000008693 nausea Effects 0.000 description 4
• 201000002528 pancreatic cancer Diseases 0.000 description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 description 4
• 239000008177 pharmaceutical agent Substances 0.000 description 4
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• 230000008673 vomiting Effects 0.000 description 4
• 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• 206010003591 Ataxia Diseases 0.000 description 3
• 208000003174 Brain Neoplasms Diseases 0.000 description 3
• 206010012289 Dementia Diseases 0.000 description 3
• 206010012735 Diarrhoea Diseases 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 208000018737 Parkinson disease Diseases 0.000 description 3
• HLCFGWHYROZGBI-JJKGCWMISA-M Potassium gluconate Chemical compound [K+].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O HLCFGWHYROZGBI-JJKGCWMISA-M 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 208000003734 Supraventricular Tachycardia Diseases 0.000 description 3
• 201000006966 adult T-cell leukemia Diseases 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 210000001185 bone marrow Anatomy 0.000 description 3
• 208000025434 cerebellar degeneration Diseases 0.000 description 3
• 238000006243 chemical reaction Methods 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000007850 degeneration Effects 0.000 description 3
• 238000013461 design Methods 0.000 description 3
• 229940000406 drug candidate Drugs 0.000 description 3
• 206010016256 fatigue Diseases 0.000 description 3
• 210000002216 heart Anatomy 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 230000008938 immune dysregulation Effects 0.000 description 3
• 230000028993 immune response Effects 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 238000009140 magnesium supplementation Methods 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 230000004060 metabolic process Effects 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 230000002107 myocardial effect Effects 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 244000052769 pathogen Species 0.000 description 3
• 230000001717 pathogenic effect Effects 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
• 239000004224 potassium gluconate Substances 0.000 description 3
• 235000013926 potassium gluconate Nutrition 0.000 description 3
• 229960003189 potassium gluconate Drugs 0.000 description 3
• 238000009138 potassium supplementation Methods 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 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 2
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
• 206010067484 Adverse reaction Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 206010003658 Atrial Fibrillation Diseases 0.000 description 2
• 206010003694 Atrophy Diseases 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
• 206010065553 Bone marrow failure Diseases 0.000 description 2
• 208000018084 Bone neoplasm Diseases 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
• 206010009900 Colitis ulcerative Diseases 0.000 description 2
• 208000032170 Congenital Abnormalities Diseases 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• 102000004420 Creatine Kinase Human genes 0.000 description 2
• 108010042126 Creatine kinase Proteins 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• 108010002156 Depsipeptides Proteins 0.000 description 2
• 206010012438 Dermatitis atopic Diseases 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 2
• 102000003964 Histone deacetylase Human genes 0.000 description 2
• 108090000353 Histone deacetylase Proteins 0.000 description 2
• 208000023105 Huntington disease Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 206010020751 Hypersensitivity Diseases 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 208000001089 Multiple system atrophy Diseases 0.000 description 2
• 240000008790 Musa x paradisiaca Species 0.000 description 2
• 206010028289 Muscle atrophy Diseases 0.000 description 2
• 206010028372 Muscular weakness Diseases 0.000 description 2
• 206010029240 Neuritis Diseases 0.000 description 2
• 206010033128 Ovarian cancer Diseases 0.000 description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 description 2
• 206010033799 Paralysis Diseases 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• 206010038389 Renal cancer Diseases 0.000 description 2
• 208000000453 Skin Neoplasms Diseases 0.000 description 2
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 description 2
• 206010047115 Vasculitis Diseases 0.000 description 2
• 229960000583 acetic acid Drugs 0.000 description 2
• 230000006838 adverse reaction Effects 0.000 description 2
• 125000000217 alkyl group Chemical group 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 description 2
• 239000002260 anti-inflammatory agent Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 201000008937 atopic dermatitis Diseases 0.000 description 2
• 230000037444 atrophy Effects 0.000 description 2
• 235000021015 bananas Nutrition 0.000 description 2
• 229960005069 calcium Drugs 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 229940044683 chemotherapy drug Drugs 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 230000036461 convulsion Effects 0.000 description 2
• 230000001054 cortical effect Effects 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 231100000135 cytotoxicity Toxicity 0.000 description 2
• 230000003013 cytotoxicity Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 2
• 229940043264 dodecyl sulfate Drugs 0.000 description 2
• 231100000371 dose-limiting toxicity Toxicity 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 239000004052 folic acid antagonist Substances 0.000 description 2
• VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound 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 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 2
• 235000008191 folinic acid Nutrition 0.000 description 2
• 239000011672 folinic acid Substances 0.000 description 2
• 235000013305 food Nutrition 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 238000001415 gene therapy Methods 0.000 description 2
• 230000002489 hematologic effect Effects 0.000 description 2
• 201000001421 hyperglycemia Diseases 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000007794 irritation Effects 0.000 description 2
• 201000010982 kidney cancer Diseases 0.000 description 2
• 229960001691 leucovorin Drugs 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 201000007270 liver cancer Diseases 0.000 description 2
• 208000014018 liver neoplasm Diseases 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 201000005202 lung cancer Diseases 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• 229910001629 magnesium chloride Inorganic materials 0.000 description 2
• 229960002337 magnesium chloride Drugs 0.000 description 2
• 235000011147 magnesium chloride Nutrition 0.000 description 2
• 239000001755 magnesium gluconate Substances 0.000 description 2
• 235000015778 magnesium gluconate Nutrition 0.000 description 2
• 229960003035 magnesium gluconate Drugs 0.000 description 2
• OVGXLJDWSLQDRT-UHFFFAOYSA-L magnesium lactate Chemical compound [Mg+2].CC(O)C([O-])=O.CC(O)C([O-])=O OVGXLJDWSLQDRT-UHFFFAOYSA-L 0.000 description 2
• 239000000626 magnesium lactate Substances 0.000 description 2
• 235000015229 magnesium lactate Nutrition 0.000 description 2
• 229960004658 magnesium lactate Drugs 0.000 description 2
• 239000000395 magnesium oxide Substances 0.000 description 2
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
• 229960000869 magnesium oxide Drugs 0.000 description 2
• 235000012245 magnesium oxide Nutrition 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• IAKLPCRFBAZVRW-XRDLMGPZSA-L magnesium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;hydrate Chemical compound O.[Mg+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O IAKLPCRFBAZVRW-XRDLMGPZSA-L 0.000 description 2
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• 239000003697 methyltransferase inhibitor Substances 0.000 description 2
• 208000005264 motor neuron disease Diseases 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 201000000585 muscular atrophy Diseases 0.000 description 2
• 230000036473 myasthenia Effects 0.000 description 2
• 230000000926 neurological effect Effects 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
• 230000002688 persistence Effects 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• 229940127557 pharmaceutical product Drugs 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 229950010765 pivalate Drugs 0.000 description 2
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 230000033764 rhythmic process Effects 0.000 description 2
• 230000001953 sensory effect Effects 0.000 description 2
• 235000014214 soft drink Nutrition 0.000 description 2
• 239000007787 solid Substances 0.000 description 2
• 208000002320 spinal muscular atrophy Diseases 0.000 description 2
• 201000011549 stomach cancer Diseases 0.000 description 2
• 208000011117 substance-related disease Diseases 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• MHFUWOIXNMZFIW-WNQIDUERSA-N (2s)-2-hydroxypropanoic acid;n-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide Chemical compound C[C@H](O)C(O)=O.C1CN(C)CCN1C1=CC(NC2=NNC(C)=C2)=NC(SC=2C=CC(NC(=O)C3CC3)=CC=2)=N1 MHFUWOIXNMZFIW-WNQIDUERSA-N 0.000 description 1
• SNAJPQVDGYDQSW-DYCFWDQMSA-N (4r,7s,10r,13s,16r)-7-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-16-[[(2r)-2-amino-3-phenylpropanoyl]amino]-13-[(4-hydroxyphenyl)methyl]-10-(1h-indol-3-ylmethyl)-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxami Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC1=O)C(=O)N[C@@H]([C@H](O)C)C(N)=O)C1=CC=CC=C1 SNAJPQVDGYDQSW-DYCFWDQMSA-N 0.000 description 1
• FAYAUAZLLLJJGH-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[5-[2-(4-thieno[3,2-d]pyrimidinylamino)ethyl]-2-thiazolyl]urea Chemical compound ClC1=CC=CC(NC(=O)NC=2SC(CCNC=3C=4SC=CC=4N=CN=3)=CN=2)=C1 FAYAUAZLLLJJGH-UHFFFAOYSA-N 0.000 description 1
• IKBSEBRGSVFUHM-UHFFFAOYSA-N 1-[3-[4-(3-bromo-2h-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-(2-pyrrolidin-1-ylethylamino)phenyl]-4,4,4-trifluorobutan-1-one Chemical compound C1=C(C(=O)CCC(F)(F)F)C=C(N2CCN(CC2)C=2C=3C(Br)=NNC=3N=CN=2)C(C)=C1NCCN1CCCC1 IKBSEBRGSVFUHM-UHFFFAOYSA-N 0.000 description 1
• OVOUKWFJRHALDD-UHFFFAOYSA-N 2-[2-(2-acetyloxyethoxy)ethoxy]ethyl acetate Chemical compound CC(=O)OCCOCCOCCOC(C)=O OVOUKWFJRHALDD-UHFFFAOYSA-N 0.000 description 1
• QINPEPAQOBZPOF-UHFFFAOYSA-N 2-amino-n-[3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl]-2-methylpropanamide Chemical compound COC1=CC=C(Cl)C(NC=2C(=NC3=CC=CC=C3N=2)NS(=O)(=O)C=2C=C(NC(=O)C(C)(C)N)C=CC=2)=C1 QINPEPAQOBZPOF-UHFFFAOYSA-N 0.000 description 1
• SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• FGTCROZDHDSNIO-UHFFFAOYSA-N 3-(4-quinolinylmethylamino)-N-[4-(trifluoromethoxy)phenyl]-2-thiophenecarboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)C1=C(NCC=2C3=CC=CC=C3N=CC=2)C=CS1 FGTCROZDHDSNIO-UHFFFAOYSA-N 0.000 description 1
• IAYGCINLNONXHY-LBPRGKRZSA-N 3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-3-piperidinyl]-2-thiophenecarboxamide Chemical compound NC(=O)NC=1C=C(C=2C=C(F)C=CC=2)SC=1C(=O)N[C@H]1CCCNC1 IAYGCINLNONXHY-LBPRGKRZSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 description 1
• ZLHFILGSQDJULK-UHFFFAOYSA-N 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3C4=CC=C(Cl)C=C4C(=NCC3=CN=2)C=2C(=CC=CC=2F)OC)=C1 ZLHFILGSQDJULK-UHFFFAOYSA-N 0.000 description 1
• GPSZYOIFQZPWEJ-UHFFFAOYSA-N 4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine Chemical compound N1=C(N)SC(C=2N=C(NC=3C=CC(=CC=3)N3CCOCC3)N=CC=2)=C1C GPSZYOIFQZPWEJ-UHFFFAOYSA-N 0.000 description 1
• ALKJNCZNEOTEMP-UHFFFAOYSA-N 4-n-(5-cyclopropyl-1h-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-n-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound O1N=C(C(C)C)C=C1CNC1=NC(NC=2NN=C(C=2)C2CC2)=CC(N2CCN(C)CC2)=N1 ALKJNCZNEOTEMP-UHFFFAOYSA-N 0.000 description 1
• ZHJGWYRLJUCMRT-QGZVFWFLSA-N 5-[6-[(4-methyl-1-piperazinyl)methyl]-1-benzimidazolyl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]-2-thiophenecarboxamide Chemical compound O([C@H](C)C=1C(=CC=CC=1)C(F)(F)F)C(=C(S1)C(N)=O)C=C1N(C1=C2)C=NC1=CC=C2CN1CCN(C)CC1 ZHJGWYRLJUCMRT-QGZVFWFLSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
• 208000004998 Abdominal Pain Diseases 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
• ULXXDDBFHOBEHA-ONEGZZNKSA-N Afatinib Chemical compound N1=CN=C2C=C(OC3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-ONEGZZNKSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 244000144725 Amygdalus communis Species 0.000 description 1
• 241000208223 Anacardiaceae Species 0.000 description 1
• 208000032467 Aplastic anaemia Diseases 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 206010003662 Atrial flutter Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
• 208000023328 Basedow disease Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 208000024806 Brain atrophy Diseases 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
• 235000017647 Brassica oleracea var italica Nutrition 0.000 description 1
• 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
• 206010006482 Bronchospasm Diseases 0.000 description 1
• 206010006895 Cachexia Diseases 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 108010077544 Chromatin Proteins 0.000 description 1
• 241000555825 Clupeidae Species 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 206010010774 Constipation Diseases 0.000 description 1
• 244000019459 Cynara cardunculus Species 0.000 description 1
• 235000019106 Cynara scolymus Nutrition 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
• 208000005156 Dehydration Diseases 0.000 description 1
• 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
• DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 1
• 206010013654 Drug abuse Diseases 0.000 description 1
• 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
• 206010013911 Dysgeusia Diseases 0.000 description 1
• 208000012661 Dyskinesia Diseases 0.000 description 1
• 208000032274 Encephalopathy Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102000003951 Erythropoietin Human genes 0.000 description 1
• 108090000394 Erythropoietin Proteins 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 208000004332 Evans syndrome Diseases 0.000 description 1
• 206010016212 Familial tremor Diseases 0.000 description 1
• MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 1
• 208000024412 Friedreich ataxia Diseases 0.000 description 1
• 201000011240 Frontotemporal dementia Diseases 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• KGPGFQWBCSZGEL-ZDUSSCGKSA-N GSK690693 Chemical compound C=12N(CC)C(C=3C(=NON=3)N)=NC2=C(C#CC(C)(C)O)N=CC=1OC[C@H]1CCCNC1 KGPGFQWBCSZGEL-ZDUSSCGKSA-N 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 208000007569 Giant Cell Tumors Diseases 0.000 description 1
• 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 206010018901 Haemoglobinaemia Diseases 0.000 description 1
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
• 102000001554 Hemoglobins Human genes 0.000 description 1
• 108010054147 Hemoglobins Proteins 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 208000001799 Hereditary Optic Atrophies Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 206010062904 Hormone-refractory prostate cancer Diseases 0.000 description 1
• 241000598436 Human T-cell lymphotropic virus Species 0.000 description 1
• 201000001431 Hyperuricemia Diseases 0.000 description 1
• 208000013038 Hypocalcemia Diseases 0.000 description 1
• 208000019025 Hypokalemia Diseases 0.000 description 1
• 206010021027 Hypomagnesaemia Diseases 0.000 description 1
• 206010021036 Hyponatraemia Diseases 0.000 description 1
• 208000029663 Hypophosphatemia Diseases 0.000 description 1
• 208000001953 Hypotension Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• 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
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
• 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
• 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 206010024229 Leprosy Diseases 0.000 description 1
• 208000009829 Lewy Body Disease Diseases 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
• 206010025327 Lymphopenia Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 208000026072 Motor neurone disease Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• 208000036572 Myoclonic epilepsy Diseases 0.000 description 1
• 206010061533 Myotonia Diseases 0.000 description 1
• FOFDIMHVKGYHRU-UHFFFAOYSA-N N-(1,3-benzodioxol-5-ylmethyl)-4-(4-benzofuro[3,2-d]pyrimidinyl)-1-piperazinecarbothioamide Chemical compound C12=CC=CC=C2OC2=C1N=CN=C2N(CC1)CCN1C(=S)NCC1=CC=C(OCO2)C2=C1 FOFDIMHVKGYHRU-UHFFFAOYSA-N 0.000 description 1
• XKFTZKGMDDZMJI-HSZRJFAPSA-N N-[5-[(2R)-2-methoxy-1-oxo-2-phenylethyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methyl-1-piperazinyl)benzamide Chemical compound O=C([C@H](OC)C=1C=CC=CC=1)N(CC=12)CC=1NN=C2NC(=O)C(C=C1)=CC=C1N1CCN(C)CC1 XKFTZKGMDDZMJI-HSZRJFAPSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 208000030852 Parasitic disease Diseases 0.000 description 1
• 244000025272 Persea americana Species 0.000 description 1
• 235000008673 Persea americana Nutrition 0.000 description 1
• 244000046052 Phaseolus vulgaris Species 0.000 description 1
• 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
• 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
• 241000018646 Pinus brutia Species 0.000 description 1
• 235000011613 Pinus brutia Nutrition 0.000 description 1
• 208000002151 Pleural effusion Diseases 0.000 description 1
• 206010036105 Polyneuropathy Diseases 0.000 description 1
• 241000206607 Porphyra umbilicalis Species 0.000 description 1
• NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
• 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
• 208000033526 Proximal spinal muscular atrophy type 3 Diseases 0.000 description 1
• 244000018633 Prunus armeniaca Species 0.000 description 1
• 235000009827 Prunus armeniaca Nutrition 0.000 description 1
• 206010038910 Retinitis Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
• 240000003768 Solanum lycopersicum Species 0.000 description 1
• 206010041349 Somnolence Diseases 0.000 description 1
• 235000009337 Spinacia oleracea Nutrition 0.000 description 1
• 244000300264 Spinacia oleracea Species 0.000 description 1
• 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 1
• 206010041925 Staphylococcal infections Diseases 0.000 description 1
• 241000862969 Stella Species 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 206010042600 Supraventricular arrhythmias Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 206010057644 Testis cancer Diseases 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 206010044074 Torticollis Diseases 0.000 description 1
• 208000000323 Tourette Syndrome Diseases 0.000 description 1
• 208000016620 Tourette disease Diseases 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• 108090001027 Troponin Proteins 0.000 description 1
• 102000004903 Troponin Human genes 0.000 description 1
• 102000013394 Troponin I Human genes 0.000 description 1
• 108010065729 Troponin I Proteins 0.000 description 1
• 102100040653 Tryptophan 2,3-dioxygenase Human genes 0.000 description 1
• 101710136122 Tryptophan 2,3-dioxygenase Proteins 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 102000004243 Tubulin Human genes 0.000 description 1
• 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 208000002495 Uterine Neoplasms Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 240000006365 Vitis vinifera Species 0.000 description 1
• 235000014787 Vitis vinifera Nutrition 0.000 description 1
• 208000008383 Wilms tumor Diseases 0.000 description 1
• FPVRUILUEYSIMD-RPRRAYFGSA-N [(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(OC(C)=O)[C@@]1(C)C[C@@H]2O FPVRUILUEYSIMD-RPRRAYFGSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• MGVGMXLGOKTYKP-ZFOBEOMCSA-N acetic acid;(6s,8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-17-(2-hydroxyacetyl)-6,10,13-trimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-3-one Chemical compound CC(O)=O.C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 MGVGMXLGOKTYKP-ZFOBEOMCSA-N 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• 235000020224 almond Nutrition 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• 229950010817 alvocidib 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
• 125000003277 amino group Chemical class 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 230000000202 analgesic effect Effects 0.000 description 1
• 229940035676 analgesics Drugs 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 208000022531 anorexia Diseases 0.000 description 1
• 239000000730 antalgic agent Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000001142 anti-diarrhea Effects 0.000 description 1
• 230000003474 anti-emetic effect Effects 0.000 description 1
• 230000003432 anti-folate effect Effects 0.000 description 1
• 230000001062 anti-nausea Effects 0.000 description 1
• 230000001754 anti-pyretic effect Effects 0.000 description 1
• 239000003416 antiarrhythmic agent Substances 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940125714 antidiarrheal agent Drugs 0.000 description 1
• 239000003793 antidiarrheal agent Substances 0.000 description 1
• 229940125683 antiemetic agent Drugs 0.000 description 1
• 239000002111 antiemetic agent Substances 0.000 description 1
• 229940127074 antifolate Drugs 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 239000002221 antipyretic Substances 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 208000011775 arteriosclerosis disease Diseases 0.000 description 1
• 235000016520 artichoke thistle Nutrition 0.000 description 1
• 125000005362 aryl sulfone group Chemical group 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 206010003549 asthenia Diseases 0.000 description 1
• 238000001479 atomic absorption spectroscopy Methods 0.000 description 1
• 230000001746 atrial effect Effects 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 231100000877 autonomic nervous system dysfunction Toxicity 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 229960000397 bevacizumab Drugs 0.000 description 1
• 239000012867 bioactive agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000000740 bleeding effect Effects 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 238000004820 blood count Methods 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 235000020113 brazil nut Nutrition 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 235000020226 cashew nut Nutrition 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 229960005395 cetuximab Drugs 0.000 description 1
• 210000003483 chromatin Anatomy 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 238000004737 colorimetric analysis Methods 0.000 description 1
• 238000003926 complexometric titration Methods 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 229960002448 dasatinib Drugs 0.000 description 1
• 229960003603 decitabine Drugs 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 229960003657 dexamethasone acetate Drugs 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• YKZPPPNXRZHVGX-PXYKVGKMSA-L dipotassium;(2s)-2-aminobutanedioate;hydron;hydrate Chemical compound [H+].[H+].O.[K+].[K+].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O YKZPPPNXRZHVGX-PXYKVGKMSA-L 0.000 description 1
• ZQGJCHHKJNSPMS-UHFFFAOYSA-L disodium;[6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-3-oxopyrido[3,2-b][1,4]oxazin-4-yl]methyl phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].COC1=C(OC)C(OC)=CC(NC=2N=C(NC=3N=C4N(COP([O-])([O-])=O)C(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=C1 ZQGJCHHKJNSPMS-UHFFFAOYSA-L 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 206010013663 drug dependence Diseases 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 238000003370 dye binding method Methods 0.000 description 1
• 201000009028 early myoclonic encephalopathy Diseases 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 238000004993 emission spectroscopy Methods 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
• 229940105423 erythropoietin Drugs 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 201000006517 essential tremor Diseases 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 210000003414 extremity Anatomy 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000005048 flame photometry Methods 0.000 description 1
• 238000002637 fluid replacement therapy Methods 0.000 description 1
• 229960001048 fluorometholone Drugs 0.000 description 1
• FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 229960002584 gefitinib Drugs 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
• 230000002068 genetic effect Effects 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 208000035474 group of disease Diseases 0.000 description 1
• 239000003966 growth inhibitor Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000004217 heart function Effects 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 208000010710 hepatitis C virus infection Diseases 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 208000008675 hereditary spastic paraplegia Diseases 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 230000000705 hypocalcaemia Effects 0.000 description 1
• 230000036543 hypotension Effects 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 229960002411 imatinib Drugs 0.000 description 1
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
• 230000005934 immune activation Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 208000018197 inherited torticollis Diseases 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 201000004815 juvenile spinal muscular atrophy Diseases 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 229960004891 lapatinib Drugs 0.000 description 1
• BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• MPVGZUGXCQEXTM-UHFFFAOYSA-N linifanib Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)C=2C=3C(N)=NNC=3C=CC=2)=C1 MPVGZUGXCQEXTM-UHFFFAOYSA-N 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 229960001078 lithium Drugs 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 231100001023 lymphopenia Toxicity 0.000 description 1
• 235000021333 magnesium rich food Nutrition 0.000 description 1
• 206010025482 malaise Diseases 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 230000036244 malformation Effects 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• MMNNTJYFHUDSKL-UHFFFAOYSA-N methyl n-[6-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxoisoindol-1-yl]-1h-benzimidazol-2-yl]carbamate Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1C(C1=CC=CC=C1C1=O)(O)N1C1=CC(Cl)=CC=C1C MMNNTJYFHUDSKL-UHFFFAOYSA-N 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 229960001664 mometasone Drugs 0.000 description 1
• QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
• 210000000214 mouth Anatomy 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 210000000944 nerve tissue Anatomy 0.000 description 1
• 201000002120 neuroendocrine carcinoma Diseases 0.000 description 1
• 201000011519 neuroendocrine tumor Diseases 0.000 description 1
• 230000002232 neuromuscular Effects 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229960001346 nilotinib Drugs 0.000 description 1
• HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 231100000957 no side effect Toxicity 0.000 description 1
• 235000014571 nuts Nutrition 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 229960001972 panitumumab Drugs 0.000 description 1
• 229960005489 paracetamol Drugs 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 229960003407 pegaptanib Drugs 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 238000009520 phase I clinical trial Methods 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 208000019629 polyneuritis Diseases 0.000 description 1
• 229940068988 potassium aspartate Drugs 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
• 229940094025 potassium bicarbonate Drugs 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• 229960002816 potassium chloride Drugs 0.000 description 1
• 239000001508 potassium citrate Substances 0.000 description 1
• 229960002635 potassium citrate Drugs 0.000 description 1
• QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
• 235000011082 potassium citrates Nutrition 0.000 description 1
• 208000024896 potassium deficiency disease Diseases 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 229940069337 potassium orotate Drugs 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• DHBUISJCVRMTAZ-UHFFFAOYSA-M potassium;2,4-dioxo-1h-pyrimidine-6-carboxylate Chemical compound [K+].[O-]C(=O)C1=CC(=O)NC(=O)N1 DHBUISJCVRMTAZ-UHFFFAOYSA-M 0.000 description 1
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
• 238000004313 potentiometry Methods 0.000 description 1
• 229960000214 pralatrexate Drugs 0.000 description 1
• OGSBUKJUDHAQEA-WMCAAGNKSA-N pralatrexate Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CC(CC#C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OGSBUKJUDHAQEA-WMCAAGNKSA-N 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 238000002203 pretreatment Methods 0.000 description 1
• 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000005412 pyrazyl group Chemical group 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• CVWXJKQAOSCOAB-UHFFFAOYSA-N quizartinib Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=CC(=CC=2)C=2N=C3N(C4=CC=C(OCCN5CCOCC5)C=C4S3)C=2)=N1 CVWXJKQAOSCOAB-UHFFFAOYSA-N 0.000 description 1
• 229960003876 ranibizumab Drugs 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• OWBFCJROIKNMGD-BQYQJAHWSA-N rigosertib Chemical compound COC1=CC(OC)=CC(OC)=C1\C=C\S(=O)(=O)CC1=CC=C(OC)C(NCC(O)=O)=C1 OWBFCJROIKNMGD-BQYQJAHWSA-N 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 235000019512 sardine Nutrition 0.000 description 1
• 231100000004 severe toxicity Toxicity 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 229960003787 sorafenib Drugs 0.000 description 1
• 230000001148 spastic effect Effects 0.000 description 1
• 230000005418 spin wave Effects 0.000 description 1
• 208000015339 staphylococcus aureus infection Diseases 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 210000003523 substantia nigra Anatomy 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000007939 sustained release tablet Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 206010042772 syncope Diseases 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000000472 traumatic effect Effects 0.000 description 1
• 208000032527 type III spinal muscular atrophy Diseases 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• 230000004222 uncontrolled growth Effects 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 206010046766 uterine cancer Diseases 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 235000015192 vegetable juice Nutrition 0.000 description 1
• 230000002861 ventricular Effects 0.000 description 1
• 208000003663 ventricular fibrillation Diseases 0.000 description 1
• 206010047302 ventricular tachycardia Diseases 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 208000016261 weight loss Diseases 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1