CA3220332A1 - Composition et methode de double ciblage dans le traitement de tumeurs neuroendocrines - Google Patents
Composition et methode de double ciblage dans le traitement de tumeurs neuroendocrines Download PDFInfo
- Publication number
- CA3220332A1 CA3220332A1 CA3220332A CA3220332A CA3220332A1 CA 3220332 A1 CA3220332 A1 CA 3220332A1 CA 3220332 A CA3220332 A CA 3220332A CA 3220332 A CA3220332 A CA 3220332A CA 3220332 A1 CA3220332 A1 CA 3220332A1
- Authority
- CA
- Canada
- Prior art keywords
- composition
- group
- compound
- tumor
- tat
- Prior art date
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 186
- 238000011282 treatment Methods 0.000 title claims abstract description 67
- 201000011519 neuroendocrine tumor Diseases 0.000 title claims abstract description 34
- 230000008685 targeting Effects 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 16
- 230000009977 dual effect Effects 0.000 title claims abstract description 13
- 102000008092 Norepinephrine Plasma Membrane Transport Proteins Human genes 0.000 claims abstract description 42
- 108010049586 Norepinephrine Plasma Membrane Transport Proteins Proteins 0.000 claims abstract description 42
- 239000000126 substance Substances 0.000 claims abstract description 12
- ABSNGNUGFQIDDO-UHFFFAOYSA-N 2-benzylguanidine Chemical compound NC(N)=NCC1=CC=CC=C1 ABSNGNUGFQIDDO-UHFFFAOYSA-N 0.000 claims description 68
- 150000001875 compounds Chemical class 0.000 claims description 51
- PPJYSSNKSXAVDB-UHFFFAOYSA-N 3,3',5,5'-tetraiodothyroacetic acid Chemical compound IC1=CC(CC(=O)O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 PPJYSSNKSXAVDB-UHFFFAOYSA-N 0.000 claims description 33
- 206010029260 Neuroblastoma Diseases 0.000 claims description 31
- 239000002202 Polyethylene glycol Substances 0.000 claims description 29
- 229920001223 polyethylene glycol Polymers 0.000 claims description 29
- 210000004881 tumor cell Anatomy 0.000 claims description 23
- 229920000642 polymer Polymers 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 15
- 150000003852 triazoles Chemical class 0.000 claims description 15
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 12
- 206010052399 Neuroendocrine tumour Diseases 0.000 claims description 10
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 10
- 208000016065 neuroendocrine neoplasm Diseases 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229940044551 receptor antagonist Drugs 0.000 claims description 7
- 239000002464 receptor antagonist Substances 0.000 claims description 7
- 125000002560 nitrile group Chemical group 0.000 claims description 6
- 208000021010 pancreatic neuroendocrine tumor Diseases 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 208000017084 enterochromaffin cell serotonin-producing pancreatic neuroendocrine tumor Diseases 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 4
- UOWZUVNAGUAEQC-UHFFFAOYSA-N tiratricol Chemical compound IC1=CC(CC(=O)O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 UOWZUVNAGUAEQC-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 2
- 208000033383 Neuroendocrine tumor of pancreas Diseases 0.000 claims description 2
- 206010067517 Pancreatic neuroendocrine tumour Diseases 0.000 claims description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M nitrite group Chemical group N(=O)[O-] IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 31
- 230000015572 biosynthetic process Effects 0.000 abstract description 26
- 238000003786 synthesis reaction Methods 0.000 abstract description 25
- 108010078791 Carrier Proteins Proteins 0.000 abstract description 10
- 229940127449 Integrin Receptor Antagonists Drugs 0.000 abstract description 4
- 239000005495 thyroid hormone Substances 0.000 abstract description 4
- 229940036555 thyroid hormone Drugs 0.000 abstract description 4
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 abstract description 3
- 150000003943 catecholamines Chemical class 0.000 abstract description 3
- 238000002059 diagnostic imaging Methods 0.000 abstract description 2
- 206010028980 Neoplasm Diseases 0.000 description 98
- 239000005557 antagonist Substances 0.000 description 52
- 210000004027 cell Anatomy 0.000 description 32
- 241000699670 Mus sp. Species 0.000 description 26
- 125000005647 linker group Chemical group 0.000 description 20
- -1 TAT Chemical compound 0.000 description 17
- 102000006495 integrins Human genes 0.000 description 15
- 108010044426 integrins Proteins 0.000 description 15
- 230000037361 pathway Effects 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 230000017074 necrotic cell death Effects 0.000 description 12
- 201000011510 cancer Diseases 0.000 description 11
- 230000035899 viability Effects 0.000 description 11
- 238000003384 imaging method Methods 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 230000004614 tumor growth Effects 0.000 description 10
- 208000028591 pheochromocytoma Diseases 0.000 description 9
- PDWUPXJEEYOOTR-UHFFFAOYSA-N 2-[(3-iodophenyl)methyl]guanidine Chemical group NC(=N)NCC1=CC=CC(I)=C1 PDWUPXJEEYOOTR-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000011260 co-administration Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000001629 suppression Effects 0.000 description 6
- 230000003833 cell viability Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 235000015320 potassium carbonate Nutrition 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 4
- RQJDUEKERVZLLU-UHFFFAOYSA-N 4-Hydroxybenzylamine Chemical class NCC1=CC=C(O)C=C1 RQJDUEKERVZLLU-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 208000002458 carcinoid tumor Diseases 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 230000008034 disappearance Effects 0.000 description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000003032 molecular docking Methods 0.000 description 4
- 229960002748 norepinephrine Drugs 0.000 description 4
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 125000005490 tosylate group Chemical group 0.000 description 4
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 229940123712 Thyroid hormone receptor antagonist Drugs 0.000 description 3
- 230000001772 anti-angiogenic effect Effects 0.000 description 3
- 230000004700 cellular uptake Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000011284 combination treatment Methods 0.000 description 3
- 229940125758 compound 15 Drugs 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 3
- PONJIMVVHPQAJL-UHFFFAOYSA-N tert-butyl n-[(4-hydroxyphenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(O)C=C1 PONJIMVVHPQAJL-UHFFFAOYSA-N 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 102000008607 Integrin beta3 Human genes 0.000 description 2
- 108010020950 Integrin beta3 Proteins 0.000 description 2
- 206010061332 Paraganglion neoplasm Diseases 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 208000007660 Residual Neoplasm Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000003200 antithyroid agent Substances 0.000 description 2
- 229940072107 ascorbate Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 239000002585 base Substances 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
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 150000005829 chemical entities Chemical class 0.000 description 2
- 229910052681 coesite Inorganic materials 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 2
- 229910052906 cristobalite Inorganic materials 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000004886 head movement Effects 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 150000002871 norepinephrines Chemical class 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 208000007312 paraganglioma Diseases 0.000 description 2
- 229960005141 piperazine Drugs 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052682 stishovite Inorganic materials 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- GYALMLCJYDIGKG-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]-n-(pyrazole-1-carboximidoyl)carbamate Chemical compound CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C(=N)N1C=CC=N1 GYALMLCJYDIGKG-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 108090000721 thyroid hormone receptors Proteins 0.000 description 2
- 102000004217 thyroid hormone receptors Human genes 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 229910052905 tridymite Inorganic materials 0.000 description 2
- 230000010304 tumor cell viability Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- XWNJMSJGJFSGRY-UHFFFAOYSA-N 2-(benzylamino)-3,7-dihydropurin-6-one Chemical compound N1C=2N=CNC=2C(=O)N=C1NCC1=CC=CC=C1 XWNJMSJGJFSGRY-UHFFFAOYSA-N 0.000 description 1
- LTHQYKLNICEFNE-UHFFFAOYSA-N BrCCOCCOCCOCCOCCOCCOCCN=[N+]=[N-] Chemical compound BrCCOCCOCCOCCOCCOCCOCCN=[N+]=[N-] LTHQYKLNICEFNE-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010007275 Carcinoid tumour Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 101100440985 Danio rerio crad gene Proteins 0.000 description 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 101100440987 Mus musculus Cracd gene Proteins 0.000 description 1
- 101100467905 Mus musculus Rdh16 gene Proteins 0.000 description 1
- 238000012565 NMR experiment Methods 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 206010040830 Skin discomfort Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- HHRFWSALGNYPHA-UHFFFAOYSA-N [N].C1CNCCN1 Chemical compound [N].C1CNCCN1 HHRFWSALGNYPHA-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 102000019997 adhesion receptor Human genes 0.000 description 1
- 108010013985 adhesion receptor Proteins 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical group 0.000 description 1
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
- 235000018660 ammonium molybdate Nutrition 0.000 description 1
- 239000011609 ammonium molybdate Substances 0.000 description 1
- 229940010552 ammonium molybdate Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 238000012650 click reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000000816 effect on animals Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- PDWUPXJEEYOOTR-IUAIQHPESA-N iobenguane (123I) Chemical compound NC(N)=NCC1=CC=CC([123I])=C1 PDWUPXJEEYOOTR-IUAIQHPESA-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
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- MUTCAPXLKRYEPR-ITWZMISCSA-N methyl (e,3r,5s)-7-[4-bromo-2,3-bis(4-fluorophenyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyhept-6-enoate Chemical compound COC(=O)C[C@H](O)C[C@H](O)\C=C\N1C(C(C)C)=C(Br)C(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 MUTCAPXLKRYEPR-ITWZMISCSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000012154 norepinephrine uptake Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000000376 reactant Substances 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
- 238000005549 size reduction Methods 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical class [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- QFNFDHNZVTWZED-UHFFFAOYSA-N tert-butyl n-[[(2-methylpropan-2-yl)oxycarbonylamino]-pyrazol-1-ylmethylidene]carbamate Chemical compound CC(C)(C)OC(=O)NC(=NC(=O)OC(C)(C)C)N1C=CC=N1 QFNFDHNZVTWZED-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0052—Small organic molecules
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
L'invention concerne des compositions chimiques et leurs procédés de synthèse. Les compositions de l'invention sont dirigées contre des antagonistes du récepteur de l'intégrine ???3 de l'hormone thyroïdienne conjugués à des cibles du transporteur de norépinéphrine (NET) ou du transporteur de catécholamine. Les compositions ont un effet de double ciblage et une efficacité de ciblage accrue dans le traitement et l'imagerie diagnostique de tumeurs neuroendocrines.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17/340,843 | 2021-06-07 | ||
| US17/340,843 US11351137B2 (en) | 2018-04-11 | 2021-06-07 | Composition and method for dual targeting in treatment of neuroendocrine tumors |
| PCT/US2022/031876 WO2022260918A1 (fr) | 2021-06-07 | 2022-06-02 | Composition et méthode de double ciblage dans le traitement de tumeurs neuroendocrines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3220332A1 true CA3220332A1 (fr) | 2022-12-15 |
Family
ID=84425339
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3220332A Pending CA3220332A1 (fr) | 2021-06-07 | 2022-06-02 | Composition et methode de double ciblage dans le traitement de tumeurs neuroendocrines |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP4351650A1 (fr) |
| CN (1) | CN117412772A (fr) |
| AU (1) | AU2022287943A1 (fr) |
| CA (1) | CA3220332A1 (fr) |
| WO (1) | WO2022260918A1 (fr) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6207665B1 (en) * | 1997-06-12 | 2001-03-27 | Schering Aktiengesellschaft | Piperazine derivatives and their use as anti-inflammatory agents |
| NO20220050A1 (no) * | 2005-11-21 | 2008-08-12 | Novartis Ag | Neuroendokrin tumorbehandling |
| EP2268317B1 (fr) * | 2008-03-14 | 2020-02-26 | VisEn Medical, Inc. | Agents de ciblage de l'intégrine, et procédés d'utilisation in vivo et in vitro associés |
| US10328043B1 (en) * | 2018-04-11 | 2019-06-25 | Nanopharmaceuticals, Llc. | Composition and method for dual targeting in treatment of neuroendocrine tumors |
| US10961204B1 (en) * | 2020-04-29 | 2021-03-30 | Nanopharmaceuticals Llc | Composition of scalable thyrointegrin antagonists with improved blood brain barrier penetration and retention into brain tumors |
-
2022
- 2022-06-02 AU AU2022287943A patent/AU2022287943A1/en active Pending
- 2022-06-02 WO PCT/US2022/031876 patent/WO2022260918A1/fr active Application Filing
- 2022-06-02 EP EP22820793.2A patent/EP4351650A1/fr active Pending
- 2022-06-02 CN CN202280039629.XA patent/CN117412772A/zh active Pending
- 2022-06-02 CA CA3220332A patent/CA3220332A1/fr active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP4351650A1 (fr) | 2024-04-17 |
| CN117412772A (zh) | 2024-01-16 |
| WO2022260918A1 (fr) | 2022-12-15 |
| AU2022287943A1 (en) | 2023-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11077082B2 (en) | Composition and method for dual targeting in treatment of neuroendocrine tumors | |
| EP3455206B1 (fr) | Conjugués chimiques de dérivés du bleu d'evans et leur utilisation comme agents de radiothérapie et d'imagerie | |
| JP2020063241A5 (fr) | ||
| JP7449864B2 (ja) | エバンスブルー誘導体の化学結合体ならびに前立腺癌を標的とするための放射線療法および造影剤としてのその使用 | |
| CN116617420A (zh) | 靶向成纤维细胞活化蛋白α的化合物、药物组合物及用途 | |
| KR20200011950A (ko) | 방사성 의약품, 방사성 영상화제 및 이의 용도 | |
| US10709790B2 (en) | Chemical conjugates of Evans Blue derivatives and their use in the production of long-acting therapeutics | |
| CA2405469A1 (fr) | Composes a base de peptides | |
| US11497819B2 (en) | PSMA ligands for imaging and endoradiotherapy | |
| JP2020097605A (ja) | 血清半減期を延長するための、調節可能リンカーを介した薬学的活性剤とトランスサイレチンリガンドのコンジュゲーション | |
| EP3209336A1 (fr) | Inhibiteurs marqués 18f de l'antigène membranaire spécifique de la prostate (psma), leur utilisation comme agents d'imagerie et agents pharmaceutiques pour le traitement du cancer de la prostate | |
| EP3692032A1 (fr) | Conjugués chimiques de dérivés du bleu d'evans et leur utilisation comme agents de radiothérapie et d'imagerie | |
| JP6047581B2 (ja) | 金属放射性医薬品のためのケージアミン配位子 | |
| EP4142798A1 (fr) | Composition d'antagonistes de la thyrointégrine évolutifs présentant une pénétration de la barrière hémato-encéphalique et une rétention dans les tumeurs cérébrales améliorées | |
| US9364570B2 (en) | Functionalisation of cage amine ligands for metallo-radiopharmaceuticals | |
| CA3220332A1 (fr) | Composition et methode de double ciblage dans le traitement de tumeurs neuroendocrines | |
| US11351137B2 (en) | Composition and method for dual targeting in treatment of neuroendocrine tumors | |
| FR2967671A1 (fr) | Complexe de technetium 99m en tant qu'outil de diagnostic in vivo des tumeurs cancereuses | |
| JP2024520888A (ja) | 神経内分泌腫瘍の治療における二重標的化のための組成物および方法 | |
| Yao et al. | Synthesis and evaluation of novel radioiodinated PSMA targeting ligands for potential radiotherapy of prostate cancer | |
| RU2789198C2 (ru) | Композиция и способ двойного нацеливания при лечении нейроэндокринных опухолей | |
| WO2010083154A2 (fr) | Polymères de poly(éthylèneglycol) à segments hétérofonctionnels utilisés en tant que supports d'administration | |
| WO2023107412A1 (fr) | Antagonistes de thyrointégrine conjugués à un polymère |