JP2009531283A - 眼系疾患の処置のための組成物および方法 - Google Patents
眼系疾患の処置のための組成物および方法 Download PDFInfo
- Publication number
- JP2009531283A JP2009531283A JP2008552923A JP2008552923A JP2009531283A JP 2009531283 A JP2009531283 A JP 2009531283A JP 2008552923 A JP2008552923 A JP 2008552923A JP 2008552923 A JP2008552923 A JP 2008552923A JP 2009531283 A JP2009531283 A JP 2009531283A
- Authority
- JP
- Japan
- Prior art keywords
- seq
- azepanyl
- amino
- group
- ethyl
- 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
- 238000000034 method Methods 0.000 title claims abstract description 127
- 239000000203 mixture Substances 0.000 title claims abstract description 115
- 238000011282 treatment Methods 0.000 title claims description 24
- 201000010099 disease Diseases 0.000 title abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 25
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims abstract description 138
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims abstract description 132
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 17
- 239000003112 inhibitor Substances 0.000 claims description 94
- -1 hetero compound Chemical class 0.000 claims description 77
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 claims description 62
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 claims description 59
- 125000004432 carbon atom Chemical group C* 0.000 claims description 56
- 230000000694 effects Effects 0.000 claims description 54
- 239000007943 implant Substances 0.000 claims description 53
- 125000001424 substituent group Chemical group 0.000 claims description 50
- 125000003729 nucleotide group Chemical group 0.000 claims description 49
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 49
- 108020004459 Small interfering RNA Proteins 0.000 claims description 48
- 102000039446 nucleic acids Human genes 0.000 claims description 44
- 108020004707 nucleic acids Proteins 0.000 claims description 44
- 150000007523 nucleic acids Chemical group 0.000 claims description 44
- 150000001875 compounds Chemical class 0.000 claims description 43
- 239000002773 nucleotide Substances 0.000 claims description 40
- 108091034117 Oligonucleotide Proteins 0.000 claims description 38
- 230000002207 retinal effect Effects 0.000 claims description 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 32
- 230000014509 gene expression Effects 0.000 claims description 31
- 108091030071 RNAI Proteins 0.000 claims description 27
- 230000009368 gene silencing by RNA Effects 0.000 claims description 27
- 108020004999 messenger RNA Proteins 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 230000027455 binding Effects 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 208000017442 Retinal disease Diseases 0.000 claims description 19
- 125000002950 monocyclic group Chemical group 0.000 claims description 19
- 229920001184 polypeptide Polymers 0.000 claims description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 239000004055 small Interfering RNA Substances 0.000 claims description 15
- 230000000295 complement effect Effects 0.000 claims description 14
- 239000004005 microsphere Substances 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 101710163270 Nuclease Proteins 0.000 claims description 10
- 229940121384 cxc chemokine receptor type 4 (cxcr4) antagonist Drugs 0.000 claims description 10
- 239000012634 fragment Substances 0.000 claims description 10
- 125000003367 polycyclic group Chemical group 0.000 claims description 10
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 9
- 239000005557 antagonist Substances 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 230000003834 intracellular effect Effects 0.000 claims description 9
- 108010061299 CXCR4 Receptors Proteins 0.000 claims description 8
- 102000012000 CXCR4 Receptors Human genes 0.000 claims description 8
- 239000002576 chemokine receptor CXCR4 antagonist Substances 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 8
- 238000013519 translation Methods 0.000 claims description 8
- 239000003981 vehicle Substances 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 7
- 125000005156 substituted alkylene group Chemical group 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 108700026244 Open Reading Frames Proteins 0.000 claims description 5
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
- 239000000539 dimer Substances 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 125000004419 alkynylene group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 230000001413 cellular effect Effects 0.000 claims description 4
- 239000013604 expression vector Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 150000002391 heterocyclic compounds Chemical group 0.000 claims description 3
- 230000002452 interceptive effect Effects 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 3
- HQGRTAMXYWZZOR-JNLGVIEDSA-N (2s)-n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]piperidine-2-carboxamide Chemical compound O=C([C@H]1NCCCC1)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 HQGRTAMXYWZZOR-JNLGVIEDSA-N 0.000 claims description 2
- SDFYFIRUYZGZPG-GMUMFXLYSA-N (3r)-n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]piperidine-3-carboxamide Chemical compound O=C([C@H]1CNCCC1)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 SDFYFIRUYZGZPG-GMUMFXLYSA-N 0.000 claims description 2
- SDFYFIRUYZGZPG-XPWZEYHZSA-N (3s)-n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]piperidine-3-carboxamide Chemical compound O=C([C@@H]1CNCCC1)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 SDFYFIRUYZGZPG-XPWZEYHZSA-N 0.000 claims description 2
- APQRNAUXFIHFMW-BSSNWTCHSA-N (3s)-n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpyrrolidin-2-yl]ethyl]piperidine-3-carboxamide Chemical compound O=C([C@@H]1CNCCC1)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCN1C1CCCCC1 APQRNAUXFIHFMW-BSSNWTCHSA-N 0.000 claims description 2
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 108091028664 Ribonucleotide Proteins 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 2
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 claims description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 2
- 125000005647 linker group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- NICFYINMVCBKEL-UHFFFAOYSA-N n-(2-aminoethyl)-n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)N(CCN)CCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 NICFYINMVCBKEL-UHFFFAOYSA-N 0.000 claims description 2
- DAKZISABEDGGSV-UHFFFAOYSA-N n-(2-aminoethyl)acetamide Chemical group CC(=O)NCCN DAKZISABEDGGSV-UHFFFAOYSA-N 0.000 claims description 2
- FYYOLKFRSBAUGY-UHFFFAOYSA-N n-[2-(3-aminopropyl)-1-cyclohexylpyrrolidin-3-yl]-4-(azepan-1-yl)pyrimidin-2-amine Chemical compound NCCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCN1C1CCCCC1 FYYOLKFRSBAUGY-UHFFFAOYSA-N 0.000 claims description 2
- OWMARXKWPWKPDH-UHFFFAOYSA-N n-[2-[1-cyclohexyl-3-[(4-pyrrolidin-1-ylpyrimidin-2-yl)amino]piperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCC2)CCCN1C1CCCCC1 OWMARXKWPWKPDH-UHFFFAOYSA-N 0.000 claims description 2
- OYINMNOEWYITSF-UHFFFAOYSA-N n-[2-[1-ethyl-3-[(4-piperidin-1-ylpyrimidin-2-yl)amino]piperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1N(CC)CCCC1NC(N=1)=NC=CC=1N1CCCCC1 OYINMNOEWYITSF-UHFFFAOYSA-N 0.000 claims description 2
- WOXPRFMBRXGQGJ-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-(3-hydroxypropyl)piperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1N(CCCO)CCCC1NC(N=1)=NC=CC=1N1CCCCCC1 WOXPRFMBRXGQGJ-UHFFFAOYSA-N 0.000 claims description 2
- VNEOBUHJYVLPCF-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-(oxan-4-yl)piperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCOCC1 VNEOBUHJYVLPCF-UHFFFAOYSA-N 0.000 claims description 2
- ZDPBLMOKKGUWQH-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-(thian-4-yl)piperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCSCC1 ZDPBLMOKKGUWQH-UHFFFAOYSA-N 0.000 claims description 2
- ZKZWNYUCHLGVKF-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-1-ethylpiperidine-4-carboxamide Chemical compound C1CN(CC)CCC1C(=O)NCCC1N(C2CCCCC2)CCCC1NC1=NC=CC(N2CCCCCC2)=N1 ZKZWNYUCHLGVKF-UHFFFAOYSA-N 0.000 claims description 2
- BUBGSYJHKADCHW-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-1-propan-2-ylpiperidine-4-carboxamide Chemical compound C1CN(C(C)C)CCC1C(=O)NCCC1N(C2CCCCC2)CCCC1NC1=NC=CC(N2CCCCCC2)=N1 BUBGSYJHKADCHW-UHFFFAOYSA-N 0.000 claims description 2
- JLZJIEIBNPFFGX-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-4-hydroxypiperidine-4-carboxamide Chemical compound N=1C=CC(N2CCCCCC2)=NC=1NC1CCCN(C2CCCCC2)C1CCNC(=O)C1(O)CCNCC1 JLZJIEIBNPFFGX-UHFFFAOYSA-N 0.000 claims description 2
- OIGBLWTTXQMBAH-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-n-(oxan-4-yl)morpholine-2-carboxamide Chemical compound N=1C=CC(N2CCCCCC2)=NC=1NC1CCCN(C2CCCCC2)C1CCN(C1CCOCC1)C(=O)C1CNCCO1 OIGBLWTTXQMBAH-UHFFFAOYSA-N 0.000 claims description 2
- BDDIRWMLJIEXOE-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-n-(oxan-4-yl)piperidine-4-carboxamide Chemical compound N=1C=CC(N2CCCCCC2)=NC=1NC1CCCN(C2CCCCC2)C1CCN(C1CCOCC1)C(=O)C1CCNCC1 BDDIRWMLJIEXOE-UHFFFAOYSA-N 0.000 claims description 2
- HQGRTAMXYWZZOR-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]piperidine-2-carboxamide Chemical compound C1CCCNC1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 HQGRTAMXYWZZOR-UHFFFAOYSA-N 0.000 claims description 2
- GLQSEOUKPYZFPG-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 GLQSEOUKPYZFPG-UHFFFAOYSA-N 0.000 claims description 2
- JXZWSVUUKPQGQK-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpyrrolidin-2-yl]ethyl]morpholine-2-carboxamide Chemical compound C1NCCOC1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCN1C1CCCCC1 JXZWSVUUKPQGQK-UHFFFAOYSA-N 0.000 claims description 2
- VLHKNJNOBXMRRK-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-ethylpiperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1N(CC)CCCC1NC(N=1)=NC=CC=1N1CCCCCC1 VLHKNJNOBXMRRK-UHFFFAOYSA-N 0.000 claims description 2
- UWYZNDFRDXEQHY-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-propan-2-ylpiperidin-2-yl]ethyl]-1-ethylpiperidine-4-carboxamide Chemical compound C1CN(CC)CCC1C(=O)NCCC1N(C(C)C)CCCC1NC1=NC=CC(N2CCCCCC2)=N1 UWYZNDFRDXEQHY-UHFFFAOYSA-N 0.000 claims description 2
- BEDMOCAFSCVWGW-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-propan-2-ylpiperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1N(C(C)C)CCCC1NC(N=1)=NC=CC=1N1CCCCCC1 BEDMOCAFSCVWGW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 239000002336 ribonucleotide Substances 0.000 claims description 2
- 125000002652 ribonucleotide group Chemical group 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 7
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- ZCLZWGUQQLPRRR-UHFFFAOYSA-N 2-amino-n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-2-methylpropanamide Chemical compound CC(C)(N)C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 ZCLZWGUQQLPRRR-UHFFFAOYSA-N 0.000 claims 1
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims 1
- WDLGTLSQDNRFBI-FCHUYYIVSA-N 4-(azepan-1-yl)-n-[(2r,3s)-1-cyclohexyl-2-[2-(dimethylamino)ethyl]pyrrolidin-3-yl]pyrimidin-2-amine Chemical compound C([C@@H]([C@H]1CCN(C)C)NC=2N=C(C=CN=2)N2CCCCCC2)CN1C1CCCCC1 WDLGTLSQDNRFBI-FCHUYYIVSA-N 0.000 claims 1
- OTIAVLWNTIXJDO-UHFFFAOYSA-N 5-aminopentanamide Chemical compound NCCCCC(N)=O OTIAVLWNTIXJDO-UHFFFAOYSA-N 0.000 claims 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- 206010057430 Retinal injury Diseases 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims 1
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 claims 1
- 238000011065 in-situ storage Methods 0.000 claims 1
- VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims 1
- AZKSEKGMSUILDX-RBUKOAKNSA-N n-[(2r,3s)-2-(aminomethyl)-1-cyclohexylpyrrolidin-3-yl]-4-(azepan-1-yl)pyrimidin-2-amine Chemical compound C([C@@H]([C@H]1CN)NC=2N=C(C=CN=2)N2CCCCCC2)CN1C1CCCCC1 AZKSEKGMSUILDX-RBUKOAKNSA-N 0.000 claims 1
- VEPFSNSLGIQZHX-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-n-(2-methoxyethyl)piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)N(CCOC)CCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 VEPFSNSLGIQZHX-UHFFFAOYSA-N 0.000 claims 1
- PMQJRNHBTBEQND-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]morpholine-2-carboxamide Chemical compound C1NCCOC1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 PMQJRNHBTBEQND-UHFFFAOYSA-N 0.000 claims 1
- MDCVPERZCWKACQ-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 MDCVPERZCWKACQ-UHFFFAOYSA-N 0.000 claims 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims 1
- 150000001420 substituted heterocyclic compounds Chemical class 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 88
- 210000001508 eye Anatomy 0.000 description 69
- 239000003814 drug Substances 0.000 description 39
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 35
- 235000001014 amino acid Nutrition 0.000 description 31
- 150000001413 amino acids Chemical class 0.000 description 31
- 208000002780 macular degeneration Diseases 0.000 description 30
- 229920000642 polymer Polymers 0.000 description 30
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 27
- 230000001225 therapeutic effect Effects 0.000 description 26
- 238000012377 drug delivery Methods 0.000 description 25
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 24
- 102000006573 Chemokine CXCL12 Human genes 0.000 description 24
- 208000024891 symptom Diseases 0.000 description 24
- 206010064930 age-related macular degeneration Diseases 0.000 description 23
- 229940079593 drug Drugs 0.000 description 23
- 230000001939 inductive effect Effects 0.000 description 22
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 21
- 239000002245 particle Substances 0.000 description 21
- 239000004615 ingredient Substances 0.000 description 19
- 108090000623 proteins and genes Proteins 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- 102000019034 Chemokines Human genes 0.000 description 17
- 108010012236 Chemokines Proteins 0.000 description 17
- 239000000463 material Substances 0.000 description 17
- 210000001525 retina Anatomy 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 229940124597 therapeutic agent Drugs 0.000 description 16
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 15
- 239000007924 injection Substances 0.000 description 14
- 238000002347 injection Methods 0.000 description 14
- 206010012689 Diabetic retinopathy Diseases 0.000 description 13
- 230000001154 acute effect Effects 0.000 description 13
- 239000004633 polyglycolic acid Substances 0.000 description 13
- 229950008885 polyglycolic acid Drugs 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 229920000954 Polyglycolide Polymers 0.000 description 12
- 239000000872 buffer Substances 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 230000004048 modification Effects 0.000 description 12
- 238000012986 modification Methods 0.000 description 12
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 11
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 11
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 229920002988 biodegradable polymer Polymers 0.000 description 11
- 239000004621 biodegradable polymer Substances 0.000 description 11
- 229920001577 copolymer Polymers 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 239000011159 matrix material Substances 0.000 description 11
- 239000000816 peptidomimetic Substances 0.000 description 11
- 239000003755 preservative agent Substances 0.000 description 11
- 230000030833 cell death Effects 0.000 description 10
- 239000002299 complementary DNA Substances 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 201000004569 Blindness Diseases 0.000 description 9
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 9
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 9
- 108091006027 G proteins Proteins 0.000 description 9
- 102000030782 GTP binding Human genes 0.000 description 9
- 108091000058 GTP-Binding Proteins 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 9
- 208000010412 Glaucoma Diseases 0.000 description 8
- 208000001344 Macular Edema Diseases 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 8
- 206010030113 Oedema Diseases 0.000 description 8
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 8
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 8
- 206010038934 Retinopathy proliferative Diseases 0.000 description 8
- 206010046851 Uveitis Diseases 0.000 description 8
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 8
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 8
- 208000004644 retinal vein occlusion Diseases 0.000 description 8
- 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 7
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 7
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 7
- 206010025415 Macular oedema Diseases 0.000 description 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 239000002975 chemoattractant Substances 0.000 description 7
- 229920002674 hyaluronan Polymers 0.000 description 7
- 229960003160 hyaluronic acid Drugs 0.000 description 7
- 150000002430 hydrocarbons Chemical group 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 201000010230 macular retinal edema Diseases 0.000 description 7
- 230000036542 oxidative stress Effects 0.000 description 7
- 230000002335 preservative effect Effects 0.000 description 7
- 230000032258 transport Effects 0.000 description 7
- 230000004304 visual acuity Effects 0.000 description 7
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000003321 amplification Effects 0.000 description 6
- 210000000981 epithelium Anatomy 0.000 description 6
- 102000053523 human CXCR4 Human genes 0.000 description 6
- 229940014041 hyaluronate Drugs 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 238000003199 nucleic acid amplification method Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 150000003384 small molecules Chemical class 0.000 description 6
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 241000283707 Capra Species 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 5
- 108091081024 Start codon Proteins 0.000 description 5
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 210000003161 choroid Anatomy 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 210000001328 optic nerve Anatomy 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 4
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 4
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 208000009137 Behcet syndrome Diseases 0.000 description 4
- 108050006947 CXC Chemokine Proteins 0.000 description 4
- 102000019388 CXC chemokine Human genes 0.000 description 4
- 102000009410 Chemokine receptor Human genes 0.000 description 4
- 108050000299 Chemokine receptor Proteins 0.000 description 4
- 208000002691 Choroiditis Diseases 0.000 description 4
- 108091060211 Expressed sequence tag Proteins 0.000 description 4
- 208000010164 Multifocal Choroiditis Diseases 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
- 208000003971 Posterior uveitis Diseases 0.000 description 4
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 4
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 4
- 201000007737 Retinal degeneration Diseases 0.000 description 4
- 206010038848 Retinal detachment Diseases 0.000 description 4
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 4
- KITLPLLNIZOYIJ-UUOKFMHZSA-N [[(2r,3s,4r,5r)-5-(2-amino-6-oxo-7,8-dihydro-3h-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound C1=2NC(N)=NC(=O)C=2NCN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O KITLPLLNIZOYIJ-UUOKFMHZSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 4
- 229960003942 amphotericin b Drugs 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000002583 angiography Methods 0.000 description 4
- 230000001857 anti-mycotic effect Effects 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 239000002543 antimycotic Substances 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004155 blood-retinal barrier Anatomy 0.000 description 4
- 230000004378 blood-retinal barrier Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 238000003570 cell viability assay Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000035605 chemotaxis Effects 0.000 description 4
- 210000000795 conjunctiva Anatomy 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000007850 degeneration Effects 0.000 description 4
- 238000009792 diffusion process Methods 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 230000003628 erosive effect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000030279 gene silencing Effects 0.000 description 4
- 238000012226 gene silencing method Methods 0.000 description 4
- QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 4
- GCWKPPGPWZXRJG-UHFFFAOYSA-N guanidine;phosphoric acid Chemical compound NC(N)=N.OP(O)(O)=O.OP(O)(O)=O GCWKPPGPWZXRJG-UHFFFAOYSA-N 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 230000004410 intraocular pressure Effects 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 230000003278 mimic effect Effects 0.000 description 4
- 229940056360 penicillin g Drugs 0.000 description 4
- 239000000049 pigment Substances 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 239000004626 polylactic acid Substances 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 4
- 230000004264 retinal detachment Effects 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 229960002385 streptomycin sulfate Drugs 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- 230000004393 visual impairment Effects 0.000 description 4
- 210000004127 vitreous body Anatomy 0.000 description 4
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 3
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 3
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 description 3
- 108010029485 Protein Isoforms Proteins 0.000 description 3
- 102000001708 Protein Isoforms Human genes 0.000 description 3
- 206010038910 Retinitis Diseases 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 239000000074 antisense oligonucleotide Substances 0.000 description 3
- 238000012230 antisense oligonucleotides Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 210000005252 bulbus oculi Anatomy 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 201000005667 central retinal vein occlusion Diseases 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 239000000562 conjugate Substances 0.000 description 3
- 210000004087 cornea Anatomy 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 230000000593 degrading effect Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 201000011190 diabetic macular edema Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000004438 eyesight Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 229920001519 homopolymer Polymers 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 210000000554 iris Anatomy 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 238000002493 microarray Methods 0.000 description 3
- 239000011859 microparticle Substances 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 229920001610 polycaprolactone Polymers 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000003757 reverse transcription PCR Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 210000002536 stromal cell Anatomy 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 2
- VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Polymers CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 description 2
- 102100027211 Albumin Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 208000014882 Carotid artery disease Diseases 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 102100035294 Chemokine XC receptor 1 Human genes 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 101710088194 Dehydrogenase Proteins 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 206010012692 Diabetic uveitis Diseases 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- 208000002927 Hamartoma Diseases 0.000 description 2
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 2
- 241001502974 Human gammaherpesvirus 8 Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 206010022557 Intermediate uveitis Diseases 0.000 description 2
- 201000000512 Intraocular Lymphoma Diseases 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- 208000009857 Microaneurysm Diseases 0.000 description 2
- 101000617124 Mus musculus Stromal cell-derived factor 1 Proteins 0.000 description 2
- BACYUWVYYTXETD-UHFFFAOYSA-N N-Lauroylsarcosine Chemical compound CCCCCCCCCCCC(=O)N(C)CC(O)=O BACYUWVYYTXETD-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 108091093037 Peptide nucleic acid Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229920002413 Polyhexanide Polymers 0.000 description 2
- 229920001710 Polyorthoester Polymers 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 239000013614 RNA sample Substances 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 229920002125 Sokalan® Chemical class 0.000 description 2
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 2
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 2
- 208000036038 Subretinal fibrosis Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 2
- 108091036066 Three prime untranslated region Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 208000025749 Vogt-Koyanagi-Harada disease Diseases 0.000 description 2
- 208000034705 Vogt-Koyanagi-Harada syndrome Diseases 0.000 description 2
- 231100000480 WST assay Toxicity 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine group Chemical group [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 239000000464 adrenergic agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000001775 bruch membrane Anatomy 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000001332 colony forming effect Effects 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000000599 controlled substance Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- OSVXSBDYLRYLIG-UHFFFAOYSA-N dioxidochlorine(.) Chemical compound O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 208000024519 eye neoplasm Diseases 0.000 description 2
- 210000004700 fetal blood Anatomy 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 238000003500 gene array Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 108091006093 heterotrimeric G proteins Proteins 0.000 description 2
- 102000034345 heterotrimeric G proteins Human genes 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 210000002751 lymph Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical compound COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 description 2
- 230000002438 mitochondrial effect Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- FYYOLKFRSBAUGY-LEWJYISDSA-N n-[(2r,3s)-2-(3-aminopropyl)-1-cyclohexylpyrrolidin-3-yl]-4-(azepan-1-yl)pyrimidin-2-amine Chemical compound C([C@@H]([C@H]1CCCN)NC=2N=C(C=CN=2)N2CCCCCC2)CN1C1CCCCC1 FYYOLKFRSBAUGY-LEWJYISDSA-N 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000000649 photocoagulation Effects 0.000 description 2
- 238000002428 photodynamic therapy Methods 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- 229920002689 polyvinyl acetate Polymers 0.000 description 2
- 239000011118 polyvinyl acetate Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000004258 retinal degeneration Effects 0.000 description 2
- 239000000790 retinal pigment Substances 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 108700004121 sarkosyl Proteins 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 210000003786 sclera Anatomy 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- VMVKHCSARBZILS-PBGLPUTKSA-N (3r)-n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]pyrrolidine-3-carboxamide Chemical compound O=C([C@H]1CNCC1)NCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 VMVKHCSARBZILS-PBGLPUTKSA-N 0.000 description 1
- QUPFKBITVLIQNA-KPKJPENVSA-N (5e)-2-sulfanylidene-5-[[5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene]-1,3-thiazolidin-4-one Chemical compound FC(F)(F)C1=CC=CC(C=2OC(\C=C\3C(NC(=S)S/3)=O)=CC=2)=C1 QUPFKBITVLIQNA-KPKJPENVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-M (R)-lactate Chemical compound C[C@@H](O)C([O-])=O JVTAAEKCZFNVCJ-UWTATZPHSA-M 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- AVKSPBJBGGHUMW-XLPZGREQSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-4-sulfanylidenepyrimidin-2-one Chemical compound O=C1NC(=S)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 AVKSPBJBGGHUMW-XLPZGREQSA-N 0.000 description 1
- AKUNSTOMHUXJOZ-UHFFFAOYSA-N 1-hydroperoxybutane Chemical compound CCCCOO AKUNSTOMHUXJOZ-UHFFFAOYSA-N 0.000 description 1
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- OTDJAMXESTUWLO-UUOKFMHZSA-N 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-2-oxolanyl]-3H-purine-6-thione Chemical compound C12=NC(N)=NC(S)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OTDJAMXESTUWLO-UUOKFMHZSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- NLTFEDXBEGBKFR-UHFFFAOYSA-N 4-(azepan-1-yl)-n-[1-cyclohexyl-2-(3-pyrrolidin-1-ylpropyl)pyrrolidin-3-yl]pyrimidin-2-amine Chemical compound C1CCCN1CCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCN1C1CCCCC1 NLTFEDXBEGBKFR-UHFFFAOYSA-N 0.000 description 1
- MFJALSRPQJWYPI-UHFFFAOYSA-N 4-(azepan-1-yl)-n-[1-cyclohexyl-2-[3-(diethylamino)propyl]pyrrolidin-3-yl]pyrimidin-2-amine Chemical compound CCN(CC)CCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCN1C1CCCCC1 MFJALSRPQJWYPI-UHFFFAOYSA-N 0.000 description 1
- BFPBUJVKYHEUML-UHFFFAOYSA-N 4-(azepan-1-yl)-n-[1-cyclohexyl-2-[3-(dipropylamino)propyl]pyrrolidin-3-yl]pyrimidin-2-amine Chemical compound CCCN(CCC)CCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCN1C1CCCCC1 BFPBUJVKYHEUML-UHFFFAOYSA-N 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 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
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical class OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 101100309761 Aedes aegypti SDR-1 gene Proteins 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000027496 Behcet disease Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 108050005711 C Chemokine Proteins 0.000 description 1
- 102000017483 C chemokine Human genes 0.000 description 1
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- PAPPRINZLVAGDK-UBOZLPQGSA-N CC1=CC=CC=C1CC(CC[C@@H](C(=O)C2=CC=C(C=C2)CNCC3=NC=CN3)C(=O)N[C@@H](C)C4=CC=CC5=CC=CC=C54)(N)N Chemical compound CC1=CC=CC=C1CC(CC[C@@H](C(=O)C2=CC=C(C=C2)CNCC3=NC=CN3)C(=O)N[C@@H](C)C4=CC=CC5=CC=CC=C54)(N)N PAPPRINZLVAGDK-UBOZLPQGSA-N 0.000 description 1
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 1
- 102000004298 CX3C Chemokine Receptor 1 Human genes 0.000 description 1
- 101150066398 CXCR4 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 208000003569 Central serous chorioretinopathy Diseases 0.000 description 1
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 1
- 101710112015 Chemokine XC receptor 1 Proteins 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 239000004155 Chlorine dioxide Substances 0.000 description 1
- 206010070957 Choroidal haemangioma Diseases 0.000 description 1
- 241000252203 Clupea harengus Species 0.000 description 1
- 208000016134 Conjunctival disease Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010058202 Cystoid macular oedema Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 229930182843 D-Lactic acid Natural products 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 208000028506 Familial Exudative Vitreoretinopathies Diseases 0.000 description 1
- 102000013818 Fractalkine Human genes 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000008069 Geographic Atrophy Diseases 0.000 description 1
- VSRCAOIHMGCIJK-SRVKXCTJSA-N Glu-Leu-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O VSRCAOIHMGCIJK-SRVKXCTJSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 101000804783 Homo sapiens Chemokine XC receptor 1 Proteins 0.000 description 1
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 102000009617 Inorganic Pyrophosphatase Human genes 0.000 description 1
- 108010009595 Inorganic Pyrophosphatase Proteins 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 102100035304 Lymphotactin Human genes 0.000 description 1
- 102000043131 MHC class II family Human genes 0.000 description 1
- 108091054438 MHC class II family Proteins 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 108010049175 N-substituted Glycines Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102100038434 Neuroplastin Human genes 0.000 description 1
- 108700038050 Neuroplastin Proteins 0.000 description 1
- 241000221960 Neurospora Species 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108010043958 Peptoids Proteins 0.000 description 1
- 108010081690 Pertussis Toxin Proteins 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 241000282374 Puma concolor Species 0.000 description 1
- 208000030374 Pupillary disease Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 206010064714 Radiation retinopathy Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000008709 Retinal Telangiectasis Diseases 0.000 description 1
- 201000007527 Retinal artery occlusion Diseases 0.000 description 1
- 206010038899 Retinal telangiectasia Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 206010038935 Retinopathy sickle cell Diseases 0.000 description 1
- 102100040756 Rhodopsin Human genes 0.000 description 1
- 108090000820 Rhodopsin Proteins 0.000 description 1
- 206010039705 Scleritis Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 102000003800 Selectins Human genes 0.000 description 1
- 108090000184 Selectins Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010045517 Serum Amyloid P-Component Proteins 0.000 description 1
- 206010040925 Skin striae Diseases 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 108050001286 Somatostatin Receptor Proteins 0.000 description 1
- 102000011096 Somatostatin receptor Human genes 0.000 description 1
- 208000004350 Strabismus Diseases 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 206010058990 Venous occlusion Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 208000029977 White Dot Syndromes Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- HZEBOMOKUNIRRA-UHFFFAOYSA-N [4-[2-(3-aminopropyl)-3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]pyrrolidin-1-yl]piperidin-1-yl]-cyclohexylmethanone Chemical compound NCCCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCN1C(CC1)CCN1C(=O)C1CCCCC1 HZEBOMOKUNIRRA-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009824 affinity maturation Effects 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
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 238000012197 amplification kit Methods 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000011948 assay development Methods 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 201000009310 astigmatism Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 239000005667 attractant Substances 0.000 description 1
- 201000007917 background diabetic retinopathy Diseases 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 210000002960 bfu-e Anatomy 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000744 blepharospasm Effects 0.000 description 1
- 206010005159 blepharospasm Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 235000010410 calcium alginate Nutrition 0.000 description 1
- 239000000648 calcium alginate Substances 0.000 description 1
- 229960002681 calcium alginate Drugs 0.000 description 1
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=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](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000019398 chlorine dioxide Nutrition 0.000 description 1
- 229910001919 chlorite Inorganic materials 0.000 description 1
- 229910052619 chlorite group Inorganic materials 0.000 description 1
- QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical compound OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 description 1
- 210000004240 ciliary body Anatomy 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 201000010206 cystoid macular edema Diseases 0.000 description 1
- 229940022769 d- lactic acid Drugs 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000008497 endothelial barrier function Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000005081 epithelial layer Anatomy 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- BFMKFCLXZSUVPI-UHFFFAOYSA-N ethyl but-3-enoate Chemical class CCOC(=O)CC=C BFMKFCLXZSUVPI-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 201000006902 exudative vitreoretinopathy Diseases 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 208000024386 fungal infectious disease Diseases 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- YQOKLYTXVFAUCW-UHFFFAOYSA-N guanidine;isothiocyanic acid Chemical compound N=C=S.NC(N)=N YQOKLYTXVFAUCW-UHFFFAOYSA-N 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 235000019514 herring Nutrition 0.000 description 1
- 102000055647 human CSF2RB Human genes 0.000 description 1
- 102000043525 human CXCL12 Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 201000001371 inclusion conjunctivitis Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229940116871 l-lactate Drugs 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 108010019677 lymphotactin Proteins 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910001510 metal chloride Inorganic materials 0.000 description 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
- 229960004329 metformin hydrochloride Drugs 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- QXDXQFZGUZFMFQ-XZOQPEGZSA-N n-[(2r,3s)-2-(5-aminopentyl)-1-cyclohexylpyrrolidin-3-yl]-4-(azepan-1-yl)pyrimidin-2-amine Chemical compound C([C@@H]([C@H]1CCCCCN)NC=2N=C(C=CN=2)N2CCCCCC2)CN1C1CCCCC1 QXDXQFZGUZFMFQ-XZOQPEGZSA-N 0.000 description 1
- OWIVCJDVGKSZCY-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-(1,3-dihydroxypropan-2-yl)piperidin-2-yl]ethyl]piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)NCCC1N(C(CO)CO)CCCC1NC(N=1)=NC=CC=1N1CCCCCC1 OWIVCJDVGKSZCY-UHFFFAOYSA-N 0.000 description 1
- JABUACRJVFRTHC-UHFFFAOYSA-N n-[2-[3-[[4-(azepan-1-yl)pyrimidin-2-yl]amino]-1-cyclohexylpiperidin-2-yl]ethyl]-n-(2-hydroxyethyl)piperidine-4-carboxamide Chemical compound C1CNCCC1C(=O)N(CCO)CCC1C(NC=2N=C(C=CN=2)N2CCCCCC2)CCCN1C1CCCCC1 JABUACRJVFRTHC-UHFFFAOYSA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 108091008104 nucleic acid aptamers Proteins 0.000 description 1
- 238000002966 oligonucleotide array Methods 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 229940023490 ophthalmic product Drugs 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 238000002751 oxidative stress assay Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 208000001297 phlebitis Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 1
- 229960002169 plerixafor Drugs 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004584 polyacrylic acid Chemical class 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 201000004849 posterior scleritis Diseases 0.000 description 1
- 201000002267 posterior uveal melanoma Diseases 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 201000010041 presbyopia Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 208000014733 refractive error Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 210000001927 retinal artery Anatomy 0.000 description 1
- 230000004283 retinal dysfunction Effects 0.000 description 1
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000037390 scarring Effects 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
- 230000028327 secretion Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000008684 selective degradation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical group [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000009221 stress response pathway Effects 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000003536 tetrazoles Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 206010044325 trachoma Diseases 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 210000001745 uvea Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 206010055031 vascular neoplasm Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000007998 vessel formation Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 239000007966 viscous suspension Substances 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1793—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/195—Chemokines, e.g. RANTES
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Ophthalmology & Optometry (AREA)
- Cell Biology (AREA)
- Endocrinology (AREA)
- Communicable Diseases (AREA)
- Oncology (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)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76489206P | 2006-02-02 | 2006-02-02 | |
| PCT/IB2007/003262 WO2008029276A2 (en) | 2006-02-02 | 2007-02-02 | Compositions and methods for the treatment of ophthalmic disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009531283A true JP2009531283A (ja) | 2009-09-03 |
| JP2009531283A5 JP2009531283A5 (enExample) | 2010-03-25 |
Family
ID=39157630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008552923A Pending JP2009531283A (ja) | 2006-02-02 | 2007-02-02 | 眼系疾患の処置のための組成物および方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7964191B2 (enExample) |
| EP (3) | EP2407171A3 (enExample) |
| JP (1) | JP2009531283A (enExample) |
| AU (1) | AU2007293169A1 (enExample) |
| BR (1) | BRPI0707446A2 (enExample) |
| CA (1) | CA2640080A1 (enExample) |
| ES (1) | ES2385924T3 (enExample) |
| WO (1) | WO2008029276A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014522840A (ja) * | 2011-07-06 | 2014-09-08 | ノバルティス アーゲー | 核酸を含む水中油型エマルジョン |
| JPWO2016194869A1 (ja) * | 2015-05-29 | 2018-03-22 | 生化学工業株式会社 | グリコサミノグリカン誘導体とケモカイン受容体活性調節材とを含む組成物 |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080220049A1 (en) * | 2003-12-05 | 2008-09-11 | Adnexus, A Bristol-Myers Squibb R&D Company | Compositions and methods for intraocular delivery of fibronectin scaffold domain proteins |
| KR20060129246A (ko) | 2003-12-05 | 2006-12-15 | 컴파운드 쎄라퓨틱스, 인크. | 타입 2 혈관 내피 성장 인자 수용체의 억제제 |
| JP5272408B2 (ja) * | 2005-02-25 | 2013-08-28 | 小野薬品工業株式会社 | 含窒素複素環化合物およびその医薬用途 |
| US20090105182A1 (en) * | 2006-06-02 | 2009-04-23 | Alcon Research, Ltd. | RNAi-MEDIATED INHIBITION OF STROMAL CELL-DERIVED FACTOR 1-RELATED TARGETS FOR TREATMENT OF NEOVASCULARIZATION-RELATED CONDITIONS |
| WO2008009437A2 (en) | 2006-07-18 | 2008-01-24 | Noxxon Pharma Ag | Sdf-i binding nucleic acids |
| CA2670471A1 (en) | 2006-11-22 | 2008-06-05 | Adnexus, A Bristol-Myers Squibb R&D Company (A Delaware Corporation) | Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including igf-ir |
| US11078262B2 (en) * | 2007-04-30 | 2021-08-03 | Allergan, Inc. | High viscosity macromolecular compositions for treating ocular conditions |
| KR101589442B1 (ko) * | 2007-08-06 | 2016-02-01 | 녹손 파르마 아게 | 에스디에프-1 결합형 핵산 및 이의 용도 |
| CN102007145A (zh) | 2008-02-14 | 2011-04-06 | 百时美施贵宝公司 | 基于结合egfr的工程化蛋白质的靶向治疗剂 |
| EP2799448A1 (en) | 2008-05-22 | 2014-11-05 | Bristol-Myers Squibb Company | Multivalent fibronectin based scaffold domain proteins |
| US11029313B2 (en) | 2008-09-26 | 2021-06-08 | The General Hospital Corporation | Method of treating cervical neoplasia in patients infected with human papilloma virus |
| WO2010037042A2 (en) | 2008-09-26 | 2010-04-01 | The General Hospital Corporation | Methods for detecting and treating cancer |
| TWI496582B (zh) | 2008-11-24 | 2015-08-21 | 必治妥美雅史谷比公司 | 雙重專一性之egfr/igfir結合分子 |
| US20100204325A1 (en) * | 2009-02-11 | 2010-08-12 | Allergan, Inc. | Valproic acid drug delivery systems and intraocular therapeutic uses thereof |
| EA025415B1 (ru) | 2010-01-11 | 2016-12-30 | Инотек Фармасьютикалз Корпорейшн | Комбинация, набор и способ снижения внутриглазного давления |
| EP2569325A4 (en) | 2010-03-26 | 2013-10-09 | Inotek Pharmaceuticals Corp | METHOD FOR REDUCING INNER EYE PRESSURE IN HUMANS USING N6-CYCLOPENTYLADENOSINE (CPA), CPA DERIVATIVES OR PRODRUGS THEREOF |
| EP2576615B1 (en) | 2010-05-26 | 2016-03-30 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins having improved stability |
| MX350258B (es) | 2011-07-06 | 2017-08-31 | Novartis Ag | Emulsiones cationicas de aceite en agua. |
| US9278991B2 (en) | 2012-01-26 | 2016-03-08 | Inotek Pharmaceuticals Corporation | Anhydrous polymorphs of [(2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)} methyl nitrate and processes of preparation thereof |
| CA2903114A1 (en) | 2013-03-15 | 2014-09-25 | Inotek Pharmaceuticals Corporation | Ophthalmic formulations |
| WO2015015401A2 (en) | 2013-08-02 | 2015-02-05 | Pfizer Inc. | Anti-cxcr4 antibodies and antibody-drug conjugates |
| WO2015031722A1 (en) | 2013-08-30 | 2015-03-05 | Ramot At Tel-Aviv University Ltd. | Method for treating amyotrophic lateral sclerosis by inhibition of cxcr4/cxcl12 signaling |
| EP3373941A4 (en) * | 2015-11-09 | 2019-03-27 | Aperisys, Inc. | MODIFIED IMMUNOCELLS AND USES THEREOF |
| CN109053697A (zh) * | 2018-09-27 | 2018-12-21 | 张淑华 | 一种用于抗癌的嘧啶类化合物及其制备方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999048528A1 (en) * | 1998-03-24 | 1999-09-30 | Chugai Seiyaku Kabushiki Kaisha | Vascularization inhibitors |
| WO2000031271A1 (en) * | 1998-11-24 | 2000-06-02 | Hisamitsu Pharmaceutical Co., Inc. | Hiv infection inhibitors |
| JP2002506830A (ja) * | 1998-03-13 | 2002-03-05 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | 治療的ケモカイン受容体アンタゴニスト |
| JP2002508958A (ja) * | 1998-01-15 | 2002-03-26 | ビー・テイー・ジー・インターナシヨナル・リミテツド | Ccr5あるいはcxcr4を開裂するリボザイム核酸 |
| WO2003102131A2 (en) * | 2002-04-22 | 2003-12-11 | Sirna Therapeutics Inc. | Nucleic acid mediated disruption of hiv fusogenic peptide interactions |
| WO2004087068A2 (en) * | 2003-03-27 | 2004-10-14 | Emory University | Cxcr4 antagonists and methods of their use |
Family Cites Families (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4521210A (en) | 1982-12-27 | 1985-06-04 | Wong Vernon G | Eye implant for relieving glaucoma, and device and method for use therewith |
| US4997652A (en) | 1987-12-22 | 1991-03-05 | Visionex | Biodegradable ocular implants |
| US4853224A (en) | 1987-12-22 | 1989-08-01 | Visionex | Biodegradable ocular implants |
| US5164188A (en) | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
| CA2088258C (en) | 1990-07-27 | 2004-09-14 | Phillip Dan Cook | Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression |
| KR0185215B1 (ko) | 1990-11-30 | 1999-05-01 | 요시다 쇼오지 | 서방성 안구삽입용 약제 |
| DK1695979T3 (da) | 1991-12-24 | 2011-10-10 | Isis Pharmaceuticals Inc | Gappede modificerede oligonukleotider |
| US5874082A (en) * | 1992-07-09 | 1999-02-23 | Chiron Corporation | Humanized anti-CD40 monoclonal antibodies and fragments capable of blocking B cell proliferation |
| JP3015464B2 (ja) | 1992-07-23 | 2000-03-06 | アイシス・ファーマシューティカルス・インコーポレーテッド | 新規2’−0−アルキルヌクレオシドおよびホスホロアミダイトの製造法およびその使用 |
| WO1994019023A1 (en) | 1993-02-19 | 1994-09-01 | Isis Pharmaceuticals, Inc. | Cyclobutyl antisense oligonucleotides, methods of making and use thereof |
| WO1995003009A1 (en) | 1993-07-22 | 1995-02-02 | Oculex Pharmaceuticals, Inc. | Method of treatment of macular degeneration |
| US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
| US5869079A (en) | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
| US6369116B1 (en) | 1995-06-02 | 2002-04-09 | Oculex Pharmaceuticals, Inc. | Composition and method for treating glaucoma |
| US6506770B1 (en) | 1996-06-06 | 2003-01-14 | Anormed, Inc. | Antiviral compounds |
| US5994515A (en) | 1996-06-25 | 1999-11-30 | Trustees Of The University Of Pennsylvania | Antibodies directed against cellular coreceptors for human immunodeficiency virus and methods of using the same |
| ES2232005T3 (es) | 1997-08-11 | 2005-05-16 | Allergan, Inc. | Dispositivo de implante biodegradable esteril que contiene retinoide con biocompatibilidad mejorada y metodo de preparacion. |
| CA2245224A1 (en) | 1998-08-14 | 2000-02-14 | Jiang-Hong Giong | Chemokine receptor antagonists and chemotherapeutics |
| CA2305787A1 (en) | 2000-05-09 | 2001-11-09 | The University Of British Columbia | Cxcr4 antagonist treatment of hematopoietic cells |
| AU4325499A (en) | 1998-06-01 | 1999-12-20 | University Of Maryland Biotechnology Institute | Receptor ligand antagonist complexes and their use in treating or preventing receptor mediated diseases |
| US20050202005A1 (en) | 1998-07-31 | 2005-09-15 | The Trustees Of Columbia University In The City Of New York | Uses of inhibitors for the activation of CXCR4 receptor by SDF-1 in treating rheumatoid arthritis |
| WO2000006086A2 (en) | 1998-07-31 | 2000-02-10 | The Trustees Of Columbia University In The City Of New York | Use of inhibitors of the activation of cxcr4 receptor by sdf-1 in treating rheumatoid arthritis |
| US20050220787A1 (en) | 2002-11-07 | 2005-10-06 | Lobo Peter I | Naturally occuring IgM antibodies that bind to lymphocytes |
| US20030099645A1 (en) | 2000-10-10 | 2003-05-29 | Lobo Peter Isaac | Naturally occuring IgM antibodies that bind to membrane receptors on lymphocytes |
| US6610834B1 (en) | 1998-11-18 | 2003-08-26 | Peter I. Lobo | Human IgM antibodies to chemokine receptors |
| CA2369292C (en) | 1999-04-09 | 2010-09-21 | Kyowa Hakko Kogyo Co. Ltd. | Method of modulating the activity of functional immune molecules |
| US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
| US6949243B1 (en) | 1999-11-24 | 2005-09-27 | Schering Corporation | Methods of inhibiting metastasis |
| WO2001044229A1 (en) | 1999-12-17 | 2001-06-21 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds |
| US20030220482A1 (en) | 2000-02-03 | 2003-11-27 | Ziwei Huang | Novel peptide antagonist of CXCR4 derived from the N-terminus of the viral chemokine vMIP-II |
| JP2003522186A (ja) | 2000-02-04 | 2003-07-22 | アメリカ合衆国 | 病原体に対する宿主免疫応答を誘導するか、またはhiv感染を抑制するfprクラス受容体に対するリガンド |
| US6726918B1 (en) | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
| WO2002022599A2 (en) | 2000-09-15 | 2002-03-21 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds |
| US20030165988A1 (en) | 2002-02-08 | 2003-09-04 | Shaobing Hua | High throughput generation of human monoclonal antibody against peptide fragments derived from membrane proteins |
| US6699493B2 (en) | 2000-11-29 | 2004-03-02 | Oculex Pharmaceuticals, Inc. | Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor |
| US20060019917A1 (en) | 2001-05-18 | 2006-01-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of stromal cell-derived factor-1 (SDF-1) gene expression using short interfering nucleic acid (siNA) |
| US20050124569A1 (en) | 2001-05-18 | 2005-06-09 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of CXCR4 gene expression using short interfering nucleic acid (siNA) |
| JPWO2002094261A1 (ja) | 2001-05-24 | 2004-09-02 | 呉羽化学工業株式会社 | 含窒素化合物からなるcxcr4拮抗作用を有する薬剤 |
| JPWO2003029218A1 (ja) | 2001-09-28 | 2005-01-13 | 呉羽化学工業株式会社 | 新規含窒素化合物及びその用途 |
| US7354932B2 (en) | 2001-12-21 | 2008-04-08 | Anormed, Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
| IL161784A0 (en) | 2001-12-21 | 2005-11-20 | Anormed Inc | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
| AU2002356400A1 (en) | 2001-12-31 | 2003-07-30 | Consejo Superior De Investigaciones Cientificas | Functional inactivation of cxcr4-mediated responses in growth hormone transgenic mice through socs3 upregulation |
| US20040018528A1 (en) | 2002-05-17 | 2004-01-29 | Sugen, Inc. | Novel biomarkers of tyrosine kinase inhibitor exposure and activity in mammals |
| US7148342B2 (en) * | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| US20050002939A1 (en) | 2002-12-23 | 2005-01-06 | Albert Zlotnik | Tumor killing/tumor regression using CXCR4 antagonists |
| EP1613613B1 (en) | 2003-04-11 | 2021-06-02 | Genzyme Corporation | Cxcr4 chemokine receptor binding compounds |
| WO2005002522A2 (en) | 2003-06-30 | 2005-01-13 | Caritas St. Elizabeth's Medical Center Of Boston, Inc. | Compositions and methods for treating tissue ischemia |
| US20050266009A1 (en) | 2003-06-30 | 2005-12-01 | Savient Pharmaceuticals, Inc. | Antibodies and uses thereof |
| US20050019927A1 (en) | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
| WO2005080410A1 (en) | 2004-02-20 | 2005-09-01 | Genesis Research And Development Corporation Limited | Targeted delivery of rna interference molecules for the treatment of ige-mediated disorders |
| US7674829B2 (en) | 2004-03-26 | 2010-03-09 | Novaremed Limited | Compounds for the treatment of AIDS and other viral diseases |
| EP1796675A4 (en) * | 2004-10-01 | 2009-03-04 | Merck & Co Inc | COMPOSITIONS AND METHODS FOR THE TREATMENT OF EYE DISEASES |
| BRPI0518582A2 (pt) | 2004-11-24 | 2008-11-25 | Therakine Corp | implante para liberaÇço de medicamento intra-ocular |
| CA2593578C (en) * | 2005-01-07 | 2013-11-05 | Emory University | Cxcr4 antagonists for the treatment of medical disorders |
| EP1838321A4 (en) * | 2005-01-07 | 2009-03-18 | Univ Emory | CXCR4 ANTAGONISTS FOR THE TREATMENT OF HIV INFECTION |
| JP5272408B2 (ja) | 2005-02-25 | 2013-08-28 | 小野薬品工業株式会社 | 含窒素複素環化合物およびその医薬用途 |
| US20060257359A1 (en) * | 2005-02-28 | 2006-11-16 | Cedric Francois | Modifying macrophage phenotype for treatment of disease |
| US7427605B2 (en) * | 2005-03-31 | 2008-09-23 | Calando Pharmaceuticals, Inc. | Inhibitors of ribonucleotide reductase subunit 2 and uses thereof |
-
2007
- 2007-02-02 BR BRPI0707446-8A patent/BRPI0707446A2/pt not_active Application Discontinuation
- 2007-02-02 EP EP11177758A patent/EP2407171A3/en not_active Ceased
- 2007-02-02 AU AU2007293169A patent/AU2007293169A1/en not_active Abandoned
- 2007-02-02 EP EP11177757A patent/EP2397148A3/en not_active Withdrawn
- 2007-02-02 EP EP07848839A patent/EP1993584B1/en active Active
- 2007-02-02 JP JP2008552923A patent/JP2009531283A/ja active Pending
- 2007-02-02 ES ES07848839T patent/ES2385924T3/es active Active
- 2007-02-02 WO PCT/IB2007/003262 patent/WO2008029276A2/en not_active Ceased
- 2007-02-02 US US11/670,883 patent/US7964191B2/en active Active
- 2007-02-02 CA CA002640080A patent/CA2640080A1/en not_active Abandoned
-
2011
- 2011-06-10 US US13/158,084 patent/US20120003275A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002508958A (ja) * | 1998-01-15 | 2002-03-26 | ビー・テイー・ジー・インターナシヨナル・リミテツド | Ccr5あるいはcxcr4を開裂するリボザイム核酸 |
| JP2002506830A (ja) * | 1998-03-13 | 2002-03-05 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | 治療的ケモカイン受容体アンタゴニスト |
| WO1999048528A1 (en) * | 1998-03-24 | 1999-09-30 | Chugai Seiyaku Kabushiki Kaisha | Vascularization inhibitors |
| WO2000031271A1 (en) * | 1998-11-24 | 2000-06-02 | Hisamitsu Pharmaceutical Co., Inc. | Hiv infection inhibitors |
| WO2003102131A2 (en) * | 2002-04-22 | 2003-12-11 | Sirna Therapeutics Inc. | Nucleic acid mediated disruption of hiv fusogenic peptide interactions |
| WO2004087068A2 (en) * | 2003-03-27 | 2004-10-14 | Emory University | Cxcr4 antagonists and methods of their use |
Non-Patent Citations (3)
| Title |
|---|
| INVEST.OPHTHALMOL.VIS.SCI., vol. 46, JPN6012019333, 2005, pages 1412, ISSN: 0002201475 * |
| J M BUTLER, THE JOURNAL OF CLINICAL INVESTIGATION, vol. V115 N1, JPN5008024326, 1 January 2005 (2005-01-01), US, pages 86 - 93, ISSN: 0002402465 * |
| J.IMMUNOL., vol. 165, JPN6012019336, 2000, pages 4372 - 4378, ISSN: 0002201477 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014522840A (ja) * | 2011-07-06 | 2014-09-08 | ノバルティス アーゲー | 核酸を含む水中油型エマルジョン |
| US10307374B2 (en) | 2011-07-06 | 2019-06-04 | Glaxosmithkline Biologicals S.A. | Oil-in-water emulsions that contain nucleic acids |
| US11026890B2 (en) | 2011-07-06 | 2021-06-08 | Glaxosmithkline Biologicals Sa | Oil-in-water emulsions that contain nucleic acids |
| JPWO2016194869A1 (ja) * | 2015-05-29 | 2018-03-22 | 生化学工業株式会社 | グリコサミノグリカン誘導体とケモカイン受容体活性調節材とを含む組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008029276A2 (en) | 2008-03-13 |
| EP2397148A3 (en) | 2012-04-25 |
| US20120003275A1 (en) | 2012-01-05 |
| US7964191B2 (en) | 2011-06-21 |
| ES2385924T3 (es) | 2012-08-03 |
| EP1993584B1 (en) | 2012-05-30 |
| AU2007293169A1 (en) | 2008-03-13 |
| EP2407171A3 (en) | 2012-04-11 |
| CA2640080A1 (en) | 2008-03-13 |
| WO2008029276A8 (en) | 2009-08-06 |
| WO2008029276A3 (en) | 2008-12-04 |
| EP2397148A2 (en) | 2011-12-21 |
| EP2407171A2 (en) | 2012-01-18 |
| EP1993584A2 (en) | 2008-11-26 |
| BRPI0707446A2 (pt) | 2011-05-03 |
| US20070203089A1 (en) | 2007-08-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7964191B2 (en) | Compositions and methods for the treatment of ophthalmic disease | |
| JP6683686B2 (ja) | チャネル調節剤 | |
| CN102813923B (zh) | 用于治疗眼新血管疾病的组合治疗 | |
| US9062103B2 (en) | Adult stem cells/progenitor cells and stem cell proteins for treatment of eye injuries and diseases | |
| CN105582523A (zh) | 用于眼部病症的补体抑制素和其类似物 | |
| JP2020059752A (ja) | 線維性癌の治療方法 | |
| JP2019508405A (ja) | 改良された硝子体内半減期を有する組成物およびその使用 | |
| JP2007525465A (ja) | 重症急性呼吸症候群(sars)の治療のための、組成物および方法 | |
| JP2018524391A (ja) | 血管形成および血管新生に付随する障害を処置するための方法 | |
| JP2021521173A (ja) | 眼内薬物送達用の持続放出微粒子のための方法及び組成物 | |
| JP2025122152A (ja) | サイトカインモジュレーション | |
| JP2009528977A (ja) | 慢性線維形成性疾患を治療するための物質および方法 | |
| US20180355030A1 (en) | Methods and compositions for treating disorders associated with pathological neovascularization | |
| US8043609B2 (en) | Viral complement control proteins for eye disorders | |
| JP6689484B2 (ja) | 網膜炎症の治療において使用するための薬剤 | |
| US20140288010A1 (en) | Compositions and Methods for Increasing Stem Cell Survival | |
| KR20210010435A (ko) | 콜로니 자극 인자의 표적화에 의한 녹내장 및 시신경병증 치료법 | |
| WO2010048365A2 (en) | Therapeutic peptide bioconjugates | |
| CN119947731A (zh) | 含有与IFN-γ选择性结合的DNA寡核苷酸的干眼症治疗药物 | |
| WO2006077824A1 (ja) | 神経細胞再生のための医薬 | |
| JP5874124B2 (ja) | 緑内障の処置に使用するための薬学的組成物 | |
| KR20040030948A (ko) | 과민성 질환에 효과적인 il-18 저해물질 | |
| JP2008542385A (ja) | 神経損傷の抑制 | |
| JP7185655B2 (ja) | チャネル調節剤 | |
| EP3806833A1 (en) | Use of pi3kc2b inhibitors for the preservation of vascular endothelial cell barrier integrity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100202 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100202 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120417 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120717 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120724 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120817 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120824 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20120914 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20120924 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121017 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121211 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130308 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130315 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130410 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130417 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130510 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130517 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130806 |