ZA200509708B - Selective R-cadherin antagonists and methods - Google Patents
Selective R-cadherin antagonists and methods Download PDFInfo
- Publication number
- ZA200509708B ZA200509708B ZA200509708A ZA200509708A ZA200509708B ZA 200509708 B ZA200509708 B ZA 200509708B ZA 200509708 A ZA200509708 A ZA 200509708A ZA 200509708 A ZA200509708 A ZA 200509708A ZA 200509708 B ZA200509708 B ZA 200509708B
- Authority
- ZA
- South Africa
- Prior art keywords
- amino acid
- xaa
- peptide
- cadherin
- ser
- Prior art date
Links
- 108010086890 R-cadherin Proteins 0.000 title claims abstract description 124
- 102100029758 Cadherin-4 Human genes 0.000 title claims abstract description 119
- 239000005557 antagonist Substances 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims description 25
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 134
- 210000004027 cell Anatomy 0.000 claims abstract description 86
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 76
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 40
- 102000001189 Cyclic Peptides Human genes 0.000 claims abstract description 37
- 108010069514 Cyclic Peptides Proteins 0.000 claims abstract description 37
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 34
- 230000001404 mediated effect Effects 0.000 claims abstract description 29
- 229940123672 Cadherin antagonist Drugs 0.000 claims abstract description 25
- 230000008685 targeting Effects 0.000 claims abstract description 23
- 210000005166 vasculature Anatomy 0.000 claims abstract description 17
- 230000001413 cellular effect Effects 0.000 claims abstract description 15
- 230000004263 retinal angiogenesis Effects 0.000 claims abstract description 12
- 210000000130 stem cell Anatomy 0.000 claims abstract description 11
- 230000003511 endothelial effect Effects 0.000 claims abstract description 8
- 239000002243 precursor Substances 0.000 claims abstract description 6
- 230000002792 vascular Effects 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 41
- 125000004122 cyclic group Chemical group 0.000 claims description 40
- 239000000126 substance Substances 0.000 claims description 22
- 235000001014 amino acid Nutrition 0.000 claims description 13
- 230000002207 retinal effect Effects 0.000 claims description 13
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 10
- 230000002159 abnormal effect Effects 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 230000033115 angiogenesis Effects 0.000 claims description 7
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- 208000002780 macular degeneration Diseases 0.000 claims description 5
- 230000006459 vascular development Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 5
- 230000021164 cell adhesion Effects 0.000 claims 3
- 210000004962 mammalian cell Anatomy 0.000 claims 3
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 3
- 241001024304 Mino Species 0.000 claims 1
- 230000000630 rising effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 45
- 102000000905 Cadherin Human genes 0.000 description 143
- 108050007957 Cadherin Proteins 0.000 description 141
- 108050000637 N-cadherin Proteins 0.000 description 41
- 210000003995 blood forming stem cell Anatomy 0.000 description 39
- 239000010410 layer Substances 0.000 description 31
- 230000002776 aggregation Effects 0.000 description 30
- 238000004220 aggregation Methods 0.000 description 30
- 210000001525 retina Anatomy 0.000 description 25
- 238000002347 injection Methods 0.000 description 21
- 239000007924 injection Substances 0.000 description 21
- 230000014509 gene expression Effects 0.000 description 20
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 description 15
- UKTUOMWSJPXODT-GUDRVLHUSA-N Ile-Asn-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N UKTUOMWSJPXODT-GUDRVLHUSA-N 0.000 description 14
- 230000000903 blocking effect Effects 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 12
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Chemical group OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 230000003993 interaction Effects 0.000 description 10
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 9
- 239000011575 calcium Substances 0.000 description 9
- 229910052791 calcium Inorganic materials 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 108091008695 photoreceptors Proteins 0.000 description 9
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 241001529936 Murinae Species 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 238000003119 immunoblot Methods 0.000 description 7
- 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 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- HXKZJLWGSWQKEA-LSJOCFKGSA-N His-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CN=CN1 HXKZJLWGSWQKEA-LSJOCFKGSA-N 0.000 description 5
- 210000001130 astrocyte Anatomy 0.000 description 5
- 238000006471 dimerization reaction Methods 0.000 description 5
- 230000001537 neural effect Effects 0.000 description 5
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 230000004276 retinal vascularization Effects 0.000 description 4
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 3
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- 108010056325 HAV peptide Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 101000714535 Mus musculus Cadherin-2 Proteins 0.000 description 3
- 229940083963 Peptide antagonist Drugs 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000017455 cell-cell adhesion Effects 0.000 description 3
- 210000004292 cytoskeleton Anatomy 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000000869 mutational effect Effects 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 210000002867 adherens junction Anatomy 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 210000000608 photoreceptor cell Anatomy 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 230000004233 retinal vasculature Effects 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000025934 tissue morphogenesis Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 101710118833 B-cadherin Proteins 0.000 description 1
- 102000011103 Cadherin Related Proteins Human genes 0.000 description 1
- 108010023070 Cadherin Related Proteins Proteins 0.000 description 1
- 101100290380 Caenorhabditis elegans cel-1 gene Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000016362 Catenins Human genes 0.000 description 1
- 108010067316 Catenins Proteins 0.000 description 1
- 102100036988 Cyclin-dependent kinase 2-interacting protein Human genes 0.000 description 1
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical group OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 1
- 108010019063 Desmocollins Proteins 0.000 description 1
- 102000006375 Desmocollins Human genes 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
- 101000737869 Homo sapiens Cyclin-dependent kinase 2-interacting protein Proteins 0.000 description 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- HDODQNPMSHDXJT-GHCJXIJMSA-N Ile-Asn-Ser Chemical group CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O HDODQNPMSHDXJT-GHCJXIJMSA-N 0.000 description 1
- DCQMJRSOGCYKTR-GHCJXIJMSA-N Ile-Asp-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O DCQMJRSOGCYKTR-GHCJXIJMSA-N 0.000 description 1
- 102100039905 Isocitrate dehydrogenase [NADP] cytoplasmic Human genes 0.000 description 1
- -1 L-form amino acids Chemical class 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108700040559 Protocadherins Proteins 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 241001074048 Regina Species 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 210000000411 amacrine cell Anatomy 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 208000001321 ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 1 Diseases 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000002346 layers by function Substances 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000004879 molecular function Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000007512 neuronal protection Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- 210000003733 optic disk Anatomy 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000000059 patterning Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000000964 retinal cone photoreceptor cell Anatomy 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 230000004491 retinal development Effects 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 230000009790 vascular invasion Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cell Biology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US46718803P | 2003-05-01 | 2003-05-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200509708B true ZA200509708B (en) | 2006-12-27 |
Family
ID=33435033
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200509708A ZA200509708B (en) | 2003-05-01 | 2005-11-30 | Selective R-cadherin antagonists and methods |
Country Status (18)
Country | Link |
---|---|
US (2) | US7419953B2 (ko) |
EP (1) | EP1635855B1 (ko) |
JP (1) | JP4613300B2 (ko) |
KR (2) | KR101120419B1 (ko) |
CN (2) | CN103272219A (ko) |
AT (1) | ATE491718T1 (ko) |
AU (1) | AU2004236208B2 (ko) |
BR (1) | BRPI0409850A (ko) |
CA (1) | CA2523932A1 (ko) |
DE (1) | DE602004030565D1 (ko) |
DK (1) | DK1635855T3 (ko) |
ES (1) | ES2355260T3 (ko) |
MX (1) | MXPA05011751A (ko) |
PL (1) | PL1635855T3 (ko) |
PT (1) | PT1635855E (ko) |
RU (1) | RU2349598C2 (ko) |
WO (1) | WO2004099232A2 (ko) |
ZA (1) | ZA200509708B (ko) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6277824B1 (en) * | 1998-07-10 | 2001-08-21 | Adherex Technologies | Compounds and methods for modulating adhesion molecule function |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7803904B2 (en) * | 1995-09-01 | 2010-09-28 | Millennium Pharmaceuticals, Inc. | Mucosal vascular addressing and uses thereof |
DE69637155T2 (de) * | 1995-02-10 | 2008-02-07 | Millennium Pharmaceuticals, Inc., Cambridge | Addressine der schleimhaut und der blutgefässe und ihre verwendung |
AU759144B2 (en) * | 1998-05-05 | 2003-04-03 | Adherex Technologies Inc. | Compounds and methods for modulating nonclassical cadherin-mediated functions |
US6277824B1 (en) * | 1998-07-10 | 2001-08-21 | Adherex Technologies | Compounds and methods for modulating adhesion molecule function |
US20020151681A1 (en) * | 1999-03-12 | 2002-10-17 | Rosen Craig A. | Nucleic acids, proteins and antibodies |
WO2004085455A1 (en) * | 2003-03-24 | 2004-10-07 | The University Of Hong Kong | A diagnostic assay for the human virus causing severe acute respiratory syndrome (sars) |
-
2004
- 2004-04-30 ES ES04750884T patent/ES2355260T3/es not_active Expired - Lifetime
- 2004-04-30 AT AT04750884T patent/ATE491718T1/de active
- 2004-04-30 WO PCT/US2004/013212 patent/WO2004099232A2/en active Application Filing
- 2004-04-30 CN CN2013101708624A patent/CN103272219A/zh active Pending
- 2004-04-30 EP EP04750884A patent/EP1635855B1/en not_active Expired - Lifetime
- 2004-04-30 US US10/836,289 patent/US7419953B2/en not_active Expired - Fee Related
- 2004-04-30 BR BRPI0409850-1A patent/BRPI0409850A/pt active Search and Examination
- 2004-04-30 DK DK04750884.1T patent/DK1635855T3/da active
- 2004-04-30 PT PT04750884T patent/PT1635855E/pt unknown
- 2004-04-30 KR KR1020117019034A patent/KR101120419B1/ko not_active IP Right Cessation
- 2004-04-30 AU AU2004236208A patent/AU2004236208B2/en not_active Ceased
- 2004-04-30 RU RU2005137322/04A patent/RU2349598C2/ru not_active IP Right Cessation
- 2004-04-30 KR KR1020057020759A patent/KR101138633B1/ko not_active IP Right Cessation
- 2004-04-30 JP JP2006513429A patent/JP4613300B2/ja not_active Expired - Fee Related
- 2004-04-30 PL PL04750884T patent/PL1635855T3/pl unknown
- 2004-04-30 DE DE602004030565T patent/DE602004030565D1/de not_active Expired - Lifetime
- 2004-04-30 CN CN2004800184052A patent/CN1812804B/zh not_active Expired - Fee Related
- 2004-04-30 MX MXPA05011751A patent/MXPA05011751A/es active IP Right Grant
- 2004-04-30 CA CA002523932A patent/CA2523932A1/en not_active Abandoned
-
2005
- 2005-11-30 ZA ZA200509708A patent/ZA200509708B/en unknown
-
2008
- 2008-09-02 US US12/231,328 patent/US8163697B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
JP2006525344A (ja) | 2006-11-09 |
US7419953B2 (en) | 2008-09-02 |
BRPI0409850A (pt) | 2006-05-09 |
CN1812804A (zh) | 2006-08-02 |
EP1635855A4 (en) | 2007-10-10 |
MXPA05011751A (es) | 2006-02-17 |
EP1635855B1 (en) | 2010-12-15 |
EP1635855A2 (en) | 2006-03-22 |
CN1812804B (zh) | 2013-06-12 |
WO2004099232A2 (en) | 2004-11-18 |
ES2355260T3 (es) | 2011-03-24 |
RU2005137322A (ru) | 2006-06-10 |
US20050004013A1 (en) | 2005-01-06 |
DE602004030565D1 (de) | 2011-01-27 |
US8163697B2 (en) | 2012-04-24 |
PL1635855T3 (pl) | 2011-04-29 |
ATE491718T1 (de) | 2011-01-15 |
US20090124538A1 (en) | 2009-05-14 |
RU2349598C2 (ru) | 2009-03-20 |
CN103272219A (zh) | 2013-09-04 |
JP4613300B2 (ja) | 2011-01-12 |
CA2523932A1 (en) | 2004-11-18 |
PT1635855E (pt) | 2011-02-23 |
DK1635855T3 (da) | 2011-02-14 |
KR101138633B1 (ko) | 2012-07-04 |
AU2004236208B2 (en) | 2009-10-29 |
KR20110099065A (ko) | 2011-09-05 |
WO2004099232A3 (en) | 2005-05-19 |
KR101120419B1 (ko) | 2012-03-16 |
AU2004236208A1 (en) | 2004-11-18 |
KR20060009283A (ko) | 2006-01-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7189546B2 (en) | Polypeptide, cDNA encoding the same, and use of them | |
US8680047B2 (en) | Fas peptide mimetics and uses thereof | |
CZ391097A3 (cs) | Látky a peptidy vážící se na erythropoietinový receptor | |
CN1452492A (zh) | 神经保护肽 | |
US20230068507A1 (en) | Chimeric antigen receptors for removal of amyloid | |
EP1947114A1 (en) | Mutated netrin 4, fragments thereof and uses thereof as drugs | |
CN113840834A (zh) | Magea1特异性t细胞受体及其用途 | |
US20230192794A1 (en) | Engineered interleukin-22 polypeptides and uses thereof | |
US8163697B2 (en) | Selective R-cadherin antagonists and methods | |
JP2002538823A (ja) | 脊椎動物のslitDNA配列、タンパク質およびその使用 |