CN105968208A - 使用fgf23融合多肽的方法和组合物 - Google Patents
使用fgf23融合多肽的方法和组合物 Download PDFInfo
- Publication number
- CN105968208A CN105968208A CN201610245160.1A CN201610245160A CN105968208A CN 105968208 A CN105968208 A CN 105968208A CN 201610245160 A CN201610245160 A CN 201610245160A CN 105968208 A CN105968208 A CN 105968208A
- Authority
- CN
- China
- Prior art keywords
- polypeptide
- klotho
- fgf23
- seq
- fused polypeptide
- 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.)
- Withdrawn
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 722
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 682
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 681
- 238000000034 method Methods 0.000 title claims abstract description 121
- 239000000203 mixture Substances 0.000 title claims abstract description 54
- 230000004927 fusion Effects 0.000 title abstract description 21
- 102100024802 Fibroblast growth factor 23 Human genes 0.000 title description 24
- 101001051973 Homo sapiens Fibroblast growth factor 23 Proteins 0.000 title 1
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims abstract description 96
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims abstract description 96
- 238000011282 treatment Methods 0.000 claims abstract description 72
- 210000002966 serum Anatomy 0.000 claims abstract description 60
- 108090000569 Fibroblast Growth Factor-23 Proteins 0.000 claims abstract description 58
- 108020001507 fusion proteins Proteins 0.000 claims abstract description 57
- 102000037865 fusion proteins Human genes 0.000 claims abstract description 57
- 102000009490 IgG Receptors Human genes 0.000 claims abstract description 49
- 108010073807 IgG Receptors Proteins 0.000 claims abstract description 49
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 37
- 102000004042 Fibroblast Growth Factor-23 Human genes 0.000 claims abstract description 35
- 230000001965 increasing effect Effects 0.000 claims abstract description 19
- 108050007372 Fibroblast Growth Factor Proteins 0.000 claims description 165
- 102000018233 Fibroblast Growth Factor Human genes 0.000 claims description 161
- 229940126864 fibroblast growth factor Drugs 0.000 claims description 150
- 241001597008 Nomeidae Species 0.000 claims description 87
- 210000004027 cell Anatomy 0.000 claims description 84
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 83
- 230000005714 functional activity Effects 0.000 claims description 75
- 239000008194 pharmaceutical composition Substances 0.000 claims description 63
- 230000008859 change Effects 0.000 claims description 60
- 102000039446 nucleic acids Human genes 0.000 claims description 55
- 108020004707 nucleic acids Proteins 0.000 claims description 55
- 150000007523 nucleic acids Chemical class 0.000 claims description 55
- 239000003814 drug Substances 0.000 claims description 46
- 206010028980 Neoplasm Diseases 0.000 claims description 30
- 201000011510 cancer Diseases 0.000 claims description 23
- 230000001225 therapeutic effect Effects 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 230000012010 growth Effects 0.000 claims description 19
- 208000017169 kidney disease Diseases 0.000 claims description 15
- 208000004434 Calcinosis Diseases 0.000 claims description 14
- 230000001684 chronic effect Effects 0.000 claims description 13
- 208000020832 chronic kidney disease Diseases 0.000 claims description 13
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 13
- 201000005991 hyperphosphatemia Diseases 0.000 claims description 12
- 238000011321 prophylaxis Methods 0.000 claims description 9
- 210000002950 fibroblast Anatomy 0.000 claims description 8
- 230000003328 fibroblastic effect Effects 0.000 claims description 5
- 108050004036 Klotho Proteins 0.000 abstract description 313
- 239000012634 fragment Substances 0.000 abstract description 44
- 230000002265 prevention Effects 0.000 abstract description 19
- 230000035772 mutation Effects 0.000 abstract description 11
- 108091005804 Peptidases Proteins 0.000 abstract description 7
- 239000004365 Protease Substances 0.000 abstract description 7
- 230000007423 decrease Effects 0.000 abstract description 5
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 abstract description 4
- 230000002776 aggregation Effects 0.000 abstract description 3
- 238000004220 aggregation Methods 0.000 abstract description 3
- 102000015834 Klotho Human genes 0.000 abstract 2
- 238000003776 cleavage reaction Methods 0.000 abstract 1
- 230000003247 decreasing effect Effects 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 230000007017 scission Effects 0.000 abstract 1
- 102100020686 Klotho Human genes 0.000 description 377
- 235000001014 amino acid Nutrition 0.000 description 141
- 229940024606 amino acid Drugs 0.000 description 138
- 150000001413 amino acids Chemical class 0.000 description 134
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 90
- 108090000623 proteins and genes Proteins 0.000 description 90
- 201000010099 disease Diseases 0.000 description 77
- 101001139093 Homo sapiens Klotho Proteins 0.000 description 71
- 102000004169 proteins and genes Human genes 0.000 description 66
- 235000018102 proteins Nutrition 0.000 description 64
- 108010076504 Protein Sorting Signals Proteins 0.000 description 60
- 230000000694 effects Effects 0.000 description 57
- 241001465754 Metazoa Species 0.000 description 38
- 239000002773 nucleotide Substances 0.000 description 36
- 125000003729 nucleotide group Chemical group 0.000 description 36
- 208000024827 Alzheimer disease Diseases 0.000 description 35
- 102100020683 Beta-klotho Human genes 0.000 description 35
- 101710104526 Beta-klotho Proteins 0.000 description 35
- 125000000539 amino acid group Chemical group 0.000 description 35
- 238000012360 testing method Methods 0.000 description 33
- 108091008794 FGF receptors Proteins 0.000 description 30
- 241000699670 Mus sp. Species 0.000 description 29
- 108700008625 Reporter Genes Proteins 0.000 description 28
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 24
- 238000012217 deletion Methods 0.000 description 24
- 230000037430 deletion Effects 0.000 description 24
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 23
- 230000008569 process Effects 0.000 description 23
- 208000024891 symptom Diseases 0.000 description 23
- 102100031734 Fibroblast growth factor 19 Human genes 0.000 description 22
- 101000846394 Homo sapiens Fibroblast growth factor 19 Proteins 0.000 description 22
- 230000004913 activation Effects 0.000 description 22
- 239000003636 conditioned culture medium Substances 0.000 description 22
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 20
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 20
- 230000006870 function Effects 0.000 description 20
- 239000005089 Luciferase Substances 0.000 description 19
- 229960002897 heparin Drugs 0.000 description 19
- 229920000669 heparin Polymers 0.000 description 19
- 125000005647 linker group Chemical group 0.000 description 19
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 19
- 239000001963 growth medium Substances 0.000 description 18
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 18
- 238000002560 therapeutic procedure Methods 0.000 description 18
- 206010002027 Amyotrophy Diseases 0.000 description 17
- 239000002253 acid Substances 0.000 description 17
- 238000010171 animal model Methods 0.000 description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- 230000000144 pharmacologic effect Effects 0.000 description 15
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 14
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 14
- 208000023105 Huntington disease Diseases 0.000 description 14
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 14
- 210000004556 brain Anatomy 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- 101100444898 Mus musculus Egr1 gene Proteins 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 230000004071 biological effect Effects 0.000 description 13
- 239000003102 growth factor Substances 0.000 description 13
- 238000009396 hybridization Methods 0.000 description 13
- 230000004060 metabolic process Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 230000033228 biological regulation Effects 0.000 description 12
- 230000002596 correlated effect Effects 0.000 description 12
- 206010006187 Breast cancer Diseases 0.000 description 11
- 208000026310 Breast neoplasm Diseases 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 11
- 208000035475 disorder Diseases 0.000 description 11
- 230000026731 phosphorylation Effects 0.000 description 11
- 238000006366 phosphorylation reaction Methods 0.000 description 11
- 241000894007 species Species 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 230000001575 pathological effect Effects 0.000 description 10
- 230000001105 regulatory effect Effects 0.000 description 10
- 102000004877 Insulin Human genes 0.000 description 9
- 108090001061 Insulin Proteins 0.000 description 9
- 241000699660 Mus musculus Species 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 230000001276 controlling effect Effects 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 229940125396 insulin Drugs 0.000 description 9
- 230000009261 transgenic effect Effects 0.000 description 9
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 8
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 8
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 8
- 208000001132 Osteoporosis Diseases 0.000 description 8
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 8
- 206010040799 Skin atrophy Diseases 0.000 description 8
- 229910021529 ammonia Inorganic materials 0.000 description 8
- 201000008275 breast carcinoma Diseases 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 230000000875 corresponding effect Effects 0.000 description 8
- 238000005520 cutting process Methods 0.000 description 8
- 230000007850 degeneration Effects 0.000 description 8
- 206010012601 diabetes mellitus Diseases 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 208000011580 syndromic disease Diseases 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 206010003210 Arteriosclerosis Diseases 0.000 description 7
- 201000001320 Atherosclerosis Diseases 0.000 description 7
- 208000024806 Brain atrophy Diseases 0.000 description 7
- 206010008190 Cerebrovascular accident Diseases 0.000 description 7
- 206010012289 Dementia Diseases 0.000 description 7
- 206010014561 Emphysema Diseases 0.000 description 7
- 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 7
- 108060001084 Luciferase Proteins 0.000 description 7
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 208000006011 Stroke Diseases 0.000 description 7
- 230000002159 abnormal effect Effects 0.000 description 7
- 208000011775 arteriosclerosis disease Diseases 0.000 description 7
- 238000013270 controlled release Methods 0.000 description 7
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 7
- 229960003957 dexamethasone Drugs 0.000 description 7
- 235000013601 eggs Nutrition 0.000 description 7
- 239000000835 fiber Substances 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 230000013632 homeostatic process Effects 0.000 description 7
- 201000001421 hyperglycemia Diseases 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 7
- 239000010452 phosphate Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- -1 sKlotho) Proteins 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 238000011830 transgenic mouse model Methods 0.000 description 7
- 208000000044 Amnesia Diseases 0.000 description 6
- 208000002177 Cataract Diseases 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 6
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 6
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 6
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 6
- 206010025421 Macule Diseases 0.000 description 6
- 208000026139 Memory disease Diseases 0.000 description 6
- 239000002202 Polyethylene glycol Substances 0.000 description 6
- 206010040954 Skin wrinkling Diseases 0.000 description 6
- 230000032683 aging Effects 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 238000007918 intramuscular administration Methods 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 230000033001 locomotion Effects 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000006984 memory degeneration Effects 0.000 description 6
- 208000023060 memory loss Diseases 0.000 description 6
- 230000004770 neurodegeneration Effects 0.000 description 6
- 230000002981 neuropathic effect Effects 0.000 description 6
- 201000008482 osteoarthritis Diseases 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000004904 shortening Methods 0.000 description 6
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000003146 transient transfection Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000037303 wrinkles Effects 0.000 description 6
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 5
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 5
- 206010011878 Deafness Diseases 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 208000008589 Obesity Diseases 0.000 description 5
- 206010062237 Renal impairment Diseases 0.000 description 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- 230000006907 apoptotic process Effects 0.000 description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 5
- 239000000470 constituent Substances 0.000 description 5
- 238000005034 decoration Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000010370 hearing loss Effects 0.000 description 5
- 231100000888 hearing loss Toxicity 0.000 description 5
- 208000016354 hearing loss disease Diseases 0.000 description 5
- 230000001900 immune effect Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 210000003141 lower extremity Anatomy 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 231100000857 poor renal function Toxicity 0.000 description 5
- 201000001514 prostate carcinoma Diseases 0.000 description 5
- 208000001076 sarcopenia Diseases 0.000 description 5
- 230000008054 signal transmission Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 4
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 241000283073 Equus caballus Species 0.000 description 4
- 240000007049 Juglans regia Species 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 4
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 4
- 102000013275 Somatomedins Human genes 0.000 description 4
- 206010064930 age-related macular degeneration Diseases 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 238000013459 approach Methods 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000036755 cellular response Effects 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 208000016097 disease of metabolism Diseases 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 229960000310 isoleucine Drugs 0.000 description 4
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 210000000107 myocyte Anatomy 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 201000001119 neuropathy Diseases 0.000 description 4
- 230000007823 neuropathy Effects 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000004434 saccadic eye movement Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 108091005703 transmembrane proteins Proteins 0.000 description 4
- 102000035160 transmembrane proteins Human genes 0.000 description 4
- 239000004474 valine Substances 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- 208000037259 Amyloid Plaque Diseases 0.000 description 3
- 206010003694 Atrophy Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108700024394 Exon Proteins 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 230000037444 atrophy Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 235000013339 cereals Nutrition 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 238000000151 deposition Methods 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 210000002683 foot Anatomy 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 235000004554 glutamine Nutrition 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 3
- 206010025482 malaise Diseases 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 229960002930 sirolimus Drugs 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 3
- 229960001052 streptozocin Drugs 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 2
- 206010000871 Acute monocytic leukaemia Diseases 0.000 description 2
- 241000024188 Andala Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
- 241000252212 Danio rerio Species 0.000 description 2
- 101001031598 Dictyostelium discoideum Probable serine/threonine-protein kinase fhkC Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108091006020 Fc-tagged proteins Proteins 0.000 description 2
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 2
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 2
- 206010017577 Gait disturbance Diseases 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 208000008069 Geographic Atrophy Diseases 0.000 description 2
- 206010018341 Gliosis Diseases 0.000 description 2
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000282553 Macaca Species 0.000 description 2
- 208000016285 Movement disease Diseases 0.000 description 2
- 101100390675 Mus musculus Fgf15 gene Proteins 0.000 description 2
- 101100291369 Mus musculus Mip gene Proteins 0.000 description 2
- JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 102000004108 Neurotransmitter Receptors Human genes 0.000 description 2
- 108090000590 Neurotransmitter Receptors Proteins 0.000 description 2
- 241000289371 Ornithorhynchus anatinus Species 0.000 description 2
- 101150116466 PALM gene Proteins 0.000 description 2
- 241000282577 Pan troglodytes Species 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 101710092489 Protein kinase 2 Proteins 0.000 description 2
- 208000019802 Sexually transmitted disease Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 208000026214 Skeletal muscle atrophy Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 241000218636 Thuja Species 0.000 description 2
- 102000004338 Transferrin Human genes 0.000 description 2
- 108090000901 Transferrin Proteins 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 2
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 208000008383 Wilms tumor Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 241000269368 Xenopus laevis Species 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 210000000467 autonomic pathway Anatomy 0.000 description 2
- 230000035578 autophosphorylation Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002638 denervation Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 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 2
- 230000008034 disappearance Effects 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 230000005021 gait Effects 0.000 description 2
- 230000007387 gliosis Effects 0.000 description 2
- 125000003147 glycosyl group Chemical group 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 101150113725 hd gene Proteins 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000013383 initial experiment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 210000004153 islets of langerhan Anatomy 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 208000012804 lymphangiosarcoma Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 210000002161 motor neuron Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000002232 neuromuscular Effects 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000004853 protein function Effects 0.000 description 2
- 239000013014 purified material Substances 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 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 2
- 238000012216 screening Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 210000000582 semen Anatomy 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 230000025185 skeletal muscle atrophy Effects 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 239000012581 transferrin Substances 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101100230376 Acetivibrio thermocellus (strain ATCC 27405 / DSM 1237 / JCM 9322 / NBRC 103400 / NCIMB 10682 / NRRL B-4536 / VPI 7372) celI gene Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 241001614291 Anoplistes Species 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 206010003062 Apraxia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000009017 Athetosis Diseases 0.000 description 1
- 208000025978 Athletic injury Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102000007527 Autoreceptors Human genes 0.000 description 1
- 108010071131 Autoreceptors Proteins 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 1
- 241000282461 Canis lupus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 102000004031 Carboxy-Lyases Human genes 0.000 description 1
- 108090000489 Carboxy-Lyases Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000004046 Caspase-2 Human genes 0.000 description 1
- 108090000552 Caspase-2 Proteins 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 102000003908 Cathepsin D Human genes 0.000 description 1
- 108090000258 Cathepsin D Proteins 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Chinese gallotannin Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 108090000943 Cholesterol 7-alpha-monooxygenases Proteins 0.000 description 1
- 102000004410 Cholesterol 7-alpha-monooxygenases Human genes 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102100033780 Collagen alpha-3(IV) chain Human genes 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 102100038637 Cytochrome P450 7A1 Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101150046567 DAO gene Proteins 0.000 description 1
- 102000012410 DNA Ligases Human genes 0.000 description 1
- 108010061982 DNA Ligases Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 108010093668 Deubiquitinating Enzymes Proteins 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 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 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 241000026944 Giovanella Species 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010018404 Glucagonoma Diseases 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 206010056328 Hepatic ischaemia Diseases 0.000 description 1
- 108700014808 Homeobox Protein Nkx-2.2 Proteins 0.000 description 1
- 101000710873 Homo sapiens Collagen alpha-3(IV) chain Proteins 0.000 description 1
- 101000957672 Homo sapiens Cytochrome P450 7A1 Proteins 0.000 description 1
- 206010020651 Hyperkinesia Diseases 0.000 description 1
- 208000000269 Hyperkinesis Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 208000029663 Hypophosphatemia Diseases 0.000 description 1
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 1
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 244000283207 Indigofera tinctoria Species 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- 208000036232 King Evil Diseases 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- 208000018142 Leiomyosarcoma Diseases 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 239000012097 Lipofectamine 2000 Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 208000030289 Lymphoproliferative disease Diseases 0.000 description 1
- 208000007054 Medullary Carcinoma Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 108700029942 Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency Proteins 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100460498 Mus musculus Nkx2-2 gene Proteins 0.000 description 1
- 101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- OTCCIMWXFLJLIA-UHFFFAOYSA-N N-acetyl-DL-aspartic acid Natural products CC(=O)NC(C(O)=O)CC(O)=O OTCCIMWXFLJLIA-UHFFFAOYSA-N 0.000 description 1
- OTCCIMWXFLJLIA-BYPYZUCNSA-N N-acetyl-L-aspartic acid Chemical compound CC(=O)N[C@H](C(O)=O)CC(O)=O OTCCIMWXFLJLIA-BYPYZUCNSA-N 0.000 description 1
- 241000244206 Nematoda Species 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 239000012124 Opti-MEM Substances 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 235000005205 Pinus Nutrition 0.000 description 1
- 241000218602 Pinus <genus> Species 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 241000135309 Processus Species 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100281003 Rattus norvegicus Fgf23 gene Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108010052090 Renilla Luciferases Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000244200 Rhabditida Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 102100025292 Stress-induced-phosphoprotein 1 Human genes 0.000 description 1
- 206010043458 Thirst Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 206010068872 Toe walking Diseases 0.000 description 1
- 102000002070 Transferrins Human genes 0.000 description 1
- 108010015865 Transferrins Proteins 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 208000014070 Vestibular schwannoma Diseases 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 108091006088 activator proteins Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 238000012867 alanine scanning Methods 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000006933 amyloid-beta aggregation Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000020538 atrophic muscular disease Diseases 0.000 description 1
- 239000011805 ball Substances 0.000 description 1
- 229920005601 base polymer Polymers 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000000188 beta-D-glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037058 blood plasma level Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 210000002987 choroid plexus Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 210000001726 chromosome structure Anatomy 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 208000015806 constitutional megaloblastic anemia with severe neurologic disease Diseases 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000036757 core body temperature Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 208000002445 cystadenocarcinoma Diseases 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 235000014103 egg white Nutrition 0.000 description 1
- 210000000969 egg white Anatomy 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000000630 fibrocyte Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 101150046266 foxo gene Proteins 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000007160 gastrointestinal dysfunction Effects 0.000 description 1
- 238000012637 gene transfection Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 150000002333 glycines Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 208000025750 heavy chain disease Diseases 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 230000003483 hypokinetic effect Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 235000004213 low-fat Nutrition 0.000 description 1
- 229940066294 lung surfactant Drugs 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 201000007227 lymph node tuberculosis Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 239000003147 molecular marker Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 208000001611 myxosarcoma Diseases 0.000 description 1
- 239000005645 nematicide Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000007991 neuronal integrity Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000004019 papillary adenocarcinoma Diseases 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 238000009527 percussion Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 108010040003 polyglutamine Proteins 0.000 description 1
- 229920000155 polyglutamine Polymers 0.000 description 1
- 108010094020 polyglycine Proteins 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000013615 primer Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 238000003498 protein array Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001814 protein method Methods 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 210000003497 sciatic nerve Anatomy 0.000 description 1
- 108010048734 sclerotin Proteins 0.000 description 1
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 239000012209 synthetic fiber Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 239000004577 thatch Substances 0.000 description 1
- 208000001644 thecoma Diseases 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229960000874 thyrotropin Drugs 0.000 description 1
- 230000001748 thyrotropin Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 238000002689 xenotransplantation Methods 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
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/50—Fibroblast growth factor [FGF]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- 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
-
- 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
- A61K38/18—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P27/12—Ophthalmic agents for cataracts
-
- 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
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
-
- 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
-
- 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
- C12N15/62—DNA sequences coding for fusion proteins
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2405—Glucanases
- C12N9/2434—Glucanases acting on beta-1,4-glucosidic bonds
- C12N9/2445—Beta-glucosidase (3.2.1.21)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/93—Ligases (6)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01021—Beta-glucosidase (3.2.1.21)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01031—Beta-glucuronidase (3.2.1.31)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y602/00—Ligases forming carbon-sulfur bonds (6.2)
- C12Y602/01—Acid-Thiol Ligases (6.2.1)
- C12Y602/01003—Long-chain-fatty-acid-CoA ligase (6.2.1.3)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Toxicology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Plant Pathology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/696,693 US8420088B2 (en) | 2008-01-28 | 2010-01-29 | Methods and compositions using FGF23 fusion polypeptides |
| US12/696,693 | 2010-01-29 | ||
| CN201180007622.1A CN102725413B (zh) | 2010-01-29 | 2011-01-27 | 使用fgf23融合多肽的方法和组合物 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201180007622.1A Division CN102725413B (zh) | 2010-01-29 | 2011-01-27 | 使用fgf23融合多肽的方法和组合物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105968208A true CN105968208A (zh) | 2016-09-28 |
Family
ID=43828141
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201180007622.1A Active CN102725413B (zh) | 2010-01-29 | 2011-01-27 | 使用fgf23融合多肽的方法和组合物 |
| CN201610245160.1A Withdrawn CN105968208A (zh) | 2010-01-29 | 2011-01-27 | 使用fgf23融合多肽的方法和组合物 |
| CN201310049110.2A Active CN103204941B (zh) | 2010-01-29 | 2011-01-27 | 使用fgf23融合多肽的方法和组合物 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201180007622.1A Active CN102725413B (zh) | 2010-01-29 | 2011-01-27 | 使用fgf23融合多肽的方法和组合物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310049110.2A Active CN103204941B (zh) | 2010-01-29 | 2011-01-27 | 使用fgf23融合多肽的方法和组合物 |
Country Status (16)
| Country | Link |
|---|---|
| US (3) | US8420088B2 (enExample) |
| EP (2) | EP3124612A1 (enExample) |
| JP (2) | JP5964243B2 (enExample) |
| KR (1) | KR20130032296A (enExample) |
| CN (3) | CN102725413B (enExample) |
| AR (1) | AR080043A1 (enExample) |
| AU (1) | AU2011209380B2 (enExample) |
| CA (1) | CA2787285A1 (enExample) |
| EA (1) | EA201201047A1 (enExample) |
| ES (1) | ES2605302T3 (enExample) |
| MX (1) | MX336391B (enExample) |
| PL (1) | PL2529016T3 (enExample) |
| PT (1) | PT2529016T (enExample) |
| TW (2) | TWI430805B (enExample) |
| UY (1) | UY33204A (enExample) |
| WO (1) | WO2011092234A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021128065A1 (zh) * | 2019-12-25 | 2021-07-01 | 广州菲康生物技术有限公司 | 人fgf-23的荧光免疫层析试纸和人fgf-23的荧光免疫层析检测试剂盒 |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8420088B2 (en) | 2008-01-28 | 2013-04-16 | Novartis Ag | Methods and compositions using FGF23 fusion polypeptides |
| TW200936156A (en) | 2008-01-28 | 2009-09-01 | Novartis Ag | Methods and compositions using Klotho-FGF fusion polypeptides |
| EP2726511B1 (en) | 2011-07-01 | 2019-08-07 | NGM Biopharmaceuticals, Inc. | Compositions, uses and methods for treatment of metabolic disorders and diseases |
| US9290557B2 (en) | 2012-11-28 | 2016-03-22 | Ngm Biopharmaceuticals, Inc. | Compositions comprising variants and fusions of FGF19 polypeptides |
| EP2925775B1 (en) | 2012-11-28 | 2020-09-16 | NGM Biopharmaceuticals, Inc. | Compositions and methods for treatment of metabolic disorders and diseases |
| CN102961739A (zh) * | 2012-12-12 | 2013-03-13 | 黄曙 | Klotho蛋白的用途 |
| KR102724421B1 (ko) | 2012-12-27 | 2024-10-30 | 엔지엠 바이오파마슈티컬스, 아이엔씨. | 담즙산 항상성의 조절 및 담즙산 질환 및 질병의 치료 방법 |
| US9273107B2 (en) | 2012-12-27 | 2016-03-01 | Ngm Biopharmaceuticals, Inc. | Uses and methods for modulating bile acid homeostasis and treatment of bile acid disorders and diseases |
| WO2014152993A1 (en) * | 2013-03-14 | 2014-09-25 | The Board Of Regents Of The University Of Oklahoma | Use of klotho nucleic acids or proteins for treatment of diabetes and diabetes-related conditions |
| KR101492710B1 (ko) * | 2013-04-03 | 2015-02-13 | 중앙대학교 산학협력단 | Fgf23 유전자를 이용한 전립선암 진단용 마커 및 이를 이용한 전립선암 예측 및 진단 방법 |
| JP6159930B2 (ja) | 2013-10-24 | 2017-07-12 | 地方独立行政法人東京都健康長寿医療センター | 筋幹細胞又は筋芽細胞、及びそれを用いた代謝変換に関与する物質のスクリーニング方法、並びにスクリーニング方法によって得られた物質を含む医薬組成物 |
| KR102178945B1 (ko) | 2013-10-28 | 2020-11-13 | 엔지엠 바이오파마슈티컬스, 아이엔씨. | 암 모델 및 관련 방법 |
| US20150140036A1 (en) | 2013-11-13 | 2015-05-21 | Novartis Institutes For Biomedical Research, Inc. | Low, immune enhancing, dose mtor inhibitors and uses thereof |
| SI3097122T1 (sl) | 2014-01-24 | 2020-07-31 | Ngm Biopharmaceuticals, Inc. | Protitelesa, ki se vežejo v domeni beta klotho 2, in metode za njihovo uporabo |
| JP6370577B2 (ja) * | 2014-03-26 | 2018-08-08 | 国立大学法人京都工芸繊維大学 | 抗老化物質のスクリーニング方法 |
| WO2015183890A2 (en) | 2014-05-28 | 2015-12-03 | Ngm Biopharmaceuticals, Inc. | Methods and compositions for the treatment of metabolic disorders and diseases |
| CA2951153A1 (en) | 2014-06-16 | 2015-12-23 | Ngm Biopharmaceuticals, Inc. | Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| CN107108711B (zh) | 2014-10-23 | 2021-11-23 | 恩格姆生物制药公司 | 包含肽变异体的药物组合物及其使用方法 |
| US10434144B2 (en) | 2014-11-07 | 2019-10-08 | Ngm Biopharmaceuticals, Inc. | Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders |
| EA201791238A1 (ru) | 2014-12-04 | 2018-02-28 | Новартис Аг | Способы и композиции, в которых используются варианты полипептидов klotho |
| EP3253403B1 (en) | 2015-02-06 | 2021-09-01 | The Regents of The University of California | Methods and compositions for improved cognition |
| US10800843B2 (en) | 2015-07-29 | 2020-10-13 | Ngm Biopharmaceuticals, Inc. | Beta klotho-binding proteins |
| JP6728352B2 (ja) | 2015-11-09 | 2020-07-22 | エヌジーエム バイオファーマシューティカルス,インコーポレーテッド | 胆汁酸に関係した障害の治療方法 |
| EP3464608A4 (en) * | 2016-06-02 | 2020-01-29 | Klotho Therapeutics, Inc. | THERAPEUTIC RECOMBINANT KLOTHO PROTEINS, COMPOSITIONS AND METHODS THEREFOR |
| EA037848B1 (ru) * | 2016-07-14 | 2021-05-27 | Общество С Ограниченной Ответственностью "Биохимический Агент" | Гибридный белок, полинуклеотид, генетическая конструкция, продуцент, препарат для регенерации хряща (варианты) |
| CN106317226B (zh) * | 2016-08-19 | 2017-09-05 | 安源医药科技(上海)有限公司 | 用于构建融合蛋白的连接肽 |
| EP3502143A4 (en) | 2016-08-19 | 2020-07-15 | Ampsource Biopharma Shanghai Inc. | BINDING PEPTIDE FOR THE CONSTRUCTION OF A FUSION PROTEIN |
| CN106279437B (zh) | 2016-08-19 | 2017-10-31 | 安源医药科技(上海)有限公司 | 高糖基化人凝血因子viii融合蛋白及其制备方法与用途 |
| CA3034399A1 (en) | 2016-08-26 | 2018-03-01 | Ngm Biopharmaceuticals, Inc. | Methods of treating fibroblast growth factor 19-mediated cancers and tumors |
| EP3956354A1 (en) * | 2019-04-19 | 2022-02-23 | Genethon | Gene therapy of fibroblast growth factor 23 related hypophosphatemic diseases |
| US11028132B1 (en) | 2020-04-07 | 2021-06-08 | Yitzhak Rosen | Half-life optimized linker composition |
| US11981718B2 (en) | 2020-05-27 | 2024-05-14 | Ampsource Biopharma Shanghai Inc. | Dual-function protein for lipid and blood glucose regulation |
| WO2025101851A1 (en) * | 2023-11-10 | 2025-05-15 | Regeneron Pharmaceuticals, Inc. | Engineered alpha klotho polypeptides and uses thereof |
Family Cites Families (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL71691A (en) | 1984-04-27 | 1991-04-15 | Yeda Res & Dev | Production of interferon-ypsilon |
| US5128326A (en) | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
| US5266561A (en) | 1988-01-11 | 1993-11-30 | Amylin Pharmaceuticals, Inc. | Treatment of type 2 diabetes mellitus |
| EP0550436A1 (en) | 1989-11-06 | 1993-07-14 | Alkermes Controlled Therapeutics, Inc. | Protein microspheres and methods of using them |
| JPH06507782A (ja) | 1990-06-15 | 1994-09-08 | サイオス ノバ インコーポレイテッド | アルツハイマー病のアミロイド形成開症状を示すヒト以外の組換え哺乳動物 |
| US5408038A (en) * | 1991-10-09 | 1995-04-18 | The Scripps Research Institute | Nonnatural apolipoprotein B-100 peptides and apolipoprotein B-100-apolipoprotein A-I fusion peptides |
| US5912015A (en) | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
| US5420112A (en) | 1992-06-12 | 1995-05-30 | Lewis; Michael E. | Prevention and treatment of peripheral neuropathy |
| US5541094A (en) * | 1992-09-25 | 1996-07-30 | E. I. Du Pont De Nemours And Company | Glyoxylic acid/aminomethylphosphonic acid mixtures prepared using a microbial transformant |
| US5877399A (en) | 1994-01-27 | 1999-03-02 | Johns Hopkins University | Transgenic mice expressing APP-Swedish mutation develop progressive neurologic disease |
| US6187992B1 (en) | 1994-12-05 | 2001-02-13 | Merck & Co., Inc. | Transgenic mouse having a disrupted amyloid precursor protein gene |
| WO1997007788A2 (en) | 1995-08-31 | 1997-03-06 | Alkermes Controlled Therapeutics, Inc. | Composition for sustained release of an agent |
| US6194177B1 (en) | 1996-02-20 | 2001-02-27 | Applied Research Systems Ars Holding N.V. | DNA encoding a hybrid heterodimeric protein |
| JP3258027B2 (ja) | 1996-03-15 | 2002-02-18 | サマーセット・ファーマシューティカルズ・インコーポレイテッド | セレジリン投与による末梢ニューロパシーの予防および治療方法 |
| US6358752B1 (en) | 1996-09-27 | 2002-03-19 | Cornell Research Foundation, Inc. | Liposome-enhanced test device and method |
| EP0945506B1 (en) | 1996-12-26 | 2007-02-28 | Kyowa Hakko Kogyo Co., Ltd. | Proteine avec une activite de suppression du vieillissement |
| US6127598A (en) | 1997-07-25 | 2000-10-03 | The Regents Of The University Of California | NKX-2.2 and NKX-6.1 transgenic mouse models for diabetes, depression, and obesity |
| US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
| SE512663C2 (sv) | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
| WO1999051773A1 (en) | 1998-04-03 | 1999-10-14 | Phylos, Inc. | Addressable protein arrays |
| US7060479B2 (en) * | 1999-12-08 | 2006-06-13 | Serono Genetics Institute, S.A. | Full-length human cDNAs encoding potentially secreted proteins |
| US20030055231A1 (en) | 1998-10-28 | 2003-03-20 | Jian Ni | 12 human secreted proteins |
| JP4585693B2 (ja) | 1999-04-22 | 2010-11-24 | リポサイエンス、インコーポレイテッド | Ii型糖尿病を発現する危険性のnmrによる決定方法 |
| WO2001012851A2 (en) | 1999-08-12 | 2001-02-22 | Wisconsin Alumni Research Foundation | Identification of genetic markers of biological age and metabolism |
| US6569832B1 (en) | 1999-11-12 | 2003-05-27 | Novo Nordisk A/S | Inhibition of beta cell degeneration |
| US6716626B1 (en) | 1999-11-18 | 2004-04-06 | Chiron Corporation | Human FGF-21 nucleic acids |
| US6406853B1 (en) | 1999-12-23 | 2002-06-18 | The Regents Of The University Of California | Interventions to mimic the effects of calorie restriction |
| US20060160181A1 (en) * | 2000-02-15 | 2006-07-20 | Amgen Inc. | Fibroblast Growth Factor-23 molecules and uses thereof |
| JP2006238894A (ja) * | 2000-02-15 | 2006-09-14 | Amgen Inc | 線維芽細胞成長因子−23分子およびその使用 |
| JP2003531583A (ja) | 2000-03-08 | 2003-10-28 | カイロン コーポレイション | ヒトfgf−23遺伝子および遺伝子発現産物 |
| AU2001273323B2 (en) | 2000-07-19 | 2005-11-10 | Advanced Research & Technology Institute | Novel fibroblast growth factor (FGF23) and methods for use |
| CA2436661A1 (en) | 2001-01-30 | 2002-08-08 | Regeneron Pharmaceuticals, Inc. | Novel nucleic acid and polypeptide molecules |
| US7588757B2 (en) | 2001-03-14 | 2009-09-15 | Genzyme Corporation | Methods of treating Parkinson's disease using recombinant adeno-associated virus virions |
| AU2002302581A1 (en) * | 2001-04-26 | 2002-11-11 | Geneprot, Inc. | Human fibroblast growth factor-related compositions |
| EP1327443A1 (en) | 2001-12-21 | 2003-07-16 | Kyowa Hakko Kogyo Co., Ltd. | Therapeutic or preventing agent for the diseases caused by a decrease in the expression level of the klotho protein |
| US20050004348A1 (en) * | 2002-12-23 | 2005-01-06 | Miyamoto Ken-Ichi | Novel type II Na/Pi cotransporters and type II Na/Pi cotransporter expression regulatory factors |
| JP2007531707A (ja) | 2003-10-15 | 2007-11-08 | ピーディーエル バイオファーマ, インコーポレイテッド | IGの重鎖定常領域の位置250、314および/または428の変異誘発によるFc融合タンパク質血清半減期の改変 |
| TW200936156A (en) | 2008-01-28 | 2009-09-01 | Novartis Ag | Methods and compositions using Klotho-FGF fusion polypeptides |
| US8420088B2 (en) | 2008-01-28 | 2013-04-16 | Novartis Ag | Methods and compositions using FGF23 fusion polypeptides |
| US20110015345A1 (en) * | 2008-03-19 | 2011-01-20 | Ambrx, Inc. | Modified FGF-23 Polypeptides and Their Uses |
| KR101651703B1 (ko) | 2008-10-10 | 2016-08-26 | 암젠 인크 | Fgf21 돌연변이체 및 이의 용도 |
| WO2010129600A2 (en) | 2009-05-05 | 2010-11-11 | Amgen Inc. | Fgf21 mutants and uses thereof |
| US8461111B2 (en) | 2009-05-20 | 2013-06-11 | Florida State University Research Foundation | Fibroblast growth factor mutants having improved functional half-life and methods of their use |
| US20110195077A1 (en) | 2010-01-29 | 2011-08-11 | Novartis Ag | Methods and compositions using fgf23 fusion ppolypeptides |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
-
2010
- 2010-01-29 US US12/696,693 patent/US8420088B2/en not_active Expired - Fee Related
-
2011
- 2011-01-27 AR ARP110100273A patent/AR080043A1/es unknown
- 2011-01-27 PL PL11705830T patent/PL2529016T3/pl unknown
- 2011-01-27 MX MX2012008780A patent/MX336391B/es unknown
- 2011-01-27 EA EA201201047A patent/EA201201047A1/ru unknown
- 2011-01-27 KR KR1020127022498A patent/KR20130032296A/ko not_active Withdrawn
- 2011-01-27 CA CA2787285A patent/CA2787285A1/en not_active Withdrawn
- 2011-01-27 CN CN201180007622.1A patent/CN102725413B/zh active Active
- 2011-01-27 AU AU2011209380A patent/AU2011209380B2/en not_active Ceased
- 2011-01-27 WO PCT/EP2011/051112 patent/WO2011092234A1/en not_active Ceased
- 2011-01-27 PT PT117058305T patent/PT2529016T/pt unknown
- 2011-01-27 JP JP2012550437A patent/JP5964243B2/ja not_active Expired - Fee Related
- 2011-01-27 CN CN201610245160.1A patent/CN105968208A/zh not_active Withdrawn
- 2011-01-27 UY UY0001033204A patent/UY33204A/es not_active Application Discontinuation
- 2011-01-27 CN CN201310049110.2A patent/CN103204941B/zh active Active
- 2011-01-27 EP EP16184724.9A patent/EP3124612A1/en not_active Withdrawn
- 2011-01-27 EP EP11705830.5A patent/EP2529016B1/en active Active
- 2011-01-27 ES ES11705830.5T patent/ES2605302T3/es active Active
- 2011-01-28 TW TW100103508A patent/TWI430805B/zh active
- 2011-01-28 TW TW103100421A patent/TWI569805B/zh not_active IP Right Cessation
-
2013
- 2013-03-12 US US13/796,711 patent/US8932589B2/en not_active Expired - Fee Related
-
2014
- 2014-11-03 US US14/531,620 patent/US9475857B2/en active Active
-
2016
- 2016-04-25 JP JP2016087432A patent/JP2016190847A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021128065A1 (zh) * | 2019-12-25 | 2021-07-01 | 广州菲康生物技术有限公司 | 人fgf-23的荧光免疫层析试纸和人fgf-23的荧光免疫层析检测试剂盒 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102725413A (zh) | 2012-10-10 |
| CA2787285A1 (en) | 2011-08-04 |
| EP2529016A1 (en) | 2012-12-05 |
| KR20130032296A (ko) | 2013-04-01 |
| EP3124612A1 (en) | 2017-02-01 |
| EP2529016B1 (en) | 2016-08-24 |
| US20100215657A1 (en) | 2010-08-26 |
| US8932589B2 (en) | 2015-01-13 |
| UY33204A (es) | 2011-08-31 |
| CN103204941B (zh) | 2016-05-04 |
| US9475857B2 (en) | 2016-10-25 |
| JP2013517781A (ja) | 2013-05-20 |
| CN103204941A (zh) | 2013-07-17 |
| US8420088B2 (en) | 2013-04-16 |
| WO2011092234A1 (en) | 2011-08-04 |
| TWI569805B (zh) | 2017-02-11 |
| JP5964243B2 (ja) | 2016-08-03 |
| EA201201047A1 (ru) | 2013-02-28 |
| CN102725413B (zh) | 2016-05-11 |
| JP2016190847A (ja) | 2016-11-10 |
| ES2605302T3 (es) | 2017-03-13 |
| AU2011209380A1 (en) | 2012-08-09 |
| PT2529016T (pt) | 2016-12-12 |
| MX336391B (es) | 2016-01-18 |
| US20130224196A1 (en) | 2013-08-29 |
| TW201414488A (zh) | 2014-04-16 |
| AR080043A1 (es) | 2012-03-07 |
| MX2012008780A (es) | 2012-12-17 |
| US20160031961A1 (en) | 2016-02-04 |
| TWI430805B (zh) | 2014-03-21 |
| PL2529016T3 (pl) | 2017-02-28 |
| AU2011209380B2 (en) | 2013-09-12 |
| TW201129373A (en) | 2011-09-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105968208A (zh) | 使用fgf23融合多肽的方法和组合物 | |
| ES2479417T3 (es) | Métodos y composiciones que utilizan polipéptidos de fusión Klotho-FGF | |
| US9139631B2 (en) | Methods and compositions using FGF23 variant polypeptides with reduced aggregation and cleavage | |
| EP3227319B1 (en) | Methods and compositions using klotho variant polypeptides | |
| CN110041420A (zh) | 虎纹捕鸟蛛毒素-iv变体及其使用方法 | |
| US10414808B2 (en) | Huwentoxin-IV variants and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20160928 |
|
| WW01 | Invention patent application withdrawn after publication |