ZA200500342B - Therapies for renal failure using interferon-beta - Google Patents

Info

Publication number

ZA200500342B

ZA200500342B ZA200500342A ZA200500342A ZA200500342B ZA 200500342 B ZA200500342 B ZA 200500342B ZA 200500342 A ZA200500342 A ZA 200500342A ZA 200500342 A ZA200500342 A ZA 200500342A ZA 200500342 B ZA200500342 B ZA 200500342B

Authority

ZA

South Africa

Prior art keywords

ifn

glomerulonephritis

substance

composition

treatment

Prior art date

2002-07-17

Links

• Espacenet
• Global Dossier
• Discuss

• 229960001388 interferon-beta Drugs 0.000 title description 20
• 102000003996 Interferon-beta Human genes 0.000 title description 18
• 108090000467 Interferon-beta Proteins 0.000 title description 18
• 201000006370 kidney failure Diseases 0.000 title description 16
• 208000001647 Renal Insufficiency Diseases 0.000 title description 13
• 238000002560 therapeutic procedure Methods 0.000 title description 5
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 89
• 238000000034 method Methods 0.000 claims description 79
• 230000001225 therapeutic effect Effects 0.000 claims description 67
• 239000000203 mixture Substances 0.000 claims description 57
• 208000020832 chronic kidney disease Diseases 0.000 claims description 53
• 239000003814 drug Substances 0.000 claims description 52
• 238000011282 treatment Methods 0.000 claims description 46
• 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 41
• 239000000126 substance Substances 0.000 claims description 38
• 241000124008 Mammalia Species 0.000 claims description 29
• 208000022461 Glomerular disease Diseases 0.000 claims description 26
• 230000002265 prevention Effects 0.000 claims description 19
• 206010012601 diabetes mellitus Diseases 0.000 claims description 10
• 206010018378 Glomerulonephritis rapidly progressive Diseases 0.000 claims description 9
• 201000005637 crescentic glomerulonephritis Diseases 0.000 claims description 9
• 208000004883 Lipoid Nephrosis Diseases 0.000 claims description 8
• 206010029164 Nephrotic syndrome Diseases 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 201000008171 proliferative glomerulonephritis Diseases 0.000 claims description 8
• 208000024985 Alport syndrome Diseases 0.000 claims description 7
• 206010018367 Glomerulonephritis chronic Diseases 0.000 claims description 7
• 206010018374 Glomerulonephritis minimal lesion Diseases 0.000 claims description 6
• 201000008269 immune-complex glomerulonephritis Diseases 0.000 claims description 6
• 206010018370 Glomerulonephritis membranoproliferative Diseases 0.000 claims description 5
• 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 claims description 5
• 206010065673 Nephritic syndrome Diseases 0.000 claims description 5
• 208000030532 Pauci-immune glomerulonephritis Diseases 0.000 claims description 5
• 210000002469 basement membrane Anatomy 0.000 claims description 5
• 201000008350 membranous glomerulonephritis Diseases 0.000 claims description 3
• 201000005206 focal segmental glomerulosclerosis Diseases 0.000 claims 1
• 108090000623 proteins and genes Proteins 0.000 description 109
• 102000004169 proteins and genes Human genes 0.000 description 94
• 235000018102 proteins Nutrition 0.000 description 92
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 63
• 229920000642 polymer Polymers 0.000 description 63
• 241000700159 Rattus Species 0.000 description 60
• 235000001014 amino acid Nutrition 0.000 description 60
• 229940024606 amino acid Drugs 0.000 description 56
• DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 56
• 150000001413 amino acids Chemical class 0.000 description 55
• 108090000765 processed proteins & peptides Proteins 0.000 description 54
• 210000004027 cell Anatomy 0.000 description 53
• 102000004196 processed proteins & peptides Human genes 0.000 description 44
• 235000002639 sodium chloride Nutrition 0.000 description 40
• 229920001184 polypeptide Polymers 0.000 description 39
• 229920001223 polyethylene glycol Polymers 0.000 description 38
• 201000001474 proteinuria Diseases 0.000 description 37
• 230000001434 glomerular Effects 0.000 description 36
• 239000002202 Polyethylene glycol Substances 0.000 description 35
• 239000011780 sodium chloride Substances 0.000 description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 30
• 230000014509 gene expression Effects 0.000 description 30
• 150000007523 nucleic acids Chemical class 0.000 description 29
• 229940109239 creatinine Drugs 0.000 description 28
• -1 fused to the hinge Chemical group 0.000 description 28
• 102000039446 nucleic acids Human genes 0.000 description 28
• 108020004707 nucleic acids Proteins 0.000 description 28
• 239000013598 vector Substances 0.000 description 27
• 210000003734 kidney Anatomy 0.000 description 26
• 210000002700 urine Anatomy 0.000 description 25
• 230000000694 effects Effects 0.000 description 22
• 230000003907 kidney function Effects 0.000 description 22
• 150000001875 compounds Chemical class 0.000 description 21
• 201000010099 disease Diseases 0.000 description 20
• 239000001488 sodium phosphate Substances 0.000 description 20
• 229910000162 sodium phosphate Inorganic materials 0.000 description 20
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 20
• 210000002966 serum Anatomy 0.000 description 19
• 108060003951 Immunoglobulin Proteins 0.000 description 18
• 102000018358 immunoglobulin Human genes 0.000 description 18
• 210000000885 nephron Anatomy 0.000 description 18
• 239000002773 nucleotide Substances 0.000 description 18
• 125000003729 nucleotide group Chemical group 0.000 description 18
• 108010076504 Protein Sorting Signals Proteins 0.000 description 17
• 125000003275 alpha amino acid group Chemical group 0.000 description 17
• 239000000243 solution Substances 0.000 description 17
• 241001465754 Metazoa Species 0.000 description 16
• 108020001507 fusion proteins Proteins 0.000 description 16
• 102000037865 fusion proteins Human genes 0.000 description 16
• 229920001515 polyalkylene glycol Polymers 0.000 description 16
• 108010050904 Interferons Proteins 0.000 description 15
• 230000001684 chronic effect Effects 0.000 description 15
• 230000008021 deposition Effects 0.000 description 15
• 238000007912 intraperitoneal administration Methods 0.000 description 15
• 230000004048 modification Effects 0.000 description 15
• 238000012986 modification Methods 0.000 description 15
• 238000012959 renal replacement therapy Methods 0.000 description 15
• 238000006467 substitution reaction Methods 0.000 description 15
• 108010005716 Interferon beta-1a Proteins 0.000 description 14
• 102000014150 Interferons Human genes 0.000 description 14
• 238000010171 animal model Methods 0.000 description 14
• 230000027455 binding Effects 0.000 description 14
• 239000003550 marker Substances 0.000 description 14
• 238000002360 preparation method Methods 0.000 description 14
• 238000013519 translation Methods 0.000 description 14
• 108020004414 DNA Proteins 0.000 description 13
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 13
• 102100040019 Interferon alpha-1/13 Human genes 0.000 description 13
• 108091028043 Nucleic acid sequence Proteins 0.000 description 13
• 229920002684 Sepharose Polymers 0.000 description 13
• 125000005647 linker group Chemical group 0.000 description 13
• 239000000872 buffer Substances 0.000 description 12
• 238000006243 chemical reaction Methods 0.000 description 12
• 229940079593 drug Drugs 0.000 description 12
• 230000004054 inflammatory process Effects 0.000 description 12
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
• 230000004663 cell proliferation Effects 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 230000007423 decrease Effects 0.000 description 11
• 238000009472 formulation Methods 0.000 description 11
• 238000002347 injection Methods 0.000 description 11
• 239000007924 injection Substances 0.000 description 11
• 229940079322 interferon Drugs 0.000 description 11
• 230000000750 progressive effect Effects 0.000 description 11
• 206010018366 Glomerulonephritis acute Diseases 0.000 description 10
• 238000002835 absorbance Methods 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
• 230000001154 acute effect Effects 0.000 description 10
• 231100000851 acute glomerulonephritis Toxicity 0.000 description 10
• CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 10
• 201000000523 end stage renal failure Diseases 0.000 description 10
• 230000004927 fusion Effects 0.000 description 10
• 210000000585 glomerular basement membrane Anatomy 0.000 description 10
• 230000024924 glomerular filtration Effects 0.000 description 10
• 239000000047 product Substances 0.000 description 10
• 230000002062 proliferating effect Effects 0.000 description 10
• 230000009467 reduction Effects 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• 206010020772 Hypertension Diseases 0.000 description 9
• 206010061218 Inflammation Diseases 0.000 description 9
• 241000700605 Viruses Species 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• 238000010828 elution Methods 0.000 description 9
• 208000028208 end stage renal disease Diseases 0.000 description 9
• 239000012634 fragment Substances 0.000 description 9
• 238000000338 in vitro Methods 0.000 description 9
• 208000017169 kidney disease Diseases 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000008194 pharmaceutical composition Substances 0.000 description 9
• 239000000523 sample Substances 0.000 description 9
• 230000037390 scarring Effects 0.000 description 9
• 239000003381 stabilizer Substances 0.000 description 9
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
• 206010020880 Hypertrophy Diseases 0.000 description 8
• 229940003504 avonex Drugs 0.000 description 8
• 230000001413 cellular effect Effects 0.000 description 8
• 230000000295 complement effect Effects 0.000 description 8
• 230000006378 damage Effects 0.000 description 8
• 239000013604 expression vector Substances 0.000 description 8
• 231100000852 glomerular disease Toxicity 0.000 description 8
• 238000005259 measurement Methods 0.000 description 8
• 201000008383 nephritis Diseases 0.000 description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
• 108020003175 receptors Proteins 0.000 description 8
• 102000005962 receptors Human genes 0.000 description 8
• 150000003839 salts Chemical class 0.000 description 8
• 206010016654 Fibrosis Diseases 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 230000037396 body weight Effects 0.000 description 7
• 238000000502 dialysis Methods 0.000 description 7
• 230000004761 fibrosis Effects 0.000 description 7
• 206010061989 glomerulosclerosis Diseases 0.000 description 7
• 125000003827 glycol group Chemical group 0.000 description 7
• 230000001631 hypertensive effect Effects 0.000 description 7
• 230000002147 killing effect Effects 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 241000894007 species Species 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• 230000002485 urinary effect Effects 0.000 description 7
• 102000009027 Albumins Human genes 0.000 description 6
• 108010088751 Albumins Proteins 0.000 description 6
• 241000283690 Bos taurus Species 0.000 description 6
• 239000004471 Glycine Substances 0.000 description 6
• 108010005714 Interferon beta-1b Proteins 0.000 description 6
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 6
• 108091034117 Oligonucleotide Proteins 0.000 description 6
• 101150052863 THY1 gene Proteins 0.000 description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
• 125000003277 amino group Chemical group 0.000 description 6
• 230000000840 anti-viral effect Effects 0.000 description 6
• 239000000427 antigen Substances 0.000 description 6
• 108091007433 antigens Proteins 0.000 description 6
• 102000036639 antigens Human genes 0.000 description 6
• 208000006454 hepatitis Diseases 0.000 description 6
• 210000004969 inflammatory cell Anatomy 0.000 description 6
• 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 6
• 238000001990 intravenous administration Methods 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 210000002540 macrophage Anatomy 0.000 description 6
• 230000001404 mediated effect Effects 0.000 description 6
• 210000003584 mesangial cell Anatomy 0.000 description 6
• 229930182817 methionine Natural products 0.000 description 6
• 230000003589 nefrotoxic effect Effects 0.000 description 6
• 231100000381 nephrotoxic Toxicity 0.000 description 6
• 210000005084 renal tissue Anatomy 0.000 description 6
• 238000004513 sizing Methods 0.000 description 6
• 235000000346 sugar Nutrition 0.000 description 6
• 208000024891 symptom Diseases 0.000 description 6
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
• RYSMHWILUNYBFW-UHFFFAOYSA-N 4-amino-2-[6-(dimethylamino)purin-9-yl]-5-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N(C)C)=NC=NC=2N1C1OC(CO)C(N)C1O RYSMHWILUNYBFW-UHFFFAOYSA-N 0.000 description 5
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• 241000282412 Homo Species 0.000 description 5
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 5
• 208000013901 Nephropathies and tubular disease Diseases 0.000 description 5
• 208000036142 Viral infection Diseases 0.000 description 5
• 230000002159 abnormal effect Effects 0.000 description 5
• 238000007792 addition Methods 0.000 description 5
• 150000001299 aldehydes Chemical class 0.000 description 5
• 229960003589 arginine hydrochloride Drugs 0.000 description 5
• 230000004071 biological effect Effects 0.000 description 5
• 230000008033 biological extinction Effects 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 5
• 239000002299 complementary DNA Substances 0.000 description 5
• 238000010168 coupling process Methods 0.000 description 5
• 229960003624 creatine Drugs 0.000 description 5
• 239000006046 creatine Substances 0.000 description 5
• 238000012217 deletion Methods 0.000 description 5
• 230000037430 deletion Effects 0.000 description 5
• 239000003792 electrolyte Substances 0.000 description 5
• 230000006870 function Effects 0.000 description 5
• 210000003904 glomerular cell Anatomy 0.000 description 5
• 231100000283 hepatitis Toxicity 0.000 description 5
• 230000002757 inflammatory effect Effects 0.000 description 5
• 239000003999 initiator Substances 0.000 description 5
• 238000011862 kidney biopsy Methods 0.000 description 5
• 210000000265 leukocyte Anatomy 0.000 description 5
• 150000002632 lipids Chemical class 0.000 description 5
• 239000012669 liquid formulation Substances 0.000 description 5
• 239000006166 lysate Substances 0.000 description 5
• 230000002503 metabolic effect Effects 0.000 description 5
• 201000009925 nephrosclerosis Diseases 0.000 description 5
• 229940100595 phenylacetaldehyde Drugs 0.000 description 5
• 239000013612 plasmid Substances 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
• 230000008569 process Effects 0.000 description 5
• 230000035755 proliferation Effects 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 229940038850 rebif Drugs 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 239000013049 sediment Substances 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• 230000009385 viral infection Effects 0.000 description 5
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
• 239000004475 Arginine Substances 0.000 description 4
• 208000037157 Azotemia Diseases 0.000 description 4
• 102000004506 Blood Proteins Human genes 0.000 description 4
• 108010017384 Blood Proteins Proteins 0.000 description 4
• 108091026890 Coding region Proteins 0.000 description 4
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 4
• 241000238631 Hexapoda Species 0.000 description 4
• 102000008100 Human Serum Albumin Human genes 0.000 description 4
• 108091006905 Human Serum Albumin Proteins 0.000 description 4
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
• 102000028391 RNA cap binding Human genes 0.000 description 4
• 108091000106 RNA cap binding Proteins 0.000 description 4
• 206010038468 Renal hypertrophy Diseases 0.000 description 4
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
• 230000035508 accumulation Effects 0.000 description 4
• 238000009825 accumulation Methods 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 210000004102 animal cell Anatomy 0.000 description 4
• 229960003121 arginine Drugs 0.000 description 4
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 238000001574 biopsy Methods 0.000 description 4
• 229920001400 block copolymer Polymers 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 210000004899 c-terminal region Anatomy 0.000 description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 230000021615 conjugation Effects 0.000 description 4
• 229920001577 copolymer Polymers 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 235000018417 cysteine Nutrition 0.000 description 4
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
• 208000033679 diabetic kidney disease Diseases 0.000 description 4
• 238000003745 diagnosis Methods 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
• 150000002334 glycols Chemical class 0.000 description 4
• 208000006750 hematuria Diseases 0.000 description 4
• 208000002672 hepatitis B Diseases 0.000 description 4
• 230000006872 improvement Effects 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• 201000008627 kidney hypertrophy Diseases 0.000 description 4
• 238000011694 lewis rat Methods 0.000 description 4
• 210000004185 liver Anatomy 0.000 description 4
• 210000004072 lung Anatomy 0.000 description 4
• 201000008265 mesangial proliferative glomerulonephritis Diseases 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 238000004393 prognosis Methods 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 239000011347 resin Substances 0.000 description 4
• 229920005989 resin Polymers 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 210000000952 spleen Anatomy 0.000 description 4
• 230000003068 static effect Effects 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• 238000005303 weighing Methods 0.000 description 4
• 238000011706 wistar kyoto rat Methods 0.000 description 4
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 3
• WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 3
• 241000894006 Bacteria Species 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 241000701822 Bovine papillomavirus Species 0.000 description 3
• 238000012756 BrdU staining Methods 0.000 description 3
• 102000004127 Cytokines Human genes 0.000 description 3
• 108090000695 Cytokines Proteins 0.000 description 3
• 241000196324 Embryophyta Species 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 241000588724 Escherichia coli Species 0.000 description 3
• 102000009123 Fibrin Human genes 0.000 description 3
• 108010073385 Fibrin Proteins 0.000 description 3
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical group CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 3
• 208000024869 Goodpasture syndrome Diseases 0.000 description 3
• 208000005176 Hepatitis C Diseases 0.000 description 3
• 102000004877 Insulin Human genes 0.000 description 3
• 108090001061 Insulin Proteins 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• 241000699666 Mus <mouse, genus> Species 0.000 description 3
• 206010030113 Oedema Diseases 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• 206010061481 Renal injury Diseases 0.000 description 3
• 208000034189 Sclerosis Diseases 0.000 description 3
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
• 230000005856 abnormality Effects 0.000 description 3
• 125000000539 amino acid group Chemical group 0.000 description 3
• 230000000890 antigenic effect Effects 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 229940021459 betaseron Drugs 0.000 description 3
• 210000001736 capillary Anatomy 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 239000004202 carbamide Substances 0.000 description 3
• 150000001720 carbohydrates Chemical group 0.000 description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
• 239000013592 cell lysate Substances 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 238000010367 cloning Methods 0.000 description 3
• 238000004132 cross linking Methods 0.000 description 3
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 238000001212 derivatisation Methods 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 210000003527 eukaryotic cell Anatomy 0.000 description 3
• 229950003499 fibrin Drugs 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000000834 fixative Substances 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 229960002989 glutamic acid Drugs 0.000 description 3
• 150000004676 glycans Chemical class 0.000 description 3
• 238000001631 haemodialysis Methods 0.000 description 3
• 230000000322 hemodialysis Effects 0.000 description 3
• 229920001519 homopolymer Polymers 0.000 description 3
• 238000010166 immunofluorescence Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 229940125396 insulin Drugs 0.000 description 3
• 238000007918 intramuscular administration Methods 0.000 description 3
• 239000008176 lyophilized powder Substances 0.000 description 3
• 238000010369 molecular cloning Methods 0.000 description 3
• 210000003205 muscle Anatomy 0.000 description 3
• 230000017074 necrotic cell death Effects 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• 239000008363 phosphate buffer Substances 0.000 description 3
• 230000036470 plasma concentration Effects 0.000 description 3
• 229920000233 poly(alkylene oxides) Polymers 0.000 description 3
• 229920001583 poly(oxyethylated polyols) Polymers 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 206010038433 renal dysplasia Diseases 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 238000002741 site-directed mutagenesis Methods 0.000 description 3
• 239000001632 sodium acetate Substances 0.000 description 3
• 235000017281 sodium acetate Nutrition 0.000 description 3
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 230000001052 transient effect Effects 0.000 description 3
• 238000002054 transplantation Methods 0.000 description 3
• 210000005239 tubule Anatomy 0.000 description 3
• 230000003442 weekly effect Effects 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
• GKSPIZSKQWTXQG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[1-(pyridin-2-yldisulfanyl)ethyl]benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SSC1=CC=CC=N1 GKSPIZSKQWTXQG-UHFFFAOYSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• 102000007469 Actins Human genes 0.000 description 2
• 108010085238 Actins Proteins 0.000 description 2
• 208000009304 Acute Kidney Injury Diseases 0.000 description 2
• 206010001580 Albuminuria Diseases 0.000 description 2
• 241001156002 Anthonomus pomorum Species 0.000 description 2
• 108090001008 Avidin Proteins 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 108020004705 Codon Proteins 0.000 description 2
• 102000008186 Collagen Human genes 0.000 description 2
• 108010035532 Collagen Proteins 0.000 description 2
• 102000004266 Collagen Type IV Human genes 0.000 description 2
• 108010042086 Collagen Type IV Proteins 0.000 description 2
• 241000699802 Cricetulus griseus Species 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• 229920002307 Dextran Polymers 0.000 description 2
• 102100024746 Dihydrofolate reductase Human genes 0.000 description 2
• 108010013369 Enteropeptidase Proteins 0.000 description 2
• 102100029727 Enteropeptidase Human genes 0.000 description 2
• 241000283086 Equidae Species 0.000 description 2
• 241000701959 Escherichia virus Lambda Species 0.000 description 2
• XZWYTXMRWQJBGX-VXBMVYAYSA-N FLAG peptide Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 XZWYTXMRWQJBGX-VXBMVYAYSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• 102000016359 Fibronectins Human genes 0.000 description 2
• 108010067306 Fibronectins Proteins 0.000 description 2
• 241000233866 Fungi Species 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
• 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 description 2
• 208000029422 Hypernatremia Diseases 0.000 description 2
• 208000003623 Hypoalbuminemia Diseases 0.000 description 2
• 102000012745 Immunoglobulin Subunits Human genes 0.000 description 2
• 108010079585 Immunoglobulin Subunits Proteins 0.000 description 2
• 102000001617 Interferon Receptors Human genes 0.000 description 2
• 108010054267 Interferon Receptors Proteins 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
• 206010024602 Lipiduria Diseases 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 2
• 229930195725 Mannitol Natural products 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
• HSMNQINEKMPTIC-UHFFFAOYSA-N N-(4-aminobenzoyl)glycine Chemical compound NC1=CC=C(C(=O)NCC(O)=O)C=C1 HSMNQINEKMPTIC-UHFFFAOYSA-N 0.000 description 2
• 125000000729 N-terminal amino-acid group Chemical group 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
• 229920001213 Polysorbate 20 Polymers 0.000 description 2
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
• 238000010240 RT-PCR analysis Methods 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 208000006265 Renal cell carcinoma Diseases 0.000 description 2
• 208000033626 Renal failure acute Diseases 0.000 description 2
• 208000000223 Solitary Kidney Diseases 0.000 description 2
• 210000001744 T-lymphocyte Anatomy 0.000 description 2
• 206010053614 Type III immune complex mediated reaction Diseases 0.000 description 2
• 206010046406 Ureteric obstruction Diseases 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 239000008351 acetate buffer Substances 0.000 description 2
• 201000011040 acute kidney failure Diseases 0.000 description 2
• 208000012998 acute renal failure Diseases 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 150000001408 amides Chemical group 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 239000002260 anti-inflammatory agent Substances 0.000 description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 238000002832 anti-viral assay Methods 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 235000003704 aspartic acid Nutrition 0.000 description 2
• 229940090047 auto-injector Drugs 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• 230000004888 barrier function Effects 0.000 description 2
• 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 2
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 229960002685 biotin Drugs 0.000 description 2
• 235000020958 biotin Nutrition 0.000 description 2
• 239000011616 biotin Substances 0.000 description 2
• 238000006664 bond formation reaction Methods 0.000 description 2
• 210000002665 bowman capsule Anatomy 0.000 description 2
• 238000004364 calculation method Methods 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 230000003196 chaotropic effect Effects 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 229920001436 collagen Polymers 0.000 description 2
• 230000001268 conjugating effect Effects 0.000 description 2
• 230000001054 cortical effect Effects 0.000 description 2
• 239000007822 coupling agent Substances 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 231100000517 death Toxicity 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 108020001096 dihydrofolate reductase Proteins 0.000 description 2
• 239000000539 dimer Substances 0.000 description 2
• AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000003511 endothelial effect Effects 0.000 description 2
• 210000002919 epithelial cell Anatomy 0.000 description 2
• 210000003743 erythrocyte Anatomy 0.000 description 2
• 230000029142 excretion Effects 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 238000000855 fermentation Methods 0.000 description 2
• 230000004151 fermentation Effects 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 239000012537 formulation buffer Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 210000005086 glomerual capillary Anatomy 0.000 description 2
• 235000013922 glutamic acid Nutrition 0.000 description 2
• 239000004220 glutamic acid Substances 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 150000002314 glycerols Polymers 0.000 description 2
• 238000003306 harvesting Methods 0.000 description 2
• 230000035876 healing Effects 0.000 description 2
• 208000003215 hereditary nephritis Diseases 0.000 description 2
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
• 210000005260 human cell Anatomy 0.000 description 2
• 238000009396 hybridization Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 230000016178 immune complex formation Effects 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 238000002649 immunization Methods 0.000 description 2
• 230000016784 immunoglobulin production Effects 0.000 description 2
• 229940072221 immunoglobulins Drugs 0.000 description 2
• 239000002955 immunomodulating agent Substances 0.000 description 2
• 229940121354 immunomodulator Drugs 0.000 description 2
• 229960003444 immunosuppressant agent Drugs 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 238000002513 implantation Methods 0.000 description 2
• 238000010348 incorporation Methods 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 230000028709 inflammatory response Effects 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 238000010255 intramuscular injection Methods 0.000 description 2
• 238000010253 intravenous injection Methods 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 235000018977 lysine Nutrition 0.000 description 2
• 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 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
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 238000013507 mapping Methods 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 229940011059 p-aminohippurate Drugs 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 210000003658 parietal epithelial cell Anatomy 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 239000000816 peptidomimetic Substances 0.000 description 2
• 230000035699 permeability Effects 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 2
• 229920001993 poloxamer 188 Polymers 0.000 description 2
• 229920002401 polyacrylamide Polymers 0.000 description 2
• 229920001281 polyalkylene Polymers 0.000 description 2
• 238000003752 polymerase chain reaction Methods 0.000 description 2
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
• 229920001451 polypropylene glycol Polymers 0.000 description 2
• 229940068977 polysorbate 20 Drugs 0.000 description 2
• 229920002451 polyvinyl alcohol Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229940071643 prefilled syringe Drugs 0.000 description 2
• 210000001236 prokaryotic cell Anatomy 0.000 description 2
• 201000008158 rapidly progressive glomerulonephritis Diseases 0.000 description 2
• 230000009257 reactivity Effects 0.000 description 2
• 238000005932 reductive alkylation reaction Methods 0.000 description 2
• 201000002793 renal fibrosis Diseases 0.000 description 2
• 230000008439 repair process Effects 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 210000001995 reticulocyte Anatomy 0.000 description 2
• 210000003705 ribosome Anatomy 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 238000012163 sequencing technique Methods 0.000 description 2
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
• VIDRYROWYFWGSY-UHFFFAOYSA-N sotalol hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 VIDRYROWYFWGSY-UHFFFAOYSA-N 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 238000010254 subcutaneous injection Methods 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 230000009261 transgenic effect Effects 0.000 description 2
• 229950002929 trinitrophenol Drugs 0.000 description 2
• XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 2
• 238000002604 ultrasonography Methods 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 238000011144 upstream manufacturing Methods 0.000 description 2
• 208000009852 uremia Diseases 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000008215 water for injection Substances 0.000 description 2
• GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 1
• HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 1
• OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
• UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
• VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
• LUTLAXLNPLZCOF-UHFFFAOYSA-N 1-Methylhistidine Natural products OC(=O)C(N)(C)CC1=NC=CN1 LUTLAXLNPLZCOF-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
• BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical compound CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• DLZKEQQWXODGGZ-KCJUWKMLSA-N 2-[[(2r)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DLZKEQQWXODGGZ-KCJUWKMLSA-N 0.000 description 1
• NBGAYCYFNGPNPV-UHFFFAOYSA-N 2-aminooxybenzoic acid Chemical class NOC1=CC=CC=C1C(O)=O NBGAYCYFNGPNPV-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• 101150090724 3 gene Proteins 0.000 description 1
• 108020005065 3' Flanking Region Proteins 0.000 description 1
• BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
• BXRLWGXPSRYJDZ-VKHMYHEASA-N 3-cyano-L-alanine Chemical compound OC(=O)[C@@H](N)CC#N BXRLWGXPSRYJDZ-VKHMYHEASA-N 0.000 description 1
• OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
• CQXXYOLFJXSRMT-UHFFFAOYSA-N 5-diazocyclohexa-1,3-diene Chemical class [N-]=[N+]=C1CC=CC=C1 CQXXYOLFJXSRMT-UHFFFAOYSA-N 0.000 description 1
• LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
• 229940000681 5-hydroxytryptophan Drugs 0.000 description 1
• YCPXWRQRBFJBPZ-UHFFFAOYSA-N 5-sulfosalicylic acid Chemical compound OC(=O)C1=CC(S(O)(=O)=O)=CC=C1O YCPXWRQRBFJBPZ-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 102000013563 Acid Phosphatase Human genes 0.000 description 1
• 108010051457 Acid Phosphatase Proteins 0.000 description 1
• 229920000936 Agarose Polymers 0.000 description 1
• 206010002329 Aneurysm Diseases 0.000 description 1
• 108010005853 Anti-Mullerian Hormone Proteins 0.000 description 1
• OAMLVOVXNKILLQ-BQBZGAKWSA-N Asp-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(O)=O OAMLVOVXNKILLQ-BQBZGAKWSA-N 0.000 description 1
• 206010003694 Atrophy Diseases 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• DTUQWGWMVIHBKE-UHFFFAOYSA-N Benzeneacetaldehyde Natural products O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 1
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 101710132601 Capsid protein Proteins 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• 241000282552 Chlorocebus aethiops Species 0.000 description 1
• 206010008909 Chronic Hepatitis 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
• 206010053567 Coagulopathies Diseases 0.000 description 1
• 101710094648 Coat protein Proteins 0.000 description 1
• 108700010070 Codon Usage Proteins 0.000 description 1
• 102000001187 Collagen Type III Human genes 0.000 description 1
• 108010069502 Collagen Type III Proteins 0.000 description 1
• 208000032170 Congenital Abnormalities Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• 208000026292 Cystic Kidney disease Diseases 0.000 description 1
• 241000701022 Cytomegalovirus Species 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Polymers OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• 102000053602 DNA Human genes 0.000 description 1
• 206010014418 Electrolyte imbalance Diseases 0.000 description 1
• 206010014666 Endocarditis bacterial Diseases 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 102000003782 Eukaryotic Initiation Factor-4F Human genes 0.000 description 1
• 108010057194 Eukaryotic Initiation Factor-4F Proteins 0.000 description 1
• 102000002241 Eukaryotic Initiation Factors Human genes 0.000 description 1
• 108010014863 Eukaryotic Initiation Factors Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 208000035126 Facies Diseases 0.000 description 1
• 241000282324 Felis Species 0.000 description 1
• 229920001917 Ficoll Polymers 0.000 description 1
• 206010051283 Fluid imbalance Diseases 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 102100021181 Golgi phosphoprotein 3 Human genes 0.000 description 1
• 108060003393 Granulin Proteins 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 241000606768 Haemophilus influenzae Species 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 101710154606 Hemagglutinin Proteins 0.000 description 1
• 101000840258 Homo sapiens Immunoglobulin J chain Proteins 0.000 description 1
• 101000848718 Homo sapiens Rap guanine nucleotide exchange factor 5 Proteins 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• 108010058683 Immobilized Proteins Proteins 0.000 description 1
• 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
• 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
• 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
• 102100029571 Immunoglobulin J chain Human genes 0.000 description 1
• 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 1
• 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 1
• 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
• 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
• 206010022004 Influenza like illness Diseases 0.000 description 1
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
• JMQMNWIBUCGUDO-UHFFFAOYSA-N L-Djenkolic acid Natural products OC(=O)C(N)CSCSCC(N)C(O)=O JMQMNWIBUCGUDO-UHFFFAOYSA-N 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• FSBIGDSBMBYOPN-VKHMYHEASA-N L-canavanine Chemical compound OC(=O)[C@@H](N)CCONC(N)=N FSBIGDSBMBYOPN-VKHMYHEASA-N 0.000 description 1
• JMQMNWIBUCGUDO-WHFBIAKZSA-N L-djenkolic acid Chemical compound OC(=O)[C@@H](N)CSCSC[C@H](N)C(O)=O JMQMNWIBUCGUDO-WHFBIAKZSA-N 0.000 description 1
• UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 102000003960 Ligases Human genes 0.000 description 1
• 108090000364 Ligases Proteins 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 101001018085 Lysobacter enzymogenes Lysyl endopeptidase Proteins 0.000 description 1
• 101710125418 Major capsid protein Proteins 0.000 description 1
• PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
• 241001272720 Medialuna californiensis Species 0.000 description 1
• 208000009857 Microaneurysm Diseases 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000000112 Myalgia Diseases 0.000 description 1
• 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
• 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
• 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
• 238000011887 Necropsy Methods 0.000 description 1
• 101100498071 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cys-17 gene Proteins 0.000 description 1
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 101710141454 Nucleoprotein Proteins 0.000 description 1
• FSBIGDSBMBYOPN-UHFFFAOYSA-N O-guanidino-DL-homoserine Natural products OC(=O)C(N)CCON=C(N)N FSBIGDSBMBYOPN-UHFFFAOYSA-N 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
• 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• 206010036303 Post streptococcal glomerulonephritis Diseases 0.000 description 1
• 101710083689 Probable capsid protein Proteins 0.000 description 1
• 241001415846 Procellariidae Species 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 101710176177 Protein A56 Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 206010037394 Pulmonary haemorrhage Diseases 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 230000007022 RNA scission Effects 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
• 206010038423 Renal cyst Diseases 0.000 description 1
• 206010038481 Renal necrosis Diseases 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• FBPFZTCFMRRESA-NQAPHZHOSA-N Sorbitol Polymers OCC(O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-NQAPHZHOSA-N 0.000 description 1
• 241000256248 Spodoptera Species 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 241000187747 Streptomyces Species 0.000 description 1
• 206010042434 Sudden death Diseases 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
• 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 1
• 101710120037 Toxin CcdB Proteins 0.000 description 1
• 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
• 102000009618 Transforming Growth Factors Human genes 0.000 description 1
• 108010009583 Transforming Growth Factors Proteins 0.000 description 1
• 241000209140 Triticum Species 0.000 description 1
• 235000021307 Triticum Nutrition 0.000 description 1
• 206010048302 Tubulointerstitial nephritis Diseases 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 1
• MUXFZBHBYYYLTH-UHFFFAOYSA-N Zaltoprofen Chemical compound O=C1CC2=CC(C(C(O)=O)C)=CC=C2SC2=CC=CC=C21 MUXFZBHBYYYLTH-UHFFFAOYSA-N 0.000 description 1
• SIIZPVYVXNXXQG-KGXOGWRBSA-N [(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-4-[[(3s,4r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-3-hydroxyoxolan-2-yl]methyl [(2r,4r,5r)-2-(6-aminopurin-9-yl)-4-hydroxy-5-(phosphonooxymethyl)oxolan-3-yl] hydrogen phosphate Polymers C1=NC2=C(N)N=CN=C2N1[C@@H]1O[C@H](COP(O)(=O)OC2[C@@H](O[C@H](COP(O)(O)=O)[C@H]2O)N2C3=NC=NC(N)=C3N=C2)[C@@H](O)[C@H]1OP(O)(=O)OCC([C@@H](O)[C@H]1O)OC1N1C(N=CN=C2N)=C2N=C1 SIIZPVYVXNXXQG-KGXOGWRBSA-N 0.000 description 1
• PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
• 229940124532 absorption promoter Drugs 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 238000003916 acid precipitation Methods 0.000 description 1
• FUGCXLNGEHFIOA-UHFFFAOYSA-L acid red 44 Chemical compound [Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=CC2=C1 FUGCXLNGEHFIOA-UHFFFAOYSA-L 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 208000038016 acute inflammation Diseases 0.000 description 1
• 230000006022 acute inflammation Effects 0.000 description 1
• 201000005638 acute proliferative glomerulonephritis Diseases 0.000 description 1
• 210000000577 adipose tissue Anatomy 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 238000002299 affinity electrophoresis Methods 0.000 description 1
• 125000003172 aldehyde group Chemical group 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 125000005365 aminothiol group Chemical group 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000001064 anti-interferon Effects 0.000 description 1
• 239000000868 anti-mullerian hormone Substances 0.000 description 1
• 230000003064 anti-oxidating effect Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
• 108010092854 aspartyllysine Proteins 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000037444 atrophy Effects 0.000 description 1
• 208000009361 bacterial endocarditis Diseases 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 235000015278 beef Nutrition 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 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 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 238000006065 biodegradation reaction Methods 0.000 description 1
• 230000007698 birth defect Effects 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 238000009534 blood test Methods 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 238000006473 carboxylation reaction Methods 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000006041 cell recruitment Effects 0.000 description 1
• 210000002421 cell wall Anatomy 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 239000000919 ceramic Substances 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 238000012412 chemical coupling Methods 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 239000002975 chemoattractant Substances 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 238000011210 chromatographic step Methods 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 239000007979 citrate buffer Substances 0.000 description 1
• 230000035602 clotting Effects 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 230000001447 compensatory effect Effects 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 239000003636 conditioned culture medium Substances 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 201000003278 cryoglobulinemia Diseases 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• OOTFVKOQINZBBF-UHFFFAOYSA-N cystamine Chemical compound CCSSCCN OOTFVKOQINZBBF-UHFFFAOYSA-N 0.000 description 1
• 229940099500 cystamine Drugs 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 235000013365 dairy product Nutrition 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000000326 densiometry Methods 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 125000005442 diisocyanate group Chemical group 0.000 description 1
• GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
• ZLFRJHOBQVVTOJ-UHFFFAOYSA-N dimethyl hexanediimidate Chemical compound COC(=N)CCCCC(=N)OC ZLFRJHOBQVVTOJ-UHFFFAOYSA-N 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• SILCDLWESNHZKB-UHFFFAOYSA-L disodium 4-hydroxy-4-oxobutanoate Chemical compound [Na+].[Na+].OC(=O)CCC([O-])=O.OC(=O)CCC([O-])=O SILCDLWESNHZKB-UHFFFAOYSA-L 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 230000009429 distress Effects 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 230000002918 effect on proteinuria Effects 0.000 description 1
• 238000001962 electrophoresis Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 150000002222 fluorine compounds Chemical class 0.000 description 1
• 230000006251 gamma-carboxylation Effects 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 238000001502 gel electrophoresis Methods 0.000 description 1
• 238000002523 gelfiltration Methods 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 150000002303 glucose derivatives Polymers 0.000 description 1
• 150000002304 glucoses Polymers 0.000 description 1
• 125000002791 glucosyl group Polymers C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
• 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
• 102000005396 glutamine synthetase Human genes 0.000 description 1
• 108020002326 glutamine synthetase Proteins 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 230000002414 glycolytic effect Effects 0.000 description 1
• 125000003147 glycosyl group Chemical group 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
• 230000036449 good health Effects 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 230000009036 growth inhibition Effects 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 230000002962 histologic effect Effects 0.000 description 1
• 230000003118 histopathologic effect Effects 0.000 description 1
• 230000003284 homeostatic effect Effects 0.000 description 1
• 102000043629 human RAPGEF5 Human genes 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• 230000004727 humoral immunity Effects 0.000 description 1
• OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
• 150000007857 hydrazones Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
• 239000012216 imaging agent Substances 0.000 description 1
• 150000002463 imidates Chemical class 0.000 description 1
• 210000001822 immobilized cell Anatomy 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 230000005965 immune activity Effects 0.000 description 1
• 230000008076 immune mechanism Effects 0.000 description 1
• 230000037189 immune system physiology Effects 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 230000000984 immunochemical effect Effects 0.000 description 1
• 238000000760 immunoelectrophoresis Methods 0.000 description 1
• 238000010185 immunofluorescence analysis Methods 0.000 description 1
• 238000003125 immunofluorescent labeling Methods 0.000 description 1
• 230000009851 immunogenic response Effects 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 239000003547 immunosorbent Substances 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000010952 in-situ formation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 201000007119 infective endocarditis Diseases 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000004941 influx Effects 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 238000009830 intercalation Methods 0.000 description 1
• 230000002687 intercalation Effects 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 201000006334 interstitial nephritis Diseases 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229960004502 levodopa Drugs 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 238000002595 magnetic resonance imaging Methods 0.000 description 1
• 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
• GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical compound [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229940071648 metered dose inhaler Drugs 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 238000006011 modification reaction Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 239000000178 monomer Substances 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 210000004897 n-terminal region Anatomy 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 238000006386 neutralization reaction Methods 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 238000010606 normalization Methods 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 238000002515 oligonucleotide synthesis Methods 0.000 description 1
• 229920001542 oligosaccharide Polymers 0.000 description 1
• 150000002482 oligosaccharides Chemical class 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 210000000287 oocyte Anatomy 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 238000005457 optimization Methods 0.000 description 1
• 210000004789 organ system Anatomy 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 208000035824 paresthesia Diseases 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000006320 pegylation Effects 0.000 description 1
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
• 238000012510 peptide mapping method Methods 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 229920000765 poly(2-oxazolines) Polymers 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 229920002627 poly(phosphazenes) Polymers 0.000 description 1
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 230000008488 polyadenylation Effects 0.000 description 1
• 229920001610 polycaprolactone Polymers 0.000 description 1
• 229920002721 polycyanoacrylate Polymers 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 239000002861 polymer material Substances 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920006324 polyoxymethylene Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229950008882 polysorbate Drugs 0.000 description 1
• 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002250 progressing effect Effects 0.000 description 1
• 230000007425 progressive decline Effects 0.000 description 1
• 208000037821 progressive disease Diseases 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 230000009145 protein modification Effects 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 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 1
• 239000012713 reactive precursor Substances 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 230000036573 scar formation Effects 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 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 1
• 229960002930 sirolimus Drugs 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 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
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• OESFSXYRSCBAQJ-UHFFFAOYSA-M sodium;3-carboxy-3,5-dihydroxy-5-oxopentanoate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC([O-])=O OESFSXYRSCBAQJ-UHFFFAOYSA-M 0.000 description 1
• VBGUQBPWJMPQBI-UHFFFAOYSA-M sodium;butanedioic acid;4-hydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)CCC(O)=O.OC(=O)CCC([O-])=O VBGUQBPWJMPQBI-UHFFFAOYSA-M 0.000 description 1
• JISIBLCXFLGVJX-UHFFFAOYSA-M sodium;butanedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CCC(O)=O JISIBLCXFLGVJX-UHFFFAOYSA-M 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 125000006850 spacer group Chemical group 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 210000003699 striated muscle Anatomy 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 239000008362 succinate buffer Substances 0.000 description 1
• KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
• 230000019635 sulfation Effects 0.000 description 1
• 238000005670 sulfation reaction Methods 0.000 description 1
• 238000006277 sulfonation reaction Methods 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 230000001839 systemic circulation Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229960001967 tacrolimus Drugs 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 229920001897 terpolymer Polymers 0.000 description 1
• 229960000278 theophylline Drugs 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 150000007970 thio esters Chemical class 0.000 description 1
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
• RUELTTOHQODFPA-UHFFFAOYSA-N toluene 2,6-diisocyanate Chemical compound CC1=C(N=C=O)C=CC=C1N=C=O RUELTTOHQODFPA-UHFFFAOYSA-N 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000007070 tosylation reaction Methods 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 230000010474 transient expression Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 108010060175 trypsinogen activation peptide Proteins 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 230000006442 vascular tone Effects 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 230000009278 visceral effect Effects 0.000 description 1
• 239000002699 waste material Substances 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1