JP2003519097A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2003519097A5 JP2003519097A5 JP2001517091A JP2001517091A JP2003519097A5 JP 2003519097 A5 JP2003519097 A5 JP 2003519097A5 JP 2001517091 A JP2001517091 A JP 2001517091A JP 2001517091 A JP2001517091 A JP 2001517091A JP 2003519097 A5 JP2003519097 A5 JP 2003519097A5
- Authority
- JP
- Japan
- Prior art keywords
- fgf
- vegf
- dose
- factor
- angiogenesis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 157
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 151
- 239000002870 angiogenesis inducing agent Substances 0.000 description 108
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 103
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 102
- 229940126864 fibroblast growth factor Drugs 0.000 description 97
- 210000004165 myocardium Anatomy 0.000 description 89
- 238000000034 method Methods 0.000 description 86
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 72
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 71
- 238000002347 injection Methods 0.000 description 71
- 239000007924 injection Substances 0.000 description 71
- 238000011282 treatment Methods 0.000 description 64
- 230000033115 angiogenesis Effects 0.000 description 60
- 239000012634 fragment Substances 0.000 description 57
- 239000000203 mixture Substances 0.000 description 57
- 125000003275 alpha amino acid group Chemical group 0.000 description 53
- 239000008194 pharmaceutical composition Substances 0.000 description 51
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 47
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 44
- 208000029078 coronary artery disease Diseases 0.000 description 42
- 229920000669 heparin Polymers 0.000 description 42
- 229960002897 heparin Drugs 0.000 description 42
- 230000001965 increasing effect Effects 0.000 description 42
- 210000002216 heart Anatomy 0.000 description 39
- 101001051969 Bos taurus Fibroblast growth factor 2 Proteins 0.000 description 37
- 101001052035 Homo sapiens Fibroblast growth factor 2 Proteins 0.000 description 35
- 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 34
- 230000010412 perfusion Effects 0.000 description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
- 230000000694 effects Effects 0.000 description 30
- 230000000302 ischemic effect Effects 0.000 description 30
- 208000010125 myocardial infarction Diseases 0.000 description 30
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 27
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 27
- 108090000623 proteins and genes Proteins 0.000 description 27
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 26
- 210000004351 coronary vessel Anatomy 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 25
- 230000002107 myocardial effect Effects 0.000 description 24
- 230000002491 angiogenic effect Effects 0.000 description 23
- 230000017531 blood circulation Effects 0.000 description 23
- 235000018102 proteins Nutrition 0.000 description 23
- 102000004169 proteins and genes Human genes 0.000 description 23
- 125000000539 amino acid group Chemical group 0.000 description 22
- 230000002792 vascular Effects 0.000 description 22
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 21
- 239000011780 sodium chloride Substances 0.000 description 21
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 20
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 20
- 230000008859 change Effects 0.000 description 19
- 230000006870 function Effects 0.000 description 19
- 239000000902 placebo Substances 0.000 description 19
- 150000001413 amino acids Chemical class 0.000 description 18
- 238000001802 infusion Methods 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 17
- 229940068196 placebo Drugs 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 17
- 210000001367 artery Anatomy 0.000 description 16
- 235000018417 cysteine Nutrition 0.000 description 16
- 239000003937 drug carrier Substances 0.000 description 16
- 241000282412 Homo Species 0.000 description 15
- 230000000747 cardiac effect Effects 0.000 description 15
- 239000002299 complementary DNA Substances 0.000 description 15
- 125000000151 cysteine group Chemical class N[C@@H](CS)C(=O)* 0.000 description 15
- 230000001939 inductive effect Effects 0.000 description 15
- 238000006467 substitution reaction Methods 0.000 description 15
- 206010002383 Angina Pectoris Diseases 0.000 description 14
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 14
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 238000002595 magnetic resonance imaging Methods 0.000 description 13
- 244000309715 mini pig Species 0.000 description 13
- 238000002399 angioplasty Methods 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 238000001990 intravenous administration Methods 0.000 description 12
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 12
- 230000004087 circulation Effects 0.000 description 11
- 230000001976 improved effect Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 101150021185 FGF gene Proteins 0.000 description 10
- 102000001708 Protein Isoforms Human genes 0.000 description 10
- 108010029485 Protein Isoforms Proteins 0.000 description 10
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 10
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 230000003247 decreasing effect Effects 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 230000006872 improvement Effects 0.000 description 10
- 230000033001 locomotion Effects 0.000 description 10
- 230000010016 myocardial function Effects 0.000 description 10
- 230000000284 resting effect Effects 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 102100028043 Fibroblast growth factor 3 Human genes 0.000 description 9
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 9
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 9
- 241000282887 Suidae Species 0.000 description 9
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 9
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 238000012377 drug delivery Methods 0.000 description 9
- 239000003102 growth factor Substances 0.000 description 9
- 230000004217 heart function Effects 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 9
- 238000002600 positron emission tomography Methods 0.000 description 9
- 102000004196 processed proteins & peptides Human genes 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 241000283690 Bos taurus Species 0.000 description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 8
- 108090000378 Fibroblast growth factor 3 Proteins 0.000 description 8
- 108090000380 Fibroblast growth factor 5 Proteins 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 230000001684 chronic effect Effects 0.000 description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 239000001509 sodium citrate Substances 0.000 description 8
- 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 8
- 239000003981 vehicle Substances 0.000 description 8
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 7
- 206010061216 Infarction Diseases 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 108700020796 Oncogene Proteins 0.000 description 7
- 239000002738 chelating agent Substances 0.000 description 7
- 230000007574 infarction Effects 0.000 description 7
- 239000003226 mitogen Substances 0.000 description 7
- 238000013310 pig model Methods 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 108091008794 FGF receptors Proteins 0.000 description 6
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 6
- 108090000382 Fibroblast growth factor 6 Proteins 0.000 description 6
- 102100028075 Fibroblast growth factor 6 Human genes 0.000 description 6
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 229920002683 Glycosaminoglycan Polymers 0.000 description 6
- 208000001953 Hypotension Diseases 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 6
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 6
- 230000036772 blood pressure Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000012217 deletion Methods 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 230000008747 mitogenic response Effects 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 238000003259 recombinant expression Methods 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 239000003381 stabilizer Substances 0.000 description 6
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 6
- 210000003462 vein Anatomy 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 5
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 5
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 5
- 102100037680 Fibroblast growth factor 8 Human genes 0.000 description 5
- 108090000367 Fibroblast growth factor 9 Proteins 0.000 description 5
- 102100037665 Fibroblast growth factor 9 Human genes 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 238000011833 dog model Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000002124 endocrine Effects 0.000 description 5
- 210000005003 heart tissue Anatomy 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 229940035024 thioglycerol Drugs 0.000 description 5
- 230000003827 upregulation Effects 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- 108700024394 Exon Proteins 0.000 description 4
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 4
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 4
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 4
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 4
- 102000043276 Oncogene Human genes 0.000 description 4
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 229920005549 butyl rubber Polymers 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 210000004413 cardiac myocyte Anatomy 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 230000036543 hypotension Effects 0.000 description 4
- 238000007726 management method Methods 0.000 description 4
- 231100000682 maximum tolerated dose Toxicity 0.000 description 4
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 4
- 208000031225 myocardial ischemia Diseases 0.000 description 4
- 238000009520 phase I clinical trial Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 206010069729 Collateral circulation Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102100021628 Histatin-3 Human genes 0.000 description 3
- 101500025614 Homo sapiens Transforming growth factor beta-1 Proteins 0.000 description 3
- 101000742579 Homo sapiens Vascular endothelial growth factor B Proteins 0.000 description 3
- 125000000415 L-cysteinyl group Chemical group O=C([*])[C@@](N([H])[H])([H])C([H])([H])S[H] 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- XMEKHKCRNHDFOW-UHFFFAOYSA-N O.O.[Na].[Na] Chemical compound O.O.[Na].[Na] XMEKHKCRNHDFOW-UHFFFAOYSA-N 0.000 description 3
- 208000031481 Pathologic Constriction Diseases 0.000 description 3
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 3
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000005242 cardiac chamber Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000002939 deleterious effect Effects 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000000539 dimer Substances 0.000 description 3
- 238000002592 echocardiography Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 102000058223 human VEGFA Human genes 0.000 description 3
- 102000058241 human VEGFB Human genes 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000002297 mitogenic effect Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 230000000737 periodic effect Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 238000009521 phase II clinical trial Methods 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 230000036262 stenosis Effects 0.000 description 3
- 208000037804 stenosis Diseases 0.000 description 3
- 230000002861 ventricular Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 208000001778 Coronary Occlusion Diseases 0.000 description 2
- 206010011086 Coronary artery occlusion Diseases 0.000 description 2
- YTBSYETUWUMLBZ-QWWZWVQMSA-N D-threose Chemical compound OC[C@@H](O)[C@H](O)C=O YTBSYETUWUMLBZ-QWWZWVQMSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 2
- 101150009958 FLT4 gene Proteins 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- 102100027844 Fibroblast growth factor receptor 4 Human genes 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
- 101000846416 Homo sapiens Fibroblast growth factor 1 Proteins 0.000 description 2
- 101001060267 Homo sapiens Fibroblast growth factor 5 Proteins 0.000 description 2
- 101001027380 Homo sapiens Fibroblast growth factor 9 Proteins 0.000 description 2
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 2
- 125000000899 L-alpha-glutamyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 2
- 125000000010 L-asparaginyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(=O)N([H])[H] 0.000 description 2
- 125000002061 L-isoleucyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](C([H])([H])[H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 2
- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 2
- 125000002707 L-tryptophyl group Chemical group [H]C1=C([H])C([H])=C2C(C([C@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 2
- 125000003580 L-valyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(C([H])([H])[H])(C([H])([H])[H])[H] 0.000 description 2
- 101100446506 Mus musculus Fgf3 gene Proteins 0.000 description 2
- 101001027368 Mus musculus Fibroblast growth factor 9 Proteins 0.000 description 2
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
- 208000032109 Transient ischaemic attack Diseases 0.000 description 2
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 2
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 229960004308 acetylcysteine Drugs 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 208000011861 acute hypotension Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000013599 cloning vector Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 229960001089 dobutamine Drugs 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000006266 hibernation Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000007479 molecular analysis Methods 0.000 description 2
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229940037201 oris Drugs 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 229960003330 pentetic acid Drugs 0.000 description 2
- 230000037081 physical activity Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000010845 search algorithm Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 229910052716 thallium Inorganic materials 0.000 description 2
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960000187 tissue plasminogen activator Drugs 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- 201000010875 transient cerebral ischemia Diseases 0.000 description 2
- 230000001228 trophic effect Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 230000006459 vascular development Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 210000005253 yeast cell Anatomy 0.000 description 2
- BXSSCSKCOFKPOK-ARGVQFGUSA-N (2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-amino-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3- Chemical compound C([C@@H](C(=O)N[C@@H](CCCC)C(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C(C)C)C1=CC=CC=C1 BXSSCSKCOFKPOK-ARGVQFGUSA-N 0.000 description 1
- YUDPTGPSBJVHCN-DZQJYWQESA-N 4-methylumbelliferyl beta-D-galactoside Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O YUDPTGPSBJVHCN-DZQJYWQESA-N 0.000 description 1
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- -1 Amino Chemical group 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 102100030009 Azurocidin Human genes 0.000 description 1
- 101710154607 Azurocidin Proteins 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 201000000057 Coronary Stenosis Diseases 0.000 description 1
- 206010052895 Coronary artery insufficiency Diseases 0.000 description 1
- 206010011089 Coronary artery stenosis Diseases 0.000 description 1
- 206010011219 Costochondritis Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 101150019331 FGF2 gene Proteins 0.000 description 1
- 102000003956 Fibroblast growth factor 8 Human genes 0.000 description 1
- 206010016654 Fibrosis Diseases 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
- 108010024636 Glutathione Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 101001060280 Homo sapiens Fibroblast growth factor 3 Proteins 0.000 description 1
- 101001060274 Homo sapiens Fibroblast growth factor 4 Proteins 0.000 description 1
- 101001060265 Homo sapiens Fibroblast growth factor 6 Proteins 0.000 description 1
- 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 description 1
- 101000602164 Homo sapiens Platelet-derived growth factor subunit A Proteins 0.000 description 1
- 101000742599 Homo sapiens Vascular endothelial growth factor D Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101710181812 Methionine aminopeptidase Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101001060277 Mus musculus Fibroblast growth factor 3 Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000005228 Pericardial Effusion Diseases 0.000 description 1
- 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 1
- 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
- 101710106089 Protein cutoff Proteins 0.000 description 1
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 229920002684 Sepharose Polymers 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
- 208000036623 Severe mental retardation Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 208000004732 Systemic Vasculitis Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000026317 Tietze syndrome Diseases 0.000 description 1
- 102100036859 Troponin I, cardiac muscle Human genes 0.000 description 1
- 101710128251 Troponin I, cardiac muscle Proteins 0.000 description 1
- 102000004987 Troponin T Human genes 0.000 description 1
- 108090001108 Troponin T Proteins 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 208000009443 Vascular Malformations Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- ZGKJESGFAPAQKB-UHFFFAOYSA-N [4-(dimethylamino)-3-methylbutan-2-yl] 4-aminobenzoate;hydrochloride Chemical compound Cl.CN(C)CC(C)C(C)OC(=O)C1=CC=C(N)C=C1 ZGKJESGFAPAQKB-UHFFFAOYSA-N 0.000 description 1
- RXDLGFMMQFNVLI-UHFFFAOYSA-N [Na].[Na].[Ca] Chemical class [Na].[Na].[Ca] RXDLGFMMQFNVLI-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001656 angiogenetic effect Effects 0.000 description 1
- 229940124572 antihypotensive agent Drugs 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000008081 blood perfusion Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002586 coronary angiography Methods 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 229940072645 coumadin Drugs 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 210000001705 ectoderm cell Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 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
- 208000006881 esophagitis Diseases 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 230000008442 fetal wound healing Effects 0.000 description 1
- 108090000370 fibroblast growth factor 18 Proteins 0.000 description 1
- 102000003977 fibroblast growth factor 18 Human genes 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000000585 glomerular basement membrane Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 102000036208 glycosaminoglycan binding proteins Human genes 0.000 description 1
- 108091010992 glycosaminoglycan binding proteins Proteins 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000057233 human FGF5 Human genes 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000010039 intracellular degradation Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 210000001704 mesoblast Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 208000002089 myocardial stunning Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000023362 neuron cell-cell adhesion Effects 0.000 description 1
- 230000004031 neuronal differentiation Effects 0.000 description 1
- 230000007935 neutral effect Effects 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
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002746 orthostatic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000004912 pericardial fluid Anatomy 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 210000003516 pericardium Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 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
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 108700005467 recombinant KCB-1 Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 150000003354 serine derivatives Chemical class 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000012868 site-directed mutagenesis technique Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 210000003270 subclavian artery Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000003797 telogen phase Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229910021654 trace metal Inorganic materials 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
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000004855 vascular circulation Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000000982 vasogenic effect Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14874699P | 1999-08-13 | 1999-08-13 | |
| US60/148,746 | 1999-08-13 | ||
| PCT/US2000/022039 WO2001013031A2 (en) | 1999-08-13 | 2000-08-11 | Dose of an angiogenic factor and method of administering to improve myocardial blood flow |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010270963A Division JP2011052017A (ja) | 1999-08-13 | 2010-12-03 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2003519097A JP2003519097A (ja) | 2003-06-17 |
| JP2003519097A5 true JP2003519097A5 (https=) | 2011-03-03 |
| JP5704780B2 JP5704780B2 (ja) | 2015-04-22 |
Family
ID=22527174
Family Applications (7)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001517091A Expired - Lifetime JP5704780B2 (ja) | 1999-08-13 | 2000-08-11 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2010270963A Withdrawn JP2011052017A (ja) | 1999-08-13 | 2010-12-03 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2014037946A Withdrawn JP2014111649A (ja) | 1999-08-13 | 2014-02-28 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2016023483A Pending JP2016104799A (ja) | 1999-08-13 | 2016-02-10 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2017126309A Pending JP2017200945A (ja) | 1999-08-13 | 2017-06-28 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2018145738A Pending JP2018165283A (ja) | 1999-08-13 | 2018-08-02 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2020084426A Pending JP2020117546A (ja) | 1999-08-13 | 2020-05-13 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
Family Applications After (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010270963A Withdrawn JP2011052017A (ja) | 1999-08-13 | 2010-12-03 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2014037946A Withdrawn JP2014111649A (ja) | 1999-08-13 | 2014-02-28 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2016023483A Pending JP2016104799A (ja) | 1999-08-13 | 2016-02-10 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2017126309A Pending JP2017200945A (ja) | 1999-08-13 | 2017-06-28 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2018145738A Pending JP2018165283A (ja) | 1999-08-13 | 2018-08-02 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| JP2020084426A Pending JP2020117546A (ja) | 1999-08-13 | 2020-05-13 | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US20030171294A1 (https=) |
| EP (1) | EP1207900A2 (https=) |
| JP (7) | JP5704780B2 (https=) |
| AU (1) | AU6634400A (https=) |
| CA (1) | CA2381780C (https=) |
| WO (1) | WO2001013031A2 (https=) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6511477B2 (en) * | 1997-03-13 | 2003-01-28 | Biocardia, Inc. | Method of drug delivery to interstitial regions of the myocardium |
| US20020072489A1 (en) * | 1998-10-13 | 2002-06-13 | Whitehouse Martha J. | Angiogenically effective unit dose of FGF-2 and method of use |
| US6992066B2 (en) * | 1998-10-16 | 2006-01-31 | Zimmer Orthobiologics, Inc. | Povidone-containing carriers for polypeptide growth factors |
| US7087577B2 (en) * | 1998-10-16 | 2006-08-08 | Zimmer Orthobiologies, Inc. | Method of promoting natural bypass |
| JP5704780B2 (ja) * | 1999-08-13 | 2015-04-22 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
| CA2412436C (en) | 2000-06-05 | 2013-05-21 | The Trustees Of Columbia University In The City Of New York | Identification and use of human bone marrow-derived endothelial progenitor cells to improve myocardial function after ischemic injury |
| AR027161A1 (es) | 2001-05-15 | 2003-03-19 | Bio Sidus S A | Metodo para inducir la proliferacion neovascular y regeneracion tisular |
| US6872335B2 (en) * | 2002-03-12 | 2005-03-29 | Technology Resource International Corporation | Method and apparatus for holding a mold assembly and molding an optical lens using the same |
| US7798815B2 (en) * | 2002-04-03 | 2010-09-21 | University Of The West Indies | Computer-controlled tissue-based simulator for training in cardiac surgical techniques |
| US20030199464A1 (en) * | 2002-04-23 | 2003-10-23 | Silviu Itescu | Regeneration of endogenous myocardial tissue by induction of neovascularization |
| US7419951B2 (en) * | 2002-07-29 | 2008-09-02 | Hmgene Inc. | Method of reducing adipocyte growth in a subject in need thereof by administration of natriuretic peptide receptor C inhibitors |
| US8668926B1 (en) | 2003-09-15 | 2014-03-11 | Shaker A. Mousa | Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists, and formulations thereof |
| US9198887B2 (en) | 2003-09-15 | 2015-12-01 | Nanopharmaceuticals Llc | Thyroid hormone analogs and methods of use |
| AU2004273986B2 (en) | 2003-09-15 | 2010-04-22 | Nanopharmaceuticals Llc | Thyroid hormone analogs and methods of use in angiogenesis |
| WO2006081190A2 (en) | 2005-01-25 | 2006-08-03 | Five Prime Therapeutics, Inc. | Compositions and methods for treating cardiac conditions |
| US9498536B2 (en) | 2005-09-15 | 2016-11-22 | Nanopharmaceuticals Llc | Method and composition of thyroid hormone analogues and nanoformulations thereof for treating anti-inflammatory disorders |
| US10130686B2 (en) | 2005-09-15 | 2018-11-20 | Nanopharmaceuticals Llc | Method and composition of thyroid hormone analogues and nanoformulations thereof for treating inflammatory disorders |
| US20100209382A1 (en) | 2005-09-16 | 2010-08-19 | Ordway Research Institute, Inc. | Polyphenol Conjugates as RGD-Binding Compounds and Methods of Use |
| US20080058642A1 (en) * | 2006-09-05 | 2008-03-06 | Board Of Regents Of The University Of Texas System | Method for detecting coronary endothelial dysfunction and early atherosclerosis |
| AU2007353426A1 (en) | 2006-12-22 | 2008-11-20 | Albany College Of Pharmacy And Health Sciences | Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists, and formulations and uses thereof |
| EP2098244A1 (en) * | 2008-03-04 | 2009-09-09 | Medizinische Hochschule Hannover | Pharmaceutical composition for the treatment of myocardial infarction |
| US9180107B2 (en) | 2009-03-31 | 2015-11-10 | Nanopharmaceuticals Llc | Combination treatment of cancer with cetuximab and tetrac |
| CA2765792C (en) | 2009-06-17 | 2017-03-28 | Nanopharmaceuticals Llc | Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists, and formulations and uses thereof |
| CA2796459C (en) | 2010-04-16 | 2016-05-24 | Salk Institute For Biological Studies | Methods for treating metabolic disorders using fgf-1 |
| US8802240B2 (en) | 2011-01-06 | 2014-08-12 | Nanopharmaceuticals Llc | Uses of formulations of thyroid hormone analogs and nanoparticulate forms thereof to increase chemosensitivity and radiosensitivity in tumor or cancer cells |
| WO2015061331A1 (en) | 2013-10-21 | 2015-04-30 | Salk Institute For Biological Studies | Chimeric fibroblast growth factor (fgf) 2/fgf1 peptides and methods of use |
| CA2973096A1 (en) | 2015-01-06 | 2016-07-14 | Cardiovascular Biotherapeutics, Inc. | Angiogenic treatment of ischemic heart disease |
| AU2016220304B2 (en) | 2015-02-16 | 2019-07-25 | Venturis Therapeutics, Inc. | Therapeutic angiogenesis for treating erectile conditions |
| WO2017127493A1 (en) * | 2016-01-22 | 2017-07-27 | Salk Institute For Biological Studies | Fgf2 truncations and mutants and uses thereof |
| JP7074749B2 (ja) | 2016-06-07 | 2022-05-24 | ナノファーマシューティカルズ エルエルシー | αｖβ３インテグリン甲状腺アンタゴニストにコンジュゲートした非開裂性ポリマー |
| AU2019220627A1 (en) * | 2018-02-13 | 2020-09-10 | University Of Florida Research Foundation | Fibroblast growth factor analogs and uses thereof |
| US11351137B2 (en) | 2018-04-11 | 2022-06-07 | Nanopharmaceuticals Llc | Composition and method for dual targeting in treatment of neuroendocrine tumors |
| US10328043B1 (en) | 2018-04-11 | 2019-06-25 | Nanopharmaceuticals, Llc. | Composition and method for dual targeting in treatment of neuroendocrine tumors |
| US20210015934A1 (en) * | 2019-07-18 | 2021-01-21 | Venturis Therapeutics, Inc. | Method of Treating Parkinson's Disease |
| US10961204B1 (en) | 2020-04-29 | 2021-03-30 | Nanopharmaceuticals Llc | Composition of scalable thyrointegrin antagonists with improved blood brain barrier penetration and retention into brain tumors |
| US11723888B2 (en) | 2021-12-09 | 2023-08-15 | Nanopharmaceuticals Llc | Polymer conjugated thyrointegrin antagonists |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4378347A (en) * | 1980-06-30 | 1983-03-29 | Franco Wayne P | Composition for treating the heart for myocardial infarction |
| US4296100A (en) * | 1980-06-30 | 1981-10-20 | Franco Wayne P | Method of treating the heart for myocardial infarction |
| US4956455A (en) * | 1984-03-05 | 1990-09-11 | The Salk Institute For Biological Studies | Bovine fibroblast growth factor |
| US5464774A (en) * | 1984-03-05 | 1995-11-07 | The Salk Institute For Biological Studies | Bovine basic fibroblast growth factor |
| US5155214A (en) * | 1984-03-05 | 1992-10-13 | The Salk Institute For Biological Studies | Basic fibroblast growth factor |
| US5439818A (en) * | 1985-09-12 | 1995-08-08 | Scios Nova Inc. | DNA encoding human recombinant basic fibroblast growth factor |
| US5604293A (en) * | 1985-09-12 | 1997-02-18 | Scios Inc. | Recombinant human basic fibroblast growth factor |
| CA1323317C (en) * | 1987-01-16 | 1993-10-19 | Allen R. Banks | Production of fibroblast growth factor |
| US5155217A (en) * | 1987-05-29 | 1992-10-13 | The Trustees Of Columbia University In The City Of New York | Ongogene encoding polypeptide having growth factor activity |
| US5238916A (en) * | 1987-05-29 | 1993-08-24 | The Trustees Of Columbia University In The City Of New York | Oncogene encoded polypeptide having growth factor activity and methods of use thereof |
| US5750659A (en) * | 1987-06-16 | 1998-05-12 | New York University | Mammalian growth factor |
| WO1989004832A1 (en) | 1987-11-24 | 1989-06-01 | Amgen Inc. | Analogs of fibroblast growth factor |
| AU614137B2 (en) * | 1988-06-06 | 1991-08-22 | Takeda Chemical Industries Ltd. | Stabilized fgf composition and production thereof |
| GB8821795D0 (en) * | 1988-09-16 | 1988-10-19 | Erba Carlo Spa | New derivatives of human/bovine basic fibroplast growth factor |
| US5352589A (en) * | 1988-09-16 | 1994-10-04 | Farmitalia Carlo Erba S.R.L. | Deletion mutant of basic fibroblast growth factor and production thereof |
| US5137734A (en) * | 1989-03-22 | 1992-08-11 | Dana Farber Cancer Institute | Angiogenic monoglycerides |
| US5217954A (en) * | 1990-04-04 | 1993-06-08 | Scios Nova Inc. | Formulations for stabilizing fibroblast growth factor |
| US5612211A (en) * | 1990-06-08 | 1997-03-18 | New York University | Stimulation, production and culturing of hematopoietic progenitor cells by fibroblast growth factors |
| US5206354A (en) * | 1990-11-23 | 1993-04-27 | American Cyanamid Company | Dna sequence encoding active fragment of fibroblast growth factor, hbf-2 |
| ES2087207T3 (es) * | 1990-11-23 | 1996-07-16 | American Cyanamid Co | Factor del crecimiento de fibroblasto quimerico. |
| EP0539087A1 (en) * | 1991-10-21 | 1993-04-28 | Merck & Co. Inc. | Stabilized topical acidic fibroblast growth factor formulation |
| US5244460A (en) * | 1991-11-27 | 1993-09-14 | The United States Of America As Represented By The Department Of Health And Human Services | Method to foster myocardial blood vessel growth and improve blood flow to the heart |
| US5491220A (en) * | 1993-09-24 | 1996-02-13 | Yeda Research And Development Co., Ltd. | Surface loop structural analogues of fibroblast growth factors |
| US5792453A (en) * | 1995-02-28 | 1998-08-11 | The Regents Of The University Of California | Gene transfer-mediated angiogenesis therapy |
| US20010006939A1 (en) * | 1997-10-03 | 2001-07-05 | Ralph W. Niven | Secretory leukocyte protease inhibitor dry powder pharmaceutical compositions |
| ES2233101T3 (es) * | 1998-09-03 | 2005-06-01 | Chiron Corp | Dosis unitaria de fgf-2 angiogenicamente efectiva y su utilizacion. |
| US20020072489A1 (en) | 1998-10-13 | 2002-06-13 | Whitehouse Martha J. | Angiogenically effective unit dose of FGF-2 and method of use |
| US6440934B1 (en) * | 1998-10-13 | 2002-08-27 | Chiron Corporation | Angiogenically effective unit dose of FGF-2 and method of use |
| JP2002527401A (ja) * | 1998-10-13 | 2002-08-27 | カイロン コーポレイション | Ｆｇｆの脈管形成的に有効な単位用量および投与方法 |
| CA2365434A1 (en) | 1999-04-15 | 2000-10-26 | St. Elizabeth's Medical Center Of Boston | Angiogenic growth factors for treatment of peripheral neuropathy |
| JP5704780B2 (ja) * | 1999-08-13 | 2015-04-22 | ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド | 脈管形成因子の用量および心筋血流を改善するための投与方法 |
-
2000
- 2000-08-11 JP JP2001517091A patent/JP5704780B2/ja not_active Expired - Lifetime
- 2000-08-11 WO PCT/US2000/022039 patent/WO2001013031A2/en not_active Ceased
- 2000-08-11 CA CA2381780A patent/CA2381780C/en not_active Expired - Lifetime
- 2000-08-11 AU AU66344/00A patent/AU6634400A/en not_active Abandoned
- 2000-08-11 EP EP00953984A patent/EP1207900A2/en not_active Withdrawn
-
2003
- 2003-03-24 US US10/395,541 patent/US20030171294A1/en not_active Abandoned
-
2005
- 2005-09-06 US US11/220,027 patent/US7531511B2/en not_active Expired - Fee Related
-
2009
- 2009-04-06 US US12/419,038 patent/US8178493B2/en not_active Expired - Fee Related
-
2010
- 2010-12-03 JP JP2010270963A patent/JP2011052017A/ja not_active Withdrawn
-
2014
- 2014-02-28 JP JP2014037946A patent/JP2014111649A/ja not_active Withdrawn
-
2016
- 2016-02-10 JP JP2016023483A patent/JP2016104799A/ja active Pending
-
2017
- 2017-06-28 JP JP2017126309A patent/JP2017200945A/ja active Pending
-
2018
- 2018-08-02 JP JP2018145738A patent/JP2018165283A/ja active Pending
-
2020
- 2020-05-13 JP JP2020084426A patent/JP2020117546A/ja active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8178493B2 (en) | Method for inducing angiogenesis in a heart of a patient | |
| JP2003519097A5 (https=) | ||
| US7858584B2 (en) | Angiogenically effective unit dose of FGF and method of administering | |
| US20140349932A1 (en) | Angiogenically effective unit dose of fgf-2 and method of use | |
| JP2004533411A (ja) | 血管形成的に有効なｆｇｆ−２の単位用量および使用方法 | |
| EP2123292B1 (en) | Angiogenically effective unit dose of FGF-2 and method of use | |
| US9149507B2 (en) | Method of treating coronary artery disease by administering FGF-9 | |
| EP1525888B1 (en) | Angiogenically effective unit dose of FGF-2 and method of use | |
| HK1075409B (en) | Angiogenically effective unit dose of fgf-2 and method of use |