CA2976219C - Blockers of the growth hormone receptor in disease prevention and treatment - Google Patents
Blockers of the growth hormone receptor in disease prevention and treatment Download PDFInfo
- Publication number
- CA2976219C CA2976219C CA2976219A CA2976219A CA2976219C CA 2976219 C CA2976219 C CA 2976219C CA 2976219 A CA2976219 A CA 2976219A CA 2976219 A CA2976219 A CA 2976219A CA 2976219 C CA2976219 C CA 2976219C
- Authority
- CA
- Canada
- Prior art keywords
- ghr
- conditions
- compound
- diseases
- igf
- 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.)
- Active
Links
- 102100020948 Growth hormone receptor Human genes 0.000 title claims abstract description 72
- 108010068542 Somatotropin Receptors Proteins 0.000 title claims abstract description 57
- 238000011282 treatment Methods 0.000 title claims description 26
- 230000006806 disease prevention Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 72
- 239000000122 growth hormone Substances 0.000 claims abstract description 71
- 108010051696 Growth Hormone Proteins 0.000 claims abstract description 69
- 102000018997 Growth Hormone Human genes 0.000 claims abstract description 68
- 102000001712 STAT5 Transcription Factor Human genes 0.000 claims abstract description 51
- 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 claims abstract description 50
- 201000010099 disease Diseases 0.000 claims abstract description 49
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 49
- 102100032218 Cytokine-inducible SH2-containing protein Human genes 0.000 claims abstract description 38
- 108010029477 STAT5 Transcription Factor Proteins 0.000 claims abstract description 35
- 230000000694 effects Effects 0.000 claims abstract description 35
- 101710132484 Cytokine-inducible SH2-containing protein Proteins 0.000 claims abstract description 33
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 28
- 102000004877 Insulin Human genes 0.000 claims abstract description 25
- 229940125396 insulin Drugs 0.000 claims abstract description 25
- 101001075374 Homo sapiens Gamma-glutamyl hydrolase Proteins 0.000 claims abstract description 23
- 101000664737 Homo sapiens Somatotropin Proteins 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 22
- 230000014509 gene expression Effects 0.000 claims abstract description 20
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 18
- 108090001061 Insulin Proteins 0.000 claims abstract description 13
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims abstract 10
- 101001075287 Homo sapiens Growth hormone receptor Proteins 0.000 claims abstract 6
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims abstract 6
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 44
- 206010028980 Neoplasm Diseases 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 229910052736 halogen Chemical group 0.000 claims description 26
- 150000002367 halogens Chemical group 0.000 claims description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 22
- 229910006069 SO3H Inorganic materials 0.000 claims description 22
- 229910000069 nitrogen hydride Inorganic materials 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 22
- 201000011510 cancer Diseases 0.000 claims description 21
- 230000032683 aging Effects 0.000 claims description 18
- 108010033419 somatotropin-binding protein Proteins 0.000 claims description 17
- 101100534458 Homo sapiens STAT5A gene Proteins 0.000 claims description 16
- 230000001105 regulatory effect Effects 0.000 claims description 16
- 230000011664 signaling Effects 0.000 claims description 16
- 206010012601 diabetes mellitus Diseases 0.000 claims description 15
- 206010000599 Acromegaly Diseases 0.000 claims description 14
- 238000002512 chemotherapy Methods 0.000 claims description 14
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 claims description 13
- 101000976075 Homo sapiens Insulin Proteins 0.000 claims description 12
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 11
- 230000006378 damage Effects 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 239000003053 toxin Substances 0.000 claims description 8
- 231100000765 toxin Toxicity 0.000 claims description 8
- 108700012359 toxins Proteins 0.000 claims description 8
- 206010061598 Immunodeficiency Diseases 0.000 claims description 7
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 7
- 206010062016 Immunosuppression Diseases 0.000 claims description 7
- 230000001413 cellular effect Effects 0.000 claims description 7
- 230000007813 immunodeficiency Effects 0.000 claims description 7
- 230000001506 immunosuppresive effect Effects 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 230000017423 tissue regeneration Effects 0.000 claims description 7
- 230000004075 alteration Effects 0.000 claims description 4
- 230000003054 hormonal effect Effects 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- 230000008901 benefit Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 10
- 101000943420 Homo sapiens Cytokine-inducible SH2-containing protein Proteins 0.000 claims 6
- 241000699670 Mus sp. Species 0.000 description 37
- 210000004027 cell Anatomy 0.000 description 25
- 230000005764 inhibitory process Effects 0.000 description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 20
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 19
- 229960004397 cyclophosphamide Drugs 0.000 description 19
- 125000000217 alkyl group Chemical group 0.000 description 16
- 239000003814 drug Substances 0.000 description 10
- 210000000130 stem cell Anatomy 0.000 description 10
- 108060001084 Luciferase Proteins 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 230000026731 phosphorylation Effects 0.000 description 9
- 238000006366 phosphorylation reaction Methods 0.000 description 9
- 101000687808 Homo sapiens Suppressor of cytokine signaling 2 Proteins 0.000 description 8
- 239000005089 Luciferase Substances 0.000 description 8
- 102100027584 Protein c-Fos Human genes 0.000 description 8
- 102100024784 Suppressor of cytokine signaling 2 Human genes 0.000 description 8
- 230000008929 regeneration Effects 0.000 description 8
- 238000011069 regeneration method Methods 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 210000001185 bone marrow Anatomy 0.000 description 7
- 230000002068 genetic effect Effects 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 210000005259 peripheral blood Anatomy 0.000 description 7
- 239000011886 peripheral blood Substances 0.000 description 7
- -1 heat Chemical compound 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 108091008611 Protein Kinase B Proteins 0.000 description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 5
- 231100001157 chemotherapeutic toxicity Toxicity 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 238000003468 luciferase reporter gene assay Methods 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 4
- 102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 description 4
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 4
- 229940122853 Growth hormone antagonist Drugs 0.000 description 4
- 108700017836 Prophet of Pit-1 Proteins 0.000 description 4
- 101710142969 Somatoliberin Proteins 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 238000013537 high throughput screening Methods 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 150000002611 lead compounds Chemical class 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 108700037519 pegvisomant Proteins 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 230000035882 stress Effects 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 3
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 3
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 3
- 108010027814 HSP72 Heat-Shock Proteins Proteins 0.000 description 3
- 101000856606 Homo sapiens GTP-binding protein GEM Proteins 0.000 description 3
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 3
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 3
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 3
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 3
- 101100521345 Mus musculus Prop1 gene Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108010052090 Renilla Luciferases Proteins 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 230000002942 anti-growth Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000010437 gem Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 230000036542 oxidative stress Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229940099077 somavert Drugs 0.000 description 3
- 231100001274 therapeutic index Toxicity 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 102100032161 Adenylate cyclase type 5 Human genes 0.000 description 2
- 101710194247 Adenylate cyclase type 5 Proteins 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 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 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 102400001066 Growth hormone-binding protein Human genes 0.000 description 2
- 102100040352 Heat shock 70 kDa protein 1A Human genes 0.000 description 2
- 108010000521 Human Growth Hormone Proteins 0.000 description 2
- 102000002265 Human Growth Hormone Human genes 0.000 description 2
- 239000000854 Human Growth Hormone Substances 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 101001075372 Mus musculus Gamma-glutamyl hydrolase Proteins 0.000 description 2
- 101001075261 Mus musculus Growth hormone receptor Proteins 0.000 description 2
- 101150054854 POU1F1 gene Proteins 0.000 description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108010034782 Ribosomal Protein S6 Kinases Proteins 0.000 description 2
- 102000009738 Ribosomal Protein S6 Kinases Human genes 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000037328 acute stress Effects 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 230000007541 cellular toxicity Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229940126208 compound 22 Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 108091009655 growth hormone receptor binding proteins Proteins 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000670 limiting effect Effects 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
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000003652 pro-growth Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 241000701022 Cytomegalovirus Species 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-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
- 102000053602 DNA Human genes 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102100025626 GTP-binding protein GEM Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229940124013 Growth hormone receptor antagonist Drugs 0.000 description 1
- 102000016761 Haem oxygenases Human genes 0.000 description 1
- 108050006318 Haem oxygenases Proteins 0.000 description 1
- 108010020382 Hepatocyte Nuclear Factor 1-alpha Proteins 0.000 description 1
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 1
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 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 1
- 208000006302 Laron syndrome Diseases 0.000 description 1
- 244000178870 Lavandula angustifolia Species 0.000 description 1
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000836210 Mus musculus Somatotropin Proteins 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 201000005746 Pituitary adenoma Diseases 0.000 description 1
- 206010061538 Pituitary tumour benign Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000083869 Polyommatus dorylas Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 101710090875 Protein c-Fos Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 101710152244 Serine/threonine-protein kinase SCH9 Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 1
- 101710127774 Stress response protein Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 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
- 239000008272 agar Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000007960 cellular response to stress Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 238000003927 comet assay Methods 0.000 description 1
- 231100000170 comet assay Toxicity 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000010250 cytokine signaling pathway Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 235000018219 lavender Nutrition 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229960002995 pegvisomant Drugs 0.000 description 1
- 210000004976 peripheral blood cell Anatomy 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 208000021310 pituitary gland adenoma Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 230000000606 pro-mitotic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000007727 signaling mechanism Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000011255 standard chemotherapy Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- YXZRCLVVNRLPTP-UHFFFAOYSA-J turquoise blue Chemical compound [Na+].[Na+].[Na+].[Na+].[Cu+2].NC1=NC(Cl)=NC(NC=2C=C(NS(=O)(=O)C3=CC=4C(=C5NC=4NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)NC=4NC(=C6C=C(C=CC6=4)S([O-])(=O)=O)NC=4[N-]C(=C6C=CC(=CC6=4)S([O-])(=O)=O)N5)C=C3)C(=CC=2)S([O-])(=O)=O)=N1 YXZRCLVVNRLPTP-UHFFFAOYSA-J 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/72—Receptors; Cell surface antigens; Cell surface determinants for hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/26—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against hormones ; against hormone releasing or inhibiting factors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2869—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against hormone receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/75—Agonist effect on antigen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Toxicology (AREA)
- Hospice & Palliative Care (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562115356P | 2015-02-12 | 2015-02-12 | |
| US62/115,356 | 2015-02-12 | ||
| PCT/US2016/017717 WO2016130901A2 (en) | 2015-02-12 | 2016-02-12 | Blockers of the growth hormone receptor in disease prevention and treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2976219A1 CA2976219A1 (en) | 2016-08-18 |
| CA2976219C true CA2976219C (en) | 2021-05-04 |
Family
ID=56615057
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2976219A Active CA2976219C (en) | 2015-02-12 | 2016-02-12 | Blockers of the growth hormone receptor in disease prevention and treatment |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US10246446B2 (enExample) |
| EP (1) | EP3256465B1 (enExample) |
| JP (2) | JP6930916B2 (enExample) |
| KR (1) | KR20180016333A (enExample) |
| CN (1) | CN107438605B (enExample) |
| AU (1) | AU2016219173B2 (enExample) |
| BR (1) | BR112017017182A2 (enExample) |
| CA (1) | CA2976219C (enExample) |
| ES (1) | ES2871551T3 (enExample) |
| IL (1) | IL253943A0 (enExample) |
| MX (1) | MX383010B (enExample) |
| NZ (1) | NZ734252A (enExample) |
| RU (1) | RU2726254C2 (enExample) |
| WO (1) | WO2016130901A2 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11284640B2 (en) | 2017-02-14 | 2022-03-29 | University Of Southern California | Fasting mimicking diet |
| CN112153974A (zh) | 2018-03-15 | 2020-12-29 | 南加利福尼亚大学 | 禁食模仿膳食(fmd)而非仅饮水禁食促进炎症和ibd病理学的逆转 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9701010D0 (sv) * | 1997-03-19 | 1997-03-19 | Pharmacia & Upjohn Ab | Antibody |
| JPWO2002096892A1 (ja) | 2001-05-31 | 2004-09-09 | 小野薬品工業株式会社 | オキサジアゾール誘導体化合物およびその化合物を有効成分とする薬剤 |
| WO2006001770A1 (en) * | 2004-06-28 | 2006-01-05 | Biovitrum Ab | Method for identifying modulators of cytokine class i receptor |
| RU2415134C9 (ru) * | 2005-08-15 | 2011-05-27 | Этерна Центарис ГмбХ | Способ лечения или профилактики физиологических и/или патофизиологических состояний, опосредуемых рецепторами, стимулирующими секрецию гормона роста, триазолы и фармацевтическая композиция на их основе |
| US8519137B2 (en) | 2007-10-11 | 2013-08-27 | Vertex Pharmaceuticals Incorporated | Heteroaryl amides useful as inhibitors of voltage-gated sodium channels |
| AU2008352540B2 (en) * | 2008-03-14 | 2012-06-28 | Biocon Limited | A monoclonal antibody and a method thereof |
| JP5731501B2 (ja) * | 2009-07-28 | 2015-06-10 | コーニンクレッカ フィリップス エヌ ヴェ | ロック構造を有するハウジング |
| RU2014123030A (ru) * | 2011-12-22 | 2016-02-20 | Ринат Ньюросайенс Корп. | Антагонистические антитела против человеческого рецептора гормона роста и способы их применения |
| WO2013123511A1 (en) * | 2012-02-16 | 2013-08-22 | New York University | Control of hypoxia-inducible gene expression with oligooxopiperazine nonpeptidic helix mimetics |
| WO2013192165A2 (en) | 2012-06-20 | 2013-12-27 | University Of Kansas | Compounds and methods for activating the apoptotic arm of the unfolded protein response |
| KR20150124962A (ko) | 2013-02-12 | 2015-11-06 | 유니버시티 오브 써던 캘리포니아 | 화학 독성 및 연령 관련 질병으로부터 보호하기 위한 방법 및 규정식 |
-
2016
- 2016-02-12 BR BR112017017182A patent/BR112017017182A2/pt not_active IP Right Cessation
- 2016-02-12 US US14/913,130 patent/US10246446B2/en active Active
- 2016-02-12 AU AU2016219173A patent/AU2016219173B2/en not_active Ceased
- 2016-02-12 ES ES16749947T patent/ES2871551T3/es active Active
- 2016-02-12 JP JP2017541934A patent/JP6930916B2/ja active Active
- 2016-02-12 KR KR1020177024899A patent/KR20180016333A/ko not_active Ceased
- 2016-02-12 WO PCT/US2016/017717 patent/WO2016130901A2/en not_active Ceased
- 2016-02-12 MX MX2017010306A patent/MX383010B/es unknown
- 2016-02-12 NZ NZ734252A patent/NZ734252A/en not_active IP Right Cessation
- 2016-02-12 CN CN201680010133.4A patent/CN107438605B/zh active Active
- 2016-02-12 EP EP16749947.4A patent/EP3256465B1/en active Active
- 2016-02-12 RU RU2017129335A patent/RU2726254C2/ru active
- 2016-02-12 CA CA2976219A patent/CA2976219C/en active Active
-
2017
- 2017-08-10 IL IL253943A patent/IL253943A0/en unknown
-
2019
- 2019-03-27 US US16/366,662 patent/US20190276445A1/en not_active Abandoned
-
2021
- 2021-02-08 JP JP2021018032A patent/JP2021075553A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20190276445A1 (en) | 2019-09-12 |
| EP3256465A2 (en) | 2017-12-20 |
| CN107438605A (zh) | 2017-12-05 |
| MX2017010306A (es) | 2018-03-15 |
| US20170342063A1 (en) | 2017-11-30 |
| BR112017017182A2 (pt) | 2018-04-03 |
| EP3256465B1 (en) | 2021-04-07 |
| CN107438605B (zh) | 2021-03-19 |
| RU2726254C2 (ru) | 2020-07-10 |
| AU2016219173A1 (en) | 2017-08-17 |
| RU2017129335A3 (enExample) | 2019-08-07 |
| CA2976219A1 (en) | 2016-08-18 |
| JP2018506534A (ja) | 2018-03-08 |
| NZ734252A (en) | 2020-06-26 |
| JP2021075553A (ja) | 2021-05-20 |
| EP3256465A4 (en) | 2018-10-31 |
| WO2016130901A2 (en) | 2016-08-18 |
| WO2016130901A3 (en) | 2016-10-20 |
| ES2871551T3 (es) | 2021-10-29 |
| RU2017129335A (ru) | 2019-03-12 |
| KR20180016333A (ko) | 2018-02-14 |
| AU2016219173B2 (en) | 2020-02-20 |
| JP6930916B2 (ja) | 2021-09-01 |
| US10246446B2 (en) | 2019-04-02 |
| IL253943A0 (en) | 2017-10-31 |
| MX383010B (es) | 2025-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Targeting T cell activation and lupus autoimmune phenotypes by inhibiting glucose transporters | |
| US20210052526A1 (en) | Method of treating or preventing neurodegeneration | |
| CN110234647B (zh) | 用于调节免疫应答的氧杂双环庚烷 | |
| US20200377599A1 (en) | Compositions and methods for treating cancer | |
| EP3723781B1 (en) | Peptides and other agents for treating pain and increasing pain sensitivity | |
| US20190276445A1 (en) | Blockers of the growth hormone receptor in disease prevention and treatment | |
| US11919854B2 (en) | P2RX7 modulators in therapy | |
| WO2021035048A1 (en) | Use of inhibitors of yap and sox2 for the treatment of cancer | |
| WO2023053142A1 (en) | Novel combination of serotonin receptor (5-htr2b) antagonist and an immunomodulator and chemotherapeutic drugs for inhibition of cancer | |
| EP3250218B1 (en) | Naktide peptide for treating obesity | |
| US20240141436A1 (en) | Compounds, Compositions and Methods of Treatment Thereof | |
| US20100330098A1 (en) | Methods to regulate glucose metabolism | |
| WO2015073813A2 (en) | Compositions and methods for the treatment of diseases involving hippo pathway | |
| CN109475552B (zh) | 用于食欲控制和体重管理的方法和组合物 | |
| WO2018087285A1 (en) | Or10h1 antigen binding proteins and uses thereof | |
| WO2024155689A1 (en) | Compounds and methods for inhibiting type-iii receptor tyrosine kinases | |
| US20150140043A1 (en) | Immunomodulatory methods using notch agonists | |
| Park et al. | Car Receptor | |
| HK40037093A (en) | Peptides and other agents for treating pain and increasing pain sensitivity | |
| HK40037093B (en) | Peptides and other agents for treating pain and increasing pain sensitivity | |
| Sitkovsky | Pdgfr Signaling |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20190117 |