AU2009293020A1 - Inhibiting interaction between HIF-1a and p300/CBP with hydrogen bond surrogate-based helices - Google Patents
Inhibiting interaction between HIF-1a and p300/CBP with hydrogen bond surrogate-based helices Download PDFInfo
- Publication number
- AU2009293020A1 AU2009293020A1 AU2009293020A AU2009293020A AU2009293020A1 AU 2009293020 A1 AU2009293020 A1 AU 2009293020A1 AU 2009293020 A AU2009293020 A AU 2009293020A AU 2009293020 A AU2009293020 A AU 2009293020A AU 2009293020 A1 AU2009293020 A1 AU 2009293020A1
- Authority
- AU
- Australia
- Prior art keywords
- peptide
- ala
- asn
- arg
- cell
- 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.)
- Abandoned
Links
- 239000001257 hydrogen Substances 0.000 title claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 title claims description 43
- 230000003993 interaction Effects 0.000 title claims description 33
- 230000002401 inhibitory effect Effects 0.000 title description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 147
- 210000004027 cell Anatomy 0.000 claims description 81
- 238000000034 method Methods 0.000 claims description 58
- 206010021143 Hypoxia Diseases 0.000 claims description 46
- 206010028980 Neoplasm Diseases 0.000 claims description 42
- 108090000623 proteins and genes Proteins 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 34
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 29
- 150000001413 amino acids Chemical class 0.000 claims description 29
- 201000011510 cancer Diseases 0.000 claims description 28
- 238000013518 transcription Methods 0.000 claims description 28
- 230000035897 transcription Effects 0.000 claims description 28
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 26
- 150000002431 hydrogen Chemical class 0.000 claims description 25
- 238000012360 testing method Methods 0.000 claims description 15
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims description 13
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 13
- 230000033115 angiogenesis Effects 0.000 claims description 13
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 13
- 239000003446 ligand Substances 0.000 claims description 12
- 108010040163 CREB-Binding Protein Proteins 0.000 claims description 11
- 102100021975 CREB-binding protein Human genes 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 10
- 238000001727 in vivo Methods 0.000 claims description 10
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 claims description 10
- 108091006296 SLC2A1 Proteins 0.000 claims description 9
- 108091008605 VEGF receptors Proteins 0.000 claims description 9
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000000539 amino acid group Chemical group 0.000 claims description 9
- 210000004899 c-terminal region Anatomy 0.000 claims description 9
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 claims description 8
- 230000001939 inductive effect Effects 0.000 claims description 7
- 230000035755 proliferation Effects 0.000 claims description 7
- 230000004083 survival effect Effects 0.000 claims description 7
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 6
- 108010068561 Fructose-Bisphosphate Aldolase Proteins 0.000 claims description 6
- 102000001390 Fructose-Bisphosphate Aldolase Human genes 0.000 claims description 6
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 6
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 6
- 230000006907 apoptotic process Effects 0.000 claims description 6
- 208000002780 macular degeneration Diseases 0.000 claims description 6
- 102100038910 Alpha-enolase Human genes 0.000 claims description 5
- 101710165425 Alpha-enolase Proteins 0.000 claims description 5
- 108010075016 Ceruloplasmin Proteins 0.000 claims description 5
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 5
- 102400000686 Endothelin-1 Human genes 0.000 claims description 5
- 101800004490 Endothelin-1 Proteins 0.000 claims description 5
- 101710184673 Enolase 1 Proteins 0.000 claims description 5
- 102000003951 Erythropoietin Human genes 0.000 claims description 5
- 108090000394 Erythropoietin Proteins 0.000 claims description 5
- 108091052347 Glucose transporter family Proteins 0.000 claims description 5
- 102000042092 Glucose transporter family Human genes 0.000 claims description 5
- 102000002737 Heme Oxygenase-1 Human genes 0.000 claims description 5
- 108010018924 Heme Oxygenase-1 Proteins 0.000 claims description 5
- 102100030338 Hexokinase-1 Human genes 0.000 claims description 5
- 101710198391 Hexokinase-1 Proteins 0.000 claims description 5
- 102100029242 Hexokinase-2 Human genes 0.000 claims description 5
- 101710198385 Hexokinase-2 Proteins 0.000 claims description 5
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 claims description 5
- 101001124991 Homo sapiens Nitric oxide synthase, inducible Proteins 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 102100025947 Insulin-like growth factor II Human genes 0.000 claims description 5
- 102000004374 Insulin-like growth factor binding protein 3 Human genes 0.000 claims description 5
- 108090000965 Insulin-like growth factor binding protein 3 Proteins 0.000 claims description 5
- 102100034671 L-lactate dehydrogenase A chain Human genes 0.000 claims description 5
- 108010088350 Lactate Dehydrogenase 5 Proteins 0.000 claims description 5
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims description 5
- 102000004338 Transferrin Human genes 0.000 claims description 5
- 108090000901 Transferrin Proteins 0.000 claims description 5
- 229940105423 erythropoietin Drugs 0.000 claims description 5
- 229940068935 insulin-like growth factor 2 Drugs 0.000 claims description 5
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 5
- 208000032253 retinal ischemia Diseases 0.000 claims description 5
- 239000012581 transferrin Substances 0.000 claims description 5
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 4
- 208000001362 Fetal Growth Retardation Diseases 0.000 claims description 4
- 206010070531 Foetal growth restriction Diseases 0.000 claims description 4
- 102000004375 Insulin-like growth factor-binding protein 1 Human genes 0.000 claims description 4
- 108090000957 Insulin-like growth factor-binding protein 1 Proteins 0.000 claims description 4
- 230000007423 decrease Effects 0.000 claims description 4
- 201000011190 diabetic macular edema Diseases 0.000 claims description 4
- 208000030941 fetal growth restriction Diseases 0.000 claims description 4
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
- 101710131701 Adenylate kinase 3 Proteins 0.000 claims description 3
- 101710191368 GTP:AMP phosphotransferase AK3, mitochondrial Proteins 0.000 claims description 3
- 102100033512 GTP:AMP phosphotransferase AK3, mitochondrial Human genes 0.000 claims description 3
- 101710184523 GTP:AMP phosphotransferase, mitochondrial Proteins 0.000 claims description 3
- 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 claims description 3
- 101710139464 Phosphoglycerate kinase 1 Proteins 0.000 claims description 3
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 claims description 3
- 102000013009 Pyruvate Kinase Human genes 0.000 claims description 3
- 108020005115 Pyruvate Kinase Proteins 0.000 claims description 3
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 claims description 3
- 108010033576 Transferrin Receptors Proteins 0.000 claims description 3
- 102100026144 Transferrin receptor protein 1 Human genes 0.000 claims description 3
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 3
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 3
- 108010063640 adrenomedullin receptors Proteins 0.000 claims description 3
- 230000003247 decreasing effect Effects 0.000 claims description 3
- 230000003511 endothelial effect Effects 0.000 claims description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 claims description 3
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 210000005166 vasculature Anatomy 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 claims 1
- VPZKQTYZIVOJDV-LMVFSUKVSA-N Thr-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(O)=O VPZKQTYZIVOJDV-LMVFSUKVSA-N 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 43
- 210000001519 tissue Anatomy 0.000 description 29
- 239000002502 liposome Substances 0.000 description 23
- 230000027455 binding Effects 0.000 description 20
- 235000018102 proteins Nutrition 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 239000003814 drug Substances 0.000 description 16
- 230000007954 hypoxia Effects 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 14
- 229940024606 amino acid Drugs 0.000 description 13
- ZRZWBWPDBOVIGQ-OKMJTBRXSA-N chaetomin Chemical compound C1=C(C[C@]23C(N(C)[C@@](CO)(SS2)C(=O)N3C)=O)C2=CC=CC=C2N1[C@@]12C[C@]3(SS4)C(=O)N(C)[C@]4(CO)C(=O)N3[C@H]2NC2=CC=CC=C12 ZRZWBWPDBOVIGQ-OKMJTBRXSA-N 0.000 description 13
- DZRJLJPPUJADOO-UHFFFAOYSA-N chaetomin Natural products CN1C(=O)C2(Cc3cn(C)c4ccccc34)SSC1(CO)C(=O)N2C56CC78SSC(CO)(N(C)C7=O)C(=O)N8C5Nc9ccccc69 DZRJLJPPUJADOO-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 235000001014 amino acid Nutrition 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 150000003384 small molecules Chemical class 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 11
- 238000004113 cell culture Methods 0.000 description 11
- 239000012528 membrane Substances 0.000 description 11
- 210000004379 membrane Anatomy 0.000 description 11
- 210000000056 organ Anatomy 0.000 description 11
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 10
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 10
- 238000013459 approach Methods 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 230000002159 abnormal effect Effects 0.000 description 9
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 210000004185 liver Anatomy 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 238000005865 alkene metathesis reaction Methods 0.000 description 8
- 238000013461 design Methods 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 230000001146 hypoxic effect Effects 0.000 description 7
- 238000000111 isothermal titration calorimetry Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000005649 metathesis reaction Methods 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 108010049386 Aryl Hydrocarbon Receptor Nuclear Translocator Proteins 0.000 description 5
- 102100030907 Aryl hydrocarbon receptor nuclear translocator Human genes 0.000 description 5
- 101100450705 Caenorhabditis elegans hif-1 gene Proteins 0.000 description 5
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 5
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 5
- 230000006536 aerobic glycolysis Effects 0.000 description 5
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 102000037865 fusion proteins Human genes 0.000 description 5
- 108020001507 fusion proteins Proteins 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000003278 mimic effect Effects 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- -1 propenoyl Chemical group 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 230000008685 targeting Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 description 4
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 108091027981 Response element Proteins 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000006682 Warburg effect Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000006911 nucleation Effects 0.000 description 4
- 238000010899 nucleation Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000007115 recruitment Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 210000001525 retina Anatomy 0.000 description 4
- 230000002207 retinal effect Effects 0.000 description 4
- 238000006798 ring closing metathesis reaction Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000006641 stabilisation Effects 0.000 description 4
- 238000011105 stabilization Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- PZPPOCZWRGNKIR-PNVYSBBASA-N chaetocin Chemical compound N([C@@H]1N2C(=O)[C@]3(CO)SS[C@]2(C(N3C)=O)C2)C3=CC=CC=C3[C@]12[C@@]12C[C@]3(SS4)C(=O)N(C)[C@]4(CO)C(=O)N3[C@H]2NC2=CC=CC=C12 PZPPOCZWRGNKIR-PNVYSBBASA-N 0.000 description 3
- PZPPOCZWRGNKIR-UHFFFAOYSA-N chaetocin Natural products C1C2(C(N3C)=O)SSC3(CO)C(=O)N2C2NC3=CC=CC=C3C21C12CC3(SS4)C(=O)N(C)C4(CO)C(=O)N3C2NC2=CC=CC=C12 PZPPOCZWRGNKIR-UHFFFAOYSA-N 0.000 description 3
- 230000003081 coactivator Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 150000002678 macrocyclic compounds Chemical class 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000010532 solid phase synthesis reaction Methods 0.000 description 3
- 230000006694 transcriptional co-activation Effects 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 102000004379 Adrenomedullin Human genes 0.000 description 2
- 101800004616 Adrenomedullin Proteins 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 241001515917 Chaetomium globosum Species 0.000 description 2
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 2
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 2
- 108010062580 Concanavalin A Proteins 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 101100372758 Danio rerio vegfaa gene Proteins 0.000 description 2
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 101000844752 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) DNA-binding protein 7d Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 241000205091 Sulfolobus solfataricus Species 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 2
- 101150030763 Vegfa gene Proteins 0.000 description 2
- 102000053200 Von Hippel-Lindau Tumor Suppressor Human genes 0.000 description 2
- 108700031765 Von Hippel-Lindau Tumor Suppressor Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- ULCUCJFASIJEOE-NPECTJMMSA-N adrenomedullin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H]1C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)[C@@H](C)O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ULCUCJFASIJEOE-NPECTJMMSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000012152 bradford reagent Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000000978 circular dichroism spectroscopy Methods 0.000 description 2
- 238000001142 circular dichroism spectrum Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 210000004392 genitalia Anatomy 0.000 description 2
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 2
- 239000011984 grubbs catalyst Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 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
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 231100000590 oncogenic Toxicity 0.000 description 2
- 230000002246 oncogenic effect Effects 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 208000028591 pheochromocytoma Diseases 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 230000004850 protein–protein interaction Effects 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 210000001147 pulmonary artery Anatomy 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 230000006884 regulation of angiogenesis Effects 0.000 description 2
- 230000020874 response to hypoxia Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 230000006459 vascular development Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000012130 whole-cell lysate Substances 0.000 description 2
- UHEPSJJJMTWUCP-DHDYTCSHSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-[(1r)-1-hydroxyethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H]([C@@H](C)O)O2)N)[C@@H](N)C[C@H]1N UHEPSJJJMTWUCP-DHDYTCSHSA-N 0.000 description 1
- AQDZAHJUWYRHGM-INIZCTEOSA-N (3S)-3-(1H-Indol-3-ylmethyl)-3H-1,4-benzodiazepine-2,5-diol Chemical compound O=C1NC2=CC=CC=C2C(=O)N[C@H]1CC1=CNC2=CC=CC=C12 AQDZAHJUWYRHGM-INIZCTEOSA-N 0.000 description 1
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 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
- 102000008076 Angiogenic Proteins Human genes 0.000 description 1
- 108010074415 Angiogenic Proteins Proteins 0.000 description 1
- UWOPETAWXDZUJR-ACZMJKKPSA-N Asp-Cys-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O UWOPETAWXDZUJR-ACZMJKKPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000018720 Basic Helix-Loop-Helix Transcription Factors Human genes 0.000 description 1
- 108010027344 Basic Helix-Loop-Helix Transcription Factors Proteins 0.000 description 1
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000016362 Catenins Human genes 0.000 description 1
- 108010067316 Catenins Proteins 0.000 description 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 1
- 241000221955 Chaetomium Species 0.000 description 1
- 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 1
- 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 1
- 238000010485 C−C bond formation reaction Methods 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102100032257 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000006893 Fetal Hypoxia Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000058063 Glucose Transporter Type 1 Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 102000005548 Hexokinase Human genes 0.000 description 1
- 108700040460 Hexokinases Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000012819 MDM2-Inhibitor Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000004722 NADPH Oxidases Human genes 0.000 description 1
- 108010002998 NADPH Oxidases Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 101800001442 Peptide pr Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 1
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 108091006298 SLC2A3 Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100023536 Solute carrier family 2, facilitated glucose transporter member 1 Human genes 0.000 description 1
- 102100022722 Solute carrier family 2, facilitated glucose transporter member 3 Human genes 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 229930188346 Sporidesmin Natural products 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000015098 Tumor Suppressor Protein p53 Human genes 0.000 description 1
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- ZVNYJIZDIRKMBF-UHFFFAOYSA-N Vesnarinone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(C=2C=C3CCC(=O)NC3=CC=2)CC1 ZVNYJIZDIRKMBF-UHFFFAOYSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- KZENBFUSKMWCJF-UHFFFAOYSA-N [5-[5-[5-(hydroxymethyl)-2-thiophenyl]-2-furanyl]-2-thiophenyl]methanol Chemical compound S1C(CO)=CC=C1C1=CC=C(C=2SC(CO)=CC=2)O1 KZENBFUSKMWCJF-UHFFFAOYSA-N 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 238000012387 aerosolization 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
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000002701 cell growth assay Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 208000011654 childhood malignant neoplasm Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007887 hard shell capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000021991 hereditary neoplastic syndrome Diseases 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000006702 hypoxic induction Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000002334 isothermal calorimetry Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 206010024378 leukocytosis Diseases 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 239000002207 metabolite Substances 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
- 230000009401 metastasis Effects 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 239000013580 millipore water Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000007959 normoxia Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- YIYBQIKDCADOSF-UHFFFAOYSA-N pentenoic acid group Chemical group C(C=CCC)(=O)O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000006683 regulatory hydroxylation Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004233 retinal vasculature Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 108010038196 saccharide-binding proteins Proteins 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007886 soft shell capsule Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound 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
- 229960000553 somatostatin Drugs 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000012421 spiking Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229930192474 thiophene Chemical group 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 108091006108 transcriptional coactivators Proteins 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- WQAJKOXBERTWBK-UHFFFAOYSA-N verdine Natural products CC1CNC2C(C1)OC3(CCC4C5CCC6(O)CC(O)CC(O)C6(C)C5C(=O)C4=C3C)C2C WQAJKOXBERTWBK-UHFFFAOYSA-N 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/02—Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Endocrinology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2015202742A AU2015202742A1 (en) | 2008-09-18 | 2015-05-20 | Inhibiting interaction between hif-1a and p300/cbp with hydrogen bond surrogate-based helices |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9819308P | 2008-09-18 | 2008-09-18 | |
| US61/098,193 | 2008-09-18 | ||
| PCT/US2009/057592 WO2010033879A2 (en) | 2008-09-18 | 2009-09-18 | Inhibiting interaction between hif-1a and p300/cbp with hydrogen bond surrogate-based helices |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2015202742A Division AU2015202742A1 (en) | 2008-09-18 | 2015-05-20 | Inhibiting interaction between hif-1a and p300/cbp with hydrogen bond surrogate-based helices |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2009293020A1 true AU2009293020A1 (en) | 2010-03-25 |
Family
ID=42040175
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2009293020A Abandoned AU2009293020A1 (en) | 2008-09-18 | 2009-09-18 | Inhibiting interaction between HIF-1a and p300/CBP with hydrogen bond surrogate-based helices |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9399666B2 (https=) |
| EP (1) | EP2344520B1 (https=) |
| JP (2) | JP2012503013A (https=) |
| CN (1) | CN102216322A (https=) |
| AU (1) | AU2009293020A1 (https=) |
| BR (1) | BRPI0919414A2 (https=) |
| CA (1) | CA2737614A1 (https=) |
| ES (1) | ES2446249T3 (https=) |
| WO (1) | WO2010033879A2 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008061192A2 (en) * | 2006-11-15 | 2008-05-22 | Dana-Farber Cancer Institute, Inc. | Stabilized maml peptides and uses thereof |
| CN105061577A (zh) | 2006-12-14 | 2015-11-18 | 爱勒让治疗公司 | 双巯基大环化系统 |
| ES2398310T3 (es) | 2007-02-23 | 2013-03-15 | Aileron Therapeutics, Inc. | Péptidos macrocíclicos unidos a triazol |
| AU2008232709C1 (en) | 2007-03-28 | 2015-01-15 | President And Fellows Of Harvard College | Stitched polypeptides |
| US9399666B2 (en) | 2008-09-18 | 2016-07-26 | New York University | Inhibiting interaction between the HIF-1ALPHA and p300/CBP with hydrogen bond surrogate-based helices |
| ES2666458T3 (es) | 2008-09-22 | 2018-05-04 | Aileron Therapeutics, Inc. | Macrociclos peptidomiméticos |
| EP2352507A4 (en) | 2008-11-24 | 2012-04-25 | Aileron Therapeutics Inc | PEPTIDOMIMETIC MACROCYCLES WITH IMPROVED PROPERTIES |
| WO2010083347A2 (en) | 2009-01-14 | 2010-07-22 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| US20130072439A1 (en) | 2009-09-22 | 2013-03-21 | Huw M. Nash | Peptidomimetic macrocycles |
| KR20170058446A (ko) | 2010-08-13 | 2017-05-26 | 에일러론 테라퓨틱스 인코포레이티드 | 펩티도미메틱 거대고리 |
| US8511577B2 (en) | 2011-02-24 | 2013-08-20 | Nest Labs, Inc. | Thermostat with power stealing delay interval at transitions between power stealing states |
| JP6239979B2 (ja) * | 2011-03-04 | 2017-11-29 | ニューヨーク・ユニバーシティ | Rasの調節因子としての水素結合代替大環状分子 |
| AR088392A1 (es) | 2011-10-18 | 2014-05-28 | Aileron Therapeutics Inc | Macrociclos peptidomimeticos |
| CN104066435A (zh) * | 2011-12-21 | 2014-09-24 | 纽约大学 | 蛋白水解抗性的氢键替代螺旋 |
| HK1205454A1 (en) | 2012-02-15 | 2015-12-18 | Aileron Therapeutics, Inc. | Triazole-crosslinked and thioether-crosslinked peptidomimetic macrocycles |
| CA2862038C (en) | 2012-02-15 | 2021-05-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| BR112015009470A2 (pt) | 2012-11-01 | 2019-12-17 | Aileron Therapeutics Inc | aminoácidos dissubstituídos e seus métodos de preparação e uso |
| EP2945631A4 (en) * | 2013-01-19 | 2016-06-29 | Univ New York | OLIGOOXOPIPERAZINE FOR THE REACTIVATION OF P53 |
| WO2014113792A1 (en) * | 2013-01-19 | 2014-07-24 | New York University | Hydrogen-bond surrogate peptides and peptidomimetics for p53 reactivation |
| US20150065436A1 (en) * | 2013-09-03 | 2015-03-05 | University Of Southern California | INHIBITING INTERACTION BETWEEN HIF-1ALPHA AND p300/CBP WITH HYDROGEN BOND SURROGATE-BASED HELICES |
| SG11201702175YA (en) | 2014-09-24 | 2017-04-27 | Aileron Therapeutics Inc | Peptidomimetic macrocycles and formulations thereof |
| WO2016049359A1 (en) | 2014-09-24 | 2016-03-31 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| US10253067B2 (en) | 2015-03-20 | 2019-04-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| US10059741B2 (en) | 2015-07-01 | 2018-08-28 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
| JP2018528217A (ja) | 2015-09-10 | 2018-09-27 | エルロン・セラピューティクス・インコーポレイテッドAileron Therapeutics,Inc. | Mcl−1のモジュレーターとしてのペプチド模倣大環状分子 |
| WO2018008984A1 (ko) * | 2016-07-05 | 2018-01-11 | 이화여자대학교 산학협력단 | 에피디티오디옥소피페라진 화합물 또는 이의 유도체, 또는 이들의 약학적으로 허용가능한 염을 포함하는 폐동맥고혈압 예방 또는 치료용 약학적 조성물 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6986881B1 (en) | 1999-06-04 | 2006-01-17 | Dana-Farber Cancer Institute, Inc. | Identification of compounds that modify transcriptional responses to hypoxia |
| GB0211920D0 (en) | 2002-05-23 | 2002-07-03 | Isis Innovations Ltd | Assay |
| WO2005118620A2 (en) * | 2004-05-27 | 2005-12-15 | New York University | Methods for preparing internally constraied peptides and peptidomimetics |
| ITMI20042477A1 (it) | 2004-12-23 | 2005-03-23 | Cell Therapeutics Europe Srl | Uso di antibiotici a strutura dichetoditiopiperazinica per la preparazione di composizioni farmaceutiche antiangiogeniche |
| KR100860060B1 (ko) * | 2006-10-12 | 2008-09-24 | 한국과학기술연구원 | HIF-1α C-말단 펩타이드와 CBP 또는 p300단백질과의 결합을 정량분석하는 방법 및 상기 방법을이용한 단백질 복합체 형성을 저해하는 억제제의 스크리닝방법 |
| US9399666B2 (en) | 2008-09-18 | 2016-07-26 | New York University | Inhibiting interaction between the HIF-1ALPHA and p300/CBP with hydrogen bond surrogate-based helices |
| AU2009294871A1 (en) * | 2008-09-22 | 2010-03-25 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles |
-
2009
- 2009-09-18 US US13/119,108 patent/US9399666B2/en active Active
- 2009-09-18 WO PCT/US2009/057592 patent/WO2010033879A2/en not_active Ceased
- 2009-09-18 AU AU2009293020A patent/AU2009293020A1/en not_active Abandoned
- 2009-09-18 JP JP2011528020A patent/JP2012503013A/ja not_active Withdrawn
- 2009-09-18 EP EP09815315.8A patent/EP2344520B1/en not_active Not-in-force
- 2009-09-18 BR BRPI0919414A patent/BRPI0919414A2/pt not_active IP Right Cessation
- 2009-09-18 CN CN2009801461214A patent/CN102216322A/zh active Pending
- 2009-09-18 CA CA2737614A patent/CA2737614A1/en not_active Abandoned
- 2009-09-18 ES ES09815315.8T patent/ES2446249T3/es active Active
-
2014
- 2014-09-12 JP JP2014186970A patent/JP2015061833A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN102216322A (zh) | 2011-10-12 |
| WO2010033879A2 (en) | 2010-03-25 |
| US9399666B2 (en) | 2016-07-26 |
| JP2012503013A (ja) | 2012-02-02 |
| US20110245175A1 (en) | 2011-10-06 |
| BRPI0919414A2 (pt) | 2017-07-11 |
| ES2446249T3 (es) | 2014-03-06 |
| CA2737614A1 (en) | 2010-03-25 |
| EP2344520A4 (en) | 2012-03-14 |
| EP2344520A2 (en) | 2011-07-20 |
| EP2344520B1 (en) | 2013-11-13 |
| JP2015061833A (ja) | 2015-04-02 |
| WO2010033879A3 (en) | 2010-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2344520B1 (en) | Inhibiting interaction between hif-1a and p300/cbp with hydrogen bond surrogate-based helices | |
| US9663561B2 (en) | Methods of treatment of cancer using SRC-modulating peptides | |
| US9783526B2 (en) | Control of hypoxia-inducible gene expression with oligooxopiperazine nonpeptidic helix mimetics | |
| US12528846B2 (en) | BH4 stabilized peptides and uses thereof | |
| AU2023204685B2 (en) | Bcl-w polypeptides and mimetics for treating or preventing chemotherapy-induced peripheral neuropathy and hearing loss | |
| AU2018302855B2 (en) | Peptide derivative and pharmaceutical composition containing same | |
| AU2015202742A1 (en) | Inhibiting interaction between hif-1a and p300/cbp with hydrogen bond surrogate-based helices | |
| WO2003095484A2 (en) | Polypeptides increasing p53 expression | |
| GB2497719A (en) | Inhibitors of lipoprotein receptor degradation | |
| Singhal et al. | 11 Glutathione-Conjugate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK5 | Application lapsed section 142(2)(e) - patent request and compl. specification not accepted |