JP2000516585A - 血管新生阻害物質による雌生殖系の調節方法 - Google Patents
血管新生阻害物質による雌生殖系の調節方法Info
- Publication number
- JP2000516585A JP2000516585A JP10508217A JP50821798A JP2000516585A JP 2000516585 A JP2000516585 A JP 2000516585A JP 10508217 A JP10508217 A JP 10508217A JP 50821798 A JP50821798 A JP 50821798A JP 2000516585 A JP2000516585 A JP 2000516585A
- Authority
- JP
- Japan
- Prior art keywords
- angiogenesis
- agm
- mice
- inhibiting
- female
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 74
- 239000004037 angiogenesis inhibitor Substances 0.000 title claims description 36
- 229940121369 angiogenesis inhibitor Drugs 0.000 title claims description 33
- 210000004996 female reproductive system Anatomy 0.000 title description 19
- 230000001105 regulatory effect Effects 0.000 title description 7
- MSHZHSPISPJWHW-PVDLLORBSA-N O-(chloroacetylcarbamoyl)fumagillol Chemical compound C([C@H]([C@H]([C@@H]1[C@]2(C)[C@H](O2)CC=C(C)C)OC)OC(=O)NC(=O)CCl)C[C@@]21CO2 MSHZHSPISPJWHW-PVDLLORBSA-N 0.000 claims abstract description 143
- 230000033115 angiogenesis Effects 0.000 claims abstract description 122
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 61
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- 230000001850 reproductive effect Effects 0.000 claims abstract description 31
- 241000124008 Mammalia Species 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 230000035558 fertility Effects 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 230000001404 mediated effect Effects 0.000 claims abstract description 8
- 241000699670 Mus sp. Species 0.000 claims description 96
- 210000004291 uterus Anatomy 0.000 claims description 50
- 210000001519 tissue Anatomy 0.000 claims description 38
- 210000001672 ovary Anatomy 0.000 claims description 33
- 210000002826 placenta Anatomy 0.000 claims description 25
- 210000003754 fetus Anatomy 0.000 claims description 16
- 230000035935 pregnancy Effects 0.000 claims description 15
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical class O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims description 14
- 239000005557 antagonist Substances 0.000 claims description 14
- 210000001325 yolk sac Anatomy 0.000 claims description 13
- 102100023174 Methionine aminopeptidase 2 Human genes 0.000 claims description 12
- 108090000192 Methionyl aminopeptidases Proteins 0.000 claims description 12
- 230000028742 placenta development Effects 0.000 claims description 11
- 201000010260 leiomyoma Diseases 0.000 claims description 10
- 206010046798 Uterine leiomyoma Diseases 0.000 claims description 8
- -1 angiogenesis inhibitor compound Chemical class 0.000 claims description 8
- 230000016117 decidualization Effects 0.000 claims description 8
- 230000004720 fertilization Effects 0.000 claims description 8
- 208000005641 Adenomyosis Diseases 0.000 claims description 6
- 201000009273 Endometriosis Diseases 0.000 claims description 6
- 201000009274 endometriosis of uterus Diseases 0.000 claims description 6
- 201000007954 uterine fibroid Diseases 0.000 claims description 6
- 230000008175 fetal development Effects 0.000 claims description 5
- 208000032843 Hemorrhage Diseases 0.000 claims description 4
- 230000000740 bleeding effect Effects 0.000 claims description 3
- 208000025661 ovarian cyst Diseases 0.000 claims description 3
- 208000034158 bleeding Diseases 0.000 claims description 2
- 201000000322 choriocarcinoma of ovary Diseases 0.000 claims description 2
- 208000017823 ovarian ectopic pregnancy Diseases 0.000 claims description 2
- 230000001568 sexual effect Effects 0.000 claims description 2
- 238000011282 treatment Methods 0.000 description 41
- 210000002257 embryonic structure Anatomy 0.000 description 30
- 230000015572 biosynthetic process Effects 0.000 description 28
- 238000002513 implantation Methods 0.000 description 28
- 241001465754 Metazoa Species 0.000 description 27
- 230000000694 effects Effects 0.000 description 24
- 230000002357 endometrial effect Effects 0.000 description 24
- 239000000203 mixture Substances 0.000 description 21
- 210000004246 corpus luteum Anatomy 0.000 description 20
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 19
- 238000011161 development Methods 0.000 description 19
- 230000018109 developmental process Effects 0.000 description 18
- 230000009467 reduction Effects 0.000 description 17
- 210000004907 gland Anatomy 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 230000012010 growth Effects 0.000 description 15
- 230000013011 mating Effects 0.000 description 15
- 230000035755 proliferation Effects 0.000 description 15
- 206010029113 Neovascularisation Diseases 0.000 description 14
- 238000010186 staining Methods 0.000 description 14
- 210000002889 endothelial cell Anatomy 0.000 description 13
- 210000001161 mammalian embryo Anatomy 0.000 description 13
- 230000003169 placental effect Effects 0.000 description 13
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 12
- 230000000938 luteal effect Effects 0.000 description 12
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 11
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 11
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 11
- 210000004204 blood vessel Anatomy 0.000 description 11
- 210000004696 endometrium Anatomy 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 238000010254 subcutaneous injection Methods 0.000 description 11
- 239000007929 subcutaneous injection Substances 0.000 description 11
- 230000001605 fetal effect Effects 0.000 description 10
- 210000004088 microvessel Anatomy 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 210000003785 decidua Anatomy 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 230000003325 follicular Effects 0.000 description 9
- 230000035800 maturation Effects 0.000 description 9
- 230000027758 ovulation cycle Effects 0.000 description 9
- 239000000186 progesterone Substances 0.000 description 9
- 229960003387 progesterone Drugs 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 108050006400 Cyclin Proteins 0.000 description 8
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 8
- 102000009339 Proliferating Cell Nuclear Antigen Human genes 0.000 description 8
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- NGGMYCMLYOUNGM-CSDLUJIJSA-N fumagillin Chemical compound C([C@H]([C@H]([C@@H]1[C@]2(C)[C@H](O2)CC=C(C)C)OC)OC(=O)\C=C\C=C\C=C\C=C\C(O)=O)C[C@@]21CO2 NGGMYCMLYOUNGM-CSDLUJIJSA-N 0.000 description 8
- 239000003102 growth factor Substances 0.000 description 8
- 230000009545 invasion Effects 0.000 description 8
- 230000002611 ovarian Effects 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 210000001654 germ layer Anatomy 0.000 description 7
- 229940088597 hormone Drugs 0.000 description 7
- 239000005556 hormone Substances 0.000 description 7
- 210000004379 membrane Anatomy 0.000 description 7
- 230000016087 ovulation Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- NGGMYCMLYOUNGM-UHFFFAOYSA-N (-)-fumagillin Natural products O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)C=CC=CC=CC=CC(O)=O)CCC21CO2 NGGMYCMLYOUNGM-UHFFFAOYSA-N 0.000 description 6
- 208000032170 Congenital Abnormalities Diseases 0.000 description 6
- 206010010356 Congenital anomaly Diseases 0.000 description 6
- 108010054218 Factor VIII Proteins 0.000 description 6
- 102000001690 Factor VIII Human genes 0.000 description 6
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000007698 birth defect Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 235000013601 eggs Nutrition 0.000 description 6
- 229960000301 factor viii Drugs 0.000 description 6
- 229960000936 fumagillin Drugs 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 210000002459 blastocyst Anatomy 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000007943 implant Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 230000027272 reproductive process Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 230000001629 suppression Effects 0.000 description 5
- 208000006332 Choriocarcinoma Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- MSHZHSPISPJWHW-UHFFFAOYSA-N O-(chloroacetylcarbamoyl)fumagillol Chemical compound O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)NC(=O)CCl)CCC21CO2 MSHZHSPISPJWHW-UHFFFAOYSA-N 0.000 description 4
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000002491 angiogenic effect Effects 0.000 description 4
- 230000001640 apoptogenic effect Effects 0.000 description 4
- 210000002469 basement membrane Anatomy 0.000 description 4
- 230000002254 contraceptive effect Effects 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 230000012173 estrus Effects 0.000 description 4
- 230000004578 fetal growth Effects 0.000 description 4
- 230000000762 glandular Effects 0.000 description 4
- 230000009931 harmful effect Effects 0.000 description 4
- 238000011532 immunohistochemical staining Methods 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 4
- 230000000737 periodic effect Effects 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 210000004994 reproductive system Anatomy 0.000 description 4
- 150000004492 retinoid derivatives Chemical class 0.000 description 4
- 210000002536 stromal cell Anatomy 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 210000001215 vagina Anatomy 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 230000006459 vascular development Effects 0.000 description 4
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 3
- 241001225321 Aspergillus fumigatus Species 0.000 description 3
- CEVCTNCUIVEQOY-UHFFFAOYSA-N Fumagillol Natural products O1C(CC=C(C)C)C1(C)C1C(OC)C(O)CCC21CO2 CEVCTNCUIVEQOY-UHFFFAOYSA-N 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- 208000007542 Paresis Diseases 0.000 description 3
- 102000003992 Peroxidases Human genes 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001772 anti-angiogenic effect Effects 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 239000003433 contraceptive agent Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 201000003511 ectopic pregnancy Diseases 0.000 description 3
- 230000003511 endothelial effect Effects 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 239000000834 fixative Substances 0.000 description 3
- CEVCTNCUIVEQOY-STXHBLNNSA-N fumagillol Chemical compound C([C@@H](O)[C@H](C1[C@]2(C)[C@H](O2)CC=C(C)C)OC)C[C@@]21CO2 CEVCTNCUIVEQOY-STXHBLNNSA-N 0.000 description 3
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 3
- 210000002503 granulosa cell Anatomy 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000021267 infertility disease Diseases 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 208000012318 pareses Diseases 0.000 description 3
- 108040007629 peroxidase activity proteins Proteins 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000005747 tumor angiogenesis Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- SYGWGHVTLUBCEM-UHFFFAOYSA-N (3alpha,5alpha,17alphaOH)-3,17,21-Trihydroxypregnane-11,20-dione Natural products C1C(O)CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC21 SYGWGHVTLUBCEM-UHFFFAOYSA-N 0.000 description 2
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 2
- LRMDXTVKVHKWEK-UHFFFAOYSA-N 1,2-diaminoanthracene-9,10-dione Chemical compound C1=CC=C2C(=O)C3=C(N)C(N)=CC=C3C(=O)C2=C1 LRMDXTVKVHKWEK-UHFFFAOYSA-N 0.000 description 2
- AKJHMTWEGVYYSE-AIRMAKDCSA-N 4-HPR Chemical compound C=1C=C(O)C=CC=1NC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C AKJHMTWEGVYYSE-AIRMAKDCSA-N 0.000 description 2
- BOCATKBAKISRLA-UHFFFAOYSA-N 4-propyl-5-pyridin-4-yl-3h-1,3-oxazol-2-one Chemical compound N1C(=O)OC(C=2C=CN=CC=2)=C1CCC BOCATKBAKISRLA-UHFFFAOYSA-N 0.000 description 2
- ATCGGEJZONJOCL-UHFFFAOYSA-N 6-(2,5-dichlorophenyl)-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(C=2C(=CC=C(Cl)C=2)Cl)=N1 ATCGGEJZONJOCL-UHFFFAOYSA-N 0.000 description 2
- 229940122659 Angiogenesis stimulant Drugs 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000251730 Chondrichthyes Species 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- QEEBRPGZBVVINN-UHFFFAOYSA-N Desacetyl-bufotalin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C1(O)CCC2C=1C=CC(=O)OC=1 QEEBRPGZBVVINN-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 229940123011 Growth factor receptor antagonist Drugs 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000003996 Interferon-beta Human genes 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- JGPJQFOROWSRRS-UHFFFAOYSA-N LSM-2613 Chemical compound S1C=2N3C(C)=NN=C3CN=C(C=3C(=CC=CC=3)Cl)C=2C=C1CCC(=O)N1CCOCC1 JGPJQFOROWSRRS-UHFFFAOYSA-N 0.000 description 2
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 2
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 2
- 208000035752 Live birth Diseases 0.000 description 2
- KCWZGJVSDFYRIX-YFKPBYRVSA-N N(gamma)-nitro-L-arginine methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N[N+]([O-])=O KCWZGJVSDFYRIX-YFKPBYRVSA-N 0.000 description 2
- 101150044441 PECAM1 gene Proteins 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 102000004211 Platelet factor 4 Human genes 0.000 description 2
- 108090000778 Platelet factor 4 Proteins 0.000 description 2
- 102000007327 Protamines Human genes 0.000 description 2
- 108010007568 Protamines Proteins 0.000 description 2
- UIRKNQLZZXALBI-MSVGPLKSSA-N Squalamine Chemical compound C([C@@H]1C[C@H]2O)[C@@H](NCCCNCCCCN)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@H](C(C)C)OS(O)(=O)=O)[C@@]2(C)CC1 UIRKNQLZZXALBI-MSVGPLKSSA-N 0.000 description 2
- UIRKNQLZZXALBI-UHFFFAOYSA-N Squalamine Natural products OC1CC2CC(NCCCNCCCCN)CCC2(C)C2C1C1CCC(C(C)CCC(C(C)C)OS(O)(=O)=O)C1(C)CC2 UIRKNQLZZXALBI-UHFFFAOYSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 102000013394 Troponin I Human genes 0.000 description 2
- 108010065729 Troponin I Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- SYGWGHVTLUBCEM-ZIZPXRJBSA-N Urocortisone Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CC[C@@H]21 SYGWGHVTLUBCEM-ZIZPXRJBSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 2
- 229960002576 amiloride Drugs 0.000 description 2
- 229940091771 aspergillus fumigatus Drugs 0.000 description 2
- AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 2
- 229960005207 auranofin Drugs 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- QEEBRPGZBVVINN-BMPKRDENSA-N bufalin Chemical compound C=1([C@H]2CC[C@]3(O)[C@H]4[C@@H]([C@]5(CC[C@H](O)C[C@H]5CC4)C)CC[C@@]32C)C=CC(=O)OC=1 QEEBRPGZBVVINN-BMPKRDENSA-N 0.000 description 2
- 210000000845 cartilage Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 229940124558 contraceptive agent Drugs 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000001351 cycling effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002497 edematous effect Effects 0.000 description 2
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 210000005002 female reproductive tract Anatomy 0.000 description 2
- 229950003662 fenretinide Drugs 0.000 description 2
- 229940045109 genistein Drugs 0.000 description 2
- 235000006539 genistein Nutrition 0.000 description 2
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 229950010984 irsogladine Drugs 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000002596 lutein cell Anatomy 0.000 description 2
- 230000029849 luteinization Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 2
- 229950008959 marimastat Drugs 0.000 description 2
- 230000008774 maternal effect Effects 0.000 description 2
- 229960004023 minocycline Drugs 0.000 description 2
- VYGYNVZNSSTDLJ-HKCOAVLJSA-N monorden Natural products CC1CC2OC2C=C/C=C/C(=O)CC3C(C(=CC(=C3Cl)O)O)C(=O)O1 VYGYNVZNSSTDLJ-HKCOAVLJSA-N 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000003101 oviduct Anatomy 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 229940048914 protamine Drugs 0.000 description 2
- AECPBJMOGBFQDN-YMYQVXQQSA-N radicicol Chemical compound C1CCCC(=O)C[C@H]2[C@H](Cl)C(=O)CC(=O)[C@H]2C(=O)O[C@H](C)C[C@H]2O[C@@H]21 AECPBJMOGBFQDN-YMYQVXQQSA-N 0.000 description 2
- 229930192524 radicicol Natural products 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 230000008844 regulatory mechanism Effects 0.000 description 2
- 208000017443 reproductive system disease Diseases 0.000 description 2
- 229930002330 retinoic acid Natural products 0.000 description 2
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000009291 secondary effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000035938 sexual maturation Effects 0.000 description 2
- 231100000161 signs of toxicity Toxicity 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229960002256 spironolactone Drugs 0.000 description 2
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 2
- 229950001248 squalamine Drugs 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 2
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 229960000894 sulindac Drugs 0.000 description 2
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 2
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 2
- 229960005314 suramin Drugs 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 229960003433 thalidomide Drugs 0.000 description 2
- 239000003848 thrombocyte activating factor antagonist Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- 150000003648 triterpenes Chemical class 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 206010055031 vascular neoplasm Diseases 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- CQOQDQWUFQDJMK-SSTWWWIQSA-N 2-methoxy-17beta-estradiol Chemical compound C([C@@H]12)C[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]1CCC1=C2C=C(OC)C(O)=C1 CQOQDQWUFQDJMK-SSTWWWIQSA-N 0.000 description 1
- ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 229940122902 Arachidonic acid inhibitor Drugs 0.000 description 1
- 241000370685 Arge Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- JDVVGAQPNNXQDW-WCMLQCRESA-N Castanospermine Natural products O[C@H]1[C@@H](O)[C@H]2[C@@H](O)CCN2C[C@H]1O JDVVGAQPNNXQDW-WCMLQCRESA-N 0.000 description 1
- JDVVGAQPNNXQDW-TVNFTVLESA-N Castinospermine Chemical compound C1[C@H](O)[C@@H](O)[C@H](O)[C@H]2[C@@H](O)CCN21 JDVVGAQPNNXQDW-TVNFTVLESA-N 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010055665 Corneal neovascularisation Diseases 0.000 description 1
- 206010014756 Endometrial hypertrophy Diseases 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- ZPLVYYNMRMBNGE-UHFFFAOYSA-N Eponemycin Natural products CC(C)CCCCC(=O)NC(CO)C(=O)NC(CC(C)=C)C(=O)C1(CO)CO1 ZPLVYYNMRMBNGE-UHFFFAOYSA-N 0.000 description 1
- UAUDZVJPLUQNMU-UHFFFAOYSA-N Erucasaeureamid Natural products CCCCCCCCC=CCCCCCCCCCCCC(N)=O UAUDZVJPLUQNMU-UHFFFAOYSA-N 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- MCAHMSDENAOJFZ-UHFFFAOYSA-N Herbimycin A Natural products N1C(=O)C(C)=CC=CC(OC)C(OC(N)=O)C(C)=CC(C)C(OC)C(OC)CC(C)C(OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-UHFFFAOYSA-N 0.000 description 1
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
- 101000687438 Homo sapiens Prolactin Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 229940123038 Integrin antagonist Drugs 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102100026236 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010024870 Loss of libido Diseases 0.000 description 1
- 241000219823 Medicago Species 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- 206010027951 Mood swings Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100243350 Mus musculus Pecam1 gene Proteins 0.000 description 1
- 101000686934 Mus musculus Prolactin-7D1 Proteins 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 101710132082 Pyrimidine/purine nucleoside phosphorylase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 102100031372 Thymidine phosphorylase Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010046788 Uterine haemorrhage Diseases 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- VRGWBRLULZUWAJ-XFFXIZSCSA-N [(2s)-2-[(1r,3z,5s,8z,12z,15s)-5,17-dihydroxy-4,8,12,15-tetramethyl-16-oxo-18-bicyclo[13.3.0]octadeca-3,8,12,17-tetraenyl]propyl] acetate Chemical compound C1\C=C(C)/CC\C=C(C)/CC[C@H](O)\C(C)=C/C[C@@H]2C([C@@H](COC(C)=O)C)=C(O)C(=O)[C@]21C VRGWBRLULZUWAJ-XFFXIZSCSA-N 0.000 description 1
- SXEHKFHPFVVDIR-UHFFFAOYSA-N [4-(4-hydrazinylphenyl)phenyl]hydrazine Chemical compound C1=CC(NN)=CC=C1C1=CC=C(NN)C=C1 SXEHKFHPFVVDIR-UHFFFAOYSA-N 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000000648 angioblast Anatomy 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- GIXWDMTZECRIJT-UHFFFAOYSA-N aurintricarboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=CC1=C(C=1C=C(C(O)=CC=1)C(O)=O)C1=CC=C(O)C(C(O)=O)=C1 GIXWDMTZECRIJT-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- XFILPEOLDIKJHX-QYZOEREBSA-N batimastat Chemical compound C([C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)[C@H](CSC=1SC=CC=1)C(=O)NO)C1=CC=CC=C1 XFILPEOLDIKJHX-QYZOEREBSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 201000000159 corneal neovascularization Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000032692 embryo implantation Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 230000010393 epithelial cell migration Effects 0.000 description 1
- 230000008556 epithelial cell proliferation Effects 0.000 description 1
- ZPLVYYNMRMBNGE-TWOQFEAHSA-N eponemycin Chemical compound CC(C)CCCCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)=C)C(=O)[C@@]1(CO)CO1 ZPLVYYNMRMBNGE-TWOQFEAHSA-N 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- UAUDZVJPLUQNMU-KTKRTIGZSA-N erucamide Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(N)=O UAUDZVJPLUQNMU-KTKRTIGZSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 231100000547 follicle rupture Toxicity 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- VRGWBRLULZUWAJ-UHFFFAOYSA-N fusaproliferin Natural products C1C=C(C)CCC=C(C)CCC(O)C(C)=CCC2C(C(COC(C)=O)C)=C(O)C(=O)C21C VRGWBRLULZUWAJ-UHFFFAOYSA-N 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000001703 glandular epithelial cell Anatomy 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- MCAHMSDENAOJFZ-BVXDHVRPSA-N herbimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-BVXDHVRPSA-N 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940117681 interleukin-12 Drugs 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004997 mammalian reproductive system Anatomy 0.000 description 1
- 231100001052 maternal toxicity Toxicity 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- RFKMCNOHBTXSMU-UHFFFAOYSA-N methoxyflurane Chemical compound COC(F)(F)C(Cl)Cl RFKMCNOHBTXSMU-UHFFFAOYSA-N 0.000 description 1
- 229960002455 methoxyflurane Drugs 0.000 description 1
- DWCZIOOZPIDHAB-UHFFFAOYSA-L methyl green Chemical compound [Cl-].[Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC(=CC=1)[N+](C)(C)C)=C1C=CC(=[N+](C)C)C=C1 DWCZIOOZPIDHAB-UHFFFAOYSA-L 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000011278 mitosis Effects 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 238000007491 morphometric analysis Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000009707 neogenesis Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 101150006061 neur gene Proteins 0.000 description 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 1
- 231100001160 nonlethal Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001023 pro-angiogenic effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229930185346 proliferin Natural products 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000001373 regressive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000001625 seminal vesicle Anatomy 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000003684 theca cell Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 210000002993 trophoblast Anatomy 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 201000010653 vesiculitis Diseases 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
-
- 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
- A61P15/18—Feminine contraceptives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Gynecology & Obstetrics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2338596P | 1996-08-02 | 1996-08-02 | |
| US60/023,385 | 1996-08-02 | ||
| PCT/US1997/013882 WO1998005323A2 (en) | 1996-08-02 | 1997-08-01 | Method of regulating the female reproductive system through angiogenesis inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000516585A true JP2000516585A (ja) | 2000-12-12 |
| JP2000516585A5 JP2000516585A5 (enExample) | 2005-04-07 |
Family
ID=21814780
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10508217A Pending JP2000516585A (ja) | 1996-08-02 | 1997-08-01 | 血管新生阻害物質による雌生殖系の調節方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (3) | US6017949A (enExample) |
| EP (1) | EP0957910A2 (enExample) |
| JP (1) | JP2000516585A (enExample) |
| AU (2) | AU3968597A (enExample) |
| CA (1) | CA2262535A1 (enExample) |
| WO (2) | WO1998005293A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011526609A (ja) * | 2008-07-03 | 2011-10-13 | バイエル オイ | 避妊のための子宮内用送達システム |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP646A (en) * | 1995-03-27 | 1998-04-27 | Sanofi Synthelabo | Use of fumagillol and derivatives thereof for preparing medicaments against intestinal infections. |
| WO1998014169A1 (en) * | 1996-09-30 | 1998-04-09 | Brigham & Women's Hospital | Methods and compounds for treatment of abnormal uterine bleeding |
| DE69824750T2 (de) * | 1997-10-31 | 2005-07-07 | Children's Medical Center Corp., Boston | Methoden zur regulierung der grösse und des wachstums von durchblutetem normalem gewebe |
| NZ511408A (en) * | 1998-10-09 | 2004-04-30 | Licentia Ltd | Flt4 (VEGFR-3) as a target for tumor imaging and anti-tumor therapy |
| US7141607B1 (en) * | 2000-03-10 | 2006-11-28 | Insite Vision Incorporated | Methods and compositions for treating and inhibiting retinal neovascularization |
| JPWO2004022082A1 (ja) * | 2002-09-04 | 2005-12-22 | 株式会社プロテイン・エクスプレス | 胚着床制御剤 |
| WO2004103159A2 (en) * | 2003-05-14 | 2004-12-02 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for modulating endometrium |
| NZ545188A (en) * | 2003-07-14 | 2008-12-24 | Fusion Sport Internat Pty Ltd | Sports training and testing methods, apparatus and system |
| US7524811B2 (en) * | 2003-08-29 | 2009-04-28 | Children's Medical Center Corporation | Anti-angiogenic peptides from the N-terminus of endostatin |
| DE602004015142D1 (de) * | 2003-08-29 | 2008-08-28 | Childrens Medical Center | Antiangiogene peptide zur behandlung oder vorbeugung von endometriose |
| WO2009139915A2 (en) | 2008-05-15 | 2009-11-19 | The University Of North Carolina At Chapel Hill | Novel targets for regulation of angiogenesis |
| EP2317845A4 (en) * | 2008-07-18 | 2011-11-09 | Zafgen Inc | METHOD FOR TREATING AN OVERWEIGHT OR FATABLE PERSON |
| US20100159506A1 (en) * | 2008-07-25 | 2010-06-24 | Cellscape Corporation | Methods and systems for genetic analysis of fetal nucleated red blood cells |
| US8642650B2 (en) | 2008-12-04 | 2014-02-04 | Zafgen, Inc. | Methods of treating an overweight or obese subject |
| WO2010065877A2 (en) | 2008-12-04 | 2010-06-10 | Zafgen Corporation | Methods of treating an overweight or obese subject |
| WO2013055385A2 (en) | 2011-10-03 | 2013-04-18 | Zafgen Corporation | Methods of treating age related disorders |
| CN102639494B (zh) | 2009-10-09 | 2016-11-09 | 扎夫根公司 | 砜化合物及其制备和使用方法 |
| WO2011085198A1 (en) | 2010-01-08 | 2011-07-14 | Zafgen Corporation | Metap-2 inhibitor for use in treating benign prostatic hypertrophy (bph) |
| WO2011085201A1 (en) | 2010-01-08 | 2011-07-14 | Zafgen Corporation | Fumagillol type compounds and methods of making and using same |
| RU2427325C1 (ru) * | 2010-01-29 | 2011-08-27 | Государственное образовательное учреждение высшего профессионального образования "Астраханская государственная медицинская академия Федерального агентства по здравоохранению и социальному развитию" (ГОУ ВПО АГМА Росздрава) | Способ оценки эффективности лечения хронической плацентарной недостаточности в эксперименте |
| US8774488B2 (en) | 2010-03-11 | 2014-07-08 | Cellscape Corporation | Method and device for identification of nucleated red blood cells from a maternal blood sample |
| WO2011127304A2 (en) | 2010-04-07 | 2011-10-13 | Zafgen Corporation | Methods of treating an overweight subject |
| CA2796744A1 (en) | 2010-04-17 | 2011-10-20 | Bayer Healthcare Llc | Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions |
| JP2013531067A (ja) | 2010-07-19 | 2013-08-01 | バイエル ヘルスケア リミティド ライアビリティ カンパニー | 疾病及び状態の処置及び予防のためのフルオロ置換オメガ−カルボキシアリールジフェニル尿素を用いた組み合わせ薬 |
| WO2012012642A1 (en) | 2010-07-22 | 2012-01-26 | Zafgen Corporation | Tricyclic compounds and methds of making and using same |
| PH12013500934A1 (en) | 2010-11-09 | 2022-10-24 | Zafgen Inc | Crystalline solids of a metap-2 inhibitor and methods of making and using same |
| AU2011336785A1 (en) | 2010-11-29 | 2013-06-20 | Zafgen, Inc | Treatment of obesity using non-daily administration of 6-0-(4 - dimethylaminoethoxy) cinnamoyl fumagillol |
| CN103402989B (zh) | 2011-01-26 | 2016-04-06 | 扎夫根股份有限公司 | 四唑化合物及其制备和使用方法 |
| AU2012225531B2 (en) | 2011-03-08 | 2017-03-30 | Zafgen, Inc | Oxaspiro (2.5) octane derivatives and analogs |
| EP2705035B1 (en) | 2011-05-06 | 2016-12-14 | Zafgen, Inc. | Tricyclic pyrazole sulfonamide compounds and methods of making and using same |
| CN103748094B (zh) | 2011-05-06 | 2016-06-29 | 扎夫根股份有限公司 | 三环磺酰胺化合物及其制备和使用方法 |
| CA2835261C (en) | 2011-05-06 | 2019-06-04 | Zafgen, Inc. | Partially saturated tricyclic compounds and methods of making and using same |
| EP2804866B1 (en) | 2012-01-18 | 2016-11-16 | Zafgen, Inc. | Tricyclic sulfonamide compounds and methods of making and using same |
| EP2804856B1 (en) | 2012-01-18 | 2017-03-15 | Zafgen, Inc. | Tricyclic sulfone compounds and methods of making and using same |
| US9260419B2 (en) | 2012-05-07 | 2016-02-16 | Zafgen, Inc. | Polymorphic salt of a metap-2 inhibitor and methods of making and using same |
| MX2014013599A (es) | 2012-05-08 | 2015-05-11 | Zafgen Inc | Tratamiento de la obesidad hipotalamica con inhibidores de metap2. |
| US9573918B2 (en) | 2012-05-09 | 2017-02-21 | Zafgen, Inc. | Fumigillol compounds and methods of making and using same |
| EP2917197B1 (en) | 2012-11-05 | 2019-06-05 | Zafgen, Inc. | Tricyclic compounds and methods of making and using same |
| EP2925737B1 (en) | 2012-11-05 | 2017-06-14 | Zafgen, Inc. | Tricyclic compounds for use in the treatment and/or control of obesity |
| CA2890343A1 (en) | 2012-11-05 | 2014-05-08 | Zafgen, Inc. | Tricyclic compounds useful in the treatment of liver disorders |
| EP2968250B1 (en) | 2013-03-14 | 2019-06-19 | Zafgen, Inc. | Methods of treating renal disease and other disorders |
| CN106432255A (zh) | 2015-08-11 | 2017-02-22 | 扎夫根公司 | 烟曲霉素醇螺环化合物和制备和使用其的方法 |
| AR105671A1 (es) | 2015-08-11 | 2017-10-25 | Zafgen Inc | Compuestos heterocíclicos de fumagillol y sus métodos de elaboración y uso |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK168876B1 (da) * | 1982-12-20 | 1994-07-04 | Harvard College | Middel, der kan administreres oralt eller subcutant, til inhibering af angiogenese hos pattedyr samt fremgangsmåde til fremstilling af et sådant middel |
| DE3344797A1 (de) * | 1983-12-10 | 1985-06-20 | Th. Kieserling & Albrecht Gmbh & Co, 5650 Solingen | Transportvorrichtung fuer felgenrohlinge |
| US4599331A (en) * | 1984-12-24 | 1986-07-08 | Syntex (U.S.A.) Inc. | Etianic acids as antiangiogenics |
| EP0357061B1 (en) * | 1988-09-01 | 1994-06-08 | Takeda Chemical Industries, Ltd. | Angiogenesis inhibitory agent |
| US5086164A (en) * | 1989-01-10 | 1992-02-04 | Repligen Corporation | Novel methods and compositions for treatment of angiogenic diseases |
| DK0533703T3 (da) * | 1990-06-11 | 2000-08-14 | Alcon Lab Inc | Anvendelse af steroider til hæmning af angiogenese |
| FR2672801B1 (fr) * | 1991-02-14 | 1995-03-03 | Sanofi Sa | Utilisation de derives de tetrahydrothienopyridine comme inhibiteurs de l'angiogenese. |
| GB9225475D0 (en) * | 1992-12-05 | 1993-01-27 | Imp Cancer Res Tech | Compounds to combat angiogenesis |
| PT690720E (pt) * | 1993-03-12 | 2001-12-28 | Xoma Technology Ltd | Utilizacoes terapeuticas de produtos de proteina bactericida indutora de permeabilidade |
| DE69417169T2 (de) * | 1993-09-24 | 1999-07-22 | Takeda Chemical Industries, Ltd., Osaka | Antineoplastische pharmazeutische Zusammensetzung enthaltend ein Fumagillolderivat und einen Platinkomplex |
| GB9410534D0 (en) * | 1994-05-26 | 1994-07-13 | Lynxvale Ltd | Improvements in or relating to growth factor inhibitors |
| GB9410533D0 (en) | 1994-05-26 | 1994-07-13 | Lynxvale Ltd | In situ hybridisation and immuno-Chemical localisation of a growth factor |
| CZ117798A3 (cs) * | 1995-10-23 | 1998-08-12 | The Children's Medical Center Corporation | Antiangiogenní kompozice a způsoby léčby |
-
1997
- 1997-07-31 AU AU39685/97A patent/AU3968597A/en not_active Withdrawn
- 1997-07-31 WO PCT/US1997/013522 patent/WO1998005293A2/en not_active Ceased
- 1997-08-01 US US08/904,708 patent/US6017949A/en not_active Expired - Fee Related
- 1997-08-01 CA CA002262535A patent/CA2262535A1/en not_active Abandoned
- 1997-08-01 JP JP10508217A patent/JP2000516585A/ja active Pending
- 1997-08-01 EP EP97936441A patent/EP0957910A2/en not_active Withdrawn
- 1997-08-01 AU AU39107/97A patent/AU3910797A/en not_active Abandoned
- 1997-08-01 WO PCT/US1997/013882 patent/WO1998005323A2/en not_active Ceased
-
1999
- 1999-05-17 US US09/313,528 patent/US6441027B1/en not_active Expired - Lifetime
-
2001
- 2001-11-21 US US09/990,646 patent/US20020156055A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011526609A (ja) * | 2008-07-03 | 2011-10-13 | バイエル オイ | 避妊のための子宮内用送達システム |
Also Published As
| Publication number | Publication date |
|---|---|
| US6017949A (en) | 2000-01-25 |
| WO1998005293A2 (en) | 1998-02-12 |
| WO1998005323A3 (en) | 1998-05-07 |
| EP0957910A2 (en) | 1999-11-24 |
| AU3968597A (en) | 1998-02-25 |
| US6441027B1 (en) | 2002-08-27 |
| AU3910797A (en) | 1998-02-25 |
| CA2262535A1 (en) | 1998-02-12 |
| US20020156055A1 (en) | 2002-10-24 |
| WO1998005323A2 (en) | 1998-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2000516585A (ja) | 血管新生阻害物質による雌生殖系の調節方法 | |
| WO1998005323A9 (en) | Method of regulating the female reproductive system through angiogenesis inhibitors | |
| Dabrosin et al. | Therapeutic effect of angiostatin gene transfer in a murine model of endometriosis | |
| JP2001506638A (ja) | 白内障の予防または制御方法 | |
| Oliva et al. | Unopposed estrogens: current and future perspectives. | |
| Uzunlar et al. | Effects of repeated propranolol administration in a rat model of surgically induced endometriosis | |
| Segal et al. | Contraceptive Technology Current and Prospective Methods | |
| DOWNING et al. | Rat myometrial activity in vivo: Effects of oestradiol-17β and progesterone in relation to the concentrations of cytoplasmic progesterone receptors | |
| Marston et al. | The time and site of contraceptive action of an intra-uterine device in the mouse | |
| Liggins | Fetal influences on myometrial contractility | |
| Sadeq et al. | Comparative analysis of oral and local intraovarian administration of metformin and nanoparticles (NPs11) in alleviating testosterone-induced polycystic ovary syndrome in rats | |
| RU2755250C1 (ru) | Препарат на основе стероидных эстрогенов для лечения эндометриоза | |
| Kendle et al. | Investigations into the mechanism of the antifertility action of minimal doses of megestrol acetate in the rabbit | |
| David et al. | Effect of the intrauterine contraceptive device on the regeneration of rabbit endometrium | |
| Oxenreider et al. | Regression of corpora lutea in unilaterally pregnant guinea-pigs | |
| US20230381198A1 (en) | Prevention of estrus in sow and ruminants | |
| Wang et al. | Chicoric acid ameliorates rat salpingitis by inhibiting the Nrf2/Notch1 signaling pathway | |
| CN113456630B (zh) | 血管生长因子受体抑制剂的用途 | |
| Arkfeld et al. | Fertilization and Implantation | |
| Persaud | Reproductive and teratological studies with prostaglandins | |
| Kurniawati et al. | The tissue structure in the remodeling phase of a vesicovaginal fistula between the use of freeze-dried amnion and primary suturing in rabbit | |
| Bruce et al. | The effects of medroxyprogesterone acetate on the maintenance of pregnancy in ovariectomized rats and rabbits | |
| Zuckerman et al. | An experimental study of the morphogenesis of intersexuality | |
| Ikeda et al. | Bilateral testicular consequences in the unilateral vasectomy of immature rats | |
| Sathsihkumar et al. | Surgical excision of ovarian remnant tissue in a queen cat: A case report |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040730 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040730 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080129 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080423 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080609 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080529 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20080722 |