ZA200502874B - Therapeutic treatment. - Google Patents
Therapeutic treatment. Download PDFInfo
- Publication number
- ZA200502874B ZA200502874B ZA200502874A ZA200502874A ZA200502874B ZA 200502874 B ZA200502874 B ZA 200502874B ZA 200502874 A ZA200502874 A ZA 200502874A ZA 200502874 A ZA200502874 A ZA 200502874A ZA 200502874 B ZA200502874 B ZA 200502874B
- Authority
- ZA
- South Africa
- Prior art keywords
- acceptable salt
- pharmaceutically acceptable
- cancer
- substance
- composition
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims description 46
- 230000001225 therapeutic effect Effects 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims description 132
- 206010028980 Neoplasm Diseases 0.000 claims description 79
- 201000011510 cancer Diseases 0.000 claims description 66
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 49
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 46
- 229940121647 egfr inhibitor Drugs 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 28
- 241001465754 Metazoa Species 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 22
- -1 sulphonate salt Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 16
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 15
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 14
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 14
- 102000002045 Endothelin Human genes 0.000 claims description 13
- 108050009340 Endothelin Proteins 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 12
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 11
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical group C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 claims description 9
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 6
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 6
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 claims description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 6
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 6
- XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- BTYYWOYVBXILOJ-UHFFFAOYSA-N N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}but-2-ynamide Chemical compound C12=CC(NC(=O)C#CC)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 BTYYWOYVBXILOJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000005557 antagonist Substances 0.000 claims description 5
- 229950002826 canertinib Drugs 0.000 claims description 5
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 claims description 5
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 229950010993 atrasentan Drugs 0.000 claims description 4
- 229960003065 bosentan Drugs 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 230000001394 metastastic effect Effects 0.000 claims description 4
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 4
- 229940044551 receptor antagonist Drugs 0.000 claims description 4
- 239000002464 receptor antagonist Substances 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- 102000010180 Endothelin receptor Human genes 0.000 claims description 3
- 108050001739 Endothelin receptor Proteins 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- FEJVSJIALLTFRP-LJQANCHMSA-N darusentan Chemical compound COC1=CC(OC)=NC(O[C@H](C(O)=O)C(OC)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 FEJVSJIALLTFRP-LJQANCHMSA-N 0.000 claims description 3
- 229960001433 erlotinib Drugs 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 claims description 3
- 229960002578 sitaxentan Drugs 0.000 claims description 3
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- MJRGSRRZKSJHOE-UHFFFAOYSA-N 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)NC=1ON=C(C)C=1C MJRGSRRZKSJHOE-UHFFFAOYSA-N 0.000 claims description 2
- VYCMAAOURFJIHD-PJNXIOHISA-N BQ 123 Chemical compound N1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](CC(O)=O)NC(=O)[C@H]1CC1=CNC2=CC=CC=C12 VYCMAAOURFJIHD-PJNXIOHISA-N 0.000 claims description 2
- 108010030109 BQ 788 Proteins 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 2
- 229960002414 ambrisentan Drugs 0.000 claims description 2
- OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical compound O([C@@H](C(OC)(C=1C=CC=CC=1)C=1C=CC=CC=1)C(O)=O)C1=NC(C)=CC(C)=N1 OUJTZYPIHDYQMC-LJQANCHMSA-N 0.000 claims description 2
- 229940000425 combination drug Drugs 0.000 claims description 2
- 239000013256 coordination polymer Substances 0.000 claims description 2
- 108010031322 cyclo(Trp-Asp-Pro-Val-Leu) Proteins 0.000 claims description 2
- 229950008833 darusentan Drugs 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 2
- 230000000683 nonmetastatic effect Effects 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- QCVIFBRTTLMEOV-FUKQNADPSA-M sodium;(2r)-2-[[(2r)-2-[[(2s)-2-[[(2s,6r)-2,6-dimethylpiperidine-1-carbonyl]amino]-4,4-dimethylpentanoyl]amino]-3-(1-methoxycarbonylindol-3-yl)propanoyl]amino]hexanoate Chemical compound [Na+].N([C@@H](CC(C)(C)C)C(=O)N[C@H](CC=1C2=CC=CC=C2N(C(=O)OC)C=1)C(=O)N[C@H](CCCC)C([O-])=O)C(=O)N1[C@@H](C)CCC[C@H]1C QCVIFBRTTLMEOV-FUKQNADPSA-M 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 229940124530 sulfonamide Drugs 0.000 claims description 2
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 26
- 230000001772 anti-angiogenic effect Effects 0.000 claims 4
- CLSJNXXMIVKULC-MUUNZHRXSA-N (2s)-3-[2-(3,4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yl)oxy-3,3-diphenylpropanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1CCOC(C=1C=CC=CC=1)(C=1C=CC=CC=1)[C@@H](C(O)=O)OC1=NC(C)=CC(C)=N1 CLSJNXXMIVKULC-MUUNZHRXSA-N 0.000 claims 1
- OWOHLURDBZHNGG-YFKPBYRVSA-N (8ar)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1CNC(=O)[C@@H]2CCCN12 OWOHLURDBZHNGG-YFKPBYRVSA-N 0.000 claims 1
- 101000713585 Homo sapiens Tubulin beta-4A chain Proteins 0.000 claims 1
- 206010027452 Metastases to bone Diseases 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 108010047918 TAK 044 Proteins 0.000 claims 1
- 102100036788 Tubulin beta-4A chain Human genes 0.000 claims 1
- GHAFORRTMVIXHS-UHFFFAOYSA-L bromosulfophthalein sodium Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C(O)=CC=C1C1(C=2C=C(C(O)=CC=2)S([O-])(=O)=O)C(C(Br)=C(Br)C(Br)=C2Br)=C2C(=O)O1 GHAFORRTMVIXHS-UHFFFAOYSA-L 0.000 claims 1
- STSBIYSZXHSXHH-UHFFFAOYSA-N but-2-ynamide Chemical compound CC#CC(N)=O STSBIYSZXHSXHH-UHFFFAOYSA-N 0.000 claims 1
- UWHBIISPHYTOGL-PFSAEEMXSA-L disodium;2-[(2r,5s,8s,11s,14s,17r)-8-(carboxylatomethyl)-17-(1h-indol-3-ylmethyl)-14-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-5-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]-11-thiophen-2-yl-1,4,7,10,13,16-hexazacyclooctadec-2-yl]acetate Chemical compound [Na+].[Na+].C([C@H]1C(=O)N[C@@H](CC([O-])=O)C(=O)N[C@@H](C(=O)N[C@H](C(N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@H](CC([O-])=O)C(=O)N1)=O)CC(C)C)C=1SC=CC=1)C(=O)N(CC1)CCN1C1=CC=CC=C1 UWHBIISPHYTOGL-PFSAEEMXSA-L 0.000 claims 1
- 229950005376 feloprentan Drugs 0.000 claims 1
- TUYWTLTWNJOZNY-UHFFFAOYSA-N n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-[2-(2h-tetrazol-5-yl)pyridin-4-yl]pyrimidin-4-yl]-5-propan-2-ylpyridine-2-sulfonamide Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2C=C(N=CC=2)C2=NNN=N2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)C)C=N1 TUYWTLTWNJOZNY-UHFFFAOYSA-N 0.000 claims 1
- 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 claims 1
- 229950000584 tezosentan Drugs 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 14
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical class C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 13
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 12
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 12
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 12
- 239000002552 dosage form Substances 0.000 description 11
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 10
- 101800003838 Epidermal growth factor Proteins 0.000 description 9
- 102400001368 Epidermal growth factor Human genes 0.000 description 9
- 230000034994 death Effects 0.000 description 9
- 231100000517 death Toxicity 0.000 description 9
- 229940116977 epidermal growth factor Drugs 0.000 description 9
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 9
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 9
- 102100033902 Endothelin-1 Human genes 0.000 description 8
- 101800004490 Endothelin-1 Proteins 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- 206010027476 Metastases Diseases 0.000 description 8
- GTTBEUCJPZQMDZ-UHFFFAOYSA-N erlotinib hydrochloride Chemical compound [H+].[Cl-].C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 GTTBEUCJPZQMDZ-UHFFFAOYSA-N 0.000 description 7
- 102000043136 MAP kinase family Human genes 0.000 description 6
- 108091054455 MAP kinase family Proteins 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 6
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 6
- 229940122361 Bisphosphonate Drugs 0.000 description 4
- 108010069236 Goserelin Proteins 0.000 description 4
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 4
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000004663 bisphosphonates Chemical class 0.000 description 4
- 229960002913 goserelin Drugs 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 210000002307 prostate Anatomy 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108010000817 Leuprolide Proteins 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 3
- 229960004338 leuprorelin Drugs 0.000 description 3
- 210000000963 osteoblast Anatomy 0.000 description 3
- 230000001582 osteoblastic effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- NOENHWMKHNSHGX-IZOOSHNJSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-(ca Chemical compound C([C@H](C(=O)N[C@H](CCCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 NOENHWMKHNSHGX-IZOOSHNJSA-N 0.000 description 2
- HJNZCKLMRAOTMA-BRBGIFQRSA-N (2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(2s)-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(2-methyl-1h-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(4-hydr Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=C(C)NC2=CC=CC=C12 HJNZCKLMRAOTMA-BRBGIFQRSA-N 0.000 description 2
- REQFUGYVPAQCTH-UHFFFAOYSA-N 5-[[5-[(4-hydroxyphenyl)methyl]-4-[(4-methoxyphenyl)methyl]-1-methylimidazol-2-yl]amino]-3-methylimidazole-2,4-dione Chemical compound C1=CC(OC)=CC=C1CC1=C(CC=2C=CC(O)=CC=2)N(C)C(NC=2C(N(C)C(=O)N=2)=O)=N1 REQFUGYVPAQCTH-UHFFFAOYSA-N 0.000 description 2
- 108010037003 Buserelin Proteins 0.000 description 2
- 229940121889 Endothelin A receptor antagonist Drugs 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 108010021717 Nafarelin Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 108010023617 abarelix Proteins 0.000 description 2
- 229960002184 abarelix Drugs 0.000 description 2
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 2
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 108010070670 antarelix Proteins 0.000 description 2
- 229950010887 avorelin Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229960002719 buserelin Drugs 0.000 description 2
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 108700008462 cetrorelix Proteins 0.000 description 2
- 229960003230 cetrorelix Drugs 0.000 description 2
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 description 2
- 229960002286 clodronic acid Drugs 0.000 description 2
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 2
- OFQNFLLLCMQNEP-MIPXGPCFSA-N deterelix Chemical compound C([C@@H](C(=O)N[C@H](CCCCN=C(NCC)NCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 OFQNFLLLCMQNEP-MIPXGPCFSA-N 0.000 description 2
- 108700027435 detirelix Proteins 0.000 description 2
- 229950003747 detirelix Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000003062 endothelin A receptor antagonist Substances 0.000 description 2
- 230000003328 fibroblastic effect Effects 0.000 description 2
- 108700032141 ganirelix Proteins 0.000 description 2
- 229960003794 ganirelix Drugs 0.000 description 2
- GJNXBNATEDXMAK-PFLSVRRQSA-N ganirelix Chemical compound C([C@@H](C(=O)N[C@H](CCCCN=C(NCC)NCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN=C(NCC)NCC)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 GJNXBNATEDXMAK-PFLSVRRQSA-N 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 239000002474 gonadorelin antagonist Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 210000004185 liver Anatomy 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
- 239000012528 membrane Substances 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- RWHUEXWOYVBUCI-ITQXDASVSA-N nafarelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 RWHUEXWOYVBUCI-ITQXDASVSA-N 0.000 description 2
- 229960002333 nafarelin Drugs 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- ONHXPWXXSUUCDR-SLMFISIISA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-3-(4-chlorophenyl)propanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-(1-benzothiophen-3-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]a Chemical compound C([C@@H](C(=O)N[C@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C2=CC=CC=C2SC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(C)=O)C1=CC=C(O)C=C1 ONHXPWXXSUUCDR-SLMFISIISA-N 0.000 description 1
- WDYSQADGBBEGRQ-APSDYLPASA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-[(2r,3r,4r,5r,6s) Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O WDYSQADGBBEGRQ-APSDYLPASA-N 0.000 description 1
- DRPGADQFIJJWNZ-TVPLGVNVSA-N (2s)-3-(1h-indol-3-yl)-2-[(2-phenylcyclopropanecarbonyl)amino]propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C1CC1C1=CC=CC=C1 DRPGADQFIJJWNZ-TVPLGVNVSA-N 0.000 description 1
- XHCGTVHIQUXPRM-SSIREWOPSA-N (2s)-n-[(2r,4s,7r)-7-acetamido-2-amino-4-[[(2s)-2-amino-6-[(5-amino-1h-1,2,4-triazol-3-yl)amino]hexanoyl]-[(2s)-2-[[(2r)-2-amino-6-[(5-amino-1h-1,2,4-triazol-3-yl)amino]hexanoyl]amino]-4-methylpentanoyl]carbamoyl]-1-(4-chlorophenyl)-8-naphthalen-2-yl-3,6- Chemical compound C([C@@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N(C(=O)[C@@H](N)CCCCNC=1N=C(N)NN=1)C(=O)[C@@](CC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)(N(C(=O)[C@H](CO)NC(=O)[C@H](N)CC=1C=NC=CC=1)C(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCCNC(C)C)C(=O)[C@H](N)CC=1C=CC(Cl)=CC=1)CCCNC1=NNC(N)=N1 XHCGTVHIQUXPRM-SSIREWOPSA-N 0.000 description 1
- YGGIRYYNWQICCP-LDRBRYNMSA-N (2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(2s)-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-methylamino]-3-(1h-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(4-hydrox Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CNC2=CC=CC=C12 YGGIRYYNWQICCP-LDRBRYNMSA-N 0.000 description 1
- OAEWNSKRLBVVBV-QSEAXJEQSA-N (2s,3r,4s)-1-[2-(dibutylamino)-2-oxoethyl]-2-(2,2-dimethylpentyl)-4-(7-methoxy-1,3-benzodioxol-5-yl)pyrrolidine-3-carboxylic acid Chemical compound OC(=O)[C@H]1[C@H](CC(C)(C)CCC)N(CC(=O)N(CCCC)CCCC)C[C@@H]1C(C=C1OC)=CC2=C1OCO2 OAEWNSKRLBVVBV-QSEAXJEQSA-N 0.000 description 1
- OETKRDJJNWJFOP-FAYOUAAYSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[[(4S,7S,10S,13S,16R)-16-amino-7-benzyl-10-[(4-hydroxyphenyl)methyl]-6,9,12,15-tetraoxo-13-propan-2-yl-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-4-[[(2S,3S)-1-[[(2S,3S)-1-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H]1CSSC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O OETKRDJJNWJFOP-FAYOUAAYSA-N 0.000 description 1
- MBHURWYWZFYDQD-HDUXTRFBSA-N (4r)-4-[[(2r)-2-[[(2s)-2-[[(2r,3s)-2-[[(2s)-2-aminopropanoyl]amino]-3-methylpentanoyl]amino]-4-methylpent-4-enoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-5-oxopentanoic acid Chemical compound C1=CC=C2C(C[C@@H](NC(=O)[C@H](CC(C)=C)NC(=O)[C@H](NC(=O)[C@H](C)N)[C@@H](C)CC)C(=O)N[C@H](CCC(O)=O)C=O)=CNC2=C1 MBHURWYWZFYDQD-HDUXTRFBSA-N 0.000 description 1
- GEVQMCFWDDZLMU-UHFFFAOYSA-N 1-[1-(3-ethoxyphenyl)propyl]-7-(pyrimidin-5-ylmethoxy)-4,5-dihydrobenzo[g]indazole-3-carboxylic acid Chemical compound CCOC1=CC=CC(C(CC)N2C=3C4=CC=C(OCC=5C=NC=NC=5)C=C4CCC=3C(C(O)=O)=N2)=C1 GEVQMCFWDDZLMU-UHFFFAOYSA-N 0.000 description 1
- UCQSBGOFELXYIN-UHFFFAOYSA-N 1-[4-[5-[[benzyl(methyl)amino]methyl]-1-[(2,6-difluorophenyl)methyl]-2,4-dioxo-3-phenylthieno[2,3-d]pyrimidin-6-yl]phenyl]-3-methoxyurea Chemical compound C1=CC(NC(=O)NOC)=CC=C1C1=C(CN(C)CC=2C=CC=CC=2)C(C(=O)N(C=2C=CC=CC=2)C(=O)N2CC=3C(=CC=CC=3F)F)=C2S1 UCQSBGOFELXYIN-UHFFFAOYSA-N 0.000 description 1
- OIUSKDFJNIKIQX-CPFGTNEYSA-N 179910-83-9 Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@@](O)(CC=3C(O)=C4C(=O)C=5C=CC=C(C=5C(=O)C4=C(O)C=32)OC)C(=O)COC(=O)CCCC(=O)NCCCC[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CO)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2NC=NC=2)NC(=O)[C@H]2NC(=O)CC2)C(=O)NC(CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N2C(CCC2)C(=O)NCC(N)=O)CCC=C1 OIUSKDFJNIKIQX-CPFGTNEYSA-N 0.000 description 1
- CJUWBZDJMYYRDG-QFIPXVFZSA-N 3-[(2r)-2-amino-2-phenylethyl]-1-[(2,6-difluorophenyl)methyl]-5-(2-fluoro-3-methoxyphenyl)-6-methylpyrimidine-2,4-dione Chemical compound COC1=CC=CC(C=2C(N(C[C@H](N)C=3C=CC=CC=3)C(=O)N(CC=3C(=CC=CC=3F)F)C=2C)=O)=C1F CJUWBZDJMYYRDG-QFIPXVFZSA-N 0.000 description 1
- HYTQHLNYXQRMSQ-UHFFFAOYSA-N 4,4-bis(5,5-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl)-1-(3-fluorophenyl)butan-1-one Chemical compound O1CC(C)(C)COP1(=O)C(P1(=O)OCC(C)(C)CO1)CCC(=O)C1=CC=CC(F)=C1 HYTQHLNYXQRMSQ-UHFFFAOYSA-N 0.000 description 1
- AAALVYBICLMAMA-UHFFFAOYSA-N 4,5-dianilinophthalimide Chemical compound C=1C=CC=CC=1NC=1C=C2C(=O)NC(=O)C2=CC=1NC1=CC=CC=C1 AAALVYBICLMAMA-UHFFFAOYSA-N 0.000 description 1
- KPTYXJLOWLVCMU-UHFFFAOYSA-N 67252-82-8 Chemical compound C1=CC2=CC=CC=C2C2=C1C(C1OC1C(C1O)O)=C1C=C2 KPTYXJLOWLVCMU-UHFFFAOYSA-N 0.000 description 1
- 108010046892 A 75998 Proteins 0.000 description 1
- 108010031335 A 76154 Proteins 0.000 description 1
- 108700013943 AN 207 Proteins 0.000 description 1
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- TZBZGNPXKXHFKI-VZUCSPMQSA-N BE-23372M Chemical class C1=C(O)C(O)=CC=C1\C=C/1C(=O)OC(C=2C=C(O)C(O)=CC=2)=C\1 TZBZGNPXKXHFKI-VZUCSPMQSA-N 0.000 description 1
- 108010033506 BQ 238 Proteins 0.000 description 1
- 108010080719 BQ 485 Proteins 0.000 description 1
- 108010073982 BQ 610 Proteins 0.000 description 1
- 108010043529 BQ 928 Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101100127890 Caenorhabditis elegans let-23 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- XXAXVMUWHZHZMJ-UHFFFAOYSA-N Chymopapain Chemical compound OC1=CC(S(O)(=O)=O)=CC(S(O)(=O)=O)=C1O XXAXVMUWHZHZMJ-UHFFFAOYSA-N 0.000 description 1
- 108090001069 Chymopapain Proteins 0.000 description 1
- 101710137199 Class II receptor tyrosine kinase Proteins 0.000 description 1
- 101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 108010034003 Cys(11)-Cys(15)-endothelin-1 (11-21) Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- GJKXGJCSJWBJEZ-XRSSZCMZSA-N Deslorelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CNC2=CC=CC=C12 GJKXGJCSJWBJEZ-XRSSZCMZSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102000017930 EDNRB Human genes 0.000 description 1
- 108010090557 Endothelin B Receptor Proteins 0.000 description 1
- 102000003965 Endothelin-2 Human genes 0.000 description 1
- 108090000387 Endothelin-2 Proteins 0.000 description 1
- 102100029109 Endothelin-3 Human genes 0.000 description 1
- 108010072844 Endothelin-3 Proteins 0.000 description 1
- 102000048186 Endothelin-converting enzyme 1 Human genes 0.000 description 1
- 108030001679 Endothelin-converting enzyme 1 Proteins 0.000 description 1
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 108700012941 GNRH1 Proteins 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000038455 IGF Type 1 Receptor Human genes 0.000 description 1
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 1
- 108010030872 IRL 3461 Proteins 0.000 description 1
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 208000032382 Ischaemic stroke Diseases 0.000 description 1
- HKLDUJXJTQJSEJ-OLXNOMCWSA-N Kendomycin Chemical compound C1C[C@H](C)\C=C(C)\C[C@@H](C)C[C@H](C)[C@](C=C23)(O)OC2=C(C)C(=O)C(O)=C3[C@H]2[C@H](C)[C@@H](O)[C@@H](C)[C@@H]1O2 HKLDUJXJTQJSEJ-OLXNOMCWSA-N 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 102000008238 LHRH Receptors Human genes 0.000 description 1
- 108010021290 LHRH Receptors Proteins 0.000 description 1
- 206010027465 Metastases to skin Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- FTFRZXFNZVCRSK-UHFFFAOYSA-N N4-(3-chloro-4-fluorophenyl)-N6-(1-methyl-4-piperidinyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FTFRZXFNZVCRSK-UHFFFAOYSA-N 0.000 description 1
- 241000750002 Nestor Species 0.000 description 1
- 108700003013 Org 30850 Proteins 0.000 description 1
- 108010009124 PD 142893 Proteins 0.000 description 1
- 108010007647 PD 145065 Proteins 0.000 description 1
- 108010058337 PD 151242 Proteins 0.000 description 1
- 108010068767 PD 156252 Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108010053959 RES 701-1 Proteins 0.000 description 1
- 108010054051 RES 701-2 Proteins 0.000 description 1
- ZWNZDIPJNHSCRQ-UHFFFAOYSA-N RES-1149-1 Natural products C1CCC(C)(C)C2C(OC(=O)C=CC=CC=CC)C=C(C=O)C(O)(C=O)C21C ZWNZDIPJNHSCRQ-UHFFFAOYSA-N 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 1
- 108010050144 Triptorelin Pamoate Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 101100429091 Xiphophorus maculatus xmrk gene Proteins 0.000 description 1
- VJXYJONFUZXZJZ-UHFFFAOYSA-N [2-(2-aminophenyl)-1-hydroxy-1-phosphonoethyl]phosphonic acid Chemical compound NC1=CC=CC=C1CC(O)(P(O)(O)=O)P(O)(O)=O VJXYJONFUZXZJZ-UHFFFAOYSA-N 0.000 description 1
- HPPONSCISKROOD-OYLNGHKZSA-N acetic acid;(2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-1-[(2s)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1h-indol-3-yl)-1-oxopropan-2-y Chemical compound CC(O)=O.C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 HPPONSCISKROOD-OYLNGHKZSA-N 0.000 description 1
- NGCGMRBZPXEPOZ-HBBGHHHDSA-N acetic acid;(2s)-n-[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[2-[[(2s)-1-[[(2s)-1-[(2s)-2-[(2-amino-2-oxoethyl)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)- Chemical compound CC(O)=O.C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 NGCGMRBZPXEPOZ-HBBGHHHDSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- OOUACICUAVTCEC-LZHWUUGESA-N aezs-108 Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)COC(=O)CCCC(=O)NCCCC[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 OOUACICUAVTCEC-LZHWUUGESA-N 0.000 description 1
- 229960004343 alendronic acid Drugs 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 108700022499 azaline Proteins 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- 235000020964 calcitriol Nutrition 0.000 description 1
- 239000011612 calcitriol Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- ZGOVYTPSWMLYOF-QEADGSHQSA-N chembl1790180 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CC=3C=CC=CC=3)C(=O)N[C@H](C(=O)N[C@H](CCC=3C=CC(O)=CC=3)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](CCC(O)=O)C(=O)N2)[C@H](C)O)=O)NC(=O)[C@@H]([C@@H](C)O)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZGOVYTPSWMLYOF-QEADGSHQSA-N 0.000 description 1
- YTYFONCKNDOXFI-AJSFTGFASA-N chembl67074 Chemical compound C1([C@H]2/C(C(=NC(C)=C2C(=O)OC)C)=C(O)/OC(=O)C=2[C@H](/C(C(=NC=2C)C)=C(O)/OC)C=2C=C(C=CC=2)[N+]([O-])=O)=CC=CC([N+]([O-])=O)=C1 YTYFONCKNDOXFI-AJSFTGFASA-N 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 108010044165 crotoxin drug combination cardiotoxin Proteins 0.000 description 1
- 108010017327 cyclo(glutamyl-alanyl-isoleucyl-leucyl-tryptophyl) Proteins 0.000 description 1
- 108010055679 cyclo(sulfoalanyl-prolyl-valyl-leucyl-tryptophyl) Proteins 0.000 description 1
- 108010035609 cyclo(tryptophyl-aspartyl-prolyl-thianylglycyl-leucyl) Proteins 0.000 description 1
- 229940002533 cystorelin Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- SOXXAFVUSIMAGB-UHFFFAOYSA-N dechlorodihydromaldoxin Natural products COC(=O)C1=CC(OC)=CC(O)=C1OC1=CC(C)=CC(O)=C1C(O)=O SOXXAFVUSIMAGB-UHFFFAOYSA-N 0.000 description 1
- 229960002272 degarelix Drugs 0.000 description 1
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 description 1
- 108700025485 deslorelin Proteins 0.000 description 1
- 229960005408 deslorelin Drugs 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
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- XIIPOLLCNQAOCP-XQTCEJMISA-N dnc012318 Chemical compound C([C@@H]1C(=O)NCC(=O)N[C@@H](C(N[C@@H](C)C(=O)N2CCC[C@@H]2C(=O)N[C@H](CC(=O)NCC(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)=O)[C@H](O)C)C1=CNC=N1 XIIPOLLCNQAOCP-XQTCEJMISA-N 0.000 description 1
- 229950004880 edonentan Drugs 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- MLFJHYIHIKEBTQ-IYRKOGFYSA-N endothelin 2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CSSC[C@@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=3C4=CC=CC=C4NC=3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CSSC1)C1=CNC=N1 MLFJHYIHIKEBTQ-IYRKOGFYSA-N 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002710 external beam radiation therapy Methods 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 108700020746 histrelin Proteins 0.000 description 1
- 229960002193 histrelin Drugs 0.000 description 1
- HHXHVIJIIXKSOE-QILQGKCVSA-N histrelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC(N=C1)=CN1CC1=CC=CC=C1 HHXHVIJIIXKSOE-QILQGKCVSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- ASMGFLAYDQSOPU-UHFFFAOYSA-N hydroxy-[1-hydroxy-3-[methyl(3-phenoxypropyl)azaniumyl]-1-phosphonopropyl]phosphinate Chemical compound OP(=O)(O)C(O)(P(O)(O)=O)CCN(C)CCCOC1=CC=CC=C1 ASMGFLAYDQSOPU-UHFFFAOYSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 229960005236 ibandronic acid Drugs 0.000 description 1
- LWRDQHOZTAOILO-UHFFFAOYSA-N incadronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)NC1CCCCCC1 LWRDQHOZTAOILO-UHFFFAOYSA-N 0.000 description 1
- 229950006971 incadronic acid Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 108010083551 iturelix Proteins 0.000 description 1
- QRYFGTULTGLGHU-NBERXCRTSA-N iturelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CCCCNC(=O)C=1C=NC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)CCCNC(=O)C1=CC=CN=C1 QRYFGTULTGLGHU-NBERXCRTSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- 101150085091 lat-2 gene Proteins 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003822 lutrelin Drugs 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 108700003825 lysine(6)-doxorubicin LHRH Proteins 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000000684 melanotic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229950011129 minodronic acid Drugs 0.000 description 1
- VMMKGHQPQIEGSQ-UHFFFAOYSA-N minodronic acid Chemical compound C1=CC=CN2C(CC(O)(P(O)(O)=O)P(O)(O)=O)=CN=C21 VMMKGHQPQIEGSQ-UHFFFAOYSA-N 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- IAYNHDZSSDUYHY-UHFFFAOYSA-N n-(2-acetyl-4,6-dimethylphenyl)-3-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]thiophene-2-carboxamide Chemical compound CC(=O)C1=CC(C)=CC(C)=C1NC(=O)C1=C(S(=O)(=O)NC2=C(C(C)=NO2)C)C=CS1 IAYNHDZSSDUYHY-UHFFFAOYSA-N 0.000 description 1
- YYORXFZSDAHEEC-HHHXNRCGSA-N n-[(2r)-1-[2-(1h-indol-3-yl)ethylamino]-1-oxo-3-phenylpropan-2-yl]-n,3,5-trimethylbenzamide Chemical compound C([C@@H](N(C)C(=O)C=1C=C(C)C=C(C)C=1)C(=O)NCCC=1C2=CC=CC=C2NC=1)C1=CC=CC=C1 YYORXFZSDAHEEC-HHHXNRCGSA-N 0.000 description 1
- DWRROFDJWVYOHG-IAPPQJPRSA-N n-[(2r)-1-[[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-butylsulfonylamino]-3-[4-(1,2-oxazol-5-yl)phenyl]-1-oxopropan-2-yl]-n,3,5-trimethylbenzamide Chemical compound C([C@H](C(=O)N([C@@H](C(C)C)C(N)=O)S(=O)(=O)CCCC)N(C)C(=O)C=1C=C(C)C=C(C)C=1)C(C=C1)=CC=C1C1=CC=NO1 DWRROFDJWVYOHG-IAPPQJPRSA-N 0.000 description 1
- QLGKMLRGKPKGKI-MUVLZESKSA-N n-[(2s)-1-[[(2s)-1-[[1-[[(2s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(2s)-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3- Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](C)NC(=O)[C@@H](NC(=O)C(CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 QLGKMLRGKPKGKI-MUVLZESKSA-N 0.000 description 1
- NWNSIURBDQNMCZ-UHFFFAOYSA-N n-[4-[3-[[benzyl(methyl)amino]methyl]-7-[(2,6-difluorophenyl)methyl]-5-(2-methylpropanoyl)-4-oxothieno[2,3-b]pyridin-2-yl]phenyl]-1-hydroxycyclopropane-1-carboxamide Chemical compound C1=2SC(C=3C=CC(NC(=O)C4(O)CC4)=CC=3)=C(CN(C)CC=3C=CC=CC=3)C=2C(=O)C(C(=O)C(C)C)=CN1CC1=C(F)C=CC=C1F NWNSIURBDQNMCZ-UHFFFAOYSA-N 0.000 description 1
- VRUJTPHFVRXEPB-UHFFFAOYSA-N n-[[2-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n,3,3-trimethylbutanamide;hydrate Chemical compound O.CC(C)(C)CC(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C VRUJTPHFVRXEPB-UHFFFAOYSA-N 0.000 description 1
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
- 229950010733 neridronic acid Drugs 0.000 description 1
- PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 229960003978 pamidronic acid Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 108010092834 ramorelix Proteins 0.000 description 1
- 229950000277 ramorelix Drugs 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- ZWNZDIPJNHSCRQ-MOHQOPMHSA-N res-1149-1 Chemical compound C1CCC(C)(C)[C@@H]2[C@H](OC(=O)/C=C/C=C/C=C/C)C=C(C=O)[C@](O)(C=O)[C@]21C ZWNZDIPJNHSCRQ-MOHQOPMHSA-N 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960000759 risedronic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- RSGMPVJSBAIOBP-IJVOEZGUSA-M sodium;(z)-2-(2,1,3-benzothiadiazol-5-yl)-4-(3-fluoro-4-methoxyphenyl)-4-oxo-3-[(3,4,5-trimethoxyphenyl)methyl]but-2-enoate Chemical compound [Na+].C1=C(F)C(OC)=CC=C1C(=O)C(\CC=1C=C(OC)C(OC)=C(OC)C=1)=C(/C([O-])=O)C1=CC2=NSN=C2C=C1 RSGMPVJSBAIOBP-IJVOEZGUSA-M 0.000 description 1
- COKFAUSKNMGISZ-BMGIYVBOSA-M sodium;(z)-2-(2,1,3-benzothiadiazol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-[(3,4,5-trimethoxyphenyl)methyl]but-2-enoate Chemical compound [Na+].C1=CC(OC)=CC=C1C(=O)C(\CC=1C=C(OC)C(OC)=C(OC)C=1)=C(/C([O-])=O)C1=CC2=NSN=C2C=C1 COKFAUSKNMGISZ-BMGIYVBOSA-M 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 108700036944 surfagon Proteins 0.000 description 1
- 230000004654 survival pathway Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229950011372 teverelix Drugs 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 229960005324 tiludronic acid Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 229960004824 triptorelin Drugs 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
- 229960000434 triptorelin acetate Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 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
- 239000002550 vasoactive agent Substances 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0223854.1A GB0223854D0 (en) | 2002-10-12 | 2002-10-12 | Therapeutic treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200502874B true ZA200502874B (en) | 2006-02-22 |
Family
ID=9945876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200502874A ZA200502874B (en) | 2002-10-12 | 2005-04-08 | Therapeutic treatment. |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US20060122180A1 (no) |
| EP (1) | EP1553950B1 (no) |
| JP (1) | JP2006510605A (no) |
| KR (1) | KR20050056238A (no) |
| CN (1) | CN100342853C (no) |
| AR (1) | AR041595A1 (no) |
| AT (1) | ATE369136T1 (no) |
| AU (1) | AU2003269259B2 (no) |
| BR (1) | BR0315140A (no) |
| CA (1) | CA2501959A1 (no) |
| CY (1) | CY1107605T1 (no) |
| DE (1) | DE60315490T2 (no) |
| DK (1) | DK1553950T3 (no) |
| ES (1) | ES2289316T3 (no) |
| GB (1) | GB0223854D0 (no) |
| HK (1) | HK1078784A1 (no) |
| IS (1) | IS2473B (no) |
| MX (1) | MXPA05003808A (no) |
| MY (1) | MY135441A (no) |
| NO (1) | NO20051658L (no) |
| NZ (1) | NZ539137A (no) |
| PL (1) | PL375584A1 (no) |
| PT (1) | PT1553950E (no) |
| RU (1) | RU2005114487A (no) |
| SA (1) | SA04240502B1 (no) |
| TW (1) | TW200412971A (no) |
| UA (1) | UA82492C2 (no) |
| UY (1) | UY28017A1 (no) |
| WO (1) | WO2004035057A1 (no) |
| ZA (1) | ZA200502874B (no) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0218526D0 (en) * | 2002-08-09 | 2002-09-18 | Astrazeneca Ab | Combination therapy |
| GB0219660D0 (en) | 2002-08-23 | 2002-10-02 | Astrazeneca Ab | Therapeutic use |
| WO2004100991A1 (en) * | 2003-05-15 | 2004-11-25 | Universite Catholique De Louvain | Use of endothelin-1 antagonists for improving cancer therapy |
| GB0320806D0 (en) * | 2003-09-05 | 2003-10-08 | Astrazeneca Ab | Therapeutic treatment |
| GB0403744D0 (en) | 2004-02-20 | 2004-03-24 | Astrazeneca Ab | Chemical process |
| GB0425854D0 (en) * | 2004-11-25 | 2004-12-29 | Astrazeneca Ab | Therapeutic treatment |
| PT2209501E (pt) * | 2007-10-12 | 2012-02-03 | Astrazeneca Ab | Composição de zibotentan contendo manitol e celulose microcristalina |
| SG178828A1 (en) * | 2009-08-10 | 2012-04-27 | Univ Texas | Treatment of brain metastases with inhibitors of endothelin receptors in combination with a cytotoxic chemotherapy agent |
| AU2020314971A1 (en) * | 2019-07-17 | 2022-02-10 | Enb Therapeutics, Inc. | Treatment of urothelial and kidney cancers by use of endothelin B receptor antagonists |
| AU2022297082B2 (en) | 2021-06-22 | 2024-04-18 | Alchemedicine, Inc. | Compound, endothelin A receptor antagonist and pharmaceutical composition |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5514691A (en) * | 1993-05-20 | 1996-05-07 | Immunopharmaceutics, Inc. | N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin |
| US5464853A (en) * | 1993-05-20 | 1995-11-07 | Immunopharmaceutics, Inc. | N-(5-isoxazolyl)biphenylsulfonamides, N-(3-isoxazolyl)biphenylsulfonamides and derivatives thereof that modulate the activity of endothelin |
| AU661533B2 (en) * | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| US6063911A (en) * | 1993-12-01 | 2000-05-16 | Marine Polymer Technologies, Inc. | Methods and compositions for treatment of cell proliferative disorders |
| GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| UA58494C2 (uk) * | 1995-06-07 | 2003-08-15 | Зенека Лімітед | Похідні n-гетероарилпіридинсульфонаміду, фармацевтична композиція, спосіб одержання та спосіб протидії впливам ендотеліну |
| US5780435A (en) * | 1995-12-15 | 1998-07-14 | Praecis Pharmaceuticals Incorporated | Methods for treating prostate cancer with LHRH-R antagonists |
| ATE295839T1 (de) * | 1998-04-29 | 2005-06-15 | Osi Pharm Inc | N-(3-ethinylphenylamino)-6,7-bis(2-methoxyethox )-4-chinazolinamin-mesylat-anhydrat und -monohydrat |
| US6355678B1 (en) * | 1998-06-29 | 2002-03-12 | Parker Hughes Institute | Inhibitors of the EGF-receptor tyrosine kinase and methods for their use |
| GB0008368D0 (en) * | 2000-04-06 | 2000-05-24 | Astrazeneca Ab | Combination product |
| US20020055457A1 (en) * | 2000-08-07 | 2002-05-09 | Janus Todd J. | Methods of treating cancer and the pain associated therewith using endothelin antagonists |
| US20030092757A1 (en) * | 2001-04-11 | 2003-05-15 | Amitabh Singh | Favorable modulation of health-related quality of life and health-related quality-adjusted time-to-progression of disease in patients with prostate cancer |
| DE10155076A1 (de) * | 2001-11-09 | 2003-05-22 | Merck Patent Gmbh | Verwendung von Endothelin-Rezeptor-Antagonisten zur Behandlung von Tumorerkrankungen |
-
2002
- 2002-10-12 GB GBGB0223854.1A patent/GB0223854D0/en not_active Ceased
-
2003
- 2003-07-10 UA UAA200504329A patent/UA82492C2/uk unknown
- 2003-10-07 ES ES03751038T patent/ES2289316T3/es not_active Expired - Lifetime
- 2003-10-07 MX MXPA05003808A patent/MXPA05003808A/es active IP Right Grant
- 2003-10-07 AT AT03751038T patent/ATE369136T1/de active
- 2003-10-07 JP JP2004544431A patent/JP2006510605A/ja active Pending
- 2003-10-07 DK DK03751038T patent/DK1553950T3/da active
- 2003-10-07 CA CA002501959A patent/CA2501959A1/en not_active Abandoned
- 2003-10-07 EP EP03751038A patent/EP1553950B1/en not_active Expired - Lifetime
- 2003-10-07 PL PL03375584A patent/PL375584A1/xx not_active Application Discontinuation
- 2003-10-07 DE DE60315490T patent/DE60315490T2/de not_active Expired - Lifetime
- 2003-10-07 US US10/530,794 patent/US20060122180A1/en not_active Abandoned
- 2003-10-07 WO PCT/GB2003/004347 patent/WO2004035057A1/en active IP Right Grant
- 2003-10-07 BR BR0315140-9A patent/BR0315140A/pt not_active IP Right Cessation
- 2003-10-07 PT PT03751038T patent/PT1553950E/pt unknown
- 2003-10-07 AU AU2003269259A patent/AU2003269259B2/en not_active Ceased
- 2003-10-07 NZ NZ539137A patent/NZ539137A/en not_active IP Right Cessation
- 2003-10-07 RU RU2005114487/15A patent/RU2005114487A/ru unknown
- 2003-10-07 CN CNB2003801013102A patent/CN100342853C/zh not_active Expired - Fee Related
- 2003-10-07 KR KR1020057006232A patent/KR20050056238A/ko not_active Application Discontinuation
- 2003-10-09 TW TW092128113A patent/TW200412971A/zh unknown
- 2003-10-10 AR ARP030103717A patent/AR041595A1/es unknown
- 2003-10-10 MY MYPI20033877A patent/MY135441A/en unknown
- 2003-10-13 UY UY28017A patent/UY28017A1/es not_active Application Discontinuation
-
2004
- 2004-02-18 SA SA04240502A patent/SA04240502B1/ar unknown
-
2005
- 2005-04-04 NO NO20051658A patent/NO20051658L/no not_active Application Discontinuation
- 2005-04-08 ZA ZA200502874A patent/ZA200502874B/en unknown
- 2005-04-26 IS IS7825A patent/IS2473B/is unknown
- 2005-11-28 HK HK05110831A patent/HK1078784A1/xx not_active IP Right Cessation
-
2007
- 2007-10-08 CY CY20071101275T patent/CY1107605T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1553950B1 (en) | 2007-08-08 |
| DE60315490D1 (de) | 2007-09-20 |
| AU2003269259B2 (en) | 2007-03-15 |
| BR0315140A (pt) | 2005-08-16 |
| DE60315490T2 (de) | 2008-05-08 |
| UA82492C2 (uk) | 2008-04-25 |
| JP2006510605A (ja) | 2006-03-30 |
| CA2501959A1 (en) | 2004-04-29 |
| DK1553950T3 (da) | 2007-10-15 |
| IS2473B (is) | 2008-12-15 |
| NZ539137A (en) | 2008-01-31 |
| MXPA05003808A (es) | 2005-06-08 |
| GB0223854D0 (en) | 2002-11-20 |
| PL375584A1 (en) | 2005-11-28 |
| PT1553950E (pt) | 2007-09-26 |
| NO20051658L (no) | 2005-05-06 |
| TW200412971A (en) | 2004-08-01 |
| UY28017A1 (es) | 2004-04-30 |
| ATE369136T1 (de) | 2007-08-15 |
| CN100342853C (zh) | 2007-10-17 |
| KR20050056238A (ko) | 2005-06-14 |
| RU2005114487A (ru) | 2006-02-10 |
| SA04240502B1 (ar) | 2008-09-14 |
| US20060122180A1 (en) | 2006-06-08 |
| CY1107605T1 (el) | 2013-03-13 |
| AU2003269259A1 (en) | 2004-05-04 |
| MY135441A (en) | 2008-04-30 |
| ES2289316T3 (es) | 2008-02-01 |
| WO2004035057A1 (en) | 2004-04-29 |
| AR041595A1 (es) | 2005-05-26 |
| EP1553950A1 (en) | 2005-07-20 |
| HK1078784A1 (en) | 2006-03-24 |
| IS7825A (is) | 2005-04-26 |
| CN1703224A (zh) | 2005-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200502874B (en) | Therapeutic treatment. | |
| US11202779B2 (en) | Combinations for the treatment of neoplasms using quiescent cell targeting with EGFR inhibitors | |
| KR20060069857A (ko) | Ｎ-(3-메톡시-5-메틸피라진-2-일)-2-(4-[1,3,4-옥사디아졸-2-일]페닐)피리딘-3-설폰아미드 및 ｌｈｒｈ 유사체및/또는 비스포스포네이트를 포함하는 조합물 | |
| US20220401436A1 (en) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors | |
| Kovach et al. | Levamisole potentiation of fluorouracil antiproliferative activity mimicked by orthovanadate, an inhibitor of tyrosine phosphatase | |
| KR20170134462A (ko) | Mdm2 저해제와 btk 저해제의 병용 치료법 | |
| TW200416031A (en) | Therapeutic treatment | |
| EP4358965A1 (en) | Erk1/2 and shp2 inhibitors combination therapy | |
| WO2017021177A1 (en) | Pharmaceutical combinations for use in the treatment of cancer | |
| WO2008036254A2 (en) | Autophagic compounds and tyrosine kinase inhibitors for treating cancer | |
| Xu et al. | Combination of 5-fluorouracil and irinotecan on modulation of thymidylate synthase and topoisomerase I expression and cell cycle regulation in human colon cancer LoVo cells: clinical relevance | |
| US20080139457A1 (en) | Therapeutic compositions comprising chorionic gonadotropins and HMG CoA reductase inhibitors | |
| KR20220140723A (ko) | 암의 치료를 위한 약제학적 조합 | |
| CN117897158A (zh) | Erk1/2和shp2抑制剂组合疗法 | |
| WO2022218956A1 (en) | Combination comprising ribociclib and amcenestrant | |
| WO2020228656A1 (zh) | 用于联合治疗软组织肉瘤的喹啉衍生物 |