JP2004507465A - エストロゲン受容体陽性癌腫の治療方法 - Google Patents
エストロゲン受容体陽性癌腫の治療方法 Download PDFInfo
- Publication number
- JP2004507465A JP2004507465A JP2002518948A JP2002518948A JP2004507465A JP 2004507465 A JP2004507465 A JP 2004507465A JP 2002518948 A JP2002518948 A JP 2002518948A JP 2002518948 A JP2002518948 A JP 2002518948A JP 2004507465 A JP2004507465 A JP 2004507465A
- Authority
- JP
- Japan
- Prior art keywords
- rapamycin
- carbon atoms
- estrogen
- hydroxy
- pharmaceutically acceptable
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 28
- 102000015694 estrogen receptors Human genes 0.000 title claims abstract description 20
- 108010038795 estrogen receptors Proteins 0.000 title claims abstract description 20
- 201000009030 Carcinoma Diseases 0.000 title claims abstract description 16
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims abstract description 72
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims abstract description 72
- 229960002930 sirolimus Drugs 0.000 claims abstract description 72
- 239000000328 estrogen antagonist Substances 0.000 claims abstract description 53
- 241000124008 Mammalia Species 0.000 claims abstract description 13
- 230000001629 suppression Effects 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 37
- -1 idoxifine Chemical compound 0.000 claims description 33
- 150000001875 compounds Chemical class 0.000 claims description 24
- 230000001833 anti-estrogenic effect Effects 0.000 claims description 22
- 229940046836 anti-estrogen Drugs 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 12
- DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 claims description 11
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- PTBDIHRZYDMNKB-UHFFFAOYSA-N 2,2-Bis(hydroxymethyl)propionic acid Chemical compound OCC(C)(CO)C(O)=O PTBDIHRZYDMNKB-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229940011871 estrogen Drugs 0.000 claims description 9
- 239000000262 estrogen Substances 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 206010033128 Ovarian cancer Diseases 0.000 claims description 8
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 8
- 229960004622 raloxifene Drugs 0.000 claims description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 7
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 150000007857 hydrazones Chemical class 0.000 claims description 6
- 150000002923 oximes Chemical class 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229960001603 tamoxifen Drugs 0.000 claims description 4
- INEHJXCWEVNEDZ-LUDNRVPPSA-N (2s,3s)-2,3-dihydroxybutanedioic acid;(5r,6s)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O.C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 INEHJXCWEVNEDZ-LUDNRVPPSA-N 0.000 claims description 3
- UTYMHSHRSOOSEY-BYYHNAKLSA-N 4-[4-[(e)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylbutan-1-amine Chemical compound C1=CC(OCCCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 UTYMHSHRSOOSEY-BYYHNAKLSA-N 0.000 claims description 3
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 claims description 3
- JEYWNNAZDLFBFF-UHFFFAOYSA-N Nafoxidine Chemical compound C1CC2=CC(OC)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)=C1C1=CC=CC=C1 JEYWNNAZDLFBFF-UHFFFAOYSA-N 0.000 claims description 3
- OEKMGABCSLYWOP-DHUJRADRSA-N [4-[(2s)-7-(2,2-dimethylpropanoyloxy)-4-methyl-2-[4-(2-piperidin-1-ylethoxy)phenyl]-2h-chromen-3-yl]phenyl] 2,2-dimethylpropanoate Chemical compound C1=CC([C@H]2C(=C(C3=CC=C(OC(=O)C(C)(C)C)C=C3O2)C)C=2C=CC(OC(=O)C(C)(C)C)=CC=2)=CC=C1OCCN1CCCCC1 OEKMGABCSLYWOP-DHUJRADRSA-N 0.000 claims description 3
- 150000003973 alkyl amines Chemical class 0.000 claims description 3
- MCGDSOGUHLTADD-UHFFFAOYSA-N arzoxifene Chemical compound C1=CC(OC)=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 MCGDSOGUHLTADD-UHFFFAOYSA-N 0.000 claims description 3
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 claims description 3
- 229960003608 clomifene Drugs 0.000 claims description 3
- 229950004203 droloxifene Drugs 0.000 claims description 3
- HKVAMNSJSFKALM-CPXURSODSA-N everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)\C(C)=C\C=C\C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-CPXURSODSA-N 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- QZUHFMXJZOUZFI-ZQHSETAFSA-N miproxifene phosphate Chemical compound C=1C=C(C(C)C)C=CC=1C(/CC)=C(C=1C=CC(OP(O)(O)=O)=CC=1)\C1=CC=C(OCCN(C)C)C=C1 QZUHFMXJZOUZFI-ZQHSETAFSA-N 0.000 claims description 3
- 229950002366 nafoxidine Drugs 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 claims description 3
- 229960005026 toremifene Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 2
- UCJGJABZCDBEDK-UHFFFAOYSA-N bazedoxifene Chemical group C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UCJGJABZCDBEDK-UHFFFAOYSA-N 0.000 claims 2
- OLSDYZLJXRSMAZ-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methyl-1h-indol-5-ol Chemical compound N1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 OLSDYZLJXRSMAZ-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 28
- 229960000235 temsirolimus Drugs 0.000 description 28
- JICOGKJOQXTAIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 JICOGKJOQXTAIP-UHFFFAOYSA-N 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 15
- 235000002639 sodium chloride Nutrition 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- 239000000203 mixture Substances 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 230000002195 synergetic effect Effects 0.000 description 7
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000012010 growth Effects 0.000 description 5
- 239000003607 modifier Substances 0.000 description 5
- 238000010998 test method Methods 0.000 description 5
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 150000002443 hydroxylamines Chemical class 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 230000000259 anti-tumor effect 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
- 239000006185 dispersion Substances 0.000 description 3
- 229960005309 estradiol Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 150000005215 alkyl ethers Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 238000009739 binding Methods 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 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 2
- 150000002576 ketones Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 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
- 210000005075 mammary gland Anatomy 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000008169 Co-Repressor Proteins Human genes 0.000 description 1
- 108010060434 Co-Repressor Proteins Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 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
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000035327 Oestrogen receptor positive breast cancer Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- SLGBZMMZGDRARJ-UHFFFAOYSA-N Triphenylene Natural products C1=CC=C2C3=CC=CC=C3C3=CC=CC=C3C2=C1 SLGBZMMZGDRARJ-UHFFFAOYSA-N 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000005129 aryl carbonyl group Chemical group 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 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
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Natural products N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229940078456 calcium stearate Drugs 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000009104 chemotherapy regimen Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 125000005131 dialkylammonium group Chemical group 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 201000007281 estrogen-receptor positive breast cancer Diseases 0.000 description 1
- 230000001076 estrogenic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 150000005671 trienes Chemical class 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22432600P | 2000-08-11 | 2000-08-11 | |
| PCT/US2001/024615 WO2002013802A2 (en) | 2000-08-11 | 2001-08-06 | Method of treating estrogen receptor positive carcinoma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004507465A true JP2004507465A (ja) | 2004-03-11 |
| JP2004507465A5 JP2004507465A5 (enExample) | 2008-09-25 |
Family
ID=22840171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002518948A Withdrawn JP2004507465A (ja) | 2000-08-11 | 2001-08-06 | エストロゲン受容体陽性癌腫の治療方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6511986B2 (enExample) |
| EP (1) | EP1318837B1 (enExample) |
| JP (1) | JP2004507465A (enExample) |
| CN (1) | CN100448487C (enExample) |
| AR (1) | AR033555A1 (enExample) |
| AT (1) | ATE278421T1 (enExample) |
| AU (1) | AU2001283139A1 (enExample) |
| CA (1) | CA2416976C (enExample) |
| DE (1) | DE60106281T2 (enExample) |
| DK (1) | DK1318837T3 (enExample) |
| ES (1) | ES2228932T3 (enExample) |
| MX (1) | MXPA03001245A (enExample) |
| PT (1) | PT1318837E (enExample) |
| WO (1) | WO2002013802A2 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022552132A (ja) * | 2019-10-01 | 2022-12-15 | サノフイ | 新規の置換６，７－ジヒドロ－５ｈ－ベンゾ［７］アンヌレン化合物、その製造方法およびその治療的使用 |
Families Citing this family (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8512960B2 (en) * | 1997-05-23 | 2013-08-20 | A&G Pharmaceutical, Inc. | 88kDa tumorigenic growth factor and antagonists |
| US7091047B2 (en) * | 1997-05-23 | 2006-08-15 | A&G Pharmaceutical, Inc. | Methods and kits for diagnosing tumorigenicity |
| US20100111928A1 (en) * | 1997-05-23 | 2010-05-06 | A & G Pharmaceutical, Inc. | Methods and kits for diagnosis tumorgenicity |
| US6309826B1 (en) | 1997-05-23 | 2001-10-30 | Ginette Serrero | 88kDa tumorigenic growth factor and antagonists |
| US6720159B1 (en) | 1997-12-16 | 2004-04-13 | A&G Pharmaceutical, Inc. | 88KDA tumorigenic growth factor and antagonists |
| US6881548B2 (en) * | 1997-05-23 | 2005-04-19 | A&G Pharmaceutical, Inc. | Methods and kits for diagnosing tumorigenicity and determining resistance to the antineoplastic effects of antiestrogen therapy |
| US20030215445A1 (en) * | 1997-05-23 | 2003-11-20 | Ginette Serrero | Methods and compositions for inhibiting the growth of hematopoietic malignant cells |
| US7617145B1 (en) * | 2000-10-24 | 2009-11-10 | Worldwide Farm Equipment Auctions.Com Ltd. | Adaptive bidding increments in an online auction system |
| TWI286074B (en) | 2000-11-15 | 2007-09-01 | Wyeth Corp | Pharmaceutical composition containing CCI-779 as an antineoplastic agent |
| CN1551767A (zh) * | 2001-02-19 | 2004-12-01 | ��˹��ŵ�� | 癌症的治疗 |
| AU2016206379B2 (en) * | 2001-02-19 | 2017-09-14 | Novartis Ag | Cancer Treatment |
| AU2011226833B9 (en) * | 2001-02-19 | 2014-07-03 | Novartis Ag | Cancer treatment |
| EP1389209B1 (en) * | 2001-04-24 | 2009-04-08 | Purdue Research Foundation | Folate mimetics and folate-receptor binding conjugates thereof |
| CN1289075C (zh) * | 2001-07-09 | 2006-12-13 | 佐纳根有限公司 | 富含反式克罗米酚的克罗米酚组合物的用途 |
| UA77200C2 (en) | 2001-08-07 | 2006-11-15 | Wyeth Corp | Antineoplastic combination of cci-779 and bkb-569 |
| EP1478648B1 (en) | 2002-02-01 | 2014-04-30 | ARIAD Pharmaceuticals, Inc. | Phosphorus-containing compounds and uses thereof |
| KR20040106547A (ko) * | 2002-05-15 | 2004-12-17 | 엔도사이트, 인코포레이티드 | 비타민-마이토마이신 공액체 |
| US7411045B2 (en) * | 2002-11-19 | 2008-08-12 | A&G Pharmaceutical, Inc. | Autocrine growth factor receptor antibodies and methods |
| US7601332B2 (en) | 2003-01-27 | 2009-10-13 | Endocyte, Inc. | Vitamin receptor binding drug delivery conjugates |
| JP4488903B2 (ja) * | 2003-02-26 | 2010-06-23 | エイアンドジー ファーマスーティカル インコーポレイテッド | Ｂ細胞の増殖を増加させる方法 |
| UA83484C2 (uk) * | 2003-03-05 | 2008-07-25 | Уайт | Спосіб лікування раку грудей комбінацією похідного рапаміцину і інгібітора ароматази - летрозолу, фармацевтична композиція |
| KR20060006058A (ko) * | 2003-04-22 | 2006-01-18 | 와이어쓰 | 항신생물성 배합물 |
| US7368428B2 (en) * | 2003-06-23 | 2008-05-06 | A&G Pharmaceutical, Inc. | Compositions and methods for restoring sensitivity of tumor cells to antitumor therapy and inducing apoptosis |
| KR20060052880A (ko) * | 2003-07-25 | 2006-05-19 | 와이어쓰 | 동결건조된 ｃｃｉ- 779 제형 |
| EP1660010B1 (en) * | 2003-08-01 | 2013-07-24 | A & G Pharmaceutical, Inc. | Compositions and methods for restoring sensitivity to treatment with her2 antagonists |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| CN101098854B (zh) | 2004-07-23 | 2012-12-05 | 恩多塞特公司 | 二价连接体及其轭合物 |
| EP1804779A1 (en) * | 2004-10-28 | 2007-07-11 | Wyeth | Use of an mtor inhibitor in treatment of uterine leiomyoma |
| NZ556673A (en) | 2005-02-03 | 2010-03-26 | Gen Hospital Corp | Method for treating gefitinib and/or erlotinib resistant cancer with an EGFR inhibitor |
| AU2006221024A1 (en) | 2005-03-07 | 2006-09-14 | Wyeth | Oxepane isomer of 42-O-(2-hydroxy)ethyl-rapamycin |
| CN101175757B (zh) * | 2005-03-16 | 2012-11-14 | 恩多塞特公司 | 蝶酸及其缀合物的合成和纯化 |
| NZ560551A (en) * | 2005-03-22 | 2010-02-26 | Repros Therapeutics Inc | Dosing regimes for trans-clomiphene |
| RU2470668C2 (ru) * | 2005-08-19 | 2012-12-27 | Эндосайт, Инк. | Конъюгаты лиганда с несколькими лекарственными средствами |
| JP2009504783A (ja) * | 2005-08-19 | 2009-02-05 | エンドサイト，インコーポレイテッド | ビンカアルカロイド、類似体および誘導体のリガンド結合体 |
| EP3488866A1 (en) * | 2005-11-04 | 2019-05-29 | Wyeth LLC | Antineoplastic combinations with mtor inhibitor, herceptin, and/or hki-272 |
| DE102006011507A1 (de) * | 2006-03-14 | 2007-09-20 | Lts Lohmann Therapie-Systeme Ag | Wirkstoffbeladene Nanopartikel auf Basis hydrophiler Proteine |
| US20100104626A1 (en) * | 2007-02-16 | 2010-04-29 | Endocyte, Inc. | Methods and compositions for treating and diagnosing kidney disease |
| CN104127878A (zh) * | 2007-03-14 | 2014-11-05 | 恩多塞特公司 | 结合配体连接的微管溶素递药缀合物 |
| BRPI0812970A2 (pt) * | 2007-06-25 | 2019-09-24 | Endocyte Inc | conjugados contendo espaçadores hidrofílicos |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| US20090076060A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched temsirolimus |
| MX2010004195A (es) | 2007-10-16 | 2010-06-02 | Repros Therapeutics Inc | Trans-clomifeno para el sindrome metabolico. |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| EP2209374B1 (en) | 2007-10-25 | 2014-12-03 | Endocyte, Inc. | Tubulysins and processes for preparing |
| ES2531322T3 (es) | 2008-06-17 | 2015-03-13 | Wyeth Llc | Combinaciones antineoplásicas que contienen HKI-272 y vinorelbina |
| EP3175853B1 (en) | 2008-08-04 | 2023-11-01 | Wyeth LLC | Antineoplastic combinations of neratinib and capecitabine |
| PT3000467T (pt) | 2009-04-06 | 2023-03-30 | Wyeth Llc | Regime de tratamento utilizando neratinib para o cancro de mama |
| EP3205648A1 (en) | 2010-06-10 | 2017-08-16 | Seragon Pharmaceuticals, Inc. | Estrogen receptor modulators and uses thereof |
| UA113291C2 (xx) | 2011-08-04 | 2017-01-10 | Метаболіти транскломіфену і їх застосування | |
| EP2791132A4 (en) | 2011-12-14 | 2015-08-05 | Seragon Pharmaceuticals Inc | ESTROGEN RECEPTOR MODULATORS AND USES THEREOF |
| WO2013126797A1 (en) | 2012-02-24 | 2013-08-29 | Purdue Research Foundation | Cholecystokinin b receptor targeting for imaging and therapy |
| US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
| EA201590622A1 (ru) | 2012-10-16 | 2015-10-30 | Эндосайт, Инк. | Конъюгаты для доставки лекарственного средства, содержащие не встречающиеся в природе аминокислоты, и способы применения |
| CN104994877A (zh) | 2012-11-02 | 2015-10-21 | 利普生物药剂公司 | 用于癌症治疗的反式-克罗米芬 |
| RU2560708C1 (ru) * | 2014-03-24 | 2015-08-20 | Федеральное государственное бюджетное учреждение "Научно-исследовательский институт клинической и экспериментальной лимфологии" Сибирского отделения Российской академии медицинских наук (ФГБУ "НИИКЭЛ" СО РАМН) | Способ воздействия на клетки гепатокарциномы в зависимости от стадии их дифференцировки нанопрепаратами лития |
| WO2017059139A1 (en) | 2015-10-01 | 2017-04-06 | Olema Pharmaceuticals, Inc. | TETRAHYDRO-1H-PYRIDO[3,4-b]INDOLE ANTI-ESTROGENIC DRUGS |
| DK3386500T3 (da) | 2015-12-09 | 2022-12-12 | Univ Illinois | Benzothiophen-baserede selektive østrogenreceptor ned-regulatorer |
| CN109562107A (zh) | 2016-05-10 | 2019-04-02 | C4医药公司 | 用于靶蛋白降解的杂环降解决定子体 |
| CN121974842A (zh) | 2016-05-10 | 2026-05-05 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| WO2017197046A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | C3-carbon linked glutarimide degronimers for target protein degradation |
| CN109562113A (zh) | 2016-05-10 | 2019-04-02 | C4医药公司 | 用于靶蛋白降解的螺环降解决定子体 |
| CN109789143A (zh) | 2016-07-01 | 2019-05-21 | G1治疗公司 | 基于嘧啶的抗增殖剂 |
| CN110099680B (zh) | 2016-10-11 | 2021-02-05 | 杜克大学 | Er+乳腺癌的拉索昔芬治疗 |
| WO2018081168A2 (en) | 2016-10-24 | 2018-05-03 | The Board Of Trustees Of The University Of Illinois | Benzothiophene-based selective mixed estrogen receptor downregulators |
| JP7229162B2 (ja) | 2017-01-06 | 2023-02-27 | ジー１ セラピューティクス， インコーポレイテッド | 癌の治療に対する併用療法 |
| KR20190117582A (ko) | 2017-02-10 | 2019-10-16 | 쥐원 쎄라퓨틱스, 인크. | 벤조티오펜 에스트로겐 수용체 조정제 |
| EP4717317A3 (en) | 2017-06-20 | 2026-06-03 | C4 Therapeutics, Inc. | N/o-linked degrons and degronimers for protein degradation |
| EP3645001B1 (en) | 2017-06-29 | 2024-07-03 | G1 Therapeutics, Inc. | Morphic forms of git38 and methods of manufacture thereof |
| CN117771239A (zh) | 2018-04-10 | 2024-03-29 | 杜克大学 | 乳腺癌的拉索昔芬治疗 |
| EP3897631A4 (en) | 2018-12-20 | 2022-11-23 | C4 Therapeutics, Inc. | TARGETED PROTEIN BREAKDOWN |
| CA3144791A1 (en) | 2019-07-07 | 2021-01-14 | Olema Pharmaceuticals, Inc. | Regimens of estrogen receptor antagonists |
| EP4681715A3 (en) | 2019-12-20 | 2026-01-28 | C4 Therapeutics, Inc. | Isoindolinone and indazole compounds for the degradation of egfr |
| CN119823124A (zh) | 2020-03-05 | 2025-04-15 | C4医药公司 | 用于brd9的靶向降解的化合物 |
| EP4164653A4 (en) | 2020-06-15 | 2024-06-19 | G1 Therapeutics, Inc. | MORPHIC FORMS OF TRILACICLIB AND METHODS OF PREPARING THE SAME |
| CN116490186B (zh) | 2020-08-05 | 2025-10-31 | C4医药公司 | 用于ret的靶向降解的化合物 |
| BR112023024507A2 (pt) | 2021-05-26 | 2024-02-15 | C4 Therapeutics Inc | Método para tratar um câncer mediado por receptor do fator de crescimento epidérmico mutante que sofreu metástase para o cérebro ou sistema nervoso central |
| AU2022290851A1 (en) | 2021-06-08 | 2023-11-23 | C4 Therapeutics, Inc. | Therapeutics for the degradation of mutant braf |
| GB202116903D0 (en) | 2021-11-18 | 2022-01-05 | Sermonix Pharmaceuticals Inc | Lasofoxifene treatment of aromatase-resistant er+ cancer |
| KR20250055538A (ko) | 2022-08-03 | 2025-04-24 | 브리스톨-마이어스 스큅 컴퍼니 | Ret 단백질을 조정하기 위한 화합물 |
| KR20250117789A (ko) | 2022-11-04 | 2025-08-05 | 브리스톨-마이어스 스큅 컴퍼니 | Ret-ldd 단백질 분해제 |
| JP2025540906A (ja) | 2022-11-04 | 2025-12-17 | ブリストル－マイヤーズ スクイブ カンパニー | Ｒｅｔ－ｌｄｄタンパク質阻害剤 |
| CN122206684A (zh) | 2023-06-30 | 2026-06-12 | 默克专利有限公司 | 用于kras蛋白降解的异双功能化合物 |
| WO2026139448A1 (en) | 2024-12-23 | 2026-07-02 | Merck Patent Gmbh | Heterobifunctional compounds for the degradation of kras protein |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4316885A (en) | 1980-08-25 | 1982-02-23 | Ayerst, Mckenna And Harrison, Inc. | Acyl derivatives of rapamycin |
| US4650803A (en) | 1985-12-06 | 1987-03-17 | University Of Kansas | Prodrugs of rapamycin |
| US5023264A (en) | 1990-07-16 | 1991-06-11 | American Home Products Corporation | Rapamycin oximes |
| US5023263A (en) | 1990-08-09 | 1991-06-11 | American Home Products Corporation | 42-oxorapamycin |
| US5130307A (en) | 1990-09-28 | 1992-07-14 | American Home Products Corporation | Aminoesters of rapamycin |
| US5221670A (en) | 1990-09-19 | 1993-06-22 | American Home Products Corporation | Rapamycin esters |
| US5233036A (en) | 1990-10-16 | 1993-08-03 | American Home Products Corporation | Rapamycin alkoxyesters |
| US5120842A (en) | 1991-04-01 | 1992-06-09 | American Home Products Corporation | Silyl ethers of rapamycin |
| US5100883A (en) | 1991-04-08 | 1992-03-31 | American Home Products Corporation | Fluorinated esters of rapamycin |
| US5118678A (en) | 1991-04-17 | 1992-06-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5118677A (en) | 1991-05-20 | 1992-06-02 | American Home Products Corporation | Amide esters of rapamycin |
| US5162333A (en) | 1991-09-11 | 1992-11-10 | American Home Products Corporation | Aminodiesters of rapamycin |
| US5151413A (en) | 1991-11-06 | 1992-09-29 | American Home Products Corporation | Rapamycin acetals as immunosuppressant and antifungal agents |
| US5177203A (en) | 1992-03-05 | 1993-01-05 | American Home Products Corporation | Rapamycin 42-sulfonates and 42-(N-carboalkoxy) sulfamates useful as immunosuppressive agents |
| US5256790A (en) | 1992-08-13 | 1993-10-26 | American Home Products Corporation | 27-hydroxyrapamycin and derivatives thereof |
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| US5411967A (en) | 1992-10-13 | 1995-05-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5302584A (en) | 1992-10-13 | 1994-04-12 | American Home Products Corporation | Carbamates of rapamycin |
| US5480989A (en) | 1992-10-13 | 1996-01-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5489680A (en) | 1992-10-13 | 1996-02-06 | American Home Products Corporation | Carbamates of rapamycin |
| US5434260A (en) | 1992-10-13 | 1995-07-18 | American Home Products Corporation | Carbamates of rapamycin |
| US5480988A (en) | 1992-10-13 | 1996-01-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5262423A (en) | 1992-10-29 | 1993-11-16 | American Home Products Corporation | Rapamycin arylcarbonyl and alkoxycarbonyl carbamates as immunosuppressive and antifungal agents |
| US5258389A (en) | 1992-11-09 | 1993-11-02 | Merck & Co., Inc. | O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives |
| US5260300A (en) | 1992-11-19 | 1993-11-09 | American Home Products Corporation | Rapamycin carbonate esters as immuno-suppressant agents |
| US5504091A (en) | 1993-04-23 | 1996-04-02 | American Home Products Corporation | Biotin esters of rapamycin |
| US5373014A (en) | 1993-10-08 | 1994-12-13 | American Home Products Corporation | Rapamycin oximes |
| US5391730A (en) | 1993-10-08 | 1995-02-21 | American Home Products Corporation | Phosphorylcarbamates of rapamycin and oxime derivatives thereof |
| US5378836A (en) | 1993-10-08 | 1995-01-03 | American Home Products Corporation | Rapamycin oximes and hydrazones |
| US5385909A (en) | 1993-11-22 | 1995-01-31 | American Home Products Corporation | Heterocyclic esters of rapamycin |
| US5385910A (en) | 1993-11-22 | 1995-01-31 | American Home Products Corporation | Gem-distributed esters of rapamycin |
| US5385908A (en) | 1993-11-22 | 1995-01-31 | American Home Products Corporation | Hindered esters of rapamycin |
| US5389639A (en) | 1993-12-29 | 1995-02-14 | American Home Products Company | Amino alkanoic esters of rapamycin |
| US5362718A (en) | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| US5463048A (en) | 1994-06-14 | 1995-10-31 | American Home Products Corporation | Rapamycin amidino carbamates |
| US5491231A (en) | 1994-11-28 | 1996-02-13 | American Home Products Corporation | Hindered N-oxide esters of rapamycin |
| US5563145A (en) | 1994-12-07 | 1996-10-08 | American Home Products Corporation | Rapamycin 42-oximes and hydroxylamines |
| US5780462A (en) | 1995-12-27 | 1998-07-14 | American Home Products Corporation | Water soluble rapamycin esters |
| US5998402A (en) | 1996-04-19 | 1999-12-07 | American Home Products Corporation | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indoles as estrogenic agents |
| DE19624668A1 (de) | 1996-06-20 | 1998-02-19 | Klinge Co Chem Pharm Fab | Verwendung von Pyridylalkan-, Pyridylalken- bzw. Pyridylalkinsäureamiden |
| US6465445B1 (en) * | 1998-06-11 | 2002-10-15 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
-
2001
- 2001-08-06 AT AT01961914T patent/ATE278421T1/de not_active IP Right Cessation
- 2001-08-06 PT PT01961914T patent/PT1318837E/pt unknown
- 2001-08-06 MX MXPA03001245A patent/MXPA03001245A/es active IP Right Grant
- 2001-08-06 ES ES01961914T patent/ES2228932T3/es not_active Expired - Lifetime
- 2001-08-06 CN CNB018137539A patent/CN100448487C/zh not_active Expired - Fee Related
- 2001-08-06 AU AU2001283139A patent/AU2001283139A1/en not_active Abandoned
- 2001-08-06 US US09/923,217 patent/US6511986B2/en not_active Expired - Fee Related
- 2001-08-06 JP JP2002518948A patent/JP2004507465A/ja not_active Withdrawn
- 2001-08-06 WO PCT/US2001/024615 patent/WO2002013802A2/en not_active Ceased
- 2001-08-06 DK DK01961914T patent/DK1318837T3/da active
- 2001-08-06 EP EP01961914A patent/EP1318837B1/en not_active Expired - Lifetime
- 2001-08-06 DE DE60106281T patent/DE60106281T2/de not_active Expired - Fee Related
- 2001-08-06 CA CA002416976A patent/CA2416976C/en not_active Expired - Fee Related
- 2001-08-10 AR ARP010103839A patent/AR033555A1/es unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022552132A (ja) * | 2019-10-01 | 2022-12-15 | サノフイ | 新規の置換６，７－ジヒドロ－５ｈ－ベンゾ［７］アンヌレン化合物、その製造方法およびその治療的使用 |
| JP7680438B2 (ja) | 2019-10-01 | 2025-05-20 | サノフイ | 新規の置換６，７－ジヒドロ－５ｈ－ベンゾ［７］アンヌレン化合物、その製造方法およびその治療的使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1056687A1 (en) | 2004-02-27 |
| US20020045638A1 (en) | 2002-04-18 |
| CN100448487C (zh) | 2009-01-07 |
| WO2002013802A2 (en) | 2002-02-21 |
| DE60106281T2 (de) | 2005-02-24 |
| ATE278421T1 (de) | 2004-10-15 |
| CA2416976A1 (en) | 2002-02-21 |
| DE60106281D1 (de) | 2004-11-11 |
| AR033555A1 (es) | 2003-12-26 |
| ES2228932T3 (es) | 2005-04-16 |
| EP1318837B1 (en) | 2004-10-06 |
| CN1446106A (zh) | 2003-10-01 |
| DK1318837T3 (da) | 2005-01-10 |
| EP1318837A2 (en) | 2003-06-18 |
| MXPA03001245A (es) | 2003-05-27 |
| US6511986B2 (en) | 2003-01-28 |
| AU2001283139A1 (en) | 2002-02-25 |
| PT1318837E (pt) | 2004-12-31 |
| CA2416976C (en) | 2008-05-20 |
| WO2002013802A3 (en) | 2003-03-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1318837B1 (en) | Method of treating estrogen receptor positive carcinoma | |
| JP4472251B2 (ja) | 抗腫瘍剤としてのｃｃｉ−７７９の使用 | |
| RU2355399C2 (ru) | Противоопухолевые композиции, содержащие производное рапамицина и ингибитор ароматазы | |
| HK1218262A1 (zh) | 4-苯胺基-3-氰基喹啉和卡培他濱的抗腫瘤組合 | |
| JP2006524246A (ja) | 抗新生物組み合わせ | |
| JP2004507465A5 (enExample) | ||
| JP2000514415A (ja) | ソマトスタチン類似体およびラパマイシンの配合 | |
| CN101048152A (zh) | mTOR抑制剂在治疗子宫平滑肌瘤中的应用 | |
| US20220031657A1 (en) | Pharmaceutical combination comprising lsz102 and ribociclib | |
| HK1056687B (en) | Method of treating estrogen receptor positive carcinoma | |
| HK40091861A (en) | Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine | |
| HK1158056A (en) | Use of rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid as an antineoplastic agent | |
| HK1226654A (en) | Anti-tumor activity of temsirolimus in papillary renal cell cancer | |
| HK1142538A (en) | Anti-tumor activity of temsirolimus in papillary renal cell cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080806 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080806 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20091021 |