JP6484839B2 - 新規ペプチド及びその用途 - Google Patents
新規ペプチド及びその用途 Download PDFInfo
- Publication number
- JP6484839B2 JP6484839B2 JP2017565710A JP2017565710A JP6484839B2 JP 6484839 B2 JP6484839 B2 JP 6484839B2 JP 2017565710 A JP2017565710 A JP 2017565710A JP 2017565710 A JP2017565710 A JP 2017565710A JP 6484839 B2 JP6484839 B2 JP 6484839B2
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- cancer
- pharmaceutically acceptable
- present
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 74
- 206010028980 Neoplasm Diseases 0.000 claims description 43
- 201000011510 cancer Diseases 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 19
- 206010027476 Metastases Diseases 0.000 claims description 13
- 230000009401 metastasis Effects 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 230000008595 infiltration Effects 0.000 claims description 4
- 238000001764 infiltration Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000000034 method Methods 0.000 description 22
- 230000001093 anti-cancer Effects 0.000 description 16
- 230000004083 survival effect Effects 0.000 description 12
- -1 acyl azide Chemical class 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 102000004196 processed proteins & peptides Human genes 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000013642 negative control Substances 0.000 description 9
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- 230000004709 cell invasion Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 4
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000009313 farming Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000000699 topical effect Effects 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
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
- QQKAZZAULUMMKR-UHFFFAOYSA-N 2-n-hydroxybenzene-1,2-dicarboxamide Chemical compound NC(=O)C1=CC=CC=C1C(=O)NO QQKAZZAULUMMKR-UHFFFAOYSA-N 0.000 description 1
- MWOOKDULMBMMPN-UHFFFAOYSA-N 3-(2-ethyl-1,2-oxazol-2-ium-5-yl)benzenesulfonate Chemical compound O1[N+](CC)=CC=C1C1=CC=CC(S([O-])(=O)=O)=C1 MWOOKDULMBMMPN-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000011547 Bouin solution Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 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
- 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
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 238000011887 Necropsy Methods 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 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
- 238000005516 engineering process Methods 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 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
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 108010091748 peptide A Proteins 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 201000002510 thyroid cancer Diseases 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
- 230000007704 transition Effects 0.000 description 1
- 238000010877 transwell invasion assay Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Description
配列番号1のアミノ酸配列からなるペプチド(QLHLD:配列番号1)は、アニジェン(株)(AnyGen Co.、Ltd.、大韓民国)によって製造された。具体的には、Fmoc(9−fluorenyl−methoxycarbonyl)の化学的な性質を用いた固相法(solid phase method)によって合成された。より具体的には、固相樹脂(Wang resin; Sigma−aldrich社)0.55mmol/gで、ペプチドのC−末端に結合された。Fmoc−Phe−OHのアミノ酸のカップリング(coupling)は、O−ベンゾ−トリアゾール−N,N,N´,N´−テトラメチル−ウロニウム−ヘキサフルオロホスフェイト(HBTU)と共に行われた。アミノ酸側鎖は、tert−ブチルとtert−ブチルオキシカルボニルで保護された。脱保護(Deprotection)とレジン(resin)の分離は、トリフルオロ酢酸(trifluoroacetic acid)と水を95:5(v/v)の割合で混合した溶液を使用して室温で3時間実施した。粗(Crude)ペプチドは、ジエチルエーテル(diethylether)で繰り返して洗浄した後、真空乾燥し、島津5μmShimpak ODS C18 column(20x250mm)を使用して逆相高速液体クロマトグラフィー{reverse−phase hiph−performance liquid chromatography;RP−HPLC}法で精製した。精製されたペプチドは、Shimpak5μmODS C18 column(4.6x250mm)を用いて分析用逆相高速液体クロマトグラフィー(analytical RP−HPLC)法で確認した。合成されたペプチドの分子量は、マトリックス−支援レーザー脱離イオン化マススペクトロメーター{matrix−assisted laser desorption ionization(MALDI)−mass spectrometer}(Axima CFR、Kratos Analytical、Manchester、UK)を用いて測定した。
実施例1のペプチドにより癌細胞の浸潤(invasion)が阻害されるかを実験的に評価した。具体的には、実施例1のペプチドが癌細胞の浸潤を阻害する効果を評価するため、トランスウエルインベイジョンアッセイ(Transwell invasion assay)を実施した。トランスウエル(Corning cat#3422、Tewksbury MA、米国)の上部チャンバーに培地{RPMI1640培地(Welgene Inc.、大韓民国)}で成長因子軽減マトリゲル(Matrigel)(BD Biosciences、Franklin Lakes、NJ、米国)を1:1に希釈して70μlを添加した後、37℃、CO2インキュベーターで1時間コーティングプロセスを経た。10%ウシ胎児血清(FBS、Cellgro cat#35−015−CV、米国)を含む培地{RPMI1640培地(Welgene Inc.、大韓民国)}500μlを下部チャンバーに添加した後、実験群は、TGF−β1(PromoKine、ドイツ)10ng/mlを添加した。コートされた上部チャンバーを下部チャンバーに取り付けた後、甲状腺癌細胞であるSNU−790(韓国細胞株銀行)2万と共に0.5%FBSを含むRPMI1640培地100μlを上部チャンバーに添加した。このような方法で、陰性対照群及び2種の実験群を用意した。実験群は、それぞれ実施例1のペプチドが40μM、及び100μM処理され、陰性対照群では実施例1のペプチドが処理されなかった。また、対照群は、TGF−β1(Transforming growth factor beta1)を添加しないことを除いては、陰性対照群と同様の方法で用意した。
実施例1のペプチドにより癌細胞の転移が抑制されるかを実験的に評価した。具体的には、実施例1のペプチドが癌細胞の転移を抑制する効果を評価するため、4T1マウス乳癌細胞(ATCC CRL−2539、米国)を用いた肺転移モデルを用いて実験を行った。実施例1のペプチドを雌BALB/cマウス(SPF、SLC/日本)の尾の尾静脈に注射した。実験群は、投与濃度によって3群;低濃度{40μg/頭(head)}、中濃度{80μg/頭(head)}、高濃度{120μg/頭(head)}に分けた。実施例1のペプチドが投与されないことを除いては、陰性対照群は、実験群と同様に処理した。1次投与の翌日、4T1細胞(1.5x104 cells/head)をマウスの尾の尾静脈に注入した。1時間後に、実施例1のペプチドを2次投与した。ペプチド投与は、2次の投与日から最終投与日まで総3週間週3回(月曜日、水曜日、金曜日)実施した。マウスの体重は、週2回測定し、剖検は、癌細胞注入後21日目に行った。肺組織を摘出してブアン液(Bouin’s solution)で染色及び固定した後、転移性腫瘍結節の数を測定した。また、実施例1のペプチド及び4T1細胞を注入しないことを除いては、実験群と同様に処理した群(正常群)を対照群として用意した。その結果を図2に示した。図2のグラフにおいて、x軸はそれぞれの群を示し、y軸は腫瘍結節の数を示すように作成した。また、nはそれぞれ群別の個体数を示し、Pは有意確率を示す。図2に示すように、実施例1のペプチドを中農度と高濃度で投与した実験群において、腫瘍結節の数が有意に(P<0.001)減少した。特に、その中で中濃度のペプチドを投与した実験群では、癌転移の抑制効果が最も高かった。
実施例1のペプチドの抗癌効果を実験的に評価した。具体的には、実施例1のペプチドが癌で苦しむ生存している個体に与える影響を評価するため、実施例3と同様の方法で用意した動物モデルを用いて生存率を測定した。
実施例1のペプチドの抗癌効果を実験的に評価した。具体的には、実施例1のペプチドが、癌で苦しむ生存している個体に与える影響を評価するため、B16−BL6マウス黒色腫細胞(韓国細胞株銀行、大韓民国)を適用した動物モデルを用いて生存率を分析した。
実施例1と同様の方法で製造したペプチド500mgを生理食塩水に溶解して10mlの溶液とした。前記溶液を注射剤用アンプルに充填して注射剤を製造する。
Claims (5)
- 配列番号1のアミノ酸配列からなるペプチド、または薬学的に許容可能なその塩。
- 請求項1のペプチドまたは薬学的に許容可能なその塩を含む癌の治療または予防用の薬学組成物。
- 前記癌の治療または予防は、癌細胞の浸潤及び転移の中から選ばれた少なくとも一つを抑制することによりなされる請求項2に記載の薬学組成物。
- 請求項1のペプチドまたは薬学的に許容可能なその塩を用いた癌治療用または予防用の製剤。
- 癌細胞の浸潤及び転移の中から選ばれた少なくとも一つを抑制することに用いられる請求項4に記載の癌治療または予防用の製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2015-0104332 | 2015-07-23 | ||
KR1020150104332A KR101644982B1 (ko) | 2015-07-23 | 2015-07-23 | 신규 펩타이드 및 그 용도 |
PCT/KR2016/008062 WO2017014604A1 (en) | 2015-07-23 | 2016-07-22 | Novel peptide and use thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018520131A JP2018520131A (ja) | 2018-07-26 |
JP6484839B2 true JP6484839B2 (ja) | 2019-03-20 |
Family
ID=56708394
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017565710A Active JP6484839B2 (ja) | 2015-07-23 | 2016-07-22 | 新規ペプチド及びその用途 |
Country Status (10)
Country | Link |
---|---|
US (1) | US10189875B2 (ja) |
EP (1) | EP3325499A4 (ja) |
JP (1) | JP6484839B2 (ja) |
KR (1) | KR101644982B1 (ja) |
CN (1) | CN107787325B (ja) |
AU (1) | AU2016297311B2 (ja) |
BR (1) | BR112018001207A2 (ja) |
CA (1) | CA2992971C (ja) |
RU (1) | RU2693478C1 (ja) |
WO (1) | WO2017014604A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101995768B1 (ko) * | 2019-03-13 | 2019-07-03 | (주)엔솔바이오사이언스 | 신규 펩타이드 및 그 용도 |
KR102417762B1 (ko) * | 2021-11-17 | 2022-07-06 | 주식회사 엔솔바이오사이언스 | 펜타펩타이드 및 그 용도 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5039662A (en) | 1989-05-10 | 1991-08-13 | Monsanto | Peptide with anti-metastasis activity |
US5595756A (en) * | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
US6451969B1 (en) | 1999-01-15 | 2002-09-17 | The Burnham Institute | Methods for inhibiting tumor metastasis, and peptides useful therfor |
ITRM20030386A1 (it) * | 2003-08-05 | 2005-02-06 | Istituto Naz Per Le Malattie Infettive Lazz | Metodo e test diagnostici basati sull'analisi citofluorimetrica dei linfociti t antigene-specifici. |
WO2006084016A1 (en) | 2005-02-01 | 2006-08-10 | Attenuon, Llc | ACID ADDITION SALTS OF Ac-PHSCN-NH2 |
KR100794499B1 (ko) | 2006-05-16 | 2008-01-16 | 주식회사 프로메디텍 | 개구린 5로부터 합성 및 제조된 항생 및 항암 신규펩타이드 유도체 |
KR101061017B1 (ko) * | 2009-10-23 | 2011-08-31 | (주) 수파드엘릭사 | 암세포의 성장 및/또는 전이 억제용 약학 조성물 |
KR101029705B1 (ko) * | 2010-06-30 | 2011-04-18 | (주)엔솔테크 | 신규 펩타이드 및 그 용도 |
KR101500670B1 (ko) | 2010-11-02 | 2015-03-10 | 인하대학교 산학협력단 | 암전이를 억제하는 항원 펩타이드, 이를 포함하는 암전이 백신, 암전이 억제 및 치료용 조성물 그리고 암전이 관련 표적물질 및 암전이 억제물질의 스크린 방법 |
US20130302343A1 (en) * | 2011-01-04 | 2013-11-14 | Charité Universitätsmedizin Berlin | Modulators of il-12 and/or il-23 for the prevention or treatment of alzheimer's disease |
EP2807180B1 (en) * | 2012-01-24 | 2018-03-28 | InterK Peptide Therapeutics Limited | Peptide agents for cancer therapy |
JP6078844B2 (ja) | 2012-09-26 | 2017-02-15 | 公立大学法人大阪市立大学 | 癌免疫療法のためのペプチド及びその利用 |
KR102067613B1 (ko) * | 2013-03-28 | 2020-01-20 | 삼성전자주식회사 | 항 c-Met 항체 및 항 her2 항체를 포함하는 병용 투여용 조성물 |
KR101467676B1 (ko) * | 2013-04-12 | 2014-12-04 | 울산대학교 산학협력단 | 암 표적용 펩타이드 및 이의 의학적 용도 |
-
2015
- 2015-07-23 KR KR1020150104332A patent/KR101644982B1/ko active IP Right Grant
-
2016
- 2016-07-22 CA CA2992971A patent/CA2992971C/en active Active
- 2016-07-22 AU AU2016297311A patent/AU2016297311B2/en active Active
- 2016-07-22 JP JP2017565710A patent/JP6484839B2/ja active Active
- 2016-07-22 WO PCT/KR2016/008062 patent/WO2017014604A1/en active Application Filing
- 2016-07-22 CN CN201680037340.9A patent/CN107787325B/zh active Active
- 2016-07-22 BR BR112018001207A patent/BR112018001207A2/pt active Search and Examination
- 2016-07-22 EP EP16828108.7A patent/EP3325499A4/en active Pending
- 2016-07-22 RU RU2018100003A patent/RU2693478C1/ru active
- 2016-07-22 US US15/741,150 patent/US10189875B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
EP3325499A4 (en) | 2018-12-26 |
WO2017014604A1 (en) | 2017-01-26 |
AU2016297311A1 (en) | 2018-01-18 |
CA2992971A1 (en) | 2017-01-26 |
JP2018520131A (ja) | 2018-07-26 |
US10189875B2 (en) | 2019-01-29 |
RU2693478C1 (ru) | 2019-07-03 |
US20180186834A1 (en) | 2018-07-05 |
EP3325499A1 (en) | 2018-05-30 |
CN107787325B (zh) | 2021-09-10 |
CN107787325A (zh) | 2018-03-09 |
BR112018001207A2 (pt) | 2018-09-25 |
KR101644982B1 (ko) | 2016-08-02 |
AU2016297311B2 (en) | 2018-12-06 |
CA2992971C (en) | 2020-01-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102314231B1 (ko) | 전립선 암 치료용 조성물 | |
JP2018508466A (ja) | S−アルキル化ヘプシジンペプチドならびにその作製及び使用方法 | |
EP2552470B1 (en) | Peptides for promoting angiogenesis and an use thereof | |
MX2011004019A (es) | Conjugados de etoposido y doxorubicina para entrega de farmacos. | |
JP6484839B2 (ja) | 新規ペプチド及びその用途 | |
CN105524139A (zh) | 高活性的肿瘤抑制剂及其制法和应用 | |
US20200085905A1 (en) | Method of treating overweight or obesity comprising administering a pleurotus ostreatus mushroom extract or a composition comprising a pleurotus ostretus mushroom extract | |
TWI496579B (zh) | 類鋅手指胜肽、其表現質體、及包含其之醫藥組成物之用途 | |
KR102017973B1 (ko) | 항-b형 간염 바이러스 x 단백질 폴리펩티드 약제 | |
AU2019202876B2 (en) | Administration of Recombinant Collagen 7 for the Treatment of Age Related Disorders | |
JP2020525478A (ja) | 医薬的特性が改善されたプロドラッグペプチド | |
EP4223305A1 (en) | Wnt signaling pathway inhibitor | |
US9408888B2 (en) | High affinity bivalent helically constrained peptide against cancer | |
US20210070803A1 (en) | Modified peptides and associated methods of use | |
JP6858325B2 (ja) | 新規ペプチド及びその用途 | |
JP7357292B2 (ja) | 癌治療用ペプチド | |
KR20240041399A (ko) | 항암 활성을 갖는 신규한 펩타이드 및 이의 용도 | |
KR101943852B1 (ko) | 신규 펩타이드 및 그 용도 | |
KR20200113476A (ko) | 신규 화합물 및 이를 포함하는 암의 예방 또는 치료용 의약 조성물 | |
CN111732631A (zh) | 一种多肽及其在制备治疗和预防肿瘤的药物中的应用 | |
CN110078811A (zh) | 一种具有抗肿瘤活性的多肽imb-p1及其应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181026 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181218 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190107 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190124 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6484839 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |