CN113637052A - 一种治疗结肠癌的抑癌蛋白及其药物组合物 - Google Patents
一种治疗结肠癌的抑癌蛋白及其药物组合物 Download PDFInfo
- Publication number
- CN113637052A CN113637052A CN202110937090.7A CN202110937090A CN113637052A CN 113637052 A CN113637052 A CN 113637052A CN 202110937090 A CN202110937090 A CN 202110937090A CN 113637052 A CN113637052 A CN 113637052A
- Authority
- CN
- China
- Prior art keywords
- cancer
- leu
- ala
- colon cancer
- gly
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 67
- 201000011510 cancer Diseases 0.000 title claims abstract description 51
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 41
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 38
- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 29
- 208000029742 colonic neoplasm Diseases 0.000 title claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 17
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960002949 fluorouracil Drugs 0.000 claims abstract description 16
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract 2
- 231100000957 no side effect Toxicity 0.000 abstract 1
- 230000001629 suppression Effects 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 8
- 230000034994 death Effects 0.000 description 7
- 231100000517 death Toxicity 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 238000011580 nude mouse model Methods 0.000 description 6
- 230000009465 prokaryotic expression Effects 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 150000001413 amino acids Chemical group 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 241000699660 Mus musculus Species 0.000 description 4
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 4
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 206010067484 Adverse reaction Diseases 0.000 description 3
- 241000672609 Escherichia coli BL21 Species 0.000 description 3
- 101710188315 Protein X Proteins 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 108010026333 seryl-proline Proteins 0.000 description 3
- YFGUZQQCSDZRBN-DCAQKATOSA-N Asp-Pro-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O YFGUZQQCSDZRBN-DCAQKATOSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- QPRQGENIBFLVEB-BJDJZHNGSA-N Leu-Ala-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O QPRQGENIBFLVEB-BJDJZHNGSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 2
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 108010078144 glutaminyl-glycine Proteins 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 230000005760 tumorsuppression Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 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
- HHGYNJRJIINWAK-FXQIFTODSA-N Ala-Ala-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N HHGYNJRJIINWAK-FXQIFTODSA-N 0.000 description 1
- YYSWCHMLFJLLBJ-ZLUOBGJFSA-N Ala-Ala-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YYSWCHMLFJLLBJ-ZLUOBGJFSA-N 0.000 description 1
- JBVSSSZFNTXJDX-YTLHQDLWSA-N Ala-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)N JBVSSSZFNTXJDX-YTLHQDLWSA-N 0.000 description 1
- JPGBXANAQYHTLA-DRZSPHRISA-N Ala-Gln-Phe Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 JPGBXANAQYHTLA-DRZSPHRISA-N 0.000 description 1
- NJPMYXWVWQWCSR-ACZMJKKPSA-N Ala-Glu-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NJPMYXWVWQWCSR-ACZMJKKPSA-N 0.000 description 1
- WGDNWOMKBUXFHR-BQBZGAKWSA-N Ala-Gly-Arg Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N WGDNWOMKBUXFHR-BQBZGAKWSA-N 0.000 description 1
- SOBIAADAMRHGKH-CIUDSAMLSA-N Ala-Leu-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O SOBIAADAMRHGKH-CIUDSAMLSA-N 0.000 description 1
- MDNAVFBZPROEHO-UHFFFAOYSA-N Ala-Lys-Val Natural products CC(C)C(C(O)=O)NC(=O)C(NC(=O)C(C)N)CCCCN MDNAVFBZPROEHO-UHFFFAOYSA-N 0.000 description 1
- WQLDNOCHHRISMS-NAKRPEOUSA-N Ala-Pro-Ile Chemical compound [H]N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WQLDNOCHHRISMS-NAKRPEOUSA-N 0.000 description 1
- YHBDGLZYNIARKJ-GUBZILKMSA-N Ala-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N YHBDGLZYNIARKJ-GUBZILKMSA-N 0.000 description 1
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 1
- KUFVXLQLDHJVOG-SHGPDSBTSA-N Ala-Thr-Thr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](C)N)O KUFVXLQLDHJVOG-SHGPDSBTSA-N 0.000 description 1
- GHNDBBVSWOWYII-LPEHRKFASA-N Arg-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GHNDBBVSWOWYII-LPEHRKFASA-N 0.000 description 1
- IGULQRCJLQQPSM-DCAQKATOSA-N Arg-Cys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(O)=O IGULQRCJLQQPSM-DCAQKATOSA-N 0.000 description 1
- YNSGXDWWPCGGQS-YUMQZZPRSA-N Arg-Gly-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O YNSGXDWWPCGGQS-YUMQZZPRSA-N 0.000 description 1
- OOIMKQRCPJBGPD-XUXIUFHCSA-N Arg-Ile-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O OOIMKQRCPJBGPD-XUXIUFHCSA-N 0.000 description 1
- GXXWTNKNFFKTJB-NAKRPEOUSA-N Arg-Ile-Ser Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O GXXWTNKNFFKTJB-NAKRPEOUSA-N 0.000 description 1
- ZDBWKBCKYJGKGP-DCAQKATOSA-N Arg-Leu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O ZDBWKBCKYJGKGP-DCAQKATOSA-N 0.000 description 1
- YNDLOUMBVDVALC-ZLUOBGJFSA-N Asn-Ala-Ala Chemical compound C[C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CC(=O)N)N YNDLOUMBVDVALC-ZLUOBGJFSA-N 0.000 description 1
- NUHQMYUWLUSRJX-BIIVOSGPSA-N Asn-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)N)N NUHQMYUWLUSRJX-BIIVOSGPSA-N 0.000 description 1
- GZXOUBTUAUAVHD-ACZMJKKPSA-N Asn-Ser-Glu Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O GZXOUBTUAUAVHD-ACZMJKKPSA-N 0.000 description 1
- AMGQTNHANMRPOE-LKXGYXEUSA-N Asn-Thr-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O AMGQTNHANMRPOE-LKXGYXEUSA-N 0.000 description 1
- VTYQAQFKMQTKQD-ACZMJKKPSA-N Asp-Ala-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(O)=O VTYQAQFKMQTKQD-ACZMJKKPSA-N 0.000 description 1
- XBQSLMACWDXWLJ-GHCJXIJMSA-N Asp-Ala-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XBQSLMACWDXWLJ-GHCJXIJMSA-N 0.000 description 1
- RGKKALNPOYURGE-ZKWXMUAHSA-N Asp-Ala-Val Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)O RGKKALNPOYURGE-ZKWXMUAHSA-N 0.000 description 1
- SARSTIZOZFBDOM-FXQIFTODSA-N Asp-Met-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O SARSTIZOZFBDOM-FXQIFTODSA-N 0.000 description 1
- SFJUYBCDQBAYAJ-YDHLFZDLSA-N Asp-Val-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SFJUYBCDQBAYAJ-YDHLFZDLSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- BGIRVSMUAJMGOK-FXQIFTODSA-N Cys-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CS)N BGIRVSMUAJMGOK-FXQIFTODSA-N 0.000 description 1
- DQUWSUWXPWGTQT-DCAQKATOSA-N Cys-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CS DQUWSUWXPWGTQT-DCAQKATOSA-N 0.000 description 1
- IOLWXFWVYYCVTJ-NRPADANISA-N Cys-Val-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N IOLWXFWVYYCVTJ-NRPADANISA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- WVUZERSNWGUKJY-BPUTZDHNSA-N Gln-Glu-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N WVUZERSNWGUKJY-BPUTZDHNSA-N 0.000 description 1
- VSXBYIJUAXPAAL-WDSKDSINSA-N Gln-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCC(N)=O VSXBYIJUAXPAAL-WDSKDSINSA-N 0.000 description 1
- FGYPOQPQTUNESW-IUCAKERBSA-N Gln-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N FGYPOQPQTUNESW-IUCAKERBSA-N 0.000 description 1
- ZNTDJIMJKNNSLR-RWRJDSDZSA-N Gln-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZNTDJIMJKNNSLR-RWRJDSDZSA-N 0.000 description 1
- QBLMTCRYYTVUQY-GUBZILKMSA-N Gln-Leu-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O QBLMTCRYYTVUQY-GUBZILKMSA-N 0.000 description 1
- ZBKUIQNCRIYVGH-SDDRHHMPSA-N Gln-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZBKUIQNCRIYVGH-SDDRHHMPSA-N 0.000 description 1
- SBCYJMOOHUDWDA-NUMRIWBASA-N Glu-Asp-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SBCYJMOOHUDWDA-NUMRIWBASA-N 0.000 description 1
- AUTNXSQEVVHSJK-YVNDNENWSA-N Glu-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O AUTNXSQEVVHSJK-YVNDNENWSA-N 0.000 description 1
- YLJHCWNDBKKOEB-IHRRRGAJSA-N Glu-Glu-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YLJHCWNDBKKOEB-IHRRRGAJSA-N 0.000 description 1
- VOORMNJKNBGYGK-YUMQZZPRSA-N Glu-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N VOORMNJKNBGYGK-YUMQZZPRSA-N 0.000 description 1
- QDMVXRNLOPTPIE-WDCWCFNPSA-N Glu-Lys-Thr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QDMVXRNLOPTPIE-WDCWCFNPSA-N 0.000 description 1
- SYWCGQOIIARSIX-SRVKXCTJSA-N Glu-Pro-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O SYWCGQOIIARSIX-SRVKXCTJSA-N 0.000 description 1
- PHONXOACARQMPM-BQBZGAKWSA-N Gly-Ala-Met Chemical compound [H]NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(O)=O PHONXOACARQMPM-BQBZGAKWSA-N 0.000 description 1
- KMSGYZQRXPUKGI-BYPYZUCNSA-N Gly-Gly-Asn Chemical compound NCC(=O)NCC(=O)N[C@H](C(O)=O)CC(N)=O KMSGYZQRXPUKGI-BYPYZUCNSA-N 0.000 description 1
- OLPPXYMMIARYAL-QMMMGPOBSA-N Gly-Gly-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)CN OLPPXYMMIARYAL-QMMMGPOBSA-N 0.000 description 1
- YIFUFYZELCMPJP-YUMQZZPRSA-N Gly-Leu-Cys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(O)=O YIFUFYZELCMPJP-YUMQZZPRSA-N 0.000 description 1
- UUYBFNKHOCJCHT-VHSXEESVSA-N Gly-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN UUYBFNKHOCJCHT-VHSXEESVSA-N 0.000 description 1
- DBJYVKDPGIFXFO-BQBZGAKWSA-N Gly-Met-Ala Chemical compound [H]NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(O)=O DBJYVKDPGIFXFO-BQBZGAKWSA-N 0.000 description 1
- SOEGEPHNZOISMT-BYPYZUCNSA-N Gly-Ser-Gly Chemical compound NCC(=O)N[C@@H](CO)C(=O)NCC(O)=O SOEGEPHNZOISMT-BYPYZUCNSA-N 0.000 description 1
- DBUNZBWUWCIELX-JHEQGTHGSA-N Gly-Thr-Glu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O DBUNZBWUWCIELX-JHEQGTHGSA-N 0.000 description 1
- GWNIGUKSRJBIHX-STQMWFEESA-N Gly-Tyr-Arg Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)CN)O GWNIGUKSRJBIHX-STQMWFEESA-N 0.000 description 1
- KSOBNUBCYHGUKH-UWVGGRQHSA-N Gly-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CN KSOBNUBCYHGUKH-UWVGGRQHSA-N 0.000 description 1
- SYMSVYVUSPSAAO-IHRRRGAJSA-N His-Arg-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O SYMSVYVUSPSAAO-IHRRRGAJSA-N 0.000 description 1
- NJZGEXYLSFGPHG-GUBZILKMSA-N His-Gln-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N NJZGEXYLSFGPHG-GUBZILKMSA-N 0.000 description 1
- YADRBUZBKHHDAO-XPUUQOCRSA-N His-Gly-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C)C(O)=O YADRBUZBKHHDAO-XPUUQOCRSA-N 0.000 description 1
- FYTCLUIYTYFGPT-YUMQZZPRSA-N His-Gly-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CO)C(O)=O FYTCLUIYTYFGPT-YUMQZZPRSA-N 0.000 description 1
- QCBYAHHNOHBXIH-UWVGGRQHSA-N His-Pro-Gly Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)C1=CN=CN1 QCBYAHHNOHBXIH-UWVGGRQHSA-N 0.000 description 1
- UPJODPVSKKWGDQ-KLHWPWHYSA-N His-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O UPJODPVSKKWGDQ-KLHWPWHYSA-N 0.000 description 1
- MCGOGXFMKHPMSQ-AVGNSLFASA-N His-Val-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 MCGOGXFMKHPMSQ-AVGNSLFASA-N 0.000 description 1
- USXAYNCLFSUSBA-MGHWNKPDSA-N Ile-Phe-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N USXAYNCLFSUSBA-MGHWNKPDSA-N 0.000 description 1
- VEPIBPGLTLPBDW-URLPEUOOSA-N Ile-Phe-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N VEPIBPGLTLPBDW-URLPEUOOSA-N 0.000 description 1
- KCTIFOCXAIUQQK-QXEWZRGKSA-N Ile-Pro-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O KCTIFOCXAIUQQK-QXEWZRGKSA-N 0.000 description 1
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 1
- LHSGPCFBGJHPCY-UHFFFAOYSA-N L-leucine-L-tyrosine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 LHSGPCFBGJHPCY-UHFFFAOYSA-N 0.000 description 1
- 101710173438 Late L2 mu core protein Proteins 0.000 description 1
- XBBKIIGCUMBKCO-JXUBOQSCSA-N Leu-Ala-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XBBKIIGCUMBKCO-JXUBOQSCSA-N 0.000 description 1
- IBMVEYRWAWIOTN-RWMBFGLXSA-N Leu-Arg-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(O)=O IBMVEYRWAWIOTN-RWMBFGLXSA-N 0.000 description 1
- BAJIJEGGUYXZGC-CIUDSAMLSA-N Leu-Asn-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N BAJIJEGGUYXZGC-CIUDSAMLSA-N 0.000 description 1
- PJYSOYLLTJKZHC-GUBZILKMSA-N Leu-Asp-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(N)=O PJYSOYLLTJKZHC-GUBZILKMSA-N 0.000 description 1
- IIKJNQWOQIWWMR-CIUDSAMLSA-N Leu-Cys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)N IIKJNQWOQIWWMR-CIUDSAMLSA-N 0.000 description 1
- HFBCHNRFRYLZNV-GUBZILKMSA-N Leu-Glu-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HFBCHNRFRYLZNV-GUBZILKMSA-N 0.000 description 1
- CSFVADKICPDRRF-KKUMJFAQSA-N Leu-His-Leu Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C([O-])=O)CC1=CN=CN1 CSFVADKICPDRRF-KKUMJFAQSA-N 0.000 description 1
- YOKVEHGYYQEQOP-QWRGUYRKSA-N Leu-Leu-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YOKVEHGYYQEQOP-QWRGUYRKSA-N 0.000 description 1
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 description 1
- VULJUQZPSOASBZ-SRVKXCTJSA-N Leu-Pro-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O VULJUQZPSOASBZ-SRVKXCTJSA-N 0.000 description 1
- IZPVWNSAVUQBGP-CIUDSAMLSA-N Leu-Ser-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IZPVWNSAVUQBGP-CIUDSAMLSA-N 0.000 description 1
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 1
- KLSUAWUZBMAZCL-RHYQMDGZSA-N Leu-Thr-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(O)=O KLSUAWUZBMAZCL-RHYQMDGZSA-N 0.000 description 1
- UFPLDOKWDNTTRP-ULQDDVLXSA-N Leu-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CC=C(O)C=C1 UFPLDOKWDNTTRP-ULQDDVLXSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- XFIHDSBIPWEYJJ-YUMQZZPRSA-N Lys-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN XFIHDSBIPWEYJJ-YUMQZZPRSA-N 0.000 description 1
- KNKHAVVBVXKOGX-JXUBOQSCSA-N Lys-Ala-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KNKHAVVBVXKOGX-JXUBOQSCSA-N 0.000 description 1
- IRNSXVOWSXSULE-DCAQKATOSA-N Lys-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN IRNSXVOWSXSULE-DCAQKATOSA-N 0.000 description 1
- YVMQJGWLHRWMDF-MNXVOIDGSA-N Lys-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)N YVMQJGWLHRWMDF-MNXVOIDGSA-N 0.000 description 1
- KYNNSEJZFVCDIV-ZPFDUUQYSA-N Lys-Ile-Asn Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O KYNNSEJZFVCDIV-ZPFDUUQYSA-N 0.000 description 1
- CNGOEHJCLVCJHN-SRVKXCTJSA-N Lys-Pro-Glu Chemical compound NCCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O CNGOEHJCLVCJHN-SRVKXCTJSA-N 0.000 description 1
- YRAWWKUTNBILNT-FXQIFTODSA-N Met-Ala-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O YRAWWKUTNBILNT-FXQIFTODSA-N 0.000 description 1
- ZAJNRWKGHWGPDQ-SDDRHHMPSA-N Met-Arg-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N ZAJNRWKGHWGPDQ-SDDRHHMPSA-N 0.000 description 1
- IUYCGMNKIZDRQI-BQBZGAKWSA-N Met-Gly-Ala Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O IUYCGMNKIZDRQI-BQBZGAKWSA-N 0.000 description 1
- OIFHHODAXVWKJN-ULQDDVLXSA-N Met-Phe-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 OIFHHODAXVWKJN-ULQDDVLXSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 1
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- JWQWPTLEOFNCGX-AVGNSLFASA-N Phe-Glu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 JWQWPTLEOFNCGX-AVGNSLFASA-N 0.000 description 1
- LRBSWBVUCLLRLU-BZSNNMDCSA-N Phe-Leu-Lys Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(O)=O LRBSWBVUCLLRLU-BZSNNMDCSA-N 0.000 description 1
- KLXQWABNAWDRAY-ACRUOGEOSA-N Phe-Lys-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 KLXQWABNAWDRAY-ACRUOGEOSA-N 0.000 description 1
- QTVUPXHPSXZJKH-ULQDDVLXSA-N Phe-Met-His Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N QTVUPXHPSXZJKH-ULQDDVLXSA-N 0.000 description 1
- JLLJTMHNXQTMCK-UBHSHLNASA-N Phe-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=CC=C1 JLLJTMHNXQTMCK-UBHSHLNASA-N 0.000 description 1
- XYSXOCIWCPFOCG-IHRRRGAJSA-N Pro-Leu-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O XYSXOCIWCPFOCG-IHRRRGAJSA-N 0.000 description 1
- MCWHYUWXVNRXFV-RWMBFGLXSA-N Pro-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2 MCWHYUWXVNRXFV-RWMBFGLXSA-N 0.000 description 1
- WCNVGGZRTNHOOS-ULQDDVLXSA-N Pro-Lys-Tyr Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O WCNVGGZRTNHOOS-ULQDDVLXSA-N 0.000 description 1
- YDTUEBLEAVANFH-RCWTZXSCSA-N Pro-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 YDTUEBLEAVANFH-RCWTZXSCSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- GXXTUIUYTWGPMV-FXQIFTODSA-N Ser-Arg-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O GXXTUIUYTWGPMV-FXQIFTODSA-N 0.000 description 1
- VMVNCJDKFOQOHM-GUBZILKMSA-N Ser-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N VMVNCJDKFOQOHM-GUBZILKMSA-N 0.000 description 1
- AEGUWTFAQQWVLC-BQBZGAKWSA-N Ser-Gly-Arg Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O AEGUWTFAQQWVLC-BQBZGAKWSA-N 0.000 description 1
- OQPNSDWGAMFJNU-QWRGUYRKSA-N Ser-Gly-Tyr Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 OQPNSDWGAMFJNU-QWRGUYRKSA-N 0.000 description 1
- BEAFYHFQTOTVFS-VGDYDELISA-N Ser-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CO)N BEAFYHFQTOTVFS-VGDYDELISA-N 0.000 description 1
- NLOAIFSWUUFQFR-CIUDSAMLSA-N Ser-Leu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O NLOAIFSWUUFQFR-CIUDSAMLSA-N 0.000 description 1
- YUJLIIRMIAGMCQ-CIUDSAMLSA-N Ser-Leu-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YUJLIIRMIAGMCQ-CIUDSAMLSA-N 0.000 description 1
- PLQWGQUNUPMNOD-KKUMJFAQSA-N Ser-Tyr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(O)=O PLQWGQUNUPMNOD-KKUMJFAQSA-N 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- CEXFELBFVHLYDZ-XGEHTFHBSA-N Thr-Arg-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CEXFELBFVHLYDZ-XGEHTFHBSA-N 0.000 description 1
- APIQKJYZDWVOCE-VEVYYDQMSA-N Thr-Asp-Met Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(O)=O APIQKJYZDWVOCE-VEVYYDQMSA-N 0.000 description 1
- DSLHSTIUAPKERR-XGEHTFHBSA-N Thr-Cys-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(O)=O DSLHSTIUAPKERR-XGEHTFHBSA-N 0.000 description 1
- MECLEFZMPPOEAC-VOAKCMCISA-N Thr-Leu-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)N)O MECLEFZMPPOEAC-VOAKCMCISA-N 0.000 description 1
- LKJCABTUFGTPPY-HJGDQZAQSA-N Thr-Pro-Gln Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O LKJCABTUFGTPPY-HJGDQZAQSA-N 0.000 description 1
- VUXIQSUQQYNLJP-XAVMHZPKSA-N Thr-Ser-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N)O VUXIQSUQQYNLJP-XAVMHZPKSA-N 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- QNMIVTOQXUSGLN-SZMVWBNQSA-N Trp-Arg-Arg Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 QNMIVTOQXUSGLN-SZMVWBNQSA-N 0.000 description 1
- WVHUFSCKCBQKJW-HKUYNNGSSA-N Trp-Gly-Tyr Chemical compound C([C@H](NC(=O)CNC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)N)C(O)=O)C1=CC=C(O)C=C1 WVHUFSCKCBQKJW-HKUYNNGSSA-N 0.000 description 1
- GAYLGYUVTDMLKC-UWJYBYFXSA-N Tyr-Asp-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 GAYLGYUVTDMLKC-UWJYBYFXSA-N 0.000 description 1
- WVRUKYLYMFGKAN-IHRRRGAJSA-N Tyr-Glu-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 WVRUKYLYMFGKAN-IHRRRGAJSA-N 0.000 description 1
- NKUGCYDFQKFVOJ-JYJNAYRXSA-N Tyr-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NKUGCYDFQKFVOJ-JYJNAYRXSA-N 0.000 description 1
- LDKDSFQSEUOCOO-RPTUDFQQSA-N Tyr-Thr-Phe Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LDKDSFQSEUOCOO-RPTUDFQQSA-N 0.000 description 1
- AFWXOGHZEKARFH-ACRUOGEOSA-N Tyr-Tyr-His Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CC=C(O)C=C1 AFWXOGHZEKARFH-ACRUOGEOSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- RUCNAYOMFXRIKJ-DCAQKATOSA-N Val-Ala-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN RUCNAYOMFXRIKJ-DCAQKATOSA-N 0.000 description 1
- VMRFIKXKOFNMHW-GUBZILKMSA-N Val-Arg-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N VMRFIKXKOFNMHW-GUBZILKMSA-N 0.000 description 1
- XEYUMGGWQCIWAR-XVKPBYJWSA-N Val-Gln-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)NCC(=O)O)N XEYUMGGWQCIWAR-XVKPBYJWSA-N 0.000 description 1
- UZDHNIJRRTUKKC-DLOVCJGASA-N Val-Gln-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N UZDHNIJRRTUKKC-DLOVCJGASA-N 0.000 description 1
- OTJMMKPMLUNTQT-AVGNSLFASA-N Val-Leu-Arg Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N OTJMMKPMLUNTQT-AVGNSLFASA-N 0.000 description 1
- BTWMICVCQLKKNR-DCAQKATOSA-N Val-Leu-Ser Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C([O-])=O BTWMICVCQLKKNR-DCAQKATOSA-N 0.000 description 1
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 1
- VCIYTVOBLZHFSC-XHSDSOJGSA-N Val-Phe-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N2CCC[C@@H]2C(=O)O)N VCIYTVOBLZHFSC-XHSDSOJGSA-N 0.000 description 1
- 101710086987 X protein Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000001099 axilla Anatomy 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 108010042598 glutamyl-aspartyl-glycine Proteins 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 1
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 1
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 1
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 108010028295 histidylhistidine Proteins 0.000 description 1
- 108010025306 histidylleucine Proteins 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 108010034529 leucyl-lysine Proteins 0.000 description 1
- 108010090333 leucyl-lysyl-proline Proteins 0.000 description 1
- 108010012058 leucyltyrosine Proteins 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 108010003700 lysyl aspartic acid Proteins 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 108010005942 methionylglycine Proteins 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 108010024654 phenylalanyl-prolyl-alanine Proteins 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108010020755 prolyl-glycyl-glycine Proteins 0.000 description 1
- 108010053725 prolylvaline Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 239000000225 tumor suppressor protein Substances 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 108010027345 wheylin-1 peptide Proteins 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及一种用于治疗结肠癌抑癌蛋白，所述抑癌蛋白能有效地抑制结肠癌细胞的生长，且其与氟尿嘧啶组合能显著增强后者的抑癌效果。因此，本发明也提供一种治疗结肠癌的药物组合物，组合物包含本发明的抑癌蛋白和氟尿嘧啶。本发明的组合物能够显著抑制结肠癌肿瘤生长，且不存在副作用，具备良好的临床和市场推广价值。
Description
技术领域
本发明涉及生物医药技术领域，具体涉及一种人类抑癌蛋白及其在制备治疗结肠癌的药物组合物中的用途。
背景技术
癌症是严重危害人类健康的恶性疾病，世界卫生组织国际癌症研究机构(IARC)发布的2020年全球最新癌症负担数据看，2020年全球新发癌症病例1929万例，其中中国新发癌症457万人，占全球23.7％，由于中国是世界第一人口大国，癌症新发人数远超世界其他国家。2020年全球癌症死亡病例996万例，其中中国癌症死亡人数300万，占癌症死亡总人数30％，主要由于中国癌症患病人数多，癌症死亡人数位居全球第一。全球发病率前十的癌症分别是：乳腺癌、肺癌、结直肠癌、前列腺癌、胃癌、肝癌、宫颈癌、食管癌、甲状腺癌、膀胱癌。
结肠癌(Colorectal cancer,CRC)是人类高发消化道恶性肿瘤之一，好发于直肠与乙状结肠交界处，其发病率一直呈上升趋势，全球每年患结肠癌的病例超过1亿人，在全球恶性肿瘤发病率中已上升至第三位，其死亡率居恶性肿瘤死因的第二位。结肠癌以40～50岁年龄组发病率最高，男女之比为2～3：1。目前，结肠癌的治疗手段以手术治疗为主，辅以全身或局部化疗、放疗等治疗手段，但现有药物通常具有毒副作用较大、药物用量大、容易产生后天耐药性等缺点，这会对患者的治疗造成影响。近些年，生物药在肿瘤治疗领域逐渐成为热点，如利用抑癌蛋白的生物靶向治疗。利用抑癌基因来治疗或辅助治疗癌症的基因治疗方法逐渐成为一大研究方向。在抑癌基因通过其产物-抑癌蛋白抑制癌基因的表达达到治疗癌症的目的。抑癌蛋白的作用靶向性强，对正常细胞没有影响，并且效果较理想，因此抑癌蛋白、基因是一种很有发展前途的在肿瘤抑制药物和生物制剂中的用途。
发明内容
本发明的目的是提供一种抑癌蛋白，该蛋白能有效地抑制结肠癌的生长，尤其与氟尿嘧啶联合使用，更能取得优异的治疗效果。
本发明的另一目的在于提供一种用于治疗结肠癌的药物组合物，所述药物组合物中包含本发明的抑癌蛋白，优选进一步包含氟尿嘧啶和抑癌蛋白的组合。
本发明还涉及一种结肠癌治疗方法，所述方法包括给予患者施用有销量的抑癌蛋白或包含所述抑癌蛋白的药物组合物。
本发明所述的抑癌蛋白序列如SEQ ID NO.1所示。
本发明具体提供如下技术方案：
本发明提供一种用于治疗结肠癌的抑癌蛋白，所述抑癌蛋白能有效地抑制结肠癌的生长，其氨基酸序列如SEQ ID NO.1所示。
本发明提供一种用于治疗结肠癌的药物组合物，所述药物组合物包含本发明的抑癌蛋白，所述抑癌蛋白的氨基酸序列如SEQ ID NO.1所示。
本发明提供一种抑癌蛋白在制备治疗结肠癌的药物组合物中的用途，所述抑癌蛋白的氨基酸序列如SEQ ID NO.1所示。
优选地，本发明的药物组合物还含有氟尿嘧啶，所述氟尿嘧啶与抑癌蛋白的重量比为1:10-2:1，更优选地，两者的比例为1:1。
本发明的抑癌蛋白是本申请发明人在前期筛选获得的一种能够与乙型肝炎病毒(HBV)的X蛋白(HBx)相互作用的蛋白A的突变体。蛋白A是本申请发明人以乙型肝炎病毒(HBV)的X蛋白(HBx)作为诱饵，通过酵母双杂交技术筛选得到的一种蛋白，在该蛋白虽然具备一定的抑癌作用，但作用较弱，在对其进行突变研究过程中，发明人得到本申请的抑癌蛋白，本申请的抑癌蛋白不仅单独使用具备一定的抑制癌细胞作用，申请人更是意外发现，本发明的抑癌蛋白更是能显著增强氟尿嘧啶的抑癌作用。本发明的抑癌蛋白的氨基酸序列如SEQ ID NO.1所示。
本发明的抑癌蛋白通过构建重组表达大肠杆菌制备得到，具体方法为：合成表达SEQ ID NO.1所示抑癌蛋白的编码基因，将所述编码基因克隆插入到原核表达载体pET28a上得到抑癌蛋白的原核表达载体，表达载体然后转化大肠杆菌BL21，筛选阳性克隆并测序验证。将筛选到的阳性菌株培养纯化得到抑癌蛋白。
具体实施方式
下面结合实施例对本发明作进一步详细的说明。以下实施例仅用于说明本发明而不用于限制本发明的范围。实施例中未注明具体条件的实验方法，通常按照常规条件，或按照制造厂商所建议的条件。
实施例1：抑癌蛋白的制备和纯化
(1)抑癌蛋白的原核表达载体的构建：根据SEQ ID NO.1所示氨基酸序列，设计其并合成其编码序列，将其克隆到原核表达载体pET28a上得到原核表达载体，构建的原核表达载体然后转化大肠杆菌BL21，筛选阳性克隆并测序，证实构建的重组大肠杆菌BL21表达的即为SEQ ID NO.1所示的抑癌蛋白。
(2)抑癌蛋白的制备和纯化：将上述构建的重组菌株接种于浓度为50μg/ml的氨苄抗菌素的液体培养基中，37℃振荡培养至600nm吸光度值为1.5～2，IPTG(浓度为0.5mol/L)诱导表达，37℃振荡培养5小时，6000转/分钟离心15分钟收集菌体，超声破碎1-2分钟，10000转/分钟离心6分钟，弃上清，沉淀用磷酸盐缓冲液(pH7.5)重悬，再10000转/分钟离心6分钟，弃上清取沉淀，如此反复洗涤3次，即得到纯化抑癌蛋白。上述过程中液体培养基为：1升水中溶解蛋白胨15g，酵母提取物6g，NaCl 6g。
实施例2：抑癌蛋白抗肿瘤活性分析(抑瘤实验)
(1)实验动物、细胞及耗材
BALB/c品系裸鼠，6-8周齢，雌性，体重在16-18g之间；HCT116细胞系；生理盐水；0.4mm无菌注射针。
(2)HCT-116结肠癌裸鼠模型的构建
SPF级条件下，将健康的裸鼠于层流架中喂养3-6天，对裸鼠皮肤使用酒精进行多次擦拭消毒，用注射器将富集的HCT116细胞注入裸鼠右前肢腋下，每只注射1.2x107个细胞，每日观察小鼠情况，确认成瘤状况，并记录每日肿瘤大小，选取肿瘤生长至4-6mm的荷瘤小鼠进行实验。
(3)抑癌蛋白抑瘤实验
选择48只荷瘤小鼠，平均分为4组进行通过尾静脉注射的方式给予本申请抑癌蛋白的治疗，其中一组注射生理盐水(0.1L/kg)作为对照组，实验组按注射剂量分为三组(20mg/kg、50mg/kg、100mg.kg)，连续治疗4周，每周注射一次，各组均未出现显著的不良反应。实验结束后，将小鼠处死后解剖，分离肿瘤组织并称重，通过与对照组对比后计算出肿瘤抑制率。具体结果如下表1：
| 样本量(只) | 肿瘤平均重量(g) | 肿瘤抑制率(％) | |
| 对照组 | 12 | 2.03 | |
| 实验组1(10mg/kg) | 12 | 1.56 | 23.2 |
| 实验组2(50mg/kg) | 12 | 0.93 | 54.2 |
| 实验组3(100mg/kg) | 12 | 0.91 | 55.2 |
由上表实验结果可见，本申请抑癌蛋白能够有效抑制结肠癌肿瘤生长，肿瘤抑制效率高至55.2％。
实施例3：抑癌蛋白和氟尿嘧啶抗肿瘤活性分析(抑瘤实验)
实验动物、细胞及耗材及HCT-116结肠癌裸鼠模型的构建同实施例1
实验方法：
选择72只荷瘤小鼠，平均分为6组进行通过尾静脉注射的方式进行治疗，其中一组注射生理盐水(0.1L/kg)作为对照组，实验组按注射剂量分为5组，分别为氟尿嘧啶高剂量组(25mg/kg)、氟尿嘧啶低剂量组(20mg/kg)、混合组1(氟尿嘧啶20mg/kg+抑癌蛋白20mg/kg)、混合组2(氟尿嘧啶20mg/kg+抑癌蛋白50mg/kg)、混合组3(氟尿嘧啶20mg/kg+抑癌蛋白100mg/kg)，连续治疗4周，每周注射一次，各组均未出现显著的不良反应。实验结束后，将小鼠处死后解剖，分离肿瘤组织并称重，通过与对照组对比后计算出肿瘤抑制率。具体结果如下表2：
根据本实验结果可知，氟尿嘧啶组高剂量与低剂量之间几乎无差异，混合组之间差异较小，但氟尿嘧啶与本申请抑癌蛋白组合的抑癌率达到惊人的83.9％，而所有实验小鼠未见明显不良反应。说明本发明的抑癌蛋白能够有效抑制结肠癌细胞生长，其与氟尿嘧啶组合使用的效果更加优异。
序列表
<110> 牡丹江医学院
<120> 一种治疗结肠癌的抑癌蛋白及其药物组合物
<130> CP2021154
<141> 2021-08-16
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 489
<212> PRT
<213> 抑癌突变蛋白(tumor suppressor protein)
<400> 1
Met Ala Ala Ser Gly Arg Gly Leu Cys Lys Ala Val Ala Ala Ser Pro
1 5 10 15
Phe Pro Ala Trp Arg Arg Asp Val Phe Pro Lys Tyr Glu Glu Phe Gly
20 25 30
Ala Leu Ser Asp Ala Ile Ala Ser Ser Ala Thr Thr His Gly Ala Ser
35 40 45
Ile Phe Thr Glu Lys Thr Val Ala Lys Val Gln Val Asn Ser Glu Gly
50 55 60
Cys Val Gln Gly Val Val Leu Glu Asp Gly Thr Glu Val Arg Ser Lys
65 70 75 80
Met Phe Leu Ala Ala Arg Asn Ala Pro Arg Gly Gln Pro Leu Pro His
85 90 95
His Gln Cys Ser Ile His Leu Asn Cys Glu Asp Thr Leu Leu Leu Phe
100 105 110
Gly Leu Pro Gly Gly Asn Ile Phe His Cys Ala Met Ser Leu Asp Gln
115 120 125
Leu Tyr Met His Arg Leu Ala Leu Ala Ile Asp Pro Leu Leu Cys Ala
130 135 140
Ala Pro Val Asp Met Ala Val Ala Ala Thr Glu Glu Ile Ile Pro Gly
145 150 155 160
Phe Lys Phe Ser Arg Ala Ser Tyr Leu Leu Ser Leu Leu Arg Pro Gln
165 170 175
Gly Gly Leu Lys Pro Glu Tyr Asp Ala Val Val Leu Arg Leu His Leu
180 185 190
Arg Asn Pro Tyr Thr Phe Thr Pro Gln His Gly Ser Leu Ser Asp Arg
195 200 205
Met Arg Pro Arg Cys Leu Leu Leu Gly Thr Asp Met Ala Glu Asn Gln
210 215 220
Lys Gln Ile Ala Gln Phe Ser Gln Lys Asp Ala Gln Val Phe Pro Lys
225 230 235 240
Tyr Glu Glu Phe Met His Arg Leu Ala Leu Ala Ile Asp Pro Leu Leu
245 250 255
Asp Ala Ala Pro Val Asp Met Ala Tyr Leu Gln Arg Leu Gly Val Asn
260 265 270
Thr Ala Val Phe Glu Arg Arg His Val Leu Gly Gly Ala Ala Val Gly
275 280 285
Ser Gly Tyr Val Leu Leu His His Val Met Gly Gly Leu Glu Gly Met
290 295 300
Gln Gly Ala Trp Gly Tyr Val Gln Gly Gly Met Ala Gln Leu Pro Arg
305 310 315 320
Tyr Tyr His Val Leu Thr Ala Pro Ile Thr Cys Val Leu Asp Gln Trp
325 330 335
Phe Glu Ser Glu Pro Leu Lys Ala Thr Leu Ala Thr Asp Ala Val Ile
340 345 350
Gly Ala Met Thr Ser Pro His Thr Pro Val Leu Ser Asn Thr Ser Pro
355 360 365
Gln Ile Thr Phe Leu Lys Leu Thr Pro Gln Glu Trp Leu Pro Glu Glu
370 375 380
Phe Leu Glu Ala Ala Phe Gln His Gly Ser Leu Leu Gln Arg Met Arg
385 390 395 400
Ser Leu Ser Thr Leu Lys Pro Leu Leu Lys Ala Gly Arg Ile Leu Gly
405 410 415
Arg Ile Ser Gln Leu Asp Thr Arg Ser Pro Val Thr Lys Ile Asn Val
420 425 430
Ala Val Asp Arg Leu Pro Ser Phe Ala Arg Pro Val Pro Leu His Ser
435 440 445
Gly Tyr Arg Cys Pro Leu Gln Gly Leu Tyr Leu Gln Gly Ser Gly Ala
450 455 460
His Pro Gly Gly Gly Val Met Gly Ala Ala Gly Arg Asn Ala Ala His
465 470 475 480
Val Ala Phe Arg Asp Leu Lys Ser Met
485
Claims (5)
1.一种用于治疗结肠癌的抑癌蛋白，其特征在于：所述抑癌蛋白的氨基酸序列如SEQID NO.1所示。
2.一种用于治疗结肠癌的药物组合物，所述药物组合物包含权利要求1所述的抑癌蛋白。
3.根据权利要求2所述的药物组合物，其特征在于：所述药物组合物还含有氟尿嘧啶。
4.权利要求2-3任意一项所述的药物组合物，其特征在于：所述药物组合物中氟尿嘧啶与抑癌蛋白的重量比为1:10-2:1。
5.根据权利要求4所述的药物组合物，其特征在于：所述药物组合物中氟尿嘧啶与抑癌蛋白的重量比为1:1。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110937090.7A CN113637052A (zh) | 2021-08-16 | 2021-08-16 | 一种治疗结肠癌的抑癌蛋白及其药物组合物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110937090.7A CN113637052A (zh) | 2021-08-16 | 2021-08-16 | 一种治疗结肠癌的抑癌蛋白及其药物组合物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113637052A true CN113637052A (zh) | 2021-11-12 |
Family
ID=78421981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110937090.7A Pending CN113637052A (zh) | 2021-08-16 | 2021-08-16 | 一种治疗结肠癌的抑癌蛋白及其药物组合物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113637052A (zh) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1876681A (zh) * | 2006-05-26 | 2006-12-13 | 武汉大学 | 抑癌蛋白及其基因和用途 |
-
2021
- 2021-08-16 CN CN202110937090.7A patent/CN113637052A/zh active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1876681A (zh) * | 2006-05-26 | 2006-12-13 | 武汉大学 | 抑癌蛋白及其基因和用途 |
Non-Patent Citations (7)
| Title |
|---|
| 李丹,王小众,陈治新,黄月红,于皆平,陶其敏: "酵母双杂合体系筛选乙型肝炎病毒X蛋白结合蛋白", 癌症, no. 05 * |
| 梁耀东;成军;李强;王琳;陆荫英;吴君;程明亮;: "酵母双杂交技术筛选人白细胞中与乙型肝炎病毒X蛋白结合蛋白基因", 世界华人消化杂志, no. 12 * |
| 焦佰海;文艳;刘晓佳;冯悦;张阿梅;刘丽;夏雪山;: "CytoTrap酵母双杂交筛选与乙型肝炎病毒HBx蛋白相互作用的肝细胞蛋白", 南方医科大学学报, no. 04 * |
| 王琳;李克;成军;张健;邵清;: "乙型肝炎病毒X蛋白结合蛋白", 世界华人消化杂志, no. 12 * |
| 肖鸿敏;任建林;潘金水;施华秀;许鸿志;周飞;董菁;: "乙型肝炎病毒前-X融合蛋白结合蛋白的筛选", 中国肝脏病杂志(电子版), no. 02 * |
| 陈婉南;刘玲玲;吴云丽;焦伯延;林万松;林旭;: "酵母双杂交筛选与乙型肝炎病毒表面抗原中蛋白相互作用的肝细胞蛋白", 中国人兽共患病学报, no. 10 * |
| 陈芸;王小众;: "HBV X蛋白与氧化应激的相关性", 胃肠病学和肝病学杂志, no. 02 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3360893A1 (en) | High-affinity and soluble pdl-1 molecule | |
| CN106632682A (zh) | 融合蛋白ifn-elp及其应用 | |
| CN104231068A (zh) | 人白细胞介素ii突变体及其应用 | |
| US20120195895A1 (en) | Fusion Protein of an Anti-CD20 Antibody Fab Fragment and Lidamycin, a Method for Preparing the Same, and the Use Thereof | |
| CN107056887B (zh) | 一种多肽及其在制备治疗和预防肿瘤的药物中的应用 | |
| CN111777667B (zh) | 小肽及其在制备免疫调节药物中的应用 | |
| CN113292656B (zh) | 用于防治肥胖的中脑星形胶质细胞源性神经营养因子的融合蛋白 | |
| CN113637052A (zh) | 一种治疗结肠癌的抑癌蛋白及其药物组合物 | |
| JP5234846B2 (ja) | 改変ヨウ化ナトリウム共輸送体タンパク質及びその使用 | |
| CN113956344A (zh) | 一种新型治疗肝癌的fgf类似物及其应用 | |
| CN114848838A (zh) | 一种包括树突细胞外泌体的药物组合物及其应用 | |
| CN101144081B (zh) | 核苷酸分子trail及其在制备治疗肿瘤药物中的应用 | |
| CN103865899B (zh) | 具有vegfr2/kdr受体特异性的融合毒素及其编码基因与应用 | |
| CN114404598A (zh) | 脆弱拟杆菌荚膜多糖a联合pd-1抑制剂在制备治疗皮肤肿瘤的药物中的应用 | |
| CN112341523A (zh) | Dleu2编码的小肽及其在制备免疫调节药物中的应用 | |
| CN110101843A (zh) | 一种抗肿瘤蛋白质及其应用 | |
| CN114316018A (zh) | 一种fgf21蛋白类似物及其应用 | |
| CN116057071B (zh) | 重组灵芝免疫调节蛋白新突变体及其应用 | |
| CN111574590B (zh) | 一种具有抗肿瘤功能的多肽及其应用 | |
| CN116059387B (zh) | 一种抗胰腺癌的疫苗、及其医药用途 | |
| CN113912699A (zh) | 一种新型治疗乳腺癌的fgf类似物及其应用 | |
| CN112794902B (zh) | AP-2alpha抗体及其在制备宫颈癌药物中的用途 | |
| CN114522241B (zh) | 一种铝纳米晶复合免疫药物及其制备方法和应用 | |
| CN111912989B (zh) | 一种预测免疫检查点抑制剂对癌症患者的疗效的试剂盒 | |
| CN109419795B (zh) | 一种治疗肿瘤坏死因子家族相关疾病的联合用药物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20211112 |
|
| WD01 | Invention patent application deemed withdrawn after publication |