Cancer-targeting peptides and uses thereof in cancer treatment and diagnosis
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/00
A61K-031/496
A61K-047/48
A61K-045/06
A61K-038/10
A61K-049/00
C07K-005/117
A61K-031/337
C07K-007/08
A61K-031/475
A61K-051/12
A61K-031/704
A61K-009/127
출원번호
US-0816613
(2011-10-25)
등록번호
US-8846623
(2014-09-30)
국제출원번호
PCT/US2011/057637
(2011-10-25)
§371/§102 date
20130212
(20130212)
국제공개번호
WO2012/061113
(2012-05-10)
발명자
/ 주소
Yu, John
Yu, Alice L.
Wu, H. C.
Wang, Sheng-Hung
Chen, I-Ju
출원인 / 주소
Academia Sinica
대리인 / 주소
Wolf, Greenfield & Sacks, P.C.
인용정보
피인용 횟수 :
0인용 특허 :
10
초록
Cancer-targeting peptides having a PX1LX2 motif, in which X1 is His or an amino acid residue with a hydrophobic side chain and X2 is Pro, Phe, or Trp. Also disclosed herein are conjugates containing the cancer-targeting peptides and uses thereof in cancer treatment and diagnosis.
대표청구항▼
1. An isolated peptide consisting essentially of the amino acid sequence RLLDTNRPX1LX2Y (SEQ ID NO:2), in which X1 is H or an amino acid with a hydrophobic side chain, X2 is P, F, or W, wherein when X1 is L, X2 is not P, and when X2 is P, X1 is not L, and wherein the peptide binds to human glucose-r
1. An isolated peptide consisting essentially of the amino acid sequence RLLDTNRPX1LX2Y (SEQ ID NO:2), in which X1 is H or an amino acid with a hydrophobic side chain, X2 is P, F, or W, wherein when X1 is L, X2 is not P, and when X2 is P, X1 is not L, and wherein the peptide binds to human glucose-regulated protein 78 (GRP-78). 2. The isolated peptide of claim 1, wherein X1 is L, H, F, or W. 3. The isolated peptide of claim 1, wherein the peptide is RLLDTNRPX1LX2Y (SEQ ID NO:2). 4. The isolated peptide of claim 1, wherein the peptide consisting essentially of an amino acid sequence selected from the group consisting of RLLDTNRPFLPY (P-6) (SEQ ID NO:3), RLLDTNRPHLWY (P-12) (SEQ ID NO:4), RLLDTNRPFLFY (P-13) (SEQ ID NO:5), RLLDTNRPFLWY (PB-1) (SEQ ID No:11) and RLLDTNRPYLWY (PB-2) (SEQ ID No:12). 5. The isolated peptide of claim 4, wherein the peptide is selected from the group consisting of RLLDTNRPFLPY (P-6) (SEQ ID NO:3), RLLDTNRPHLWY (P-12) (SEQ ID NO:4), RLLDTNRPFLFY (P-13) (SEQ ID NO:5), RLLDTNRPFLWY (PB-1) (SEQ ID No:11) and RLLDTNRPYLWY (PB-2) (SEQ ID No:12). 6. A composition comprising (a) the peptide of claim 1, and (b) an anti-cancer agent. 7. The composition of claim 6, wherein the composition further comprises a vehicle carrier. 8. The composition of claim 7, wherein the vehicle carrier is a liposome, which encapsulates the anti-cancer agent, and wherein the peptide is attached on the surface of the liposome. 9. The composition of claim 6, wherein the peptide is pegylated. 10. The composition of claim 6, wherein the composition comprises an anti-cancer agent, which is doxorubicin, vinorelbine, vincristine, paclitaxel or lurtotecan. 11. The composition of claim 6, wherein the composition is a pharmaceutical composition, which further comprises a pharmaceutically acceptable carrier. 12. A method for delivering an anti-cancer agent to cancer cells, comprising contacting cancer cells or cells that express GRP-78 with the composition of claim 6. 13. The method of claim 12, wherein the contacting step is performed by administering the composition to a subject having or suspected of having cancer cells expressing GRP-78. 14. The method of claim 13, wherein the cancer cells expressing GRP-78 are breast cancer cells, hepatocellular carcinoma cells, prostate cancer cells, lung cancer cells, ovarian cancer cells, kidney cancer cells, uterine cervical cancer cells, melanoma cells, embryonal carcinoma cells, leukemia cells, or osteosarcoma cells. 15. The method of claim 13, wherein the subject has or is suspected of having breast cancer stem cells expressing GRP-78. 16. The method of claim 12, wherein the composition comprises an anti-cancer agent in an amount effective in treating cancer. 17. A method for treating cancer that expresses GRP-78, comprising administering to a subject in need thereof the composition of claim 11, wherein the composition comprises anti-cancer agent attached to the peptide, and wherein the anti-cancer agent is in an amount effective in treating cancer. 18. The method of claim 17, wherein the composition further comprises a liposome, which encapsulates the anti-cancer agent, and wherein the peptide is attached on the surface of the liposome. 19. The isolated peptide of claim 1, wherein the peptide includes up to 50 amino acid residues. 20. The isolated peptide of claim 19, wherein the peptide includes up to 20 amino acid residues.
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Muller,George W.; Man,Hon Wah; Zhang,Weihong, Fluoroalkoxy-substituted 1,3-dihydro-isoindolyl compounds and their pharmaceutical uses.
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