Peptide Information

General Information of This Peptide
Peptide ID
PEP00126
Peptide Name
RNWELRLK
Structure
Sequence
RNWELRLK
Peptide Type
Linear
Receptor Name
Receptor tyrosine-protein kinase erbB-2 (ERBB2)
  Receptor Info 
PDC Transmembrane Types Cell-penetrating peptides (CPPs)
Formula
C50H83N17O12
Isosmiles
[H]NCCCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC/N=C(/N)N[H])NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1cn([H])c2ccccc12)NC(=O)[C@H](CC(=O)N[H])NC(=O)[C@H](CCC/N=C(/N)N[H])N[H])C(=O)O
InChI
InChI=1S/C50H83N17O12/c1-26(2)21-35(44(74)61-32(15-10-20-59-50(56)57)42(72)65-36(22-27(3)4)45(75)63-34(48(78)79)14-7-8-18-51)66-43(73)33(16-17-40(69)70)62-46(76)37(23-28-25-60-31-13-6-5-11-29(28)31)67-47(77)38(24-39(53)68)64-41(71)30(52)12-9-19-58-49(54)55/h5-6,11,13,25-27,30,32-38,60H,7-10,12,14-24,51-52H2,1-4H3,(H2,53,68)(H,61,74)(H,62,76)(H,63,75)(H,64,71)(H,65,72)(H,66,73)(H,67,77)(H,69,70)(H,78,79)(H4,54,55,58)(H4,56,57,59)/t30-,32-,33-,34-,35-,36-,37-,38-/m0/s1
InChIKey
LKWNYHMODAEQJB-RRFBFTPKSA-N
Pharmaceutical Properties
Molecule Weight
1114.321
Polar area
518.02
Complexity
1113.640711
xlogp Value
-3.4155
Heavy Count
79
Rot Bonds
40
Hbond acc
14
Hbond Donor
17
Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
DOXO-EMCH-(RNWELRLK-PEG4)2 [Investigative]
 PDC Info 
Discovered Using Cell Line-derived Xenograft Model
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Breast cancer
Efficacy Data Tumor Growth Inhibition value (TGI)
51.1 ± 3.1%
Administration Time 14 days
Administration Dosage 5 mg/kg
MOA of PDC
Tumor-targeting peptide-drug conjugates (PDCs) have become a focus of research in recent years. However, due to the instability of peptides and their short in vivo effective half-life, they have limited clinical application. Herein, we propose a new DOX PDC based on a homodimer HER-2-targeting peptide and acid-sensitive hydrazone bond, which could enhance the anti-tumor effect of DOX and reduce systemic toxicities. The PDC could accurately deliver DOX into HER2-positive SKBR-3 cells, with it showing 2.9 times higher cellular uptake than free DOX and enhanced cytotoxicity with respect to IC50of 140 nM (vs. 410 nM for free DOX). In vitro assays showed that the PDC had high cellular internalization efficiency and cytotoxicity. In vivo anti-tumor experiments indicated that the PDC could significantly inhibit the growth of HER2-positive breast cancer xenografts in mice and reduce the side effects of DOX. In summary, we constructed a novel PDC molecule targeting HER2-positive tumors, which may overcome some deficiencies of DOX in breast cancer therapy.

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Description
In vivo anti-tumor studies were evaluated by using SKBR-3 xenografted (BALB/c nude) mice treated with the PDC, free DOX, or saline. Figure 5a demonstrates that the PDC had a much more powerful anti-tumor effect than free DOX, reducing tumor growth by 51.1 ± 3.1% on day 14 post treatment, while free DOX only achieved a 23.13 ± 2.4% reduction. Additionally, the PDC had a significantly higher tumor weight inhibition of 57.5 ± 3.4% compared to free DOX.

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In Vivo Model SKBR-3 cells female BALB/c mice xenograft model.
In Vitro Model Breast adenocarcinoma SK-BR-3 cell CVCL_0033
Revealed Based on the Cell Line Data
Click To Hide/Show 1 Activity Data Related to This Level
Experiment 1 Reporting the Activity Data of This PDC [1]
Indication Breast cancer
Efficacy Data Half Maximal Inhibitory Concentration (IC50)
140 nM
Administration Time 24 h
Evaluation Method CCK8 assay
MOA of PDC
Tumor-targeting peptide-drug conjugates (PDCs) have become a focus of research in recent years. However, due to the instability of peptides and their short in vivo effective half-life, they have limited clinical application. Herein, we propose a new DOX PDC based on a homodimer HER-2-targeting peptide and acid-sensitive hydrazone bond, which could enhance the anti-tumor effect of DOX and reduce systemic toxicities. The PDC could accurately deliver DOX into HER2-positive SKBR-3 cells, with it showing 2.9 times higher cellular uptake than free DOX and enhanced cytotoxicity with respect to IC50of 140 nM (vs. 410 nM for free DOX). In vitro assays showed that the PDC had high cellular internalization efficiency and cytotoxicity. In vivo anti-tumor experiments indicated that the PDC could significantly inhibit the growth of HER2-positive breast cancer xenografts in mice and reduce the side effects of DOX. In summary, we constructed a novel PDC molecule targeting HER2-positive tumors, which may overcome some deficiencies of DOX in breast cancer therapy.

   Click to Show/Hide
Description
Tumor-targeting peptide-drug conjugates (PDCs) have become a focus of research in recent years. However, due to the instability of peptides and their short in vivo effective half-life, they have limited clinical application. Herein, we propose a new DOX PDC based on a homodimer HER-2-targeting peptide and acid-sensitive hydrazone bond, which could enhance the anti-tumor effect of DOX and reduce systemic toxicities. The PDC could accurately deliver DOX into HER2-positive SKBR-3 cells, with it showing 2.9 times higher cellular uptake than free DOX and enhanced cytotoxicity with respect to IC50of 140 nM (vs. 410 nM for free DOX). In vitro assays showed that the PDC had high cellular internalization efficiency and cytotoxicity. In vivo anti-tumor experiments indicated that the PDC could significantly inhibit the growth of HER2-positive breast cancer xenografts in mice and reduce the side effects of DOX. In summary, we constructed a novel PDC molecule targeting HER2-positive tumors, which may overcome some deficiencies of DOX in breast cancer therapy.

   Click to Show/Hide
In Vitro Model Breast adenocarcinoma SK-BR-3 cell CVCL_0033
References
Ref 1 A Novel Homodimer Peptide-Drug Conjugate Improves the Efficacy of HER2-Positive Breast Cancer Therapy. Int J Mol Sci. 2023 Feb 27;24(5):4590. doi: 10.3390/ijms24054590.