Peptide Information
General Information of This Peptide
| Peptide ID |
PEP00009
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| Peptide Name |
ApoA-1 mimic peptide
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| Structure |
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| Sequence |
CGFAEKFKEAVKDYFAKFWD-NH2
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| Peptide Type |
Linear
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| PDC Transmembrane Types | Cell targeting peptides (CTPs) | |||||
| Formula |
C117H161N25O30S
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| Isosmiles |
[H]NCCCC[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O[H])cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN[H])NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN[H])NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCCN[H])NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@H](CS[H])N[H])C(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1cn([H])c2ccccc12)C(=O)N[C@@H](CC(=O)O)C(=O)O
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| InChI |
InChI=1S/C117H161N25O30S/c1-65(2)98(142-101(155)68(5)125-103(157)83(46-48-94(145)146)133-104(158)80(39-21-25-51-119)132-111(165)87(56-71-32-14-8-15-33-71)135-106(160)81(40-22-26-52-120)131-108(162)84(47-49-95(147)148)130-100(154)67(4)126-109(163)85(54-69-28-10-6-11-29-69)128-93(144)63-124-102(156)77(122)64-173)116(170)134-82(41-23-27-53-121)107(161)140-91(60-96(149)150)115(169)138-89(58-73-42-44-75(143)45-43-73)112(166)137-86(55-70-30-12-7-13-31-70)110(164)127-66(3)99(153)129-79(38-20-24-50-118)105(159)136-88(57-72-34-16-9-17-35-72)113(167)139-90(114(168)141-92(117(171)172)61-97(151)152)59-74-62-123-78-37-19-18-36-76(74)78/h6-19,28-37,42-45,62,65-68,77,79-92,98,123,143,173H,20-27,38-41,46-61,63-64,118-122H2,1-5H3,(H,124,156)(H,125,157)(H,126,163)(H,127,164)(H,128,144)(H,129,153)(H,130,154)(H,131,162)(H,132,165)(H,133,158)(H,134,170)(H,135,160)(H,136,159)(H,137,166)(H,138,169)(H,139,167)(H,140,161)(H,141,168)(H,142,155)(H,145,146)(H,147,148)(H,149,150)(H,151,152)(H,171,172)/t66-,67-,68-,77-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,92-,98-/m0/s1
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| InChIKey |
ATAWKVGEOOCSFU-JMZLZLHBSA-N
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| Pharmaceutical Properties |
Molecule Weight
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2429.787
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Polar area
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905.52
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Complexity
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2428.15619
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xlogp Value
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-3.2755
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Heavy Count
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173
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Rot Bonds
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86
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Hbond acc
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31
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Hbond Donor
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32
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Each Peptide-drug Conjugate Related to This Peptide
Full Information of The Activity Data of The PDC(s) Related to This Peptide
DOX-ApoA-1 mimic peptide [Investigative]
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Breast cancer | ||||
| Efficacy Data | Tumor Growth Inhibition value (TGI) |
83%
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| Administration Time | 15 days | ||||
| MOA of PDC |
Herein, we report a dual-functional sHDL (DP-sHDL) that is co-assembled from DOX-ApoA1 mimetic peptide conjugate, PSB-603 (an A2BR inhibitor), phospholipid and cholesterol oleate (CO) through a microfluidic-based methodology. We expect that DP-sHDL could accumulate in tumor, where they can target cancerous cells, CAF and tumor-associated macrophages (TAMs). The DOX would induce the ICD of cancer cells and promote DC maturation and T lymphocyte infiltration and activity. PSB-603 is expected to block the A2BR, which would down-regulate CD73 and thus ADO, leading to a decrease in the intratumoral densities of several immunosuppressive cells. By simultaneously activating anti-tumor immunity and relieving immunosuppressive microenvironment, DP-sHDL may inhibit TNBC tumor growth and prolong the survival of animals, which could be further improved when used in combination with an immune checkpoint inhibitor.
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| Description |
Given the potent effects of DP-sHDL in boosting anti-tumor immunity and relieving immunosuppressive microenvironment, its efficacy in treating TNBC model mice was evaluated. Through a 3-dose regime, DP-sHDL inhibited the growth of tumors by 84% and significantly reduced tumor burden. In contrast, DOX was less effective and caused a progressive decline in body weight. Further biochemical assays revealed that the levels of AST, CREA, CK and LDH in DOX-treated mice were significantly higher than those receiving PBS. Accordingly, inflammatory cell infiltration, cell necrosis and local swelling were observed in the heart, liver and kidneys, respectively, in the DOX-injection group. With the same regime, no visible damage was monitored in the major organs in DP-sHDL group. Based on these findings, the long-term efficacy of D-sHDL, P-sHDL and DP-sHDL were further evaluated. DP-sHDL retarded the tumor growth, and prolonged the median survival time (MST) from 18 days (PBS-treated mice) to 35 days, without body weight loss. These results proved that DP-sHDL could reduce the toxicity of DOX and effectively inhibit tumor growth.
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| In Vivo Model | Female BALB/c mice murine 4T1 breast cancer cells xenograft tumor models. | ||||
| In Vitro Model | Breast cancer | Murine 4T1 breast cancer cell | Homo sapiens | ||
References