EGFR / STAT3 double-target inhibition polypeptide as well as preparation method and application thereof

Abstract

The invention provides EGFR / STAT3 double-target inhibition polypeptide as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The structure of the EGFR / STAT3 double-target inhibition polypeptide is shown as a general formula I in the specification. The inhibition polypeptide has excellent EGFR / STAT3 affinity, can be combined with EGFR / STAT3 highly expressed in tumor cells, and inhibits tumor cell proliferation and migration by promoting EGFR ubiquitination modification degradation and stopping STAT3 dimerization; meanwhile, the toxicity to normal cells is small, the selectivity is excellent, and the tumor can be efficiently targeted. Therefore, the EGFR / STAT3 double-target inhibition polypeptide or the pharmaceutically acceptable salt thereof can be potentially used in anti-tumor clinical treatment, and has a wide development prospect.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to an EGFR / STAT3 dual-target inhibitory polypeptide, its preparation method and application. Background Technology

[0002] Malignant tumors, as common and prevalent diseases that seriously threaten human health, have become the second leading cause of death worldwide, second only to cardiovascular diseases. Chemotherapy, as a treatment for systemic tumors, has long been a core strategy in cancer treatment. In recent years, with the rapid development of molecular biology and related disciplines, cancer chemotherapy has entered a new stage of precision medicine. However, most commonly used molecularly targeted drugs in clinical practice are single-target inhibitors. Although the targets are clearly defined, they often develop drug resistance during treatment due to the activation of other signaling pathways, leading to a gradual decline in efficacy. Therefore, the development of novel anti-tumor drugs targeting multiple tumor targets has become a research hotspot in the field of cancer treatment.

[0003] Epidermal growth factor receptor (EGFR) is a key growth regulator that binds to receptor tyrosine kinases (RTKs). Under normal physiological conditions, EGFR binding to its ligand induces autophosphorylation at its intracellular tyrosine (Tyr) site, activating it and subsequently activating various downstream signal transduction pathways to regulate cell growth, proliferation, apoptosis, and other vital activities. However, in tumor cells, EGFR overexpression, mutation, and abnormal activation lead to intracellular RTK autophosphorylation, activating a series of downstream signal transduction systems, including signal transducer and activator of transcription 3 (STAT3). This, in turn, promotes tumor development by inhibiting apoptosis, inducing cell proliferation, invasion, and metastasis, and triggering inflammation and immunosuppression. Therefore, researching molecularly targeted tumor drugs that inhibit EGFR-related signal transduction pathways, targeting EGFR and its downstream transcription factor STAT3, has significant clinical implications and broad application prospects.

[0004] SH2 adaptor protein F (Src homology 2 domain containing F, SHF) is a member of the SH2 adaptor protein family and the only adaptor protein in the family with negative tumor regulation. Studies have shown that SHF can competitively bind to STAT3 through its SH2 domain, inhibiting STAT3-STAT3 dimerization and effectively suppressing tumor cell proliferation and migration. In addition, SHF can bind to the intracellular region of overexpressed EGFR in tumor cells in a ligand-dependent manner, inducing autophosphorylation at Tyr1045, recruiting the E3 ligase c-Cbl to promote EGFR ubiquitination and degradation, thereby inhibiting its recycling and exerting a synergistic anti-tumor effect. However, different Shf analogues show significant differences in negative regulation of STAT3, and compounds that negatively regulate STAT3 are still in the preclinical research stage. Summary of the Invention

[0005] Therefore, the purpose of this invention is to provide an EGFR / STAT3 dual-target inhibitory peptide, its preparation method, and its application.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides an EGFR / STAT3 dual-target inhibitory peptide, the structure of which is shown in general formula I:

[0008] General formula I: Pro-Ser-Val-Pro-Glu-Ile-Val-His-His-Tyr-Ala-Ser-Arg-Lys-Leu-Pro-Glu-Asn-Gln-Val-Trp-Tyr-His-Ala-Ile-Ser-Arg-Thr-Asp-Ala-Glu-Asn-Leu-Leu-Arg-Leu-Cys-Xaa.

[0009] Preferably, Xaa is -OH or -NH2.

[0010] This invention provides a medicament for the prevention and / or treatment of tumors, comprising the above-described EGFR / STAT3 dual-target inhibitory peptide or a pharmaceutically acceptable salt thereof.

[0011] Preferably, the drug further includes a pharmaceutically acceptable carrier.

[0012] This invention provides an application of the above-mentioned EGFR / STAT3 dual-target inhibitory peptide in the preparation of at least one of the following a to c:

[0013] a) Products that target the EGFR protein;

[0014] b. Products that target the STAT3 protein;

[0015] c. Products that target and bind to EGFR and STAT3 proteins.

[0016] This invention provides the application of the above-mentioned EGFR / STAT3 dual-target inhibitory peptide in the preparation of products for the prevention and / or treatment of tumors.

[0017] Preferably, the EGFR / STAT3 dual-target inhibitory peptide inhibits the activity of tumor cells by targeting and binding to both EGFR and STAT3 proteins.

[0018] Preferably, the tumor is a tumor that highly expresses EGFR and STAT3.

[0019] Preferably, the tumor includes one or more of lung cancer, breast cancer, and colorectal cancer.

[0020] The present invention discloses a method for preparing an EGFR / STAT3 dual-target inhibitory peptide, comprising the following steps: preparing the EGFR / STAT3 dual-target inhibitory peptide by microwave-promoted Fmoc / tBu orthogonal protected solid-phase synthesis according to the structure of the EGFR / STAT3 dual-target inhibitory peptide.

[0021] Compared with the prior art, the present invention has the following beneficial effects:

[0022] This invention provides an EGFR / STAT3 dual-target inhibitory peptide, its preparation method, and its applications. This inhibitory peptide exhibits excellent EGFR / STAT3 affinity, enabling it to bind to EGFR / STAT3 highly expressed in tumor cells. By promoting EGFR ubiquitination and degradation, it prevents STAT3 dimerization, thereby inhibiting tumor cell proliferation and migration. Simultaneously, it exhibits low cytotoxicity to normal cells and excellent selectivity, allowing for efficient tumor targeting. Therefore, this EGFR / STAT3 dual-target inhibitory peptide, or a pharmaceutically acceptable salt thereof, has broad development prospects and may be used in clinical anti-tumor treatment. Attached Figure Description

[0023] Figure 1 The tumor growth curve of HCT116 in vivo after injection of EGFR / STAT3 dual-target inhibitory peptide is shown. **P≤0.01 is the result of Student's t test relative to the blank control group.

[0024] Figure 2 The tumor weight in HCT116 cells after injection of the EGFR / STAT3 dual-target inhibitory peptide was measured. **P≤0.01 represents the Student's t-test result relative to the Saline control group. Detailed Implementation

[0025] This invention provides an EGFR / STAT3 dual-target inhibitory peptide, the structure of which is shown in general formula I:

[0026] General formula I: Pro-Ser-Val-Pro-Glu-Ile-Val-His-His-Tyr-Ala-Ser-Arg-Lys-Leu-Pro-Glu-Asn-Gln-Val-Trp-Tyr-His-Ala-Ile-Ser-Arg-Thr-Asp-Ala-Glu-Asn-Leu-Leu-Arg-Leu-Cys-Xaa.

[0027] In this invention, computer software was used to simulate the interaction between SHF (PDB: 6AMW) and EGFR (PDB: 5GTY) and STAT3 (PDB: 1BG1), respectively, to construct a diverse compound library. Through virtual screening, a novel class of EGFR / STAT3 dual-target inhibitory peptides was designed and synthesized.

[0028] In this invention, Xaa is -OH or -NH2. Specifically, in this invention, when Xaa is -NH2, it means that the hydroxyl group in the carboxyl group of the Cys structure at the C-terminus of the EGFR / STAT3 dual-target inhibitory peptide is replaced by an amino group, that is, the C-terminus of the dual-target inhibitory peptide is amidated. In this invention, when Xaa is -OH, it means that the C-terminus of the EGFR / STAT3 dual-target inhibitory peptide is Cys, that is, the C-terminus of the dual-target inhibitory peptide is not amidated. The structure of the EGFR / STAT3 dual-target inhibitory peptide is SEQ ID NO.1-Xaa, wherein the amino acid sequence of SEQ ID NO.1 is: PSVPEIVHHYASRKLPENQVWYHAISRTDAENLLRLC.

[0029] This invention provides a medicament for the prevention and / or treatment of tumors, comprising the above-described EGFR / STAT3 dual-target inhibitory peptide or a pharmaceutically acceptable salt thereof.

[0030] In this invention, the drug also includes a pharmaceutically acceptable carrier, the carrier comprising excipients such as diluents.

[0031] This invention provides an application of the above-mentioned EGFR / STAT3 dual-target inhibitory peptide in the preparation of at least one of the following a to c:

[0032] a) Products that target the EGFR protein;

[0033] b. Products that target the STAT3 protein;

[0034] c. Products that target and bind to EGFR and STAT3 proteins.

[0035] This invention provides the application of the above-mentioned EGFR / STAT3 dual-target inhibitory peptide in the preparation of products for the prevention and / or treatment of tumors.

[0036] In this invention, the EGFR / STAT3 dual-target inhibitory peptide inhibits tumor cell activity by targeting and binding to both EGFR and STAT3 proteins. The tumor is preferably a tumor with high expression of EGFR and STAT3, and more preferably, the tumor includes one or more of lung cancer, breast cancer, and colorectal cancer.

[0037] The present invention discloses a method for preparing an EGFR / STAT3 dual-target inhibitory peptide, comprising the following steps: preparing the EGFR / STAT3 dual-target inhibitory peptide by microwave-promoted Fmoc / tBu orthogonal protected solid-phase synthesis according to the structure of the EGFR / STAT3 dual-target inhibitory peptide.

[0038] In this invention, as a specific embodiment, following the peptide chain sequence shown in SEQ ID NO:1-NH2, the corresponding amino acids are sequentially linked by repeatedly performing microwave-promoted removal and coupling steps of the Fmoc protecting group from the C-terminus to the N-terminus to prepare an EGFR / STAT3 dual-target inhibitory peptide. This invention does not specifically limit the microwave-promoted removal and coupling steps of the Fmoc protecting group; methods known in the art can be used. This EGFR / STAT3 dual-target inhibitory peptide can be prepared using a microwave-promoted solid-phase synthesis method, which has the advantages of high coupling efficiency and short synthesis cycle compared to traditional liquid-phase preparation, thus facilitating industrial-scale synthesis.

[0039] In this invention, unless otherwise specified, all raw material components are commercially available products well known to those skilled in the art.

[0040] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0041] In this invention, the following abbreviations are used:

[0042] DCM: Dichloromethane; NMP: N-methylpyrrolidone; DIPEA: N,N-diisopropylethylamine; TFA: Trifluoroacetic acid; EDT: Ethylene dithiol; Fmoc: N-9-fluorenylmethoxycarbonyl; HBTU: Benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate; HOBT: 1-hydroxy-benzotriazole; ESI-MS: Electrospray mass spectrometry; Pro: Proline; Ser: Serine; Val: Valine; Glu: Glutamic acid; Ile: Isoleucine; His: Histidine; Tyr: Tyrosine; Ala: Alanine; Arg: Arginine; Lys: Lysine; Leu: Leucine; Asn: Asparagine; Gln: Glutamine; Trp: Tryptophan; Thr: Threonine; Asp: Aspartic acid; Cys: Cysteine.

[0043] Example 1

[0044] The synthesis method of Pro-Ser-Val-Pro-Glu-Ile-Val-His-His-Tyr-Ala-Ser-Arg-Lys-Leu-Pro-Glu-Asn-Gln-Val-Trp-Tyr-His-Ala-Ile-Ser-Arg-Thr-Asp-Ala-Glu-Asn-Leu-Leu-Arg-Leu-Cys-NH2 (SEQ ID NO.1-NH2, EGFR / STAT3 dual-target inhibitory peptide) is as follows:

[0045] (1) Swelling of resin

[0046] Weigh 50 mg of Fmoc-Rink amide-MBHAResin (substitution amount 0.4 mmol / g), swell it with 7 mL of DCM for 30 min, filter off the DCM, swell it with 10 mL of NMP for 30 min, and finally wash it clean with 7 mL each of NMP, DCM and NMP to obtain the swollen resin.

[0047] (2) Microwave-induced removal of Fmoc protecting groups

[0048] The swollen resin was placed in a reactor, and 7 mL of a 25% piperidine / NMP (v / v) solution containing 0.1 M HOBT was added. The reaction was carried out in a microwave reactor for 1 min at a microwave power of 15 W, with the reaction temperature controlled below 50 °C. Compressed air was used for cooling. After the reaction, the solution was filtered off. Another 7 mL of the 25% piperidine / NMP (v / v) solution containing 0.1 M HOBT was added, and the reaction was carried out in the microwave reactor for another 4 min at a microwave power of 25 W, with the reaction temperature controlled at 50 °C. Compressed air was used for cooling. After the reaction, the solution was filtered off, and the resin was washed thoroughly with NMP. The resin with the initially attached Fmoc protecting group removed was obtained.

[0049] (3) Microwave-promoted synthesis of Fmoc-Cys(Trt)-Rink amide-MBHAResin

[0050] Fmoc-Arg(Pbf)-OH (0.04 mmol), HBTU (0.04 mmol), HOBT (0.04 mmol), and DIPEA (0.08 mmol) were dissolved in 10 mL of NMP. This solution was then added to resin with the initially de-linked Fmoc protecting groups removed. The reaction was carried out in a microwave reactor for 7 min at a microwave power of 25 W and a reaction temperature controlled at 50 °C, using compressed air from an air compressor for cooling. After the reaction was complete, the reaction solution was filtered off, and the resin was washed three times with 7 mL each of DCM and NMP.

[0051] (4) Detection of coupling efficiency

[0052] Take a small amount of resin particles, wash them with ethanol, put them into a transparent vial, and add 2 drops each of 5% ninhydrin ethanol, KCN pyridine solution (2 mL 0.001 M KCN ​​diluted in 98 mL pyridine) and 80% phenol ethanol solution. Heat at 100℃ for 5 min. If the resin turns blue, it is positive and needs to be recoupled. If the resin does not turn blue, it is negative and can proceed to the next amino acid coupling cycle.

[0053] (5) Elongation of peptide chains

[0054] Following the order of the peptide chains, the deprotection and coupling steps (2) to (4) above were repeated from the C-terminus to the N-terminus to connect the corresponding amino acids. The coupling reaction was promoted by microwave for 5 to 20 minutes. A peptide-resin complex was obtained.

[0055] (6) Cleavage of peptides on resin

[0056] The obtained peptide-resin complex was placed in a reaction flask, and 10 mL of cleavage agent Reagent K (TFA / anisole / water / phenol / EDT, 82.5:5:5:5:2.5, V / V) was added to each. The mixture was first shaken at 0°C for 30 min, then reacted at room temperature for 3 h. After the reaction, the mixture was filtered, washed three times with a small amount of TFA and DCM, and the filtrates were combined. The filtrate was added to a large amount of ice-cold diethyl ether to precipitate a white flocculent precipitate, which was then centrifuged at freeze to obtain the crude target peptide. Finally, 66.3 mg of the crude target compound was obtained, with a yield of 76.8%.

[0057] (7) Purification of peptides

[0058] The crude polypeptide was dissolved in 50% acetonitrile / water and purified by preparative liquid chromatography (HPLC). The chromatographic conditions were: C18 reversed-phase column (320 mm × 28 mm, 5 μm); mobile phase A: 0.1% TFA / water (V / V), mobile phase B: 0.1% TFA / acetonitrile (V / V); mobile phase gradient: mobile phase B 40%–80%, 20 min; flow rate 6 mL / min; detection wavelength 214 nm. The collected solution was lyophilized to obtain 32.7 mg of pure product. The theoretical relative molecular mass was 4342.96. Electrospray ionization mass spectrometry (ESI-MS) m / z: calculate [M+4H] 4+ 1086.74, [M+5H] 5+ 869.59; found [M+4H] 4+ 1086.73, [M+5H] 5+ 869.59.

[0059] Example 2

[0060] Example 1: EGFR / STAT3 dual-target inhibitory peptide's targeting affinity for EGFR / STAT3

[0061] This invention uses a static adsorption equilibrium experiment to determine the targeting affinity of the EGFR / STAT3 dual-target inhibitory peptide of Example 1 for EGFR and STAT3. The steps are as follows:

[0062] EGFR and STAT3 proteins were coupled separately to CNBr-activated agarose gel 4B material, and the protein concentrations of EGFR and STAT3 were determined by the Kjeldahl method to be 92 nmol / g wet gel and 83 nmol / g wet gel, respectively. Then, 0.1 g of each wet gel was mixed with 1 mL of EGFR / STAT3 dual-target inhibitory peptide from Example 1 and control Scr peptide (a control peptide synthesized by scrambling the peptide sequence of the EGFR / STAT3 dual-target inhibitory peptide from Example 1) containing different concentration gradients (initial concentrations: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20 μM), respectively, and slowly shaken at 4°C for 12 h in 20 mM PBS solution until static adsorption equilibrium was reached. The supernatant was collected by centrifugation at 3000 rpm, and the concentration of the small peptide in the supernatant was determined at 280 nm using a NanoDrop 2000 micro-spectrophotometer. A blank agarose gel without coupled proteins was used as a blank control. Using the nonlinear fitting tool within Origin, the static adsorption maximum value Qmax (nmol / g) and equilibrium dissociation constant Kd (μmol / L) of the EGFR / STAT3 dual-target inhibitory peptide and the control Scr were obtained by fitting the Langmuir isotherm adsorption equation.

[0063] Table 1. Static adsorption maximum and equilibrium dissociation constant of EGFR / STAT3 dual-target inhibitory peptide and control Scr

[0064]

[0065]

[0066] Note: *P≤0.05 and **P≤0.01 are Student's t-test results relative to the Scr control group.

[0067] As shown in Table 1, the maximum static adsorption value (Qmax) of the immobilized EGFR (92 nmol / g wet gel) for the EGFR / STAT3 dual-target inhibitory peptide was 91.25 ± 0.73 nmol / g wet gel, and the equilibrium dissociation constant (Kd) was 0.09 ± 0.02 μmol / L. The maximum static adsorption value (Qmax) of the control Scr peptide was 15.23 ± 1.01 nmol / g wet gel, and the equilibrium dissociation constant (Kd) was 4.55 ± 0.52 μmol / L. The EGFR / STAT3 dual-target inhibitory peptide showed a two-order-of-magnitude lower equilibrium dissociation constant (Kd) than the Scr peptide, demonstrating significant targeting affinity for EGFR. Its maximum static adsorption value (Qmax) was essentially consistent with the actual protein amount (92 nmol / g wet gel) of EGFR immobilized on CNBr-activated agarose gel 4B material, conforming to a 1:1 interaction model.

[0068] The static adsorption maximum (Qmax) of the immobilized STAT3 (83 nmol / g wet gel) for the EGFR / STAT3 dual-target inhibitory peptide reached 81.27 ± 1.05 nmol / g wet gel, with an equilibrium dissociation constant (Kd) of 0.08 ± 0.03 μmol / L. In contrast, the static adsorption maximum (Qmax) of the control Scr peptide reached 12.27 ± 0.95 nmol / g wet gel, with an equilibrium dissociation constant (Kd) of 5.32 ± 0.57 μmol / L. The EGFR / STAT3 dual-target inhibitory peptide exhibited a two-order-of-magnitude lower equilibrium dissociation constant (Kd) than the Scr peptide, demonstrating a significant targeting affinity for STAT3. Its static adsorption maximum (Qmax) was essentially consistent with the actual protein amount (83 nmol / g wet gel) of STAT3 immobilized on CNBr-activated agarose gel 4B material, conforming to a 1:1 interaction model.

[0069] The above results indicate that the EGFR / STAT3 dual-target inhibitory peptide of the present invention has significant targeting affinity for both EGFR and STAT3.

[0070] Example 3

[0071] In vitro antitumor activity of the EGFR / STAT3 dual-target inhibitory peptide in Example 1

[0072] This invention uses in vitro cell proliferation experiments to determine the in vitro antitumor activity of the EGFR / STAT3 dual-target inhibitory peptide:

[0073] Human lung cancer cells A549, human rectal cancer cells HCT116, human breast cancer cells MDA-MB-231, human leukemia cells K562, and normal human umbilical vein endothelial cells HUVEC, all in good logarithmic growth phase and expressing high EGFR / STAT3, were selected and treated with 1×10⁻⁶ cells per cell line. 5 After seeding the compound at a density of 1 / mL in 96-well plates and culturing for 12 h, different concentration gradients (0.625 μmol / L, 1.25 μmol / L, 2.5 μmol / L, 5 μmol / L, 10 μmol / L, 20 μmol / L, 40 μmol / L, 80 μmol / L, and 160 μmol / L) of the example compound were added and incubated for 48 h. After incubation, 20 μL of CCK-8 solution was added to each well, and incubation was continued for 2 h. The OD value at 450 nm was then measured using a microplate reader. Finally, the IC50 of the test compound was calculated using GraphPadPrism 7.0. 50 The values ​​are shown in Table 2.

[0074] Table 2. In vitro cytotoxicity (μmol / L) of EGFR / STAT3 dual-target inhibitory peptides

[0075] Group A549 HCT116 MDA-MB-231 K562 HUVEC EGFR / STAT3 dual-target inhibitory peptide 7.32±1.21 5.24±1.17 5.27±0.73 37.23±5.3 75.74±5.9

[0076] As shown in Table 2, compared with normal cells HUVEC and tumor cells K562 with low EGFR / STAT3 expression, the EGFR / STAT3 dual-target inhibitory peptide exhibited significant cytotoxicity against tumor cells A549, HCT116, and MDA-MB-231 with high EGFR / STAT3 expression. This indicates that the EGFR / STAT3 dual-target inhibitory peptide possesses good broad-spectrum antitumor activity, low cytotoxicity to normal cells, and good selectivity.

[0077] (2) In vivo antitumor activity of EGFR / STAT3 dual-target inhibitory peptide

[0078] This invention uses a nude mouse tumor-bearing experiment to determine the in vitro antitumor activity of the compounds in the examples:

[0079] HCT116 cells were subcutaneously in the right axilla of Balb / c nude mice. The tumors were allowed to grow to 100 mm. 3 The animals were then randomly divided into a blank control group and a treatment group. The drugs were administered intratumorally every two days. The treatment group was injected with the EGFR / STAT3 dual-target inhibitory peptide prepared in Example 1 (denoted as dual-target inhibitory peptide) at a concentration of 20 μg / animal / dose. The blank control group (Saline) was injected with an equal volume of physiological saline. The tumor volume of the mice was measured the day after administration, and the antitumor effect of the compound was dynamically observed and tumor growth curves were plotted. After seven administrations, the mice were sacrificed, and the tumor masses were surgically removed and weighed.

[0080] like Figure 1 and Figure 2 As shown, the EGFR / STAT3 dual-target inhibitory peptide can significantly inhibit the growth of HCT116 tumors in nude mice, exhibiting good in vivo antitumor activity.

[0081] In summary, this invention designs a novel EGFR / STAT3 dual-target inhibitory peptide with excellent EGFR / STAT3 affinity, capable of targeting EGFR and its downstream transcription factor STAT3. By inhibiting EGFR-related signal transduction pathways, it suppresses tumor development and progression. Compared to single-target inhibitors of EGFR and STAT3, this EGFR / STAT3 dual-target inhibitory peptide effectively avoids drug interactions caused by combined drug use, reducing adverse reactions. Simultaneously, inhibiting both upstream EGFR and downstream STAT3 effectively reduces the risk of drug resistance during use. EGFR and STAT3 activation involve protein-protein interactions with a large effective area. Long peptide EGFR / STAT3 dual-target inhibitory peptides can, to some extent, compensate for the difficulty of small molecule compounds or short peptides in blocking protein-protein interactions. Therefore, the EGFR / STAT3 dual-target inhibitory peptide provided by this invention is suitable as an active ingredient in clinical anti-tumor drugs.

[0082] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. An EGFR / STAT3 dual-target inhibitory polypeptide, characterized in that, The structure of the EGFR / STAT3 dual-target inhibitory peptide is shown in general formula I: General formula I: Pro-Ser-Val-Pro-Glu-Ile-Val-His-His-Tyr-Ala-Ser-Arg-Lys-Leu-Pro-Glu-Asn-Gln-Val-Trp-Tyr-His-Ala-Ile-Ser-Arg-Thr-Asp-Ala-Glu-Asn-Leu-Leu-Arg-Leu-Cys-Xaa.

2. The EGFR / STAT3 dual-target inhibitory peptide according to claim 1, characterized in that, The Xaa is -OH or -NH2.

3. A drug for the prevention and / or treatment of tumors, characterized in that, Includes the EGFR / STAT3 dual-target inhibitory peptide of claim 1 or 2, or a pharmaceutically acceptable salt thereof.

4. The drug according to claim 3, characterized in that, The drug also includes a pharmaceutically acceptable carrier.

5. The use of the EGFR / STAT3 dual-target inhibitory peptide according to claim 1 or 2 in the preparation of at least one of the following a to c: a) Products that target the EGFR protein; b. Products that target the STAT3 protein; c. Products that target and bind to EGFR and STAT3 proteins.

6. The use of the EGFR / STAT3 dual-target inhibitory peptide according to claim 1 or 2 in the preparation of products for the prevention and / or treatment of tumors.

7. The application according to claim 6, characterized in that, The EGFR / STAT3 dual-target inhibitory peptide inhibits tumor cell activity by targeting and binding to both EGFR and STAT3 proteins.

8. The application according to claim 6, characterized in that, The tumor was a tumor that highly expressed EGFR and STAT3.

9. The application according to claim 8, characterized in that, The tumor includes one or more of lung cancer, breast cancer, and colorectal cancer.

10. A method for preparing an EGFR / STAT3 dual-target inhibitory peptide, characterized in that, The process includes the following steps: the EGFR / STAT3 dual-target inhibitory peptide as described in claim 1 or 2 is prepared by microwave-promoted Fmoc / tBu orthogonal protected solid-phase synthesis.

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