Pharmaceutical composition for preventing or treating lung cancer

Abstract

The present invention relates to a compound capable of preventing or treating lung cancer by inhibiting the expression or activity of Anoctamin 1 (ANO1), which is a calcium-activated chloride channel, and epidermal growth factor receptor (EGFR), which is an epithelial growth factor receptor. The compound of the present invention can be advantageously used alone as a composition for preventing or treating lung cancer, can be used per se as a dual-target anticancer drug for ANO1 and EGFR, and can also be used as an adjuvant or a combination preparation in combination with an EGFR-targeted therapeutic agent.

Description

Pharmaceutical composition for the prevention or treatment of lung cancer

[0001] The present invention relates to a pharmaceutical composition for the prevention or treatment of lung cancer.

[0002] The present invention claims priority based on Korean Patent Application No. 10-2024-0168772 filed on November 22, 2024 and Korean Patent Application No. 10-2025-0177466 filed on November 20, 2025, and all contents disclosed in the specifications and drawings of said applications are incorporated by reference into the present application.

[0003] The development of cancer is associated with various environmental factors, including chemicals, radiation, and viruses, as well as changes in genes related to oncogenes, tumor suppressor genes, apoptosis, and DNA repair. Recently, understanding these molecular mechanisms of cancer has made targeted anticancer therapy a new treatment method possible. Targeted therapies are generally designed to exert their effects by targeting molecules characteristic of cancer cells. Molecular targets include genes related to cancer cell signal transduction pathways, angiogenesis, the matrix, cell cycle regulators, or apoptosis. Important targeted therapies currently in use include signal transduction pathway inhibitors, such as tyrosine kinase inhibitors, and angiogenesis inhibitors. Protein tyrosine kinase has been identified as playing a crucial role in many malignant tumors. In particular, the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase of the ErbB family, is abnormally activated in many epithelial tumors, including non-small cell lung cancer (NSCLC), breast cancer, glioma, squamous cell carcinoma of the head and neck, colorectal cancer, head and neck cancer, gastric cancer, and prostate cancer, and it is known that the activation of the EGFR-tyrosine kinase causes sustained cell proliferation, invasion of surrounding tissues, distant metastasis, and angiogenesis, and increases cell survival.

[0004] Meanwhile, while the primary treatment for lung cancer in the past relied on cytotoxic chemotherapy drugs, it is reported that in the current non-small cell lung cancer treatment market, immunotherapy drugs account for about 60%, targeted anticancer drugs for about 30%, and chemotherapy drugs for about 10%. Currently, the target gene mutations for FDA-approved targeted anticancer drugs for non-small cell lung cancer include EGFR, KRAS, ALK, ROS1, BRAF, MET, RET, and HER2. Among these, the mutation frequencies are reported to be in the order of EGFR (about 28%), KRAS (about 25.3%), ALK (about 3.8%), ROS1 (about 2.6%), and RET (about 1.7%).

[0005] Among targeted anticancer drugs, EGFR targeted anticancer drugs that exert anticancer effects by blocking EGFR can be broadly classified into two mechanisms. Specifically, there are methods using antibodies that interfere with the binding of EGF and EGFR, and methods utilizing EGFR tyrosine kinase inhibitors (TKIs) that block signal transduction by binding to the intracellular tyrosine kinase (TK) domain. Among these, fourth-generation EGFR TKIs, which are currently receiving attention, primarily target the C797S mutation, which confers resistance to third-generation EGFR TKIs. While several domestic and international pharmaceutical companies are developing drugs in this class, EGFR TKIs have the limitation of repeatedly developing drug resistance during treatment because they target sites where mutations occur intensively. Specifically, it is known that resistance develops within 9 to 13 months after administration in approximately 50 to 60 percent of patients treated with first and second-generation EGFR TKIs, and one of the main causes is the Exon 20 T790M mutation. The T790M mutation involves the substitution of the 790th amino acid of the EGFR protein from threonine to methionine, which interferes with the binding of first and second-generation EGFR TKIs and can induce resistance. To overcome this problem, third-generation EGFR TKIs such as osimertinib (Tagrisso) and lazertinib (Lecraza) were developed, but subsequent resistance issues caused by new mutations or alternative signaling pathways are still being continuously reported. Therefore, in order to overcome the limitations of drug resistance caused by the use of these EGFR TKIs, there is a growing need to develop a therapeutic agent that can fundamentally suppress the occurrence of drug resistance, such as that caused by the use of EGFR TKIs, by utilizing a mechanism of action that is distinct from conventional therapeutic agents—namely, a mechanism of action that binds to an EGFR site different from the site where tyrosine kinase (TK) mutations occur and induces degradation.

[0006] The object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of lung cancer comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof.

[0007] [Chemical Formula 1]

[0008]

[0009] [Chemical Formula 2]

[0010]

[0011] Another object of the present invention is (i) one or more compounds selected from the group consisting of compounds represented by Formulas 1 and 2 or pharmaceutically acceptable salts thereof; and

[0012] (ii) Provide a pharmaceutical composition for the prevention or treatment of lung cancer comprising a targeted anticancer agent against EGFR as an active ingredient.

[0013] Another objective of the present invention is to provide a pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer agent, comprising as an active ingredient one or more compounds selected from the group consisting of compounds represented by the chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof.

[0014]

[0015] However, the technical problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by those skilled in the art to which the present invention belongs from the description below.

[0016] To achieve the above objectives, the present invention provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof.

[0017] [Chemical Formula 1]

[0018]

[0019] [Chemical Formula 2]

[0020]

[0021] In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0022] In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising a compound represented by the above formula 2 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0023] The present invention relates to (i) one or more compounds selected from the group consisting of compounds represented by the formulas 1 and 2 or pharmaceutically acceptable salts thereof; and

[0024] (ii) Provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising a targeted anticancer agent against EGFR as an active ingredient.

[0025] In addition, the present invention comprises (i) a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; and

[0026] (ii) Provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising a targeted anticancer agent against EGFR as an active ingredient.

[0027] In addition, the present invention comprises (i) a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof; and

[0028] (ii) Provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising a targeted anticancer agent against EGFR as an active ingredient.

[0029] The present invention provides a pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer agent, comprising as an active ingredient one or more compounds selected from the group consisting of compounds represented by the chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof.

[0030] In addition, the present invention provides a pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer agent, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0031] In addition, the present invention provides a pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer agent, comprising a compound represented by the above chemical formula 2 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0032] In addition, the present invention provides a method for improving or treating lung cancer, or enhancing the anticancer effect of a lung cancer anticancer agent, comprising the step of administering a pharmaceutically effective amount of a composition containing as an active ingredient one or more compounds selected from the group consisting of compounds represented by the chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof, to an individual in need thereof.

[0033] In addition, the present invention provides a method for improving or treating lung cancer, or enhancing the anticancer effect of a lung cancer anticancer agent, comprising the step of administering a pharmaceutically effective amount of a composition containing a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient to an individual in need thereof.

[0034] In addition, the present invention provides a method for improving or treating lung cancer, or enhancing the anticancer effect of a lung cancer anticancer agent, comprising the step of administering a pharmaceutically effective amount of a composition containing a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof as an active ingredient to an individual in need thereof.

[0035] In addition, the present invention provides a composition comprising one or more compounds selected from the group consisting of compounds represented by the above chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof, as an active ingredient for the prevention, improvement, or treatment of lung cancer; or for use in enhancing the anticancer effect of a lung cancer anticancer agent.

[0036] In addition, the present invention provides a use for the prevention, improvement, or treatment of lung cancer by a composition comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient; or for enhancing the anticancer effect of a lung cancer anticancer agent.

[0037] In addition, the present invention provides a use for the prevention, improvement, or treatment of lung cancer by a composition comprising a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof as an active ingredient; or for enhancing the anticancer effect of a lung cancer anticancer agent.

[0038] In addition, the present invention provides a use for a composition comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the above chemical formulas 1 and 2 or a pharmaceutically acceptable salt thereof for the prevention, improvement, or treatment of lung cancer; or for preparing a formulation that enhances the anticancer effect of a lung cancer anticancer agent.

[0039] In addition, the present invention provides a use for a composition comprising a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention, improvement, or treatment of lung cancer; or for manufacturing a formulation that enhances the anticancer effect of a lung cancer anticancer agent.

[0040] In addition, the present invention provides a use for a composition comprising a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof as an active ingredient for the prevention, improvement, or treatment of lung cancer; or for preparing a formulation that enhances the anticancer effect of a lung cancer anticancer agent.

[0041] In addition, the present invention comprises (i) one or more compounds selected from the group consisting of compounds represented by Formulas 1 and 2 or pharmaceutically acceptable salts thereof; and

[0042] (ii) A method for improving or treating lung cancer, comprising the step of administering a pharmaceutically effective amount of a composition containing a targeted anticancer agent against EGFR as an active ingredient to an individual in need thereof.

[0043] In addition, the present invention comprises (i) a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; and

[0044] (ii) A method for improving or treating lung cancer, comprising the step of administering a pharmaceutically effective amount of a composition containing a targeted anticancer agent against EGFR as an active ingredient to an individual in need thereof.

[0045] In addition, the present invention comprises (i) a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof; and

[0046] (ii) A method for improving or treating lung cancer, comprising the step of administering a pharmaceutically effective amount of a composition containing a targeted anticancer agent against EGFR as an active ingredient to an individual in need thereof.

[0047] In addition, the present invention comprises (i) one or more compounds selected from the group consisting of compounds represented by Formulas 1 and 2 or pharmaceutically acceptable salts thereof; and

[0048] (ii) Provides a use for the prevention, improvement, or treatment of lung cancer of a composition comprising an anticancer agent targeting EGFR as an active ingredient.

[0049] In addition, the present invention comprises (i) a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; and

[0050] (ii) Provides a use for the prevention, improvement, or treatment of lung cancer of a composition comprising an anticancer agent targeting EGFR as an active ingredient.

[0051] In addition, the present invention comprises (i) a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof; and

[0052] (ii) Provides a use for the prevention, improvement, or treatment of lung cancer of a composition comprising an anticancer agent targeting EGFR as an active ingredient.

[0053] In addition, the present invention comprises (i) one or more compounds selected from the group consisting of compounds represented by Formulas 1 and 2 or pharmaceutically acceptable salts thereof; and

[0054] (ii) Provides a use for manufacturing a formulation for the prevention, improvement, or treatment of lung cancer comprising a composition containing a targeted anticancer agent against EGFR as an active ingredient.

[0055] In addition, the present invention comprises (i) a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof; and

[0056] (ii) Provides a use for manufacturing a formulation for the prevention, improvement, or treatment of lung cancer comprising a composition containing a targeted anticancer agent against EGFR as an active ingredient.

[0057] In addition, the present invention comprises (i) a compound represented by Formula 2 or a pharmaceutically acceptable salt thereof; and

[0058] (ii) Provides a use for manufacturing a formulation for the prevention, improvement, or treatment of lung cancer comprising a composition containing a targeted anticancer agent against EGFR as an active ingredient.

[0059]

[0060] In one embodiment of the present invention, the lung cancer may be one or more selected from the group consisting of small cell lung cancer, non-small cell lung cancer, and adenocarcinoma, but is not limited thereto. Specifically, the lung cancer may be adenocarcinoma, but is not limited thereto.

[0061] In another embodiment of the present invention, the lung cancer may be lung cancer associated with a mutation in one or more genes selected from the group consisting of KRAS (Kirsten rat sarcoma viral oncogene homolog), p53, and EGFR (Epidermal growth factor receptor), but is not limited thereto.

[0062] In another embodiment of the present invention, the compound or a pharmaceutically acceptable salt thereof may simultaneously inhibit EGFR and ANO1, but is not limited thereto.

[0063] In another embodiment of the present invention, the compound or a pharmaceutically acceptable salt thereof is bound to a complex of EGFR and ANO1, and

[0064] The above compound or a pharmaceutically acceptable salt thereof may bind simultaneously to the juxtamembrane site of EGFR, excluding the tyrosine kinase site of EGFR; and ANO1, thereby exhibiting a preventive or therapeutic effect against lung cancer, but is not limited thereto.

[0065] In another embodiment of the present invention, the compound or a pharmaceutically acceptable salt thereof may be characterized by one or more selected from the group consisting of, but not limited to:

[0066] (a) inhibiting the proliferation or growth of cancer cells; and

[0067] (b) inhibiting the tumorigenicity of cancer cells; and

[0068] (c) Suppresses resistance of lung tumor cells to anticancer drugs.

[0069] In another embodiment of the present invention, the anticancer agent may be a targeted anticancer agent against tyrosine kinase, but is not limited thereto.

[0070] In another embodiment of the present invention, the tyrosine kinase may be EGFR (epidermal growth factor receptor), but is not limited thereto.

[0071] In another embodiment of the present invention, the pharmaceutical composition may be administered in combination with a targeted anticancer agent for tyrosine kinase, but is not limited thereto.

[0072] In another embodiment of the present invention, the pharmaceutical composition may be administered simultaneously, separately, or sequentially with the targeted anticancer agent, but is not limited thereto. Specifically, the pharmaceutical composition may be administered sequentially with the targeted anticancer agent, but is not limited thereto.

[0073] In another embodiment of the present invention, the compound or a pharmaceutically acceptable salt thereof may inhibit the resistance of lung tumor cells to a targeted anticancer agent against EGFR, but is not limited thereto.

[0074] In another embodiment of the present invention, the pharmaceutical composition may be in the form of a mixture comprising the compound or a pharmaceutically acceptable salt thereof; and a targeted anticancer agent for EGFR, but is not limited thereto.

[0075] In another embodiment of the present invention, the pharmaceutical composition may be in the form in which the compound or a pharmaceutically acceptable salt thereof and a targeted anticancer agent for EGFR are each formulated and administered simultaneously, separately, or sequentially, but is not limited thereto. Specifically, the pharmaceutical composition may be in the form in which the compound or a pharmaceutically acceptable salt thereof and a targeted anticancer agent for EGFR are each formulated and administered sequentially, but is not limited thereto.

[0076] In another embodiment of the present invention, the pharmaceutical composition may be administered simultaneously, separately, or sequentially with the lung cancer anticancer agent, but is not limited thereto. Specifically, the pharmaceutical composition may be administered sequentially with the lung cancer anticancer agent, but is not limited thereto.

[0077] In another embodiment of the present invention, the compound or a pharmaceutically acceptable salt thereof is bound to a complex of EGFR and ANO1, and

[0078] The above compound or a pharmaceutically acceptable salt thereof may simultaneously bind to the juxtamembrane site of EGFR other than the tyrosine kinase site of EGFR and ANO1 to enhance the anticancer effect of a lung cancer anticancer drug, but is not limited thereto.

[0079]

[0080] The present invention relates to a compound capable of preventing and treating lung cancer by inhibiting the expression or activity of Anoctamin 1 (ANO1), a calcium-dependent chloride channel, and the epidermal growth factor receptor (EGFR), an epidermal growth factor receptor. Specifically, it was confirmed that tumorigenicity and proliferation were significantly inhibited in lung cancer cells treated with the compound of the present invention. Furthermore, it was confirmed that tumor proliferation was inhibited when the compound of the present invention was treated in a xenograft mouse model formed by injecting lung cancer cells into mice. This inhibitory effect was found to be significantly superior compared to conventional EGFR tyrosine kinase inhibitors. Since the compound of the present invention can simultaneously inhibit ANO1 and EGFR, it was possible to exhibit a significantly superior anticancer effect through this dual inhibition. It was also confirmed that when the compound of the present invention is administered in combination with an EGFR targeted anticancer drug, it not only exhibits a synergistic anticancer effect but also inhibits the development of drug resistance in cancer cells. Accordingly, the compound of the present invention can be usefully used alone as a composition for the prevention or treatment of lung cancer, and can be used as a dual-target anticancer agent for ANO1 and EGFR, and can also be utilized as an adjuvant or combination agent in combination with an EGFR targeted therapeutic agent.

[0081] Figure 1a shows information regarding the compound of the present invention.

[0082] Figure 1b shows the analysis requesting agency, analysis method, and analysis items for EGFR mutant screening.

[0083] Figure 1c shows the results of the EGFR mutant screening.

[0084] Figure 1d shows the amino acid sequence information for EGFR.

[0085] Figure 1e shows the amino acid sequence information for ANO1.

[0086] Figures 2a and 2b show the results of tumorigenic inhibition by AON-MG23-01.

[0087] Figures 2c to 2e show the results of tumorigenic inhibition by AON-MG23-02 and osimertinib.

[0088] Figure 3 shows the results of confirming the expression levels of ANO1, phosphorylated EGFR, and EGFR protein in human lung cancer cell lines.

[0089] Figure 4 shows the inhibitory effects of the compound of the present invention and osimertinib on the expression of ANO1, phosphorylated EGFR, and EGFR proteins in human lung cancer cell lines.

[0090] Figure 5 shows the cancer growth inhibitory effect when the compound of the present invention and osimertinib, or a combination thereof, were treated in a xenograft model of an osimertinib-resistant human lung cancer cell line.

[0091] Figures 6a and 6b show a predictive model of AON-MG23-01 binding to a target protein, which is an ANO1 and EGFR complex.

[0092] Figures 6c and 6d show a predictive model of AON-MG23-02 binding to a target protein, which is an ANO1 and EGFR complex.

[0093] The present invention provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof.

[0094] [Chemical Formula 1]

[0095]

[0096] [Chemical Formula 2]

[0097]

[0098] In the entirety of the following claims, the compound represented by Formula 1 may be referred to as "N-(2-((5-chloro-2-((2-methoxy-4-(4-(4-methylpiperazine-1-yl)piperidin-1-yl)phenyl)amino)pyrimidine-4-yl)amino)phenyl)-N-cyclopropylmethanesulfonamide" or "AON-MG23-01". Additionally, in the entirety of the following claims, the compound represented by Formula 2 may be referred to as "N-(2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidine-4-yl)amino)phenyl)-N-cyclopropylmethanesulfonamide" or "AON-MG23-02".

[0099] In the present specification, including all claims below, unless otherwise noted, "compound of the present invention," "compound represented by Chemical Formula 1," or "compound represented by Chemical Formula 2," etc., are used as concepts including the compound represented by Chemical Formula 1 or the compound represented by Chemical Formula 2 itself, salts thereof, and isomers thereof.

[0100] Including all claims below, the compounds herein may have a non-aromatic double bond and one or more asymmetric centers. Thus, they may occur as racemics and racemic mixtures, a single enantiomer, individual diastereomers, diastereomer mixtures, and cis- or trans-isomers. All such isomer forms are considered.

[0101] In all claims below, the term “isomer” means a compound having the same molecular formula but different physical or chemical properties. In all claims below, the isomer may be one or more selected from the group consisting of structural isomers, enantiomers, optical isomers, stereoisomers, and diastereomers, but is not limited thereto.

[0102]

[0103] In all claims below, the term “lung cancer” in this specification may refer to cancer caused by mutations in the epithelial cells forming the trachea (airway), bronchi, or alveoli of the lungs, but is not limited thereto. Additionally, lung cancer may be classified into small cell lung cancer and non-small cell lung cancer (lung cancer that is not small cell lung cancer) according to histological type, but is not limited thereto.

[0104] In the entirety of the following claims, the lung cancer of the present invention may be one or more selected from the group consisting of small cell lung cancer, non-small cell lung cancer, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, but is not limited thereto. Specifically, in the entirety of the following claims, the lung cancer may be one or more selected from the group consisting of small cell lung cancer, non-small cell lung cancer, and adenocarcinoma, but is not limited thereto.

[0105] In the entirety of the following claims, “small cell lung cancer” primarily occurs in smokers and may progress very rapidly; due to these characteristics of small cell lung cancer, surgical treatment is rarely performed even in the early stages, and anticancer treatment and radiation therapy may be utilized as the primary treatment methods. Furthermore, in the entirety of the following claims, small cell lung cancer primarily occurs in the airway and is prone to metastasis through lymphatic vessels or blood vessels, and brain metastasis is particularly common; therefore, even if brain metastasis is not confirmed at the time of diagnosis, prophylactic radiation therapy may be performed, but is not limited thereto.

[0106] In the entire specification including the following claims, “non-small cell lung cancer” refers to cancer cells that are not small in size, which account for about 85% of lung cancers, and non-small cell lung cancer can be divided into three types based on cell size, shape and chemical composition: squamous cell carcinoma (about 30%), adenocarcinoma (about 40%), and large cell carcinoma (about 15%).

[0107] In all claims below, “squamous cell carcinoma” refers to arising from squamous epithelial cells of the bronchial mucosa of the lungs and may be found primarily in the central part of the lungs, but is not limited thereto.

[0108] In the entirety of the following claims, “adenocarcinoma” arises from glandular cells of the lung and may be found primarily in peripheral areas of the lung and outside the lung, but is not limited thereto. Additionally, in the entirety of the following claims, adenocarcinoma may include lung adenocarcinoma and bronchial adenocarcinoma, but is not limited thereto.

[0109] In all claims below, “large cell carcinoma” may refer to a carcinoma that primarily occurs in the periphery of the lungs, has large cell size, and tends to proliferate or metastasize rapidly, resulting in a poor prognosis, but is not limited thereto.

[0110] Including the entire claims below, the lung cancer of the present invention may be lung cancer associated with a mutation in one or more genes selected from the group consisting of KRAS (Kirsten rat sarcoma viral oncogene homolog), p53, and EGFR (Epidermal growth factor receptor), but is not limited thereto.

[0111] Including all claims below, lung cancer associated with a mutation in the EGFR gene may be lung cancer associated with one or more mutations selected from the group consisting of EGFR T790M mutation, EGFR C797S mutation, EGFR L858R mutation, EGFR G724S mutation, EGFR L718X mutation, and EGFR G719X mutation, but is not limited thereto.

[0112] Including the full claims below, specific embodiments relating to the A549 cell line may relate to lung cancer associated with a mutation in the KRAS gene, but are not limited thereto.

[0113] Including all claims below, specific embodiments relating to the Calu-3 cell line may relate to lung cancer associated with a mutation in the p53 gene, but are not limited thereto.

[0114] Including the full claims below, specific embodiments relating to H1975 and PC-9 cell lines may relate to lung cancer associated with mutations in the EGFR gene, but are not limited thereto.

[0115] Including the entire claims below, the compounds of the present invention or pharmaceutically acceptable salts thereof may inhibit EGFR and ANO1 simultaneously, but are not limited thereto.

[0116] In the entirety of the following claims, the cancer according to the present invention may be lung cancer that is expected to be improved or treated by simultaneously inhibiting EGFR and ANO1. Specifically, in the entirety of the following claims, the cancer according to the present invention may be lung cancer associated with one or more mutations selected from the group consisting of EGFR (Epidermal growth factor receptor) and ANO1 (Anoctamin 1). That is, the cancer according to the present invention may be lung cancer having mutations in EGFR and / or ANO1. The mutations in EGFR and / or ANO1 include amplification of the genes of EGFR and / or ANO1, overexpression of the protein, overactivation of the protein, and sustained activation of the protein. That is, the cancer according to the present invention may be lung cancer in which the expression or activity of EGFR and / or ANO1 is higher than that of normal cells. Alternatively, the cancer according to the present invention may be lung cancer in which the state of activation of EGFR and / or ANO1 is sustained. Since the compound according to the present invention can simultaneously inhibit the expression and activity of ANO1 and EGFR, it can exhibit a particularly excellent anticancer effect against lung cancer accompanied by mutations in EGFR and / or ANO1.

[0117] Furthermore, as described in the entire claim below, the compound according to the present invention can simultaneously inhibit ANO1 and EGFR (i.e., dual inhibition), and thus can exhibit a superior anticancer effect compared to a single inhibitor of ANO1 or EGFR. In particular, through EGFR inhibition, it can inhibit the development of resistance in cancer cells to the anticancer agent and enhance the anticancer effect of the said anticancer agent. For example, the inventors confirmed through experiments that the EGFR inhibitory effect of the compound of the present invention is superior to that of the conventional EGFR inhibitor Osimertinib, and that the anticancer effect is superior when the compound of the present invention is administered in combination with Osimertinib.

[0118] Including all claims below, the term “inhibition” in this specification may mean inhibiting the activity or expression of a protein or gene, and specifically, may mean inhibiting the expression of a protein or gene, but is not limited thereto.

[0119] Including all claims below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind simultaneously to EGFR and ANO1, but is not limited thereto. Specifically, including all claims below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to a juxtamembrane (JM) site of a complex comprising EGFR and ANO1, but is not limited thereto.

[0120] Including all claims below, as provided herein, a compound of the present invention or a pharmaceutically acceptable salt thereof is bound to a complex of EGFR and ANO1, and

[0121] The compound of the present invention or a pharmaceutically acceptable salt thereof may simultaneously bind to the juxtamembrane site of EGFR and ANO1, but is not limited thereto.

[0122] Including all claims below, as provided herein, a compound of the present invention or a pharmaceutically acceptable salt thereof is bound to a complex of EGFR and ANO1, and

[0123] The compound of the present invention or a pharmaceutically acceptable salt thereof may bind simultaneously to the juxtamembrane site of EGFR, excluding the tyrosine kinase site of EGFR; and ANO1, and may exhibit a preventive or therapeutic effect against lung cancer, but is not limited thereto.

[0124] Including the entire claims below, the site of ANO1 to which the compound of the present invention or a pharmaceutically acceptable salt thereof is bound may comprise one or more selected from the group consisting of the N-terminus loop site of ANO1 and the Juxtamembrane domain of EGFR, but is not limited thereto.

[0125] In the entire specification including the following claims, “complex of EGFR and ANO1” may mean a complex of EGFR and ANO1 combined, and specifically, may mean a complex of EGFR and ANO1 combined by protein-protein interaction (PPI), but is not limited thereto.

[0126] In the entirety of the following claims, “protein-protein interaction (PPI)” may mean a non-covalent physical bond or complex formation between a first protein and a second protein, and the interaction between the first protein and the second protein may include not only a direct interaction between them but also an indirect interaction mediated by another protein located between the first protein and the second protein in a signaling pathway, and the protein-protein interaction may be a single molecule reaction such as a reaction between one molecule of the first protein and one molecule of the second protein, but is not limited thereto.

[0127] Including the entire claims below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to an amino acid position of one or more ANO1 proteins selected from the group consisting of LYS173, LYS175, TYR222, PRO223, PHE224, SER225, GLU227, LYS228, GLY442, GLU444, LYS927, MET930, VAL931, PHE934, MET935, GLU938, and LYS941, but is not limited thereto.

[0128] Specifically, as per the entire claim below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to one or more amino acid positions selected from the group consisting of LYS173, LYS175, TYR222, PRO223, PHE224, SER225, GLU227, LYS228, GLY442, GLU444, LYS927, MET930, VAL931, PHE934, MET935, GLU938, and LYS941 of the ANO1 protein comprising the amino acid sequence of SEQ ID NO. 3, but is not limited thereto. Specifically, the compound of the present invention may be the compound represented by the above Formula 1, i.e., AON-MG23-01, but is not limited thereto.

[0129] Including the entire claims below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to, but is not limited to, one or more amino acid positions of an EGFR protein selected from the group consisting of GLU640, GLU642, LEU643, VAL644, PRO646, ILE695, PRO696, HIS728, GLN746, LEU747, PRO749, PHE750, GLN767, TYR768, ASN771, VAL774, GLN775, LYS778, LYS801, THR802, PRO803, GLN804, HIS805, HIS943, LEU944, PRO947, TYR953, ASP967, ALA968, and ASP969.

[0130] Specifically, as per the entire claim below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to one or more amino acid sequence positions selected from the group consisting of GLU640, GLU642, LEU643, VAL644, PRO646, ILE695, PRO696, HIS728, GLN746, LEU747, PRO749, PHE750, GLN767, TYR768, ASN771, VAL774, GLN775, LYS778, LYS801, THR802, PRO803, GLN804, HIS805, HIS943, LEU944, PRO947, TYR953, ASP967, ALA968, and ASP969 of an EGFR protein comprising the amino acid sequence of SEQ ID NO. 1, or as per the entire claim below, The compound of the present invention or a pharmaceutically acceptable salt thereof may bind to one or more amino acid sequence positions selected from the group consisting of GLU685, GLU687, LEU688, VAL689, PRO691, ILE740, PRO741, HIS773, GLN791, LEU792, PRO794, PHE795, GLN812, TYR813, ASN816, VAL819, GLN820, LYS823, LYS846, THR847, PRO848, GLN849, HIS850, HIS988, LEU989, PRO992, TYR998, ASP1012, ALA1013, and ASP1014 of an EGFR protein comprising the amino acid sequence of SEQ ID NO. 2, but is not limited thereto. Specifically, the compound of the present invention above may be a compound represented by the above chemical formula 1, i.e., AON-MG23-01, but is not limited thereto.

[0131] Including the entire claims below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to an amino acid position of one or more ANO1 proteins selected from the group consisting of GLU170, PHE171, LEU172, LYS173, LYS175, TYR222, PRO223, PHE224, SER225, GLU227, LYS228, ARG256, THR441, GLY442, GLU444, GLU446, GLU447, VAL450, LYS451, PHE679, ILE683, PRO727, MET930, and PHE934, but is not limited thereto.

[0132] Specifically, as per the entire claim below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to one or more amino acid positions selected from the group consisting of GLU170, PHE171, LEU172, LYS173, LYS175, TYR222, PRO223, PHE224, SER225, GLU227, LYS228, ARG256, THR441, GLY442, GLU444, GLU446, GLU447, VAL450, LYS451, PHE679, ILE683, PRO727, MET930, and PHE934 of the ANO1 protein comprising the amino acid sequence of SEQ ID NO. 3, but is not limited thereto. Specifically, the compound of the present invention may be the compound represented by Formula 2 above, i.e., AON-MG23-02, but is not limited thereto.

[0133] Including the entire claims below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to, but is not limited to, one or more amino acid positions of an EGFR protein selected from the group consisting of GLU640, GLU642, LEU643, VAL644, ILE658, PRO727, HIS728, GLN767, ASN771, VAL774, GLN775, LYS778, THR802, GLN804, HIS805, SER924, LYS925, ALA927, and ARG928.

[0134] Specifically, as per the entire claim below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to one or more amino acid sequence positions selected from the group consisting of GLU640, GLU642, LEU643, VAL644, ILE658, PRO727, HIS728, GLN767, ASN771, VAL774, GLN775, LYS778, THR802, GLN804, HIS805, SER924, LYS925, ALA927, and ARG928 of an EGFR protein comprising the amino acid sequence of SEQ ID NO. 1, or as per the entire claim below, the compound of the present invention or a pharmaceutically acceptable salt thereof may bind to GLU685, GLU687, LEU688, VAL689, ILE703, PRO772 of an EGFR protein comprising the amino acid sequence of SEQ ID NO. 2, It may bind to one or more amino acid sequence positions selected from the group consisting of HIS773, GLN812, ASN816, VAL819, GLN820, LYS823, THR847, GLN849, HIS850, SER969, LYS970, ALA972, and ARG973, but is not limited thereto. Specifically, the compound of the present invention may be a compound represented by Chemical Formula 2 above, i.e., AON-MG23-02, but is not limited thereto.

[0135] In this specification, including all claims below, the compound of the present invention utilizes a mechanism that degrades targets by binding to the N-terminus and loop regions of ANO1 and the JM (juxtamembrane) domain of EGFR, and can be effectively utilized as a drug to suppress resistance caused by various EGFR mutations, including T790M and C797S. Accordingly, in this specification, including all claims below, the compound of the present invention can be utilized as a composition for the prevention or treatment of lung cancer, either alone or in combination with other lung cancer treatments. Specifically, while osimertinib targets the T790M mutation, AON-MG23 can act regardless of the said mutation; thus, since the two drugs can be expected to have complementary effects, the therapeutic range of EGFR targeted therapies can be expanded to provide a resistance-suppressing effect, but is not limited thereto.

[0136] In the entire specification including the following claims, “A549” is a cell line derived from human alveolar epithelial cells, which may contain a KRAS (G12S) mutation and may be used for anticancer drug sensitivity studies, but is not limited thereto.

[0137] Including all claims below, “Calu-3” is a cell line derived from human bronchial adenocarcinoma, which may contain a p53 mutation and may be used in studies related to lung cancer and mucus secretion, but is not limited thereto.

[0138] Including all claims below, “H1975” is a cell line derived from human lung adenocarcinoma, which may include EGFR Exon 21 L858R and Exon 20 T790M mutations and may be used in studies related to resistance and tolerance to first- or second-generation EGFR TKIs, but is not limited thereto.

[0139] Including all claims below, “H1975 / OR” is an H1975-derived cell line possessing resistance and tolerance to ossimertinib. As indicated by mutation analysis results through chromosomal copy number analysis, H1975 / OR may contain multiple mutations such as T790M, L858R, and C797S, as well as G724S, L718X, and G719X. It may be used for research related to resistance and tolerance to ossimertinib, but is not limited thereto.

[0140] Including all claims below, “H1975 C797S mutant” refers to a cell line in which the C797S mutation of EGFR is overexpressed in an H1975 resistant cell line (H1975 / OR), and may be used in studies related to resistance and tolerance to osimertinib, but is not limited thereto.

[0141] In all claims below, “PC-9” is a cell line derived from human lung adenocarcinoma, which may include an EGFR Exon 19 deletion mutation and may be used for sensitivity studies to EGFR TKIs, but is not limited thereto.

[0142] Including all claims below, “PC-9 / GR” refers to a PC-9 derived cell line possessing tolerance and resistance to Gefitinib, which may be used for studies on tolerance and resistance to Gefitinib, but is not limited thereto.

[0143] In the entire specification including the following claims, it has been confirmed that the compound of the present invention exhibits an effect of inhibiting tumorigenicity in common lung cancer cell lines possessing various EGFR variants. Specifically, in the entire specification including the following claims, through specific examples regarding the H1975 cell line with EGFR Exon 21 L858R and Exon 20 T790M mutations and the PC-9 cell line with EGFR Exon 19 deletion mutation, it has been confirmed that the compound of the present invention exhibits activity in inhibiting cancer cell proliferation, growth inhibition, and tumorigenicity of cancer cells despite different resistance-related EGFR mutations. This suggests that the compound of the present invention is not limited to specific generations of EGFR tyrosine kinase inhibitors such as Osimertinib or Gefitinib, but can inhibit tumorigenicity against a wide range of EGFR variants, although it is not limited thereto.

[0144] Including all claims below, the EGFR T790M mutation may be one in which the 745th amino acid of the amino acid sequence of SEQ ID NO. 1 is substituted from threonine to methionine, and the EGFR T790M mutation may be one in which the 790th amino acid of the amino acid sequence of SEQ ID NO. 2 is substituted from threonine to methionine, but is not limited thereto.

[0145] In the entire specification including the following claims, the EGFR C797S mutation may be such that the 752nd amino acid of the amino acid sequence of SEQ ID NO. 1 is substituted from cysteine ​​to serine, and the EGFR C797S mutation may be such that the 797th amino acid of the amino acid sequence of SEQ ID NO. 2 is substituted from cysteine ​​to serine, but is not limited thereto.

[0146] In the entire specification including the following claims, the EGFR L858R mutation may be in which the 813th amino acid of the amino acid sequence of SEQ ID NO. 1 is substituted from leucine to arginine, and the EGFR L858R mutation may be in which the 858th amino acid of the amino acid sequence of SEQ ID NO. 2 is substituted from leucine to arginine, but is not limited thereto.

[0147] Including all claims below, the EGFR G724S mutation may be such that the 679th amino acid of the amino acid sequence of SEQ ID NO. 1 is substituted from glycine to serine, and the EGFR G724S mutation may be such that the 724th amino acid of the amino acid sequence of SEQ ID NO. 2 is substituted from glycine to serine, but is not limited thereto.

[0148] Including all claims below, the EGFR L718X mutation may be in which the 673rd amino acid of the amino acid sequence of SEQ ID NO. 1 is substituted with a stop codon from leucine, and the EGFR L718X mutation may be in which the 718th amino acid of the amino acid sequence of SEQ ID NO. 2 is substituted with a stop codon from leucine, but is not limited thereto.

[0149] Including all claims below, the EGFR G719X mutation may be such that the 674th amino acid of the amino acid sequence of SEQ ID NO. 1 is substituted with a stop codon from glycine, and the EGFR G719X mutation may be such that the 719th amino acid of the amino acid sequence of SEQ ID NO. 2 is substituted with a stop codon from glycine, but is not limited thereto.

[0150] Including all claims below, the compounds of the present invention or pharmaceutically acceptable salts thereof may degrade EGFR or ANO1, and specifically, the compounds of the present invention or pharmaceutically acceptable salts thereof may degrade EGFR or ANO1 simultaneously, separately, or sequentially, but are not limited thereto.

[0151] In the entirety of the following claims, the “Epidermal Growth Factor Receptor (EGFR)” is present in the cell membrane of epithelial cells and may be a receptor for epidermal growth factor (EGF) to which EGF binds, thereby promoting cell growth and differentiation. Additionally, in the entirety of the following claims, the epidermal growth factor receptor may be highly expressed in a mutated form in a number of cancers, including lung cancer and glioblastoma, and may be utilized as an important indicator for cancer metastasis and growth, but is not limited thereto.

[0152] In the entirety of the following claims, the epidermal growth factor receptor comprises any natural EGFR, which also encompasses naturally occurring variants of EGFR, e.g., splice variants or allelic variants. For example, the amino acid sequence of EGFR may be GenBank accession number AAH94761.1 or Uniprot accession number P00533, but is not limited thereto. Additionally, in the entirety of the following claims, EGFR may comprise the amino acid sequence of SEQ ID NO. 1 or 2, and specifically, in the entirety of the following claims, EGFR may consist of the amino acid sequence of SEQ ID NO. 1 or 2, but is not limited thereto.

[0153] Additionally, as per the entire claim below, the epidermal growth factor receptor may comprise an extracellular domain (ECD), a transmembrane domain (TMD) that passes through the cell membrane, a juxtamembrane domain (JMD) that connects the TMD and the cytoplasmic region, and an intracellular region, wherein the intracellular region may comprise a tyrosine kinase domain (TKD), but is not limited thereto.

[0154] In the entirety of the following claims, the membrane-adjacent domain may be used interchangeably with the membrane-adjacent region, and the membrane-adjacent domain or membrane-adjacent region may mean a segment located adjacent to the inner or outer side of the cell membrane and connecting the transmembrane domain and the intracellular region, but is not limited thereto. By example, in the entirety of the following claims, the membrane-adjacent domain or membrane-adjacent region may be represented by the structure of the EGFR transmembrane - juxtamembrane (TM-JM) segment corresponding to structure ID 2M20 of the RCSB Protein Data Bank (PDB), but is not limited thereto.

[0155] In this specification, including the entire claims below, “ANO1(Anoctamin 1)” refers to a calcium-activated chloride ion channel (Cl₂), also referred to as “transmembrane protein 16A(TMEM16A)”. - It is a channel. Specifically, it is one of the ion channels in vivo, and while it can play a role in regulating ions in normal cells, ANO1 is overexpressed in cancer cells including lung cancer, breast cancer, head and neck cancer, and brain tumors. The overexpressed ANO1 can bind to EGFR to promote the migration and growth of the cancer, thereby exhibiting a malignant effect, but is not limited to this.

[0156] In the entirety of the following claims, ANO1 comprises any natural ANO1, which also encompasses naturally occurring variants of ANO1, e.g., splice variants or allelic variants. For example, the amino acid sequence of ANO1 may be Uniprot accession number Q5XXA6, but is not limited thereto. Additionally, in the entirety of the following claims, ANO1 may comprise the amino acid sequence of SEQ ID NO. 3, and specifically, ANO1 may consist of the amino acid sequence of SEQ ID NO. 3, but is not limited thereto.

[0157] In the entire specification including the following claims, the amino acid sequence may include a sequence having 50% or more homology with each of the amino acid sequences of SEQ ID NOs 1 to 3, specifically, a sequence having 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more, 99% or more homology, or a sequence having substantial identity, but is not limited thereto.

[0158] In the entirety of the following claims, “substantial identity” means that when homology between amino acid sequences or nucleic acid sequences is compared using any various algorithm in commercial computer programs such as BLASTN, BLASTP, Gap BLAST, and PSI-BLAST, if two sequences contain the same residue at corresponding positions, preferably if they have sequence homology of at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%, they are generally considered to be “substantially identical.”

[0159] In addition, the present specification, including the entire claim below, includes a change in nucleotide sequence due to "degeneracy of the genetic code." "Degeneracy of the genetic code" means that there are multiple different codons coding for a single amino acid. For example, in the case of the amino acid leucine, it is encoded identically by various codons such as "CUU", "CUC", "CUA", "CUG", and "UUA", and this is referred to as degeneracy of the genetic code.

[0160] Including the entire claims below, the compound of the present invention or a pharmaceutically acceptable salt thereof may be characterized by one or more selected from the group consisting of, but not limited to:

[0161] (a) inhibiting the proliferation or growth of cancer cells; and

[0162] (b) inhibiting the tumorigenicity of cancer cells; and

[0163] (c) Suppresses resistance of lung tumor cells to anticancer drugs.

[0164] Including all claims below, the anticancer agent of the present invention may be a targeted anticancer agent against tyrosine kinase, but is not limited thereto.

[0165] In the entirety of the following claims, “Tyrosine Kinase (TK)” is an enzyme that activates various proteins through a signal transduction chain reaction, specifically, it may cause a phosphorylation reaction that adds a phosphate group to a protein, but is not limited thereto. Additionally, in the entirety of the following claims, the tyrosine kinase of the present invention may be one or more selected from the group consisting of EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase), ROS1 (ROS Proto-Oncogene 1), BRAF (B-Raf Proto-Oncogene), HER2 (human epidermal growth factor receptor 2), RET (Ret Proto-Oncogene), NTRK1 (Neurotrophic Receptor Tyrosine Kinase 1), MET (Mesenchymal-Epithelial Transition factor), and NRG1 (Neuregulin 1), but is not limited thereto. Specifically, as per the entire claim below, the tyrosine kinase of the present invention may be EGFR, but is not limited thereto.

[0166] In this specification, including all claims below, the term “targeted anticancer agent” means a preparation that exhibits an anticancer effect by targeting proteins or genes that are specifically altered in cancer cells or cancer tissues, and by interfering with molecular activities involved in the growth and development of cancer.

[0167] Including all claims below, the targeted anticancer agent for tyrosine kinase of the present invention may be a tyrosine kinase inhibitor, but is not limited thereto.

[0168] Including the full claims below, “Tyrosine kinase inhibitors (TKIs) are drugs that inhibit tyrosine kinase, and tyrosine kinase inhibitors may act to inhibit the phosphorylation process caused by tyrosine kinase. Additionally, tyrosine kinase inhibitors may be utilized as anticancer agents, for example, to significantly improve the prognosis of chronic myeloid leukemia or to treat non-cancer diseases such as idiopathic pulmonary fibrosis, but are not limited thereto.”

[0169] Including all claims below, the tyrosine kinase of the present invention may be an epidermal growth factor receptor (EGFR), but is not limited thereto.

[0170] Including all claims below, the pharmaceutical composition of the present invention may be administered in combination with a targeted anticancer agent for tyrosine kinase, but is not limited thereto.

[0171] Including all claims below, the pharmaceutical composition of the present invention may be administered simultaneously, separately, or sequentially with the targeted anticancer agent of the present invention, but is not limited thereto.

[0172] The present invention relates to (i) one or more compounds selected from the group consisting of compounds represented by the formulas 1 and 2 or pharmaceutically acceptable salts thereof; and

[0173] (ii) Provides a pharmaceutical composition for the prevention or treatment of lung cancer comprising a targeted anticancer agent against EGFR as an active ingredient.

[0174] In the entirety of the following claims, the targeted anticancer agent for EGFR of the present invention may be one or more selected from the group consisting of osimertinib, cetuximab, panitumumab, gefitinib, afatinib, erlotinib, and lazertinib; specifically, in the entirety of the following claims, the targeted anticancer agent for EGFR may be osimertinib or gefitinib, but is not limited thereto.

[0175] Including all claims below, the compounds of the present invention or pharmaceutically acceptable salts thereof may inhibit, but are not limited to, the resistance of lung tumor cells to targeted anticancer agents against EGFR of the present invention.

[0176] Including all claims below, the tumor cells of the present invention may include cancer cells, but are not limited thereto.

[0177] In all claims below, the term "tumor" may be a concept including "cancer" and may refer to a condition characterized by typically uncontrolled cell growth, migration, and proliferation, but is not limited thereto. Specifically, in all claims below, cancer according to the present invention includes primary and recurrent cancer, and tumor according to the present invention includes both benign and malignant tumors. In all claims below, lung tumor cells according to the present invention may mean lung cancer cells, but are not limited thereto.

[0178] In the entirety of the following claims, the pharmaceutical composition of the present invention may be in the form of a mixture comprising a compound of the present invention or a pharmaceutically acceptable salt thereof; and a targeted anticancer agent for EGFR of the present invention, but is not limited thereto. In the entirety of the following claims, the mixture may be in the form for simultaneous administration of a compound of the present invention or a pharmaceutically acceptable salt thereof; and a targeted anticancer agent for EGFR.

[0179] Including all claims below, the pharmaceutical composition of the present invention may be in the form in which the compound of the present invention or a pharmaceutically acceptable salt thereof; and the targeted anticancer agent for EGFR of the present invention are each formulated and administered simultaneously, separately, or sequentially, but is not limited thereto. In this case, the pharmaceutical composition may be a pharmaceutical composition for concomitant administration for simultaneous or sequential administration, comprising a first pharmaceutical composition containing a pharmaceutically effective amount of said compound or salt thereof as an active ingredient; and a second pharmaceutical composition containing a pharmaceutically effective amount of said targeted anticancer agent for EGFR as an active ingredient. In the case of sequential administration, the order of administration is not limited, and the administration regimen may be appropriately adjusted according to the patient's condition, etc.

[0180] In the present specification, including all claims below, where the pharmaceutical composition is a pharmaceutical composition for combination therapy for sequential administration, the composition may be such that the compound or its salt ("first component") is administered first, followed by the administration of a targeted anticancer agent for EGFR ("second component"), and the reverse order is also possible.

[0181] Including all claims below, in this specification, when a compound according to the present invention is used in combination with an anticancer agent, the compound may be administered simultaneously, separately, or sequentially with the anticancer agent. Even when administered sequentially with the anticancer agent, the order of administration is not limited, but the administration regimen may be appropriately adjusted according to the type of cancer, the type of anticancer agent, the patient's condition, etc.

[0182] The present invention provides a pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer agent, comprising as an active ingredient one or more compounds selected from the group consisting of compounds represented by the chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof.

[0183] Including all claims below, the anticancer agent for lung cancer may be used interchangeably with, but is not limited to, anticancer agents for lung tumors.

[0184] Including all claims below, the lung cancer anticancer agent of the present invention may be a targeted anticancer agent for tyrosine kinase, but is not limited thereto.

[0185] In this specification, including all claims below, “enhancement of anticancer effect” refers to any effect that can consequently strengthen the function of an anticancer agent. This concept encompasses not only enhancing the anticancer effects of the anticancer agent, such as inhibiting tumor growth, inhibiting tumor metastasis, and inhibiting tumor recurrence, but also enhancing the anticancer effect by inhibiting the formation of resistance or tolerance in cancer cells to the anticancer agent. In this specification, including all claims below, “enhancement of anticancer effect” may mean further enhancement of the inhibition of cancer cell growth or the inhibition of resistance to the anticancer agent by the anticancer agent, but is not limited thereto.

[0186] Accordingly, the compound according to the present invention can be used as a compound for co-administration with a known anticancer agent (e.g., a targeted anticancer agent against tyrosine kinase) for the purpose of enhancing the anticancer effect of a lung cancer anticancer agent.

[0187] Including all claims below, the pharmaceutical composition of the present invention may be administered simultaneously, separately, or sequentially with the lung cancer anticancer agent of the present invention, but is not limited thereto.

[0188] Including all claims below, as provided herein, a compound of the present invention or a pharmaceutically acceptable salt thereof is bound to a complex of EGFR and ANO1, and

[0189] The compound of the present invention or a pharmaceutically acceptable salt thereof may simultaneously bind to the juxtamembrane site of EGFR and ANO1, but is not limited thereto.

[0190] Including all claims below, as provided herein, a compound of the present invention or a pharmaceutically acceptable salt thereof is bound to a complex of EGFR and ANO1, and

[0191] The compound of the present invention or a pharmaceutically acceptable salt thereof may simultaneously bind to the juxtamembrane site of EGFR other than the tyrosine kinase site of EGFR and ANO1 to enhance the anticancer effect of a lung cancer anticancer agent, but is not limited thereto.

[0192] The present invention provides a pharmaceutical composition for inhibiting anticancer drug resistance in lung cancer, comprising as an active ingredient one or more compounds selected from the group consisting of compounds represented by the chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof.

[0193] Including all claims below, the present specification may include a pharmaceutically acceptable salt of one or more compounds selected from the group consisting of compounds represented by chemical formulas 1 and 2 as an active ingredient.

[0194] In all claims below, the term "pharmaceuticalally acceptable salt" may include, but is not limited to, a salt derived from a pharmaceutically acceptable inorganic acid, organic acid, or base. Additionally, said derivatives may include, but are not limited to, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable anhydrides, pharmaceutically acceptable enantiomers, pharmaceutically acceptable esters, pharmaceutically acceptable polymorphs, pharmaceutically acceptable prodrugs, pharmaceutically acceptable complexes, etc.

[0195] Including all claims below, the term “pharmaceuticalally acceptable” in this specification may mean, but is not limited to, a compound or composition that is suitable for use in contact with tissues of a subject (e.g., human) and within the scope of sound medical judgment, having a reasonable benefit / risk ratio without excessive toxicity, irritation, allergic reaction, or other problems or complications.

[0196] Including all claims below, examples of suitable acids in this specification include hydrochloric acid, bromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid, benzoic acid, malonic acid, gluconic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, etc. Acid addition salts may be prepared by conventional methods, for example, by dissolving a compound in an excess amount of an aqueous acid solution and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone, or acetonitrile. Alternatively, they may be prepared by heating an equal molar amount of the compound and an acid or alcohol in water, followed by evaporating and drying the mixture, or by suction filtration of the precipitated salt, but are not limited thereto.

[0197] In the entire specification including the following claims, salts derived from suitable bases may include, but are not limited to, alkali metals such as sodium and potassium, alkaline earth metals such as magnesium, and ammonium. Alkali metal or alkaline earth metal salts can be obtained, for example, by dissolving a compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and then evaporating and drying the filtrate. In this case, it is particularly suitable for pharmaceutical purposes to produce sodium, potassium, or calcium salts as metal salts, and the corresponding silver salts can be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate), but are not limited thereto.

[0198] Including all claims below, the scope of the compounds of the present invention may include, but is not limited to, all isomers, hydrates, and solvates that can be prepared by conventional methods as well as pharmaceutically acceptable salts.

[0199] In the entire specification including the following claims, one or more compounds selected from the group consisting of compounds represented by Formulas 1 and 2 of the present invention may include all compounds exhibiting substantially the same structure, functional group, and function as one or more compounds selected from the group consisting of compounds represented by Formulas 1 and 2 among various compounds such as intermediate reactants and secondary products that appear through metabolism or chemical reactions inside or outside the human body, but are not limited thereto.

[0200] In the entire specification including the following claims, the content of one or more compounds selected from the group consisting of compounds represented by Formulas 1 and 2 in the composition of the present invention may be appropriately adjusted according to the symptoms of the disease, the degree of progression of symptoms, the condition of the patient, etc., and may, for example, be 0.0001 to 99.9% by weight or 0.001 to 50% by weight based on the total weight of the composition, but is not limited thereto. The above content ratio may be a value based on the dry weight after removing the solvent, but is not limited thereto.

[0201] Including all claims below, the pharmaceutical composition according to the present invention may further comprise, but is not limited to, suitable carriers, excipients, and diluents commonly used in the manufacture of pharmaceutical compositions. The excipients may be, for example, one or more selected from the group consisting of diluents, binders, disintegrants, lubricants, adsorbents, humectants, film-coating materials, and controlled-release additives.

[0202] Including all claims below, as set forth herein, the pharmaceutical composition according to the present invention may be formulated and used in the form of external preparations such as powders, granules, sustained-release granules, enteric granules, liquids, ophthalmic preparations, oleic acid preparations, emulsions, suspensions, ethanol preparations, troches, aromatic preparations, limonene adrenergic preparations, tablets, sustained-release tablets, enteric tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, irrigation solutions, warning agents, lotions, pastes, sprays, inhalants, patches, sterile injectable solutions, or aerosols, respectively, according to conventional methods, and said external preparations may be used as creams, gels, patches, sprays, ointments, warning agents, lotions, liniments, pastes, or cataplasms, etc. It may have a formulation, but is not limited thereto.

[0203] Including all claims below, carriers, excipients, and diluents that may be included in the pharmaceutical composition according to the present invention include, but are not limited to, lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0204] Including all claims below, the formulation may be prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants, but is not limited thereto.

[0205] Including all claims below, as an additive to tablets, powders, granules, capsules, pills, and lozenges according to the present invention, excipients such as corn starch, potato starch, wheat starch, lactose, sucrose, glucose, fructose, D-mannitol, precipitated calcium carbonate, synthetic aluminum silicate, calcium monohydrogen phosphate, calcium sulfate, sodium chloride, sodium bicarbonate, refined lanolin, microcrystalline cellulose, dextrin, sodium alginate, methylcellulose, sodium carboxymethylcellulose, kaolin, urea, colloidal silica gel, hydroxypropyl starch, hydroxypropylmethylcellulose (HPMC) 1928, HPMC 2208, HPMC 2906, HPMC 2910, propylene glycol, casein, calcium lactate, primogel, etc.; Gelatin, gum arabic, ethanol, agar powder, cellulose phthalate, carboxymethylcellulose, calcium carboxymethylcellulose, glucose, purified water, sodium casein, glycerin, stearic acid, sodium carboxymethylcellulose, sodium methylcellulose, methylcellulose, microcrystalline cellulose, dextrin, hydroxycellulose, hydroxypropyl starch, hydroxymethylcellulose, refined shellac, starch paste, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, etc. may be used as binders, and hydroxypropylmethylcellulose, corn starch, agar powder, methylcellulose, bentonite, hydroxypropyl starch, sodium carboxymethylcellulose, sodium alginate, Calcium carboxymethylcellulose, calcium citrate, sodium lauryl sulfate, anhydrous silica, 1-hydroxypropylcellulose, dextran, ion exchange resin, polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate, polyvinylpyrrolidone, calcium phosphate, gelled starch, gum arabic, amylopectin, pectin, sodium polyphosphate, ethylcellulose, sucrose, magnesium aluminum silicate, D-sorbitol solution, hard anhydrous silica, etc. disintegrants;Lubricants such as calcium stearate, magnesium stearate, stearic acid, hydrogenated vegetable oil, talc, lycopodium pods, kaolin, petroleum jelly, sodium stearate, cocoa paste, sodium salicylate, magnesium salicylate, polyethylene glycol (PEG) 4000, PEG 6000, liquid paraffin, hydrogenated soybean oil (Lubri wax), aluminum stearate, zinc stearate, sodium lauryl sulfate, magnesium oxide, macrogol, synthetic aluminum silicate, anhydrous silica, higher fatty acids, higher alcohols, silicone oil, paraffin oil, polyethylene glycol fatty acid ether, starch, sodium chloride, sodium acetate, sodium oleate, dl-leucine, and hard anhydrous silica may be used, but are not limited thereto.

[0206] Including all claims below, as used in this specification, additives to the liquid formulation according to the present invention may include water, dilute hydrochloric acid, dilute sulfuric acid, sodium citrate, monostearic acid sucroses, polyoxyethylene sorbitol fatty acid esters (tween esters), polyoxyethylene monoalkyl ethers, lanolin ethers, lanolin esters, acetic acid, hydrochloric acid, water ammonia, ammonium carbonate, potassium hydroxide, sodium hydroxide, prolamine, polyvinylpyrrolidone, ethylcellulose, sodium carboxymethylcellulose, etc., but are not limited thereto.

[0207] Including all claims below, the syrup formulation according to the present invention may use a solution of white sugar, other sugars or sweeteners, etc., and as necessary, may use flavorings, coloring agents, preservatives, stabilizers, suspending agents, emulsifiers, viscosity enhancers, etc., but is not limited thereto.

[0208] Including all claims below, the emulsion according to the present invention may use purified water, and may use emulsifiers, preservatives, stabilizers, fragrances, etc. as needed, but is not limited thereto.

[0209] Including all claims below, the suspending agent according to the present invention may use suspending agents such as acacia, tragacanthus, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, microcrystalline cellulose, sodium alginate, hydroxypropylmethylcellulose (HPMC), HPMC 1828, HPMC 2906, HPMC 2910, etc., and may use surfactants, preservatives, stabilizers, coloring agents, and fragrances as needed, but is not limited thereto.

[0210] Including all claims below, the injectable formulation according to the present invention comprises: solvents such as distilled water for injection, 0.9% sodium chloride injection solution, Ringer's injection solution, dextrose injection solution, dextrose + sodium chloride injection solution, PEG, lactated Ringer's injection solution, ethanol, propylene glycol, non-volatile oils—sesame oil, cottonseed oil, peanut oil, soybean oil, corn oil, ethyl oleate, isopropyl myristate, and benzene benzoate; and solubilizing agents such as sodium benzoate, sodium salicylate, sodium acetate, urea, urethane, monoethylacetamide, butazolidine, propylene glycol, Tween, nijungtinamide, hexamine, and dimethylacetamide; Buffers such as weak acids and their salts (acetic acid and sodium acetate), weak bases and their salts (ammonia and ammonium acetate), organic compounds, proteins, albumin, peptone, and gums; isotonic agents such as sodium chloride; stabilizers such as sodium bisulfite (NaHSO3), carbon dioxide gas, sodium metabisulfite (Na2S2O5), sodium sulfite (Na2SO3), nitrogen gas (N2), and ethylenediaminetetraacetic acid; sulfating agents such as sodium bisulfide 0.1%, sodium formaldehyde sulfoxylate, thiourea, disodium ethylenediaminetetraacetic acid, and sodium bisulfite acetone; analgesics such as benzyl alcohol, chlorobutanol, procaine hydrochloride, glucose, and calcium gluconate; It may include suspending agents such as sodium CMC, sodium alginate, Tween 80, and aluminum monostearate, but is not limited thereto.

[0211] Including all claims below, as provided herein, the suppositories according to the present invention comprise: cocoa gluten, lanolin, Witepsol, polyethylene glycol, glycerogelatin, methylcellulose, carboxymethylcellulose, a mixture of stearic acid and oleic acid, Subanal, cottonseed oil, peanut oil, palm oil, cocoa butter + cholesterol, lecithin, lanette wax, glycerol monostearate, Tween or Spandex, Imhausen, monollene (propylene glycol monostearate), glycerin, Adeps solidus, Buytyrum Tego-G, Cebes Pharma 16, hexalide base 95, Cotomar, Hydroccote SP, S-70-XXA, S-70-XX75 (S-70-XX95), Bases such as Hydrokote 25, Hydrokote 711, Idropostal, Massa estrarium (A, AS, B, C, D, E, I, T), Massa-MF, Masupol, Masupol-15, Neosupostal-N, Paramount-B, Suposiro (OSI, OSIX, A, B, C, D, H, L), suppository base type IV (AB, B, A, BC, BBG, E, BGF, C, D, 299), Supostal (N, Es), Wecobi (W, R, S, M, Fs), and Tegestor triglyceride base (TG-95, MA, 57) may be used, but are not limited thereto.

[0212] In the entirety of the following claims, solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid dosage forms are prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the extract. In addition, lubricants such as magnesium styrate and talc may be used in addition to simple excipients, but are not limited thereto.

[0213] In the entire specification including the following claims, liquid formulations for oral administration include suspensions, liquid formulations, emulsions, syrups, etc., and may include various excipients, such as humectants, sweeteners, flavorings, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. Non-aqueous solvents and suspensions may include, but are not limited to, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.

[0214] Including all claims below, the pharmaceutical composition according to the present invention may be administered in a pharmaceutically effective amount, but is not limited thereto. Including all claims below, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level may be determined based on factors including the type and severity of the patient's disease, drug activity, sensitivity to the drug, time of administration, route of administration and elimination rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field, but is not limited thereto.

[0215] Including all claims below, the pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered as a single or multiple doses, but is not limited thereto. It is important to administer an amount that obtains maximum effect with a minimum amount without side effects, taking all of the above factors into consideration; this can be easily determined by a person skilled in the art to which the present invention pertains, but is not limited thereto.

[0216] Including all claims below, the pharmaceutical composition of the present invention may be administered to an individual by various routes, but is not limited thereto. Including all claims below, all modes of administration may be anticipated, for example, by oral administration, subcutaneous injection, intraperitoneal administration, intramuscular injection, intrathecal (intradural) injection, sublingual administration, buccal mucosal administration, rectal insertion, vaginal insertion, ocular administration, ear administration, nasal administration, inhalation, spray through the mouth or nose, skin administration, transdermal administration, etc.

[0217] In all claims below, as set forth in this specification, the dosage of the pharmaceutical composition of the present invention may be determined according to the type of active ingredient drug, along with various relevant factors such as the disease to be treated, the route of administration, the patient's age, gender, weight, and the severity of the disease, but is not limited thereto. Specifically, the effective dosage of the composition according to the present invention may vary depending on the patient's age, gender, and weight, and generally, 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight, may be administered daily or every other day, or divided into 1 to 3 doses per day. However, since the dosage may be increased or decreased depending on the route of administration, the severity of the disease, gender, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

[0218] Additionally, as provided herein, including the entire claim below, the pharmaceutical composition of the present invention or the compound of the present invention comprises 1 to 100 mg, 5 to 100 mg, 10 to 100 mg, 15 to 100 mg, 20 to 100 mg, 25 to 100 mg, 30 to 100 mg, 35 to 100 mg, 40 to 100 mg, 45 to 100 mg, 50 to 100 mg, 55 to 100 mg, 60 to 100 mg, 65 to 100 mg, 70 to 100 mg, 75 to 100 mg, 1 to 90 mg, 5 to 90 mg, 10 to 90 mg, 15 to 90 mg, 20 to 90 mg, 25 to 90 mg, 30 to 90 mg, per kg of body weight. 35 to 90 mg, 40 to 90 mg, 45 to 90 mg, 50 to 90 mg, 55 to 90 mg, 60 to 90 mg, 65 to 90 mg, 70 to 90 mg, 75 to 90 mg, 1 to 80 mg, 5 to 80 mg, 10 to 80 mg, 15 to 80 mg, 20 to 80 mg, 25 to 80 mg, 30 to 80 mg, 35 to 80 mg, 40 to 80 mg, 45 to 80 mg, 50 to 80 mg, 55 to 80 mg, 60 to 80 mg, 65 to 80 mg, 70 to 80 mg, 75 to 80 mg, 1 to 75 mg, 5 to 75 mg, 10 to 75 mg, 15 to 75 mg, 20 to 75 mg, 25 to 75 mg, 30 to 75 mg, 35 to 75 mg, 40 to 75 mg, 45 to 75 mg, 50 to 75 mg, 55 to 75 mg, 60 to 75 mg, 65 to 75 mg, 70 to 75 mg, 1 mg or more, 5 mg or more, 10 mg or more, 15 mg or more, 20 mg or more, 25 mg or more, 30 mg or more, 35 mg or more, 40 mg or more, 45 mg or more, 50 mg or more, 55 mg or more, 60 mg or more, 65 mg or more, 70 mg or more, or 75 mg or more may be administered,It is not limited to this.

[0219] In the entirety of the following claims, the term “individual” in this specification means an object requiring treatment for a disease and may be used interchangeably with a patient. More specifically, the term “individual” may mean mammals such as human or non-human primates, mice, rats, dogs, cats, horses, and cattle, but is not limited thereto.

[0220] Including all claims below, the term “administration” in this specification may mean providing a specific composition of the present invention to an individual by any suitable method, but is not limited thereto.

[0221] In all claims below, the term “prevention” means any act of suppressing or delaying the onset of a target disease, the term “treatment” means any act of improving or beneficially altering a target disease and associated metabolic abnormality symptoms by administering a pharmaceutical composition according to the present invention, and the term “improvement” may mean any act of reducing parameters related to a target disease, e.g., the severity of symptoms, by administering a composition according to the present invention, but is not limited thereto.

[0222] The present invention provides a kit for the prevention or treatment of lung cancer comprising the pharmaceutical composition of the present invention. In addition, the present invention provides a kit for enhancing the anticancer effect of a lung cancer anticancer agent comprising the pharmaceutical composition of the present invention.

[0223] In all claims below, the term "Kit" in this specification refers to a combination of substances or devices, etc., for the prevention or treatment of lung cancer or for enhancing the anticancer effect of a lung cancer anticancer drug using a compound according to the present invention, and there are no limitations on the specific form. A kit according to the present invention may include, but is not limited to, a compound according to the present invention as well as one or more other constituent compositions, solutions, or devices suitable for the prevention, improvement, or treatment of diseases, in order to prevent and / or treat lung cancer-related diseases or enhance the anticancer effect of a lung cancer anticancer drug.

[0224] Including all claims below, the kit may be one or more selected from the group consisting of microarrays, aptamer chip kits, ELISA (Enzyme Linked Immunosorbent Assay) kits, blotting kits, immunoprecipitation kits, immunofluorescence test kits, protein chip kits, reverse transcription polymerase chain reaction (RT-PCR) kits, and qRT-PCR kits, but is not limited thereto.

[0225] Including all claims below, the kit may include, but is not limited to, other components, compositions, solutions, devices, etc. that are typically required for the measurement or detection methods thereof, in addition to the above-mentioned formulations. Specific examples may include, but are not limited to, components necessary for sample collection tools for individuals, blood storage, management, etc. In this case, each component may be applied one or more times without limitation, there is no restriction on the order in which each substance is applied, and the application of each substance may proceed simultaneously or sequentially.

[0226] In all claims below, the kit may include, but is not limited to, a container; instructions; etc. The container may serve to package the formulation and may serve to store and secure it, but is not limited thereto. The material of the container may take the form, for example, a bottle, a tub, a sachet, an envelope, a tube, an ampoule, etc., and may be formed partially or wholly from plastic, glass, paper, foil, wax, etc., but is not limited thereto. The container may be fitted with a cap that is initially part of the container or may be attached to the container by mechanical, adhesive, or other means and may be fully or partially detachable, and may also be fitted with a stopper that allows access to the contents by a needle, but is not limited thereto. The kit may include an outer package, and the outer package may include instructions for the use of the components, but is not limited thereto.

[0227] Including all claims below, the kit may further include instructions, but is not limited thereto. Additionally, in the present invention, the instructions may describe a method for providing information necessary for the prevention or treatment of lung cancer or for enhancing the anticancer effect of a lung cancer anticancer agent according to the present invention, but is not limited thereto.

[0228]

[0229]

[0230] Preferred embodiments are presented below to aid in understanding the present invention. However, the following embodiments are provided merely to facilitate a better understanding of the invention, and the scope of the invention is not limited by the following embodiments.

[0231]

[0232] [Example]

[0233]

[0234] Example 1.1. Preparation of the compounds of the present invention, AON-MG23-01 and AON-MG23-02

[0235]

[0236] 1-1. Preparation of N-(2-((5-chloro-2-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-N-cyclopropylmethanesulfonamide (AON-MG23-01)

[0237] [Reaction Equation 1]

[0238]

[0239]

[0240] The AON-MG23-01 compound was prepared using the above Reaction Scheme 1. The specific preparation method is as follows:

[0241]

[0242] <Step 1> Synthesis of N-cyclopropyl-N-(2-nitrophenyl)methanesulfonamide

[0243] [Reaction Equation 2]

[0244]

[0245] 1-Fluoro-2-nitrobenzene (1.00 eq) and cyclopropylamine (1.00 eq) were dissolved in acetonitrile (ACN), and methanesulfonyl chloride (MsCl, 1.0 eq) was slowly added at 0°C, followed by stirring at the same temperature for 1 hour. Then, cesium carbonate (Cs2CO3, 5.00 eq) was added at the same temperature, followed by reflux and stirring overnight. After the reaction was complete, the temperature was lowered to room temperature and extracted using ethyl acetate and water. The organic layer was mixed with anhydrous sodium sulfate and stirred, filtered using a filter, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by column chromatography (hexane:ethyl acetate = 3:1) to synthesize a pale yellow solid N-cyclopropyl-N-(2-nitrophenyl)methanesulfonamide, and the yield was 36%.

[0246]

[0247] <Step 2> Synthesis of N-(2-aminophenyl)-N-cyclopropylmethanesulfonamide

[0248] [Reaction Equation 3]

[0249]

[0250]

[0251] N-cyclopropyl-N-(2-nitrophenyl)methanesulfonamide (1.00 eq) synthesized in Step 1 was added to 1,4-dioxane and water (3:1) and stirred. Then, the reactor was cooled to 0°C, and zinc (Zn, 10.0 eq) and ammonium chloride (NH4Cl, 10.0 eq) were added. Subsequently, the temperature was gradually increased while stirring for 4 hours. After the reaction was complete, the mixture was filtered using Celite, and the filtrate was extracted with ethyl acetate and water. The organic layer was mixed with anhydrous sodium sulfate and stirred, then filtered using a filter, and the filtrate was concentrated under reduced pressure. The concentrated residue was used in Step 3 without a separate purification process.

[0252]

[0253] <Step 3> Synthesis of N-cyclopropyl-N-(2-((2,5-dichloropyrimidine-4-yl)amino)phenyl)methanesulfonamide

[0254] [Reaction Equation 4]

[0255]

[0256] N-(2-aminophenyl)-N-cyclopropylmethanesulfonamide (1.00 eq) synthesized in Step 2 was added to isopropyl alcohol (IPA), and 2,4,5-trichloropyrimidine (1.1 eq) and N,N-diisopropylethylamine (DIPEA, 2.5 eq) were added at room temperature, followed by reflux and overnight stirring. After the reaction was complete, the mixture was evaporated under reduced pressure and extracted using water and dichloromethane. The organic layer was washed with 2N hydrochloric acid, and the organic layer was stirred with anhydrous sodium sulfate. Then, the mixture was filtered using a filter, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by column chromatography (hexane:ethyl acetate = 3:1) to synthesize a pale yellow solid N-cyclopropyl-N-(2-((2,5-dichloropyrimidine-4-yl)amino)phenyl)methanesulfonamide, and the yield was 58.9%.

[0257]

[0258] <Step 4> Synthesis of N-(2-((5-chloro-2-((2-methoxy-4-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)phenyl)amino)pyrimidine-4-yl)amino)phenyl)-N-cyclopropylmethanesulfonamide

[0259] [Reaction Equation 5]

[0260]

[0261]

[0262] N-cyclopropyl-N-(2-((2,5-dichloropyrimidine-4-yl)amino)phenyl)methanesulfonamide (1.00 eq) synthesized in Step 3 was added to ethanol (EtOH), and 2-methoxy-4-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)aniline (1.00 eq) and trifluoroacetic acid (TFA, 1.95 eq) were added at room temperature and stirred overnight under reflux. After the reaction was complete, the mixture was neutralized with 1N sodium hydroxide solution and extracted with water and ethyl acetate. The organic layer was mixed with anhydrous sodium sulfate and stirred, then filtered using a filter, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by column chromatography (hexane:ethyl acetate = 3:1) to synthesize a yellow solid N-(2-((5-chloro-2-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-N-cyclopropylmethanesulfonamide (AON-MG23-01), and the yield was 14%.

[0263] H NMR (500 MHz, DMSO-d6) δ 8.33 (s, 1H), 8.19 (s, 1H), 8.09 (s, 1H), 7.99 (s, 1H), 7.62 (dd, J = 7.9, 1.6 Hz, 1H), 7.35 (d, J = 8.7 Hz, 1H), 7.23 (t, J = 7.8 Hz, 1H), 7.15 (td, J = 7.6, 1.5 Hz, 1H), 6.62 (d, J = 2.5 Hz, 1H), 6.47 (dd, J = 8.7, 2.5 Hz, 1H), 3.75 - 3.71 (m, 5H), 3.25 - 3.22 (m, 4H), 2.67 (td, J = 12.2, 2.4 Hz, 2H), 2.55 - 2.44 (m, 4H), 2.38 - 2.27 (m, 4H), 2.15 (s, 3H), 1.85 (d, J = 11.5 Hz, 2H), 1.52 (qd, J = 12.1, 3.9 Hz, 2H), 1.01 - 0.93 (m, 2H), 0.55 - 0.49 (m, 1H), 0.17 - 0.12 (m, 1H). HRMS: 640.2708, cal: 640.2711.

[0264]

[0265] 1-2. Preparation of N-(2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)-N-cyclopropylmethanesulfonamide (AON-MG23-02)

[0266] [Reaction Equation 6]

[0267]

[0268] Steps 1, 2, and 3 were performed identically to the AON-MG23-01 compound, and in Step 4, the synthesis was carried out using 1-(4-amino-3-methoxyphenyl)-N,N-dimethylpiperidine-4-amine instead of 2-methoxy-4-(4-(4-methylpiperazine-1-yl)piperidine-1-yl)aniline.

[0269] Specifically, N-cyclopropyl-N-(2-((2,5-dichloropyrimidine-4-yl)amino)phenyl)methanesulfonamide (1.00 eq) synthesized in Step 3 was added to ethanol (EtOH), and 1-(4-amino-3-methoxyphenyl)-N,N-dimethylpiperidin-4-amine (1.00 eq) and trifluoroacetic acid (TFA, 1.95 eq) were added at room temperature, followed by reflux and stirring overnight. After the reaction was complete, the mixture was neutralized with a 1N sodium hydroxide solution and extracted with water and ethyl acetate. The organic layer was mixed with anhydrous sodium sulfate and stirred, then filtered using a filter, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by column chromatography (hexane:ethyl acetate = 3:1) to synthesize a yellow solid N-(2-((5-chloro-2-((4-(4-(dimethylamino)piperidin-1-yl)-2-methoxyphenyl)amino)pyrimidin-4-yl)amino)phenyl)-N-cyclopropylmethanesulfonamide (AON-MG23-02), and the yield was 25%.

[0270] 1H NMR (500 MHz, DMSO-d6) δ 8.33 (s, 1H), 8.19 (s, 1H), 8.09 (s, 1H), 7.99 (s, 1H), 7.62 (dd, J = 7.8, 1.6 Hz, 1H), 7.35 (d, J = 8.7 Hz, 1H),7.22 (d, J = 8.1 Hz, 1H), 7.15 (td, J = 7.6, 1.6 Hz, 1H), 6.63 (d, J = 2.5 Hz, 1H), 6.48(dd, J = 8.7, 2.5 Hz, 1H), 3.75 (s, 3H), 3.72 (d, J = 12.2 Hz, 2H), 3.23 (m, 4H), 2.68 (td, J = 12.1, 2.5 Hz, 2H), 2.22 (s, 6H), 1.86 (d, J = 12.4 Hz, 2H), 1.51 (qd, J = 12.0,3.9 Hz, 2H), 1.04 - 0.92 (m, 2H), 0.55 - 0.49 (m, 1H), 0.17 - 0.14 (m, 1H). HRMS:585.2294, cal: 585.2289.

[0271]

[0272] Compounds according to the present invention were prepared through the above steps, and their structural formulas are shown in Table 1 and Figure 1a below. "Ms" below refers to methylsulfonyl, i.e., -SO2(CH3).

[0273] [Table 1]

[0274]

[0275]

[0276] Example 1.2. Confirmation of mutation analysis results of the cell line used in the present invention

[0277]

[0278] In this embodiment, the mutations in the cell line used in the present invention were confirmed through chromosome copy number analysis. The present invention relates to A549 (Korea Cell Line Bank, 10185), H1975 (ATCC, CRL-5908), H1975 / OR (Verusingam ND et al. Generation of osimertinib-resistant cells from epidermal growth factor receptor L858R / T790M mutant non-small cell lung carcinoma cell line. J Chin Med Assoc. 2021 Mar 1;84(3):248-254.), H1975-C797S mutant (Creative Biogene, CSC-RO0455, Human EGFR-T790M / C797S / L858R Stable Cell Line), Calu-3 (ATCC, HTB-55), PC-9 (Accegen, ABC-TC0907), and PC-9 / GR (Lee TG et al. al. The combination of osimertinib with Raf inhibitor overcomes osimertinib resistance induced by The cell line (KRAS amplification in EGFR-mutated lung cancer cells. Exp Cell Res. 2023 Sep 1;430(1):113722.) was used in the following examples. Among them, the chromosomal copy numbers of the H1975 and H1975 / OR cell lines were analyzed to identify mutations (Fig. 1b), and as a result, it was found that the H1975 / OR cell line contained not only EGFR T790M, L858R, and C797S mutations but also multiple EGFR-related mutations such as G724S, L718X, and G719X (Fig. 1c).The fact that the H1975 / OR cell line contains multiple mutations suggests that the H1975 / OR cell line has the characteristic of exhibiting resistance to EGFR TKIs, and further indicates that it can be utilized in research related to resistance and tolerance to Osimertinib.

[0279]

[0280] Example 2. Confirmation of the inhibitory effect of the compound of the present invention on cell proliferation and tumorigenicity

[0281]

[0282] In this embodiment, a clonal formation assay was performed on lung cancer cell lines to confirm the cancer cell proliferation inhibitory effect of the compounds of the present invention and osimertinib, a third-generation EGFR tyrosine kinase inhibitor. The clonal formation assay is an in vitro cell survival / proliferation test that evaluates the ability of a single cell to proliferate indefinitely and form at least 50 cell colonies. That is, this embodiment confirmed the clonal formation inhibitory effect of the compounds of the present invention, AON-MG23-01 and AON-MG23-02 (Fig. 1a), in lung cancer cell lines, and compared the tumor proliferation inhibitory effect with that of osimertinib, a standard drug used as an EGFR targeted therapy in lung cancer treatment.

[0283] Specifically, lung cancer cell lines were seeded into a 6-well cell culture plate at a density of 250 or 1,000 cells per well. The next day, the cell culture medium was removed and replaced with a cell culture medium containing the compounds of the present invention, AON-MG23-01 and AON-MG23-02, and Osimertinib at concentrations of 0 nM, 250 nM, 500 nM, or 0 nM, 10 nM, 50 nM, 100 nM. After treatment with the compounds of the present invention or Osimertinib, the cells were cultured for 6 to 7 days or 14 days. Subsequently, the resulting cell colonies were stained and photographed, observed under a microscope, and the number of cell colonies in the captured images was measured and analyzed using Image J software.

[0284]

[0285] As a result, it was confirmed that the compound of the present invention AON-MG23-01 (Figs. 2a and 2b) or AON-MG23-02 (Figs. 2c to 2e) inhibits the proliferation (tumorigenicity) of lung cancer cell lines.

[0286]

[0287] Example 3. Confirmation of ANO1, phosphorylated EGFR, and EGFR protein expression in lung cancer cell lines

[0288]

[0289] In this example, the expression of ANO1, EGFR, and phosphorylated EGFR proteins in human lung cancer cell lines was confirmed. Specifically, human lung cancer cell lines were cultured in 100 mm dishes covering at least 70% of the dish area. After culture, the cells were harvested and lysed to perform Western blot. Antibodies used for Western blot included an anti-ANO1 antibody (Abcam, ab53212), an anti-phosphorylated EGFR antibody (Cell Signaling, #4407S), an anti-EGFR antibody (Cell Signaling, #4267S), and an anti-GAPDH antibody (Cell Signaling, #5174). Protein concentration was quantified using the BSA method (Protein Quantitation Assay, Bovine serum albumin assay) (Pierce, Cat.23225). After lysing the cells, the proteins obtained therefrom were separated by molecular weight using SDS-PAGE with equal amounts (10 μg). The proteins were then transferred to a polyvinylidene fluoride membrane (PVDF, Bio-rad) and treated with 5% blocking buffer (5% Skim milk in TBS-T, Tris-buffered saline buffer containing 0.1% Tween 20) at room temperature for 1 hour. Subsequently, the primary antibody was applied to the membrane and reacted at 4°C for 18 hours. After the reaction was complete, the membrane was washed three times with TBS-T for 10 minutes at room temperature. Next, the membrane was reacted with a secondary antibody (bethyl, #A90-117P, #A120-101P) labeled with horseradish peroxidase at room temperature for 1 hour, and then washed three times with TBS-T for 10 minutes each. After washing, the membrane was treated with an ECL kit (Thermo, West Pico Plus) and reacted, and visualized using a Da Vinci-Q (Youngin Lab Plus) instrument.The visualized results were analyzed by quantifying the amount of each protein using Image J software.

[0290] As a result, the expression of ANO1, EGFR, and phosphorylated EGFR proteins was checked in six types of lung cancer cell lines, and it was confirmed that ANO1 and EGFR were expressed in all cell lines, but phosphorylated EGFR was expressed in four types of cell lines (Fig. 3).

[0291]

[0292] Example 4. Confirmation of the inhibitory effects of the compound of the present invention on ANO1, phosphorylated EGFR, and EGFR protein expression

[0293]

[0294] In this example, it was confirmed whether the compound of the present invention affects ANO1, phosphorylated EGFR, and EGFR protein expression in human lung cancer cell lines. Specifically, human lung cancer cell line H1975 in a 60 mm dish was 3×10 5 In terms of cell / dish density, H1975 / OR cells are 6×10 5The cells were seeded at a cell / dish density. After culturing for 24 hours, the compound of the present invention, AON-MG23-02, and the EGFR tyrosine kinase inhibitor, osimertinib, were each treated at a concentration of 1 μM, while the untreated control group was treated with DMSO and cultured for 48 hours. After culturing, the cells were harvested and lysed to perform Western blot. Antibodies used for Western blot included an anti-ANO1 antibody (Abcam, ab53212), an anti-phosphorylated EGFR antibody (Cell Signaling, #4407S), an anti-EGFR antibody (Cell Signaling, #4267S), and an anti-GAPDH antibody (Cell Signaling, #5174). Protein concentration was quantified using the BSA method (Protein Quantitation Assay, Bovine serum albumin assay) (Pierce, Cat.23225). After lysing the cells, the proteins obtained therefrom were separated by molecular weight using SDS-PAGE with equal amounts (10 μg). The proteins were then transferred to a polyvinylidene fluoride membrane (PVDF, Bio-rad) and treated with 5% blocking buffer (5% Skim milk in TBS-T, Tris-buffered saline buffer containing 0.1% Tween 20) at room temperature for 1 hour. Subsequently, the primary antibody was applied to the membrane and reacted at 4°C for 18 hours. After the reaction was complete, the membrane was washed three times with TBS-T for 10 minutes at room temperature. Next, the membrane was reacted with a secondary antibody labeled with horseradish peroxidase (bethyl, #A90-117P, #A120-101P) at room temperature for 1 hour, and then washed three times with TBS-T for 10 minutes each.After washing, the membrane was treated with an ECL kit (Thermo, West Pico Plus) to induce a reaction, and the results were visualized using a Da Vinci-Q (Youngin Lab Plus) instrument. The visualized results were analyzed by quantifying the amount of each protein using Image J software. Specifically, in this example, among six types of lung cancer cell lines, H1975 cells and H1975 / OR cells resistant to osimertinib, a representative EGFR tyrosine kinase inhibitor, were treated with an appropriate amount of AON-MG23-02, and a test was conducted to confirm that the expression of target proteins ANO1, EGFR, and phosphorylated EGFR proteins was inhibited.

[0295] As a result, in H1975 cells, the degree of inhibition of ANO1 and EGFR phosphorylation proteins by the compound AON-MG23-02 of the present invention and osimertinib was similar, but in the case of EGFR, it was confirmed that the inhibitory effect on protein expression was significantly increased in AON-MG23-02 compared to osimertinib (Fig. 4). In addition, in H1975 / OR, a cell line resistant to osimertinib, it was confirmed that while osimertinib inhibited only EGFR phosphorylation proteins, the compound AON-MG23-02 of the present invention inhibited EGFR proteins as well as EGFR phosphorylation proteins. In conclusion, it was confirmed that there are significant differences in their respective mechanisms, as EGFR tyrosine kinase inhibitors such as osimertinib inhibit cell proliferation activity by inhibiting the phosphorylation of EGFR, whereas AON-MG23 inhibits lung cancer cell activity by simultaneously binding to the complex of ANO1 and EGFR and sequentially degrading the two target proteins.

[0296]

[0297] Example 5. Confirmation of the cancer growth inhibitory effect of the compound of the present invention

[0298]

[0299] In this embodiment, the cancer growth inhibitory effect of the compound of the present invention was confirmed in a xenograft model of an osimertinib-resistant human lung cancer cell line. Specifically, to confirm the in vivo cancer growth inhibitory effect of the compound of the present invention, H1975 / OR cells, a human lung cancer cell line resistant to osimertinib, were subcutaneously transplanted into nude mice. After an appropriate period, the compound of the present invention was orally administered daily for 4 weeks, either alone or in combination with osimertinib, and the tumor growth inhibitory effect was confirmed to verify the anticancer effect. Specifically, 1×10⁶ H1975 / OR cells, an osimertinib-resistant human lung cancer cell line 6 The cells were diluted in HBSS to a concentration of 100 µl / cells and prepared according to the number of animals to be treated, and 100 µl of the cell suspension was filled into a 1 ml syringe. The prepared lung cancer cells were injected and implanted into the subcutaneous tissue of the right lower dorsal region of nude mice, and the volume of the grown tumor was approximately 40 mm². 3 Upon reaching [date], group separation was initiated, and AON-MG23-02 and the control drug osimertinib, as set according to the study plan, were administered orally according to the established cycles and doses. The AON-MG23-02 monotherapy group was administered orally at a dose of 75 mg / kg daily for 4 weeks, and the control drug osimertinib was also administered orally at a dose of 5 mg in the same cycle. The combination therapy group was administered osimertinib 5 mg / kg, followed immediately by oral administration of AON-MG23-02 at 25, 50, or 75 mg / kg. Survival rate, changes in body weight, and changes in tumor size were periodically measured and recorded from 20 days after drug administration until the end of the study. Tumor volume (TV) was calculated using the maximum length (L) and perpendicular width (W) values ​​of the tumor using the following [Equation 1].

[0300] [Mathematical Formula 1]

[0301] TV (mm 3 )= L (mm) XW 2 (mm 2 )X(1 / 2)

[0302] As a result, due to the characteristics of the osimertinib-resistant human lung cancer cell line, osimertinib monotherapy was ineffective, and a large number of individuals were identified in the high-dose monotherapy group of the compound of the present invention (A75) and the combination therapy group of the compound of the present invention and osimertinib, in which cancer growth was reduced and disappeared (Fig. 5). This suggests that an anticancer effect can be exerted not only when the compound of the present invention is administered alone, but also when the compound of the present invention is administered in combination with osimertinib.

[0303]

[0304] The experiment regarding this embodiment was repeated at least three times, and the results were expressed as mean ± standard deviation. Statistical significance was confirmed using Student's t-test, and if P < 0.05, it was determined to be statistically significant. * indicates P < 0.01, and **** indicates P < 0.0001.

[0305]

[0306] Example 6. Confirmation of the predicted binding result between ANO1, the target protein of the compound of the present invention, and the EGFR complex.

[0307]

[0308] In this embodiment, the results of a prediction simulation of binding between the compounds of the present invention, AON-MG23-01 and AON-MG23-02, and the target proteins, ANO1 and EGFR complex, were confirmed. Specifically, the 3D structure of the target proteins, ANO1 and EGFR complex, was constructed as a PDB using the AlphaFoldServer platform (AlphaFold Server) based on the respective nucleotide sequences of ANO1 and EGFR proteins. In addition, SMILES for each compound, AON-MG23-01 and AON-MG23-02, were constructed using the SwissTargetPrediction DrugDesign program for the Autodock VINA docking program.

[0309] The Autodock VINA docking program was used to predict the binding between the tertiary structure of the constructed ANO1 and EGFR complex and the compounds of the present invention, AON-MG23-01 and AON-MG23-02. In addition, for the binding between AON-MG23-01 and AON-MG23-02 and the target proteins ANO1 and EGFR complex, a model with high binding affinity was selected based on the vina score, which indicates intermolecular binding affinity, and the cavity volume, which indicates the binding space within the protein.

[0310]

[0311] As a result, the docking simulation results are as follows. As a result of the binding simulation between the ANO1 and EGFR complex and AON-MG23-01, the vina score, which indicates the binding affinity of the molecule, was -8.6 as shown in Figures 6a and 6b, and the cavity volume, which indicates the binding space measured within the protein and used to evaluate the possibility of binding, was confirmed to be 22184.

[0312] As a result of the binding simulation between the ANO1 and EGFR complex and AON-MG23-02, as shown in Figures 6c and 6d, the vina score, which indicates the binding affinity of the molecule, was -8.4, and the cavity volume, which indicates the binding space measured within the protein and used to evaluate the possibility of binding, was confirmed to be 22184.

[0313] In other words, AON-MG23-01 and AON-MG23-02 were confirmed to possess material properties exhibiting high binding affinity to the complex of ANO1 and EGFR, respectively. Furthermore, through this binding prediction test, AON-MG23-01 and AON-MG23-02 exhibited a common binding pattern to the binding site between ANO1 and EGFR JM (juxtamembrane) within the complex of the target proteins ANO1 and EGFR. Although the respective binding sites showed slight differences, it was confirmed that they commonly bound to the JM (juxtamembrane) site rather than the EGFR TK (tyrosine kinase) site.

[0314]

[0315] This research regarding the present invention was supported by the Starting growth Technological R&D Program (TIPS Program, No.RS-2023-00285168) funded by the Ministry of SMEs and Startups (MSS, Korea) in 2023.

[0316]

[0317] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will understand that other specific forms can be easily modified without altering the technical spirit or essential features of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

[0318]

[0319] The present invention relates to a compound capable of preventing and treating lung cancer by inhibiting the expression or activity of Anoctamin 1 (ANO1), a calcium-dependent chloride channel, and the epidermal growth factor receptor (EGFR), an epidermal growth factor receptor. Specifically, it was confirmed that tumorigenicity and proliferation were significantly inhibited in lung cancer cells treated with the compound of the present invention. Furthermore, it was confirmed that tumor proliferation was inhibited when the compound of the present invention was treated in a xenograft mouse model formed by injecting lung cancer cells into mice. This inhibitory effect was found to be significantly superior compared to conventional EGFR tyrosine kinase inhibitors. Since the compound of the present invention can simultaneously inhibit ANO1 and EGFR, it was possible to exhibit a significantly superior anticancer effect through this dual inhibition. It was also confirmed that when the compound of the present invention is administered in combination with an EGFR targeted anticancer drug, it not only exhibits a synergistic anticancer effect but also inhibits the development of drug resistance in cancer cells. Therefore, the compound of the present invention can be usefully used alone as a composition for the prevention or treatment of lung cancer, and can be used as a dual-target anticancer agent for ANO1 and EGFR itself, and can also be utilized as an adjuvant or combination agent in combination with EGFR targeted therapies, thus having industrial applicability.

Claims

1. A pharmaceutical composition for the prevention or treatment of lung cancer comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof. [Chemical Formula 1] [Chemical Formula 2] 2. In Paragraph 1, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the lung cancer is one or more selected from the group consisting of small cell lung cancer, non-small cell lung cancer, and adenocarcinoma.

3. In Paragraph 1, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the lung cancer is associated with a mutation in one or more genes selected from the group consisting of KRAS (Kirsten rat sarcoma viral oncogene homolog), p53, and EGFR (Epidermal growth factor receptor).

4. In Paragraph 1, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the above compound or a pharmaceutically acceptable salt thereof simultaneously inhibits EGFR and ANO1 (Anoctamin 1).

5. In Paragraph 1, The above compound or a pharmaceutically acceptable salt thereof binds to a complex of EGFR and ANO1, and A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the above compound or a pharmaceutically acceptable salt thereof simultaneously binds to the juxtamembrane site of EGFR, excluding the tyrosine kinase site of EGFR; and ANO1, thereby exhibiting a preventive or therapeutic effect against lung cancer.

6. In Paragraph 1, A pharmaceutical composition for the prevention or treatment of lung cancer, wherein the above compound or a pharmaceutically acceptable salt thereof is characterized by one or more selected from the group consisting of: (a) inhibiting the proliferation or growth of cancer cells; and (b) inhibiting the tumorigenicity of cancer cells; and (c) Suppresses resistance of lung tumor cells to anticancer drugs.

7. In Paragraph 6, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the above anticancer agent is a targeted anticancer agent against tyrosine kinase.

8. In Paragraph 7, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the above tyrosine kinase is EGFR (epidermal growth factor receptor).

9. In Paragraph 1, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized by being administered in combination with a targeted anticancer agent for tyrosine kinase.

10. In Paragraph 9, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the above pharmaceutical composition is administered simultaneously, separately, or sequentially with the above-mentioned targeted anticancer agent.

11. (i) One or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or pharmaceutically acceptable salts thereof; and (ii) A pharmaceutical composition for the prevention or treatment of lung cancer comprising an anticancer agent targeting EGFR as an active ingredient. [Chemical Formula 1] [Chemical Formula 2] 12. In Paragraph 11, A pharmaceutical composition for the prevention or treatment of lung cancer, wherein the above compound or a pharmaceutically acceptable salt thereof inhibits the resistance of lung tumor cells to a targeted anticancer agent against the above EGFR.

13. In Paragraph 11, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the above pharmaceutical composition is in the form of a mixture comprising the compound or a pharmaceutically acceptable salt thereof; and a targeted anticancer agent for the EGFR.

14. In Paragraph 11, A pharmaceutical composition for the prevention or treatment of lung cancer, characterized in that the above pharmaceutical composition comprises the compound or a pharmaceutically acceptable salt thereof; and a targeted anticancer agent for EGFR, each formulated and administered simultaneously, separately, or sequentially.

15. A pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer agent, comprising as an active ingredient one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or a pharmaceutically acceptable salt thereof. [Chemical Formula 1] [Chemical Formula 2] 16. In Paragraph 15, A pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer drug, characterized in that the above pharmaceutical composition is administered simultaneously, separately, or sequentially with the above lung cancer anticancer drug.

17. In Paragraph 15, The above compound or a pharmaceutically acceptable salt thereof binds to a complex of EGFR and ANO1, and A pharmaceutical composition for enhancing the anticancer effect of a lung cancer anticancer drug, characterized in that the above compound or a pharmaceutically acceptable salt thereof simultaneously binds to the juxtamembrane site of EGFR, excluding the tyrosine kinase site of EGFR; and ANO1, thereby enhancing the anticancer effect of the lung cancer anticancer drug.

18. Improvement or treatment of lung cancer, comprising the step of administering a pharmaceutically effective amount of a composition comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2 or a pharmaceutically acceptable salt thereof to an individual in need thereof; or a method for enhancing the anticancer effect of a lung cancer anticancer agent. [Chemical Formula 1] [Chemical Formula 2] 19. Prevention, improvement, or treatment of lung cancer of a composition comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2 or a pharmaceutically acceptable salt thereof; or use for enhancing the anticancer effect of a lung cancer anticancer agent. [Chemical Formula 1] [Chemical Formula 2] 20. Prevention, improvement, or treatment of lung cancer by a composition comprising, as an active ingredient, one or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2 or a pharmaceutically acceptable salt thereof; or use for manufacturing a preparation for enhancing the anticancer effect of a lung cancer anticancer agent. [Chemical Formula 1] [Chemical Formula 2] 21.(i) One or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or pharmaceutically acceptable salts thereof; and (ii) A method for improving or treating lung cancer, comprising the step of administering a pharmaceutically effective amount of a composition containing a targeted anticancer agent against EGFR as an active ingredient to an individual in need thereof. [Chemical Formula 1] [Chemical Formula 2] 22. (i) One or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or pharmaceutically acceptable salts thereof; and (ii) Use of a composition comprising an active ingredient that is a targeted anticancer agent against EGFR for the prevention, improvement, or treatment of lung cancer. [Chemical Formula 1] [Chemical Formula 2] 23. (i) One or more compounds selected from the group consisting of compounds represented by the following chemical formulas 1 and 2, or pharmaceutically acceptable salts thereof; and (ii) Use for manufacturing a formulation for the prevention, improvement, or treatment of lung cancer comprising a composition containing a targeted anticancer agent against EGFR as an active ingredient. [Chemical Formula 1] [Chemical Formula 2]

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