Use of a pharmaceutical composition for treating lung cancer

Abstract

Provided is a use of a pharmaceutical composition comprising a diarylheptanoid compound or a pharmaceutically acceptable salt thereof having a structure represented by Formula (I). The symbols in Formula (I) are as defined in the specification, and the compound can inhibit the growth of lung cancer cells. Thus, the pharmaceutical composition can be used for the manufacture of a medicament for treating lung cancer.

Description

Technical Field

[0001] This invention relates to the use of a pharmaceutical composition, particularly the use of a pharmaceutical composition comprising a diarylheptane compound or a pharmaceutically acceptable salt thereof for the treatment of lung cancer. Background Technology

[0002] Cancer, also known as malignant tumor, is a disease caused by the abnormal proliferation of cells, which may invade other parts of the body. It is caused by the abnormality of the mechanism controlling cell division and proliferation.

[0003] Based on differences in biological characteristics, treatment, and prognosis, lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). Approximately 85-90% of lung cancers are NSCLC, with lung adenocarcinoma being the most common type, especially among women and non-smokers. Treatment for lung cancer often depends on the patient's age, medical history, current health status, cancer cell morphology, and disease stage. Generally, small cell lung cancer is characterized by rapid division and proliferation, so it can metastasize quickly; therefore, treatment primarily involves systemic chemotherapy or radiation therapy. Non-small cell lung cancer grows more slowly, and metastasis occurs more gradually. Treatment principles depend on the clinical stage of the disease. Early-stage (Stage I and II) NSCLC is primarily treated with complete surgical resection of the tumor. Locally extended stage (Stage III) includes malignant pericardial or pleural effusions and distant metastases (Stage IV), or patients whose physical condition precludes surgical resection. Treatment principles primarily involve chemotherapy or chemotherapy combined with radiation therapy.

[0004] However, treating metastatic or recurrent advanced non-small cell lung cancer (NSCLC) after chemotherapy presents a significant challenge. Current clinical research confirms that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can serve as second-line treatment after first-line chemotherapy failure. However, approximately 40-80% of NSCLC patients carry EGFR gene mutations, which cause overexpression of the epidermal growth factor receptor, leading to rapid cancer growth, metastasis, and drug resistance. Clinically, almost all patients treated with EGFR-TKIs relapse within two years, and currently, there are no effective drugs available after relapse. Summary of the Invention

[0005] In view of this, one object of the present invention is to provide the use of a pharmaceutical composition for the preparation of a medicament for treating lung cancer. The pharmaceutical composition comprises a diarylheptane compound or a pharmaceutically acceptable salt thereof, which inhibits the growth of non-small cell lung cancer cells resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TTA inhibitors). It is intended for use alone or in combination with clinically available EGFR-TTA inhibitors to treat EGFR-mutated lung cancer resistant to EGFR-TTA inhibitors.

[0006] One aspect of the present invention is the use of a pharmaceutical composition for preparing a medicament for treating lung cancer, wherein the pharmaceutical composition comprises a diarylheptane compound or a pharmaceutically acceptable salt thereof, said diarylheptane compound being selected from:

[0007] , ,

[0008] and ;

[0009] One dosage form of the pharmaceutical composition includes hard gelatin capsules, soft gelatin capsules, tablets, parenteral injections, and oral suspensions;

[0010] One dosage of the pharmaceutical composition is from 0.1 mg to 2000 mg per day;

[0011] The lung cancer in question is non-small cell lung cancer.

[0012] According to the aforementioned use of the pharmaceutical composition, the pharmaceutical composition may further comprise an epidermal growth factor receptor-tyrosine kinase inhibitor. Preferably, the epidermal growth factor receptor-tyrosine kinase inhibitor may be osimertinib, gefitinib, erlotinib, or afatinib.

[0013] Based on the aforementioned use of the pharmaceutical composition, the lung cancer may be resistant to epidermal growth factor receptor-tyrosine kinase inhibitors.

[0014] The foregoing summary is intended to provide a simplified overview of this disclosure, enabling the reader to gain a basic understanding of its contents. This summary is not a complete overview of the invention and is not intended to identify key / critical elements of the embodiments or define the scope of the invention. Attached Figure Description

[0015] To make the above and other objects, features, advantages and embodiments of the present invention more apparent and understandable, the accompanying drawings are described below:

[0016] Figure 1A The figure shows the analytical results of the diarylheptane compounds of the present invention inhibiting the growth of H1650 cells.

[0017] Figure 1B , Figure 1C and Figure 1D The figure shows the analysis results of the diarylheptane compounds of the present invention inhibiting the growth of non-small cell lung cancer cells resistant to epidermal growth factor receptor-tyrosine kinase inhibitors.

[0018] Figure 2A Figure showing the analysis results of the inhibition of tumor growth in GR6 tumor mice by treating the compound alone for 35 days;

[0019] Figure 2B Figure showing the analysis results of the inhibition of tumor growth in GR8 tumor mice by treating the compound alone for 35 days;

[0020] Figure 2C Figure showing the analysis results of the inhibition of HCC827 tumor growth in mice treated with the compound alone for 35 days.

[0021] Figure 2D A statistical graph showing the change in body weight in tumor-bearing mice treated with the compound alone for 35 days;

[0022] Figure 3A A graph showing the combined analysis results of tumor re-progression in mice treated with compound 35d and osimertinib to inhibit GR6 tumors; and

[0023] Figure 3B A statistical graph showing the changes in body weight in GR6 tumor mice treated with compound 35d and osimertinib combined. Detailed Implementation

[0024] This invention proposes a novel use for a pharmaceutical composition comprising a diarylheptane compound or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for treating lung cancer. The diarylheptane compound of this invention has a structure shown in formula (I):

[0025]

[0026] Formula (I),

[0027] Where R a R b R a 'and R b Independently, it is H, C1-C2 alkyl, C1-C3 alkoxy, OH, or -OC(=O)Rd , where R d It is a C1-C3 alkyl or C1-C3 alkanol; R c H, C1-C2 alkyl, C3-C6 unsaturated alkyl with double or triple bonds, or C7-C12 arylalkyl; and R e and R e 'Independently H, C1-C6 alkyl or C1-C6 alkoxy.

[0028] R of the diarylheptane compounds of the present invention a R b R a 'and R b At least one of them can be -OC (=O)R d And R d It is a C1-C3 alkyl or C1-C3 alkanol. Furthermore, when R... c When H is present, the diarylheptane compounds are interconvertible between ketone and enol forms.

[0029] The pharmaceutical compositions of the present invention may further comprise epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in combination with diarylheptane compounds or pharmaceutically acceptable salts thereof, wherein the EGFR-TKIs may be osimertinib, gefitinib, erlotinib, or afatinib. The pharmaceutical compositions of the present invention are intended to treat non-small cell lung cancer, which may be resistant to EGFR-TKIs.

[0030] Unless otherwise stated, all technical terms, symbols, or other scientific terms used in this specification have the meanings known to those skilled in the art to which this invention pertains, unless the context of their use indicates otherwise. In some cases, terms with known meanings are defined herein for the purpose of clarity and / or immediate reference, and these definitions incorporated herein should be interpreted as not necessarily differing materially from their known meanings in the art. Many techniques and procedures described or referenced herein are well known and are often used by those skilled in the art in a conventional manner. Where appropriate, unless otherwise stated, the procedures for using commercially available kits and reagents are generally performed according to the manufacturer's instructions and / or parameters.

[0031] Unless otherwise stated, the terms "a" and "an" used herein and in this specification mean that the grammatical object in the text is one or more (i.e., at least one). Furthermore, "class" is an abbreviation for all members included in that class; for example, "C1-C3 alkyl" is an abbreviation for all C1-C3 alkyl groups, such as methyl, ethyl, propyl, and their isomers.

[0032] The diarylheptane compounds and their pharmaceutically acceptable salts disclosed in this invention can be verified by in vitro experiments to inhibit the growth of non-small cell lung cancer cells resistant to EGFR-TKIs. Furthermore, they can be verified by in vivo experiments to demonstrate that the compounds disclosed herein and / or at least one of their pharmaceutically acceptable salts can be administered to animals (e.g., mouse models) with EGFR-TKI-resistant lung cancer and achieve therapeutic effects. Positive results in one or more tests are sufficient to demonstrate the actual efficacy of the tested compounds and / or salts. Appropriate dosage ranges and routes of administration for animals (e.g., humans) can be determined based on the experimental results.

[0033] Useful pharmaceutical dosage forms for administering the diarylheptane compounds of the present invention and their pharmaceutically acceptable salts include, but are not limited to, hard and soft gelatin capsules, tablets, parenteral injections, and oral suspensions. The dosage determined by factors including the subject's age, health and weight, severity of illness, type of concurrent treatment (if any), frequency of treatment, and nature of the desired effect. Typically, the daily dose of the active ingredient can be non-quantitative, for example, from 0.1 to 2000 mg daily. For example, 10-500 mg once or multiple times daily may effectively achieve the desired results.

[0034] When the diarylheptane compounds of the present invention and their pharmaceutically acceptable salts are administered stepwise or in combination with at least one other therapeutic agent, the same dosage form can generally be used. When drugs are administered in physical combination, the dosage form and route of administration should be selected based on the compatibility of the combined drugs. Therefore, "co-administration" as used in this specification should be understood to include the administration of at least two agents concurrently or sequentially, or as a fixed-dose combination of at least two active components.

[0035] This specification allows diarylheptane compounds and their pharmaceutically acceptable salts to be used as the sole active ingredient, or in combination with at least one second active ingredient selected from, for example, other active ingredients known to be used in the treatment of patients with non-small cell lung cancer, particularly EGFR-TKIs.

[0036] The present invention will be further illustrated by the following specific test examples, which are intended to enable those skilled in the art to fully utilize and practice the present invention without excessive interpretation. These test examples should not be regarded as a limitation on the scope of the present invention, but are used to illustrate how to implement the materials and methods of the present invention.

[0037] 1. The structure of the diarylheptane compounds of the present invention

[0038] The diarylheptane compounds of this invention are designed using curcumin (CCM) as a directing compound, and have a structure as shown in formula (I):

[0039]

[0040] Formula (I),

[0041] Please refer to Table 1 below for examples of the diarylheptane compounds of the present invention: Compound 1, Compound 21a, Compound 21b, Compound 22a, Compound 22b, Compound 23a, Compound 23b, Compound 24a, Compound 24b, Compound 25, Compound 26, Compound 27, Compound 31, Compound 33, Compound 35a, Compound 35c, Compound 35d, Compound 35e, Compound 36, and Compound 37. a R b R a '、R b '、R c R e and R e The substituent represented by '.

[0042] Table 1

[0043] compound <![CDATA[R a ]]> <![CDATA[R a ']]> <![CDATA[R b ]]> <![CDATA[R b ']]> <![CDATA[R c ]]> <![CDATA[R e , R e ']]> 1 OH OH <![CDATA[OCH3]]> <![CDATA[OCH3]]> H H 21a <![CDATA[OCH3]]> <![CDATA[OCH3]]> H H 21b <![CDATA[OCH3]]> <![CDATA[OCH3]]> OH H H 22a <![CDATA[OCH3]]> <![CDATA[OCH3]]> H H 22b <![CDATA[OCH3]]> <![CDATA[OCH3]]> OH H H 23a H H H H 23b H H OH H H 24a <![CDATA[OCH3]]> <![CDATA[OCH3]]> H H 24b OH <![CDATA[OCH3]]> <![CDATA[OCH3]]> H H 25 OH <![CDATA[OCH3]]> <![CDATA[OCH3]]> H H 26 <![CDATA[OC2H5]]> <![CDATA[OC2H5]]> H H 27 <![CDATA[OC2H5]]> <![CDATA[OC2H5]]> H H 31 <![CDATA[C2H5]]> <![CDATA[C2H5]]> H <![CDATA[C2H5]]> 33 <![CDATA[OCH3]]> <![CDATA[OCH3]]> <![CDATA[OCH3]]> H H 35a <![CDATA[OCH3]]> <![CDATA[OCH3]]> <![CDATA[CH3]]> H 35c <![CDATA[OCH3]]> <![CDATA[OCH3]]> benzyl H 35d <![CDATA[OCH3]]> <![CDATA[OCH3]]> propargyl H 35e <![CDATA[OCH3]]> <![CDATA[OCH3]]> Allyl H 36 H H <![CDATA[CH3]]> H 37 <![CDATA[OCH3]]> <![CDATA[OCH3]]> <![CDATA[CH3]]> H

[0044] Among them, compound 21a-((1E,3Z,6E)-3-hydroxy-5-dioxyhept-1,3,6-trien-1,7-diyl)bis(2-methoxy-4,1-epoxyphenyl)bis(3-hydroxy-2-hydroxymethyl)-2-methylpropionate, compound 35a-((1E,6E)-4,4-dimethyl-3,5-diepoxyhept-1,6-dien-1,7-diyl)bis(2-methoxy-4,1-epoxyphenyl)bis(3-hydroxy-2-hydroxymethyl)-2-methylpropionate, and compound 35d-((1E,6E)-3,5-diepoxy-4,4-di(prop-2-yn-1-yl)hept-1,6-dien-1 The chemical structures of compounds 36-((1E,6E)-4,4-dimethyl-3,5-di-heptyl-1,6-diene-1,7-diyl)bis(4,1-heptyl)bis(3-hydroxy-2-(hydroxymethyl)-2-methylpropionate), 37-((1E,6E)-4,4-dimethyl-3,5-di-heptyl-1,6-diene-1,7-diyl)bis(2-methoxy-5,1-heptyl)bis(3-hydroxy-2-(hydroxymethyl)-2-methylpropionate) are shown in Table 2.

[0045] Table 2

[0046] compound Chemical structure 21a 35a 35d 36 37

[0047] Compound 21a possesses a heptadecene-3,5-dione moiety, which readily interconverts between ketone and enol forms. The 3- or 5-OH groups of the enol form are hydrogen-bonded to adjacent 5- or 3-C=O groups, respectively, to stabilize its structure. In this invention, the two methyl functionalities are incorporated at the 4-position of compound 21a, providing ((1E,6E)-4,4-dimethyl-3,5-di-side-oxyheptene-1,6-diene-1,7-diyl)bis(2-methoxy-4,1-epoxyphenyl)bis(3-hydroxy-2-hydroxymethyl)-2-methylpropionate (35a), which has been found to have a stable ketone form and is not stable to tautomerization. Furthermore, in this invention, compound 35a is used as a novel directing compound and a series of its 4,4-dialkyl derivatives (compounds 35a, 35d, 36, and 37) with stable ketone forms are derived.

[0048] 2. The diarylheptane compounds of the present invention exhibit inhibitory effects on the growth of EGFR gene-mutant non-small cell lung cancer cells and non-small cell lung cancer cells resistant to EGFR-TKIs.

[0049] In the experiment, EGFR gene-mutant non-small cell lung cancer cells were first treated with the diarylheptane compound of the present invention, and then cell viability was measured by crystal violet staining to determine the IC50 of the diarylheptane compound of the present invention in EGFR gene-mutant non-small cell lung cancer cells. 50 The values ​​were used to determine the inhibitory effect of the diarylheptane compounds of the present invention on the growth of EGFR gene-mutant non-small cell lung cancer cells.

[0050] In lung cancer, EGFR gene mutations are most commonly found in exons 18-21, the intracellular tyrosine kinase coding region. The most common mutation forms include the E746-A750del mutation in exon 19 and the L858R point mutation in exon 21. These two mutations account for approximately 85%-90% of EGFR gene mutations. Tumor cells with these two mutations are sensitive to EGFR-TKIs and are called activating mutations. Some tumor cells can undergo secondary mutations, the most common being the T790M mutation in exon 20, which is a drug-resistant mutation. Please refer to [link to relevant documentation]. Figure 1A The figure shows the analysis results of the diarylheptane compounds of the present invention inhibiting the growth of H1650 cells. H1650 cells are EGFR gene exon 19 with the E746-A750del mutation. CCM is curcumin, BDMC is bisdemethoxycurcumin, and the IC50 of the compounds is... 50 Values ​​> 16 μM indicate that H1650 cells did not achieve 50% cell growth inhibition after treatment with compounds at concentrations up to 16 μM. Figure 1A The data are expressed as mean ± SD (n = 3).

[0051] Figure 1A The IC50 values ​​in H1650 cells after 3 days of treatment with 22 diarylheptane compounds (including BDMC) and curcumin were determined. 50 The values ​​showed that 18 diarylheptane compounds, including compounds 1, 24b, 23b, 33, 25, 35b, 22a, 21a, 22b, 26, 36, 35a, 35c, 27, 31, 37, 35e, and 35d, exhibited significantly better inhibitory activity against H1650 cell growth than the parent compound curcumin. ** indicates p < 0.05, *** indicates p < 0.01, and **** indicates p < 0.001.

[0052] In the experiment, compounds 21a, 35a, 35d, 36, or 37 were treated with seven other non-small cell lung cancer cells resistant to EGFR-TKIs, followed by cell viability assays to measure the IC50 of the diarylheptane compounds of the present invention in non-small cell lung cancer cells resistant to EGFR-TKIs. 50 The values ​​were used to determine the inhibitory effects of the diarylheptane compounds of the present invention on the growth of non-small cell lung cancer cells resistant to EGFR-TKIs. The EGFR-TKI-resistant non-small cell lung cancer cells used in the experiment included H1975 cells, GR2 cells, GR5 cells, GR6 cells, GR8 cells, GR9 cells, and GR10 cells. H1975 cells had an L858R point mutation in exon 21, but also a secondary T790M mutation in exon 20. GR2, GR5, GR6, GR8, GR9, and GR10 cells were gefitinib-resistant cell lines obtained by treating HCC827 cells as parent cells with gefitinib. Both HCC827 and H1650 cells were non-small cell lung cancer cells with an E746-A750del mutation in EGFR exon 19.

[0053] Please refer to Figure 1B , Figure 1C and Figure 1D , Figure 1B The figure shows the analytical results of the diarylheptane compounds of this invention inhibiting the growth of H1975 cells. Figure 1C The figure shows the analytical results of the diarylheptane compounds of the present invention inhibiting the growth of GR2, GR5, GR6, GR8, GR9, and GR10 cells. Figure 1D After treating GR2, GR5, GR6, GR8, GR9, and GR10 cells with the compound for 35 days and gefitinib, respectively, the IC50 value was determined. 50 The graph shows the percentage change in values. Figure 1B and Figure 1C The data in the figure are expressed as mean ± SD (n = 3), while IC 50 A value > 16 μM indicates that treatment with compounds at concentrations up to 16 μM did not achieve 50% cell growth inhibition. Figure 1D In this context, Gef represents gefitinib.

[0054] Figure 1B IC50 values ​​were measured in H1975 cells after treatment with compounds 21a, 35a, 35d, 36, 37, and curcumin for 3 days. 50The results showed that compounds 21a, 35a, 35d, 36, and 37 of the present invention exhibited significantly better inhibitory activity against H1975 cell growth than curcumin.

[0055] Figure 1C IC50 values ​​were measured after treating GR2, GR5, GR6, GR8, GR9, and GR10 cells with compounds 21a, 35a, 35d, 36, 37, and curcumin for 3 days. 50 The results showed that compounds 21a, 35a, 35d, 36, and 37 of the present invention exhibited significantly superior inhibitory activity against the growth of GR2, GR5, GR6, GR8, GR9, and GR10 cells compared to curcumin.

[0056] Depend on Figure 1B and Figure 1C The results showed that all non-small cell lung cancer cells resistant to EGFR-TKIs were more sensitive to compounds 21a, 35a, 35d, 36, and 37 than curcumin, achieving 50% cell growth inhibition at significantly lower concentrations.

[0057] Figure 1D To measure the IC50 of HCC827, GR2, GR5, GR6, GR8, GR9, and GR10 cells after treatment with compound 35d and gefitinib for 3 days, respectively. 50 The IC50 values ​​were then measured for GR2, GR5, GR6, GR8, GR9, and GR10 cells. 50 The value and IC50 measured in HCC827 cells 50 The analysis results are shown in the figure obtained by comparing the values. Figure 1D The results showed that all gefitinib-resistant cell lines were indirectly sensitive to compound 35d, and all gefitinib-resistant cell lines were >200-fold more resistant to gefitinib (Gef) than their parent cells, HCC827 cells.

[0058] 3. Anticancer activity of compound 35d against GR6, GR8 and HCC827 tumors.

[0059] To verify the in vivo anticancer efficacy of the diarylheptane compounds of the present invention, xenografted GR6 tumor mouse models, GR8 tumor mouse models, and HCC827 tumor mouse models were first established. The GR6 tumor mice, GR8 tumor mice, and HCC827 tumor mice were treated with the compound at 100 mg / kg per day for 35 days, and the tumor size and body weight of the GR6 tumor mice, GR8 tumor mice, and HCC827 tumor mice were recorded.

[0060] Please refer to Figures 2A to 2D , Figure 2A The figure shows the analysis results of the inhibition of tumor growth in GR6 tumor mice by treating the compound alone for 35 days. Figure 2B The figure shows the analysis results of the inhibition of tumor growth in GR8 tumor mice by treating the compound alone for 35 days. Figure 2C The figure shows the analysis results of the inhibition of tumor growth in HCC827 tumor mice by treating the compound alone for 35 days. Figure 2D A statistical graph showing the change in body weight in tumor-bearing mice treated with the compound alone for 35 days. Figures 2A to 2C The data are expressed as mean ± SEM (n = 10).

[0061] Figures 2A to 2C The results showed that compound 35d significantly inhibited tumor growth in GR6 and GR8 tumor mice, but its effect on inhibiting tumor growth in HCC827 tumor mice was less significant. Figure 2D The results showed that the body weight of tumor-bearing mice did not decrease significantly after being treated with the compound for more than one month (35 days).

[0062] 4. Combination use of compound 35d with osimertinib inhibits GR6 tumor re-progression.

[0063] EGFR-TKIs are currently the standard treatment for non-small cell lung cancer (NSCLC) patients with EGFR gene mutations. This study further tested whether the diarylheptane compound of this invention, when used in combination with known compounds, could improve the treatment efficacy for NSCLC. In the study, GR6 tumor mice were divided into four groups: one group received 100 mg / kg of the compound daily for 35 days (denoted as 35d); one group received 1 mg / kg of osimertinib daily (denoted as Osi); one group received a combination of 100 mg / kg of the compound daily for 35 days and 1 mg / kg of osimertinib daily (denoted as 35d+Osi); and the remaining group was a control group that did not receive any treatment.

[0064] Please refer to Figure 3A and Figure 3B , Figure 3A The figure shows the combined analysis results of tumor re-progression in mice treated with compound 35d and osimertinib that inhibited GR6 tumors. Figure 3B A statistical graph showing the weight changes in GR6 tumor mice treated with compound 35d and osimertinib combined, where... Figure 3A and Figure 3B The data are expressed as mean ± SEM (n = 10).

[0065] Figure 3A The results showed that although the tumor size of GR6 tumor mice in the Osi group decreased initially after osimertinib treatment, the treated tumors subsequently regrowed, indicating that the tumors of GR6 tumor mice were EGFR-TKI resistant. However, both the group treated with compound 35d alone and the group treated with compound 35d in combination with osimertinib significantly inhibited tumor progression in GR6 tumor mice. Figure 3B The results showed that treatment with compound 35d alone or in combination with osimertinib did not significantly reduce the body weight of mice.

[0066] In summary, this invention proposes a novel use for a pharmaceutical composition in the preparation of a medicament for treating lung cancer. The pharmaceutical composition comprises a diarylheptane compound or a pharmaceutically acceptable salt thereof, which inhibits the growth of EGFR gene-mutant non-small cell lung cancer cells and EGFR-TKI-resistant non-small cell lung cancer cells. It is used to prepare a medicament for treating lung cancer, and when used in combination with EGFR-TKIs, it exhibits a synergistic effect, further enhancing the efficacy of lung cancer treatment, particularly for treating EGFR gene-mutant lung cancer with EGFR-TKI resistance. This invention has potential application in the biomedical and healthcare market.

[0067] However, the present invention has been disclosed above with reference to embodiments, but it is not intended to limit the present invention. Any person skilled in the art can make various modifications and refinements without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be determined by the appended claims.

Claims

1. The use of a pharmaceutical composition, characterized in that, This pharmaceutical composition is for preparing a medicament for treating lung cancer, wherein the pharmaceutical composition comprises a diarylheptane compound or a pharmaceutically acceptable salt thereof, the diarylheptane compound being selected from: 、 、 and ; One dosage form of the pharmaceutical composition includes hard gelatin capsules, soft gelatin capsules, tablets, parenteral injections, and oral suspensions; One dosage of the pharmaceutical composition is from 0.1 mg to 2000 mg per day; The lung cancer in question is non-small cell lung cancer.

2. The use of the pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition further contains an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs).

3. The use of the pharmaceutical composition according to claim 2, characterized in that, The epidermal growth factor receptor-tyrosine kinase inhibitors are osimertinib, gefitinib, erlotinib, or afatinib.

4. The use of the pharmaceutical composition according to claim 1, characterized in that, This lung cancer is resistant to epidermal growth factor receptor-tyrosine kinase inhibitors.

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