Tranexamic acid arginine and histidine mimetics as therapeutic agents
By using arginine mimics (TA-R) compounds, the vitality and immune evasion of cancer cells are suppressed, and the problem that existing treatment methods are difficult to effectively inhibit cancer cells and virus replication is solved, and effective for cancers such as breast cancer is achieved treat.
Patent Information
- Application Number
- CN202380042961.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-03-27
- Filing Date
- 2023-03-27
- Publication Date
- 2025-02-18
AI Technical Summary
Existing treatments are difficult to effectively inhibit the vitality of cancer cells and the replication of viruses or microorganisms, especially in breast cancer and other types of cancer.
Arginine mimics (TA-R), such as trans-4-guanidine methylcyclohexanecarboxylic acid, amino ((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl) Amino)methylimmonium chloride, etc., as compositions or treatment methods, inhibit cell viability, reduce the expression of MYC oncogene, reduce histone acetylation, and inhibit p300 acetyltransferase by preserving the spatial relationship between carboxyl and guanidine groups of amino acids. activity and block T-cell-based immunity.
TA-R compounds significantly inhibit the vitality of breast cancer cells, reduce oncogene expression, and reduce the immune evasion ability of cancer cells, thus providing an effective method to prevent or treat cancer.
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Figure CN119486730A_ABST
Abstract
Description
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] This patent application claims priority to U.S. Provisional Application No. 63 / 324,115 filed on March 27, 2022, and the entire disclosure of which is hereby incorporated herein by reference. Technical Field
[0003] The present disclosure relates generally to therapeutic agents, and more particularly, but not by way of limitation, to tranexamic acid-like arginine and histidine mimetics as therapeutic agents. Background Art
[0004] This section provides background information to facilitate a better understanding of the various aspects of the present disclosure. It should be understood that the statements in this section of the document should be read in this light, and not as admissions of prior art.
[0005] Tranexamic acid (TA) is a clinically used agent that prevents plasmin formation by occupying the lysine (Lys) binding site of plasminogen. TA is a synthetic analog of Lys made by inserting a cyclohexyl ring between the carboxyl and amino side chains of Lys. Although used as an antifibrinolytic in the past, TA has recently been shown to inhibit the viability of a wide range of human and murine cancer cell lines and inhibit the replication of a variety of viruses and microorganisms. Summary of the invention
[0006] This Summary is provided to introduce a selection of concepts that are further described below in the Detailed Description. This Summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used to help limit the scope of the claimed subject matter.
[0007] In one embodiment, the present disclosure relates to a composition for preventing or treating cancer. In general, the composition includes an arginine mimetic (TA-R), which may include, but is not limited to, trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxylcyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxylcyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), compounds having cycloalkanes containing two or more functional groups outside the cycloalkanes, derivatives thereof, salts thereof, and combinations thereof.
[0008] In some embodiments, the concentration of arginine mimetics is in the range of 0.5 to 20% (w / v). In some embodiments, arginine mimetics preserve the spatial relationship between the carboxyl and guanidinium groups of amino acids. In some embodiments, arginine mimetics inhibit the viability of cells. In some embodiments, cells include cancer cells. In some embodiments, cancer cells are breast cancer cells. In some embodiments, arginine mimetics reduce the expression of MYC oncogenes. In some embodiments, arginine mimetics reduce histone acetylation. In some embodiments, arginine mimetics inhibit p300 acetyltransferase activity. In some embodiments, arginine mimetics reduce programmed death ligand 1 (PD-L1) expression in cancer cells, thereby blocking T cell-based immunity.
[0009] In further embodiments, the disclosure relates to a method of preventing or treating cancer. Generally, the method comprises administering an arginine mimetic (TA-R) to a subject. In some embodiments, TA-R may include, but is not limited to, trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe), and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), compounds having a cycloalkane containing two or more functional groups outside the cycloalkane, derivatives thereof, salts thereof, and combinations thereof.
[0010] In some embodiments, the concentration of the arginine mimetic is in the range of 0.5 to 20% (w / v). In some embodiments, the method further includes preserving the spatial relationship between the carboxyl and guanidine groups of the amino acid by the arginine mimetic. In some embodiments, the method further includes inhibiting the viability of the cell by the arginine mimetic. In some embodiments, the cell includes a cancer cell. In some embodiments, the cancer cell is a breast cancer cell. In some embodiments, the method further includes reducing the expression of the MYC oncogene by the arginine mimetic. In some embodiments, the method further includes reducing histone acetylation by the arginine mimetic. In some embodiments, the method further includes inhibiting p300 acetyltransferase activity by the arginine mimetic. In some embodiments, the method further includes reducing programmed death ligand 1 (PD-L1) expression in cancer cells and blocking T cell-based immunity by the arginine mimetic.
[0011] In another embodiment, the present disclosure relates to a composition for preventing or treating cancer, preventing, treating or inhibiting viral or microbial infection or replication, or preventing, treating or inhibiting disease. Generally speaking, the composition includes at least one of an arginine mimetic (TA-R) or a histidine mimetic (TA-H).
[0012] In some embodiments, at least one of TA-R or TA-H is TA-R, which may include but is not limited to trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), compounds having cycloalkanes containing two or more functional groups outside the cycloalkanes, derivatives thereof, salts thereof, and combinations thereof. In some embodiments, the concentration of at least one of TA-R or TA-H is in the range of 0.5 to 20% (w / v). In some embodiments, the at least one of TA-R or TA-H preserves the spatial relationship of the carboxyl and guanidine groups of the amino acids. In some embodiments, the at least one of TA-R or TA-H treats or prevents the development or growth of cancer, viral or microbial infection, or the development of another disease. In some embodiments, the cancer is skin cancer. In some embodiments, the cancer is breast cancer. In some embodiments, the at least one of TA-R or TA-H reduces the expression of the MYC oncogene. In some embodiments, the at least one of TA-R or TA-H reduces histone acetylation. In some embodiments, the at least one of TA-R or TA-H inhibits p300 acetyltransferase activity. In some embodiments, the at least one of TA-R or TA-H reduces the expression of programmed death ligand 1 (PD-L1) in cancer cells, thereby blocking T cell-based immunity.
[0013] In further embodiments, the present disclosure relates to a method of preventing or treating cancer, preventing, treating or inhibiting viral or microbial infection or replication, or preventing, treating or inhibiting disease. Generally, the method comprises administering to a subject at least one of an arginine mimetic (TA-R) or a histidine mimetic (TA-H).
[0014] In some embodiments, at least one of TA-R or TA-H is TA-R, which may include but is not limited to trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), compounds having cycloalkanes containing two or more functional groups outside the cycloalkanes, derivatives thereof, salts thereof, and combinations thereof. In some embodiments, the concentration of at least one of TA-R or TA-H is in the range of 0.5 to 20% (w / v). In some embodiments, the method further comprises preserving the spatial relationship of the carboxyl and guanidine groups of the amino acids by at least one of TA-R or TA-H. In some embodiments, the method further comprises treating or preventing the development or growth of cancer, viral or microbial infection, or the development of another disease by at least one of TA-R or TA-H. In some embodiments, the cancer is skin cancer. In some embodiments, the cancer is breast cancer. In some embodiments, the method further comprises reducing the expression of the MYC oncogene by at least one of TA-R or TA-H. In some embodiments, the method further comprises reducing histone acetylation by at least one of TA-R or TA-H. In some embodiments, the method further comprises inhibiting p300 acetyltransferase activity by at least one of TA-R or TA-H. In some embodiments, the method further comprises reducing programmed death ligand 1 (PD-L1) expression in cancer cells and blocking T cell-based immunity by at least one of TA-R or TA-H. BRIEF DESCRIPTION OF THE DRAWINGS
[0015] A more complete understanding of the subject matter of the present disclosure may be obtained by reference to the following detailed description when taken in conjunction with the accompanying drawings, in which:
[0016] Figure 1 Illustration of arginine mimetics (TA-R) inspired by tranexamic acid (TA).
[0017] Figure 2 It was shown that TA-R compounds reduced breast cancer cells (MDA-MB-468) more than tranexamic acid (TA); the curve of cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3) was truncated due to insolubility. DETAILED DESCRIPTION
[0018] It is to be understood that the following disclosure provides many different embodiments, or examples for realizing different features of various embodiments. Specific examples of components and arrangements are described below to simplify the disclosure. These are of course only examples and are not intended to be limiting. The section headings used herein are for organizational purposes and should not be construed as limiting the subject matter described.
[0019] As used herein, the term "tranexamic acid" - a class, type of compound or mimetic - refers to a compound having a cycloalkane containing two or more functional groups outside the cycloalkane. For example, in the case of tranexamic acid (a "lysine mimetic"), the cycloalkane can be a cyclohexane having two functional groups: (1) an aminomethyl group on the C4 atom; and (2) a carboxylic acid group on the C1 atom, thus having an amine group similar to that of lysine. In the case of an "arginine mimetic", the cycloalkane can be a cyclohexane having two functional groups: (1) a guanidinomethyl group on the C4 atom; and (2) a carboxylic acid group on the C1 atom, thus having a guanidino group similar to that of arginine. It should be noted that the above are only examples, and various configurations are readily contemplated. For example, the cycloalkane can be a cyclopentane, and the functional groups need not be on the C4 and C1 atoms. In addition, the functional groups are not limited to carboxyl groups, but can include various functional groups, such as ester groups. Other examples include, but are not limited to:
[0020] trans-4-guanidinemethylcyclohexanecarboxylic acid;
[0021] Amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride;
[0022] Amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride;
[0023] cis-Amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride;
[0024] cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride; and
[0025] cis-3-(Guandinomethyl)cyclopentane-1-carboxylic acid.
[0026] Although used in the past as an antifibrinolytic, tranexamic acid (TA) has recently been shown to inhibit the viability of a wide range of human and murine cancer cell lines, and to inhibit the replication of a variety of viruses and microorganisms. There are plasmin-dependent and plasmin-independent biochemical mechanisms responsible for this response, including inhibition of protein synthesis and inhibition of lysine (Lys) acetylation. More specifically, it has also recently been shown that the fundamental mode of action (MOA) of TA is that it mimics (antagonizes) not only Lys, but also arginine (Arg) and histidine (His), three positively charged amino acids that are essential for electrostatic bonding required in a variety of protein-protein interactions and other processes involved in the development of cancer, viral and microbial replication, and other diseases and conditions.
[0027] In addition to blocking the Lys binding site on plasminogen to inhibit the formation of plasmin, specific examples of this essential MOA that have been demonstrated include, for example, inhibiting Lys acetylation (required for the production of proteins involved in viral replication and the development of cancer and other diseases) and occupying the cationic amino acid transporter (CAT) required for the transport of Lys, Arg and His into the cell, thereby depriving the cell of these amino acids and inhibiting the proliferation of proteins required for viral replication and cancer growth.
[0028] Based on the hypothesis that synthetic "tranexamic acid" mimetics of Arg or synthetic "tranexamic acid" mimetics of His may be more effective than TA against certain cancers, viruses, or other diseases or conditions - whether because Arg or His plays a more important role in these cases or for other reasons - the present disclosure relates to the formation of various synthetic "tranexamic acid" mimetics of Arg tested against common breast cancer lines. The present disclosure shows that all Arg mimetics are indeed significantly more effective than TA in inhibiting the vitality of this type of cancer. Therefore, the present disclosure opens up the possibility of using synthetic "tranexamic acid" mimetics of Arg and "tranexamic acid" mimetics of His against viruses, microorganisms, cancers and other diseases or conditions when TA does not provide inhibition or sufficient inhibition, and using them in combination with TA or with other drugs to provide higher efficacy or safety.
[0029] The development results of several TA-R molecules are reported herein, including, for example, biological testing. The following is a summary of the various TA-R abbreviations used herein: trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1); amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe); amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2); cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3); cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4).
[0030] Arginine mimetics designed and prepared compounds. It was initially estimated that TA mimics Lys by preserving the 1,6-connectivity between the carboxyl functionality and the amino group present on the Lys side chain. It is known that the trans stereochemistry of TA and the cyclohexyl ring is important for plasminogen binding, the former maintaining an extended conformation of the molecule and the latter providing stabilizing van der Waals contacts within the Lys binding site. By analogy, several Arg mimetics were identified and the biological evaluation of the preservation of the spatial relationship (e.g. 1,5-connectivity) of the carboxyl and guanidinium groups of the amino acid (except TA-R1 and TA-R1OMe) was studied. These molecular targets are in Figure 1 The compounds are identified by the name TAR and supplemented with various important descriptors. The comparative compounds TA and TA-NAc (N-acetylcysteine; NAc) evaluated in parallel are also shown.
[0031] Operation Example
[0032] Reference is now made to more specific embodiments of the present disclosure and data supporting these embodiments. However, it should be noted that the following disclosure is for illustrative purposes only and is not intended to limit the scope of the claimed subject matter in any way.
[0033] Biological Testing
[0034] Effect of Compounds on Cell Viability. MDA-MB 468 triple-negative breast cancer cells were seeded in 96-well plates at 6,250 cells per well and incubated overnight at 37°C. The cells were then treated with Figure 1 Increasing concentrations of each TA analog as indicated in were incubated for 72 hours at 37° C. Cell viability was assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay according to the manufacturer's instructions.
[0035] Inhibition of p300 acetyltransferase activity. The p300 enzyme assay was performed with TA, TA-NAc, and TA-R2 using commercially available recombinant p300 and recombinant commercially available histone H3 and tritiated acetyl CoA as substrates. The p300 assay was performed in the presence of increasing concentrations of each compound, and the acetylation of p300 was assessed by scintillation counting of histone H3 adsorbed onto 1 cm x 1 cm nitrocellulose squares after extensive washing of the nitrocellulose squares with 20% trichloroacetic acid.
[0036] Results and discussion
[0037] Chemical synthesis and solubility.TA was purchased from a commercial source, and TA-NAc was prepared directly by acetylation of TA based on standard procedures.TA-NAc was isolated and tested as its sodium salt which exhibited better water solubility.
[0038] TA-R1—R4 can be obtained from their corresponding amino acids by treatment with methylisothiourea hemisulfate. TA-R1 (trans-4-guanidinemethylcyclohexanecarboxylic acid; GMCHA) was prepared in one step from TA using this reagent, but exhibited poor water solubility in its neutral form and in its salt form. Esterification of TA-R1 to produce TA-R1OMe, a novel compound, improved solubility for preparation of 2% (w / v) solutions in phosphate buffered saline (PBS) buffer (pH=7.4) and biological testing. TA-R2 was prepared in one step from commercially available trans-4-aminocyclohexanecarboxylic acid and showed good water solubility.
[0039] The synthesis of the amino acids required for TA-R3 / R4 requires a multistep synthetic approach. Briefly, the preparation of TA-R3, a novel compound, begins with cis-1,3-cyclohexanedicarboxylic acid and proceeds through eight sequential synthetic steps to obtain the product as its HCl salt. Protection / deprotection of the amino group is required to facilitate purification, as is a stepwise oxidation sequence from the alcohol to the carboxylic acid. The compound exhibits poor aqueous solubility (~0.1% in PBS buffer), but this is remedied by esterification to produce TA-R3OMe (to prepare approximately 2% solution). The method for preparing TA-R4, a known compound, requires an additional step to produce the starting dicarboxylic acid, in this case by oxidative cleavage of norbornene. TA-R4 exhibits adequate solubility in its neutral form (approximately 2% solution in PBS buffer). All final compounds are prepared by 1 H nuclear magnetic resonance (NMR), 13 The proteins were fully characterized by C NMR and high-resolution electrospray ionization mass spectrometry (HRMS-ESI).
[0040] Biological results
[0041] TA-R compounds inhibit cancer cell viability in vitro. MTT cell viability assay showed that the tested TA-R compounds inhibited the viability of breast cancer (MDA-MB-468) cells to a greater extent than TA (or TA-NAc; data not shown) Figure 2 ).
[0042] Biochemical evaluation of breast cancer cells treated with TA-R2. Immunoblot analysis of MDA-MB-468 cells treated with TA-R2 relative to TA and TA-NAc (NAc-TA) showed that TA-R2 reduced the expression of the MYC oncogene to a greater extent than TA or NAc-TA at the same concentration. High (2%) TA-R2 reduced programmed death ligand 1 (PD-L1), while the other two compounds did not. This is important because PD-L1 expression in cancer cells blocks T cell-based immunity. Therefore, it is predicted that TA-R2 will increase anti-cancer immunity in immune-competent systems. Histone acetyltransferase (HAT) enzyme assays were used to determine whether TA-R2 inhibits p300 activity. Although TA (2%) did not affect p300 acetylation of histone 3 (H3) in vitro, TA-R2 reduced histone acetylation more strongly than the other two compounds. This is consistent with the hypothesis that TA acts in part by inhibiting acetyltransferases such as p300 / CPB that acetylate histones. No acetylation was observed in controls following omission of H3 / p300 or acetyl coenzyme A (acetyl-CoA).
[0043] in conclusion
[0044] All TA-R analogs tested showed higher cytotoxic potency than TA against the MDA-MB-468 triple-negative breast cancer cell line, with IC values of TA-R1-OMe, TA-R3, and TA-R3-OMe being 50 The value is about 1 / 10 times. The low solubility difficulty of some analogs was solved in some cases by generating ester derivatives and in other cases by producing salt forms of the compound (or both). One of the analogs tested, TA-R2, downregulated the expression of the MYC oncogene and reduced histone acetylation to a greater extent than TA at a concentration of 2% (w / v), and unlike TA, TA-R2 downregulated MYC at 0.5%. Overall, these results indicate that replacing the amine group of TA or TA-inspired compounds with a guanidine group can enhance anticancer potency and anticancer activity through biochemical mechanisms that overlap with the biochemical mechanism of TA.
[0045] Based on the above results, although TA has been shown to antagonize Lys, Arg, and His, it is clear that Arg mimetics, such as the TA-R molecules discussed above, are more effective than TA in some cases. It is easy to imagine that there are other cases. For example, Arg deprivation has been identified as a treatment for other types of cancer and the virus that caused the COVID-19 pandemic (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). If TA-R is more effective than TA in antagonizing Arg (which is possible), it will be more effective in these other therapeutic areas.
[0046] Additionally, based on the data presented herein, it is further contemplated that the use of the TA-R mimetics discussed herein may provide a means of improving the efficacy of radiation therapy for certain tumor types, such as glioblastoma, since Arg deprivation has been shown to improve the effectiveness of radiation therapy for these tumors. Furthermore, since Arg is also involved in aspects of the physiological response to traumatic brain injury, the mimetics disclosed herein may be used to treat brain injuries, including, for example, concussions.
[0047] Although various embodiments of the present disclosure have been shown in the drawings and described in the foregoing detailed description, it is to be understood that the present disclosure is not limited to the embodiments disclosed herein, but is capable of many rearrangements, modifications and substitutions without departing from the spirit of the present disclosure as set forth herein.
[0048] As will be understood by one of ordinary skill in the art, the term "substantially" is defined as being largely, but not necessarily completely, of what is specified. In any disclosed embodiment, the terms "substantially," "approximately," "roughly," and "about" may be replaced with "within [percentage] of what is specified," where the percentage includes 0.1%, 1%, 5%, and 10%.
[0049] The features of several embodiments are summarized above so that those skilled in the art can better understand aspects of the present disclosure. Those skilled in the art should recognize that they can easily use the present disclosure as a basis for designing or modifying other methods and structures to achieve the same purpose and / or realize the same advantages of the embodiments introduced herein. Those skilled in the art should also recognize that such equivalent constructions do not deviate from the spirit and scope of the present disclosure, and they can make various changes, substitutions and modifications herein without departing from the spirit and scope of the present disclosure. The scope of the present invention should only be determined by the terms of the following claims. The term "comprising" in the claims is intended to mean "at least including" so that the list of elements listed in the claims is an open group. Unless specifically excluded, the terms "one", "a kind of" and other singular terms are intended to include their plural forms.
Claims
1. A composition for preventing or treating cancer, comprising: Arginine mimetics (TA-R) selected from the group consisting of trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), compounds having a cycloalkane containing two or more functional groups outside the cycloalkane, derivatives thereof, salts thereof and combinations thereof.
2. The composition according to claim 1, wherein the concentration of the arginine mimetic is in the range of 0.5 to 20% (w / v).
3. The composition of claim 1, wherein the arginine mimetic preserves the spatial relationship of the carboxyl group and the guanidinium group of the amino acid.
4. The composition of claim 1, wherein the arginine mimetic inhibits cell viability.
5. The composition of claim 4, wherein the cells comprise cancer cells. The composition according to claim 5 , wherein the cancer cells are breast cancer cells.
7. The composition of claim 1, wherein the arginine mimetic reduces expression of the MYC oncogene.
8. The composition of claim 1, wherein the arginine mimetic reduces histone acetylation.
9. The composition of claim 1, wherein the arginine mimetic inhibits p300 acetyltransferase activity.
10. The composition of claim 1, wherein the arginine mimetic reduces programmed death ligand 1 (PD-L1) expression in cancer cells, thereby blocking T cell-based immunity.
11. A method for preventing or treating cancer, comprising: administering an arginine mimetic (TA-R) to the subject; and Wherein the TA-R is selected from the group consisting of trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), compounds having cycloalkanes containing two or more functional groups outside cycloalkanes, their derivatives, their salts and combinations thereof.
12. The method of claim 11, wherein the concentration of the arginine mimetic is in the range of 0.5 to 20% (w / v).
13. The method of claim 11, further comprising preserving the spatial relationship of the carboxyl group and the guanidinium group of the amino acid by the arginine mimetic.
14. The method of claim 11, further comprising inhibiting the viability of cells by the arginine mimetic.
15. The method of claim 14, wherein the cells comprise cancer cells.
16. The composition of claim 15, wherein the cancer cells are breast cancer cells.
17. The method of claim 11, further comprising reducing the expression of MYC oncogene by the arginine mimetic.
18. The method of claim 11, further comprising reducing histone acetylation by the arginine mimetic.
19. The method of claim 11, further comprising inhibiting p300 acetyltransferase activity by the arginine mimetic.
20. The method of claim 11, further comprising: Reducing programmed death ligand 1 (PD-L1) expression in cancer cells by the arginine mimetic; and Blocking T cell-based immunity.
21. A composition for preventing or treating cancer, preventing, treating or inhibiting viral or microbial infection or replication, or preventing, treating or inhibiting disease, the composition comprising at least one of an arginine mimetic (TA-R) or a histidine mimetic (TA-H).
22. The composition of claim 21, wherein the at least one of TA-R or TA-H comprises a TA-R selected from the group consisting of trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), a compound having a cycloalkane containing two or more functional groups other than a cycloalkane, a derivative thereof, a salt thereof, and a combination thereof.
23. The composition of claim 21, wherein the concentration of the at least one of TA-R or TA-H is in the range of 0.5 to 20% (w / v).
24. The composition of claim 21, wherein the at least one of TA-R or TA-H conserves the spatial relationship of the carboxyl group and the guanidinium group of the amino acid.
25. The composition of claim 21, wherein the at least one of TA-R or TA-H treats or prevents the development or growth of cancer, a viral or microbial infection, or the development of another disease.
26. The composition of claim 25, wherein the cancer is skin cancer.
27. The composition of claim 25, wherein the cancer is breast cancer.
28. The composition of claim 21, wherein the at least one of TA-R or TA-H reduces expression of the MYC oncogene.
29. The composition of claim 21, wherein the at least one of TA-R or TA-H reduces histone acetylation.
30. The composition of claim 21, wherein the at least one of TA-R or TA-H inhibits p300 acetyltransferase activity.
31. The composition of claim 21, wherein the at least one of TA-R or TA-H reduces programmed death ligand 1 (PD-L1) expression in cancer cells, thereby blocking T cell-based immunity.
32. A method for preventing or treating cancer, preventing, treating or inhibiting viral or microbial infection or replication, or preventing, treating or inhibiting disease, the method comprising: At least one of an arginine mimetic (TA-R) or a histidine mimetic (TA-H) is administered to the subject.
33. The method of claim 32, wherein the at least one of TA-R or TA-H comprises a TA-R selected from the group consisting of trans-4-guanidinomethylcyclohexanecarboxylic acid (TA-R1), amino((((1r,4r)-4-(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R1-OMe), amino(((1r,4r)-4-carboxycyclohexyl)amino)methaniminium chloride (TA-R2), cis-amino(((3-carboxycyclohexyl)methyl)amino)methaniminium chloride (TA-R3), cis-amino(((3(methoxycarbonyl)cyclohexyl)methyl)amino)methaniminium chloride (TA-R3-OMe) and cis-3-(guanidinomethyl)cyclopentane-1-carboxylic acid (TA-R4), a compound having a cycloalkane containing two or more functional groups other than a cycloalkane, a derivative thereof, a salt thereof, and a combination thereof.
34. The method of claim 32, wherein the concentration of the at least one of TA-R or TA-H is in the range of 0.5 to 20% (w / v).
35. The method of claim 32, further comprising conserving the spatial relationship of the carboxyl group and the guanidinium group of the at least one amino acid by TA-R or TA-H.
36. The method of claim 32, further comprising treating or preventing the development or growth of cancer, a viral or microbial infection, or the development of another disease by said at least one of TA-R or TA-H.
37. The method of claim 36, wherein the cancer is skin cancer.
38. The method of claim 36, wherein the cancer is breast cancer.
39. The method of claim 32, further comprising reducing expression of a MYC oncogene by said at least one of TA-R or TA-H.
40. The method of claim 32, further comprising reducing histone acetylation by said at least one of TA-R or TA-H.
41. The method of claim 32, further comprising inhibiting p300 acetyltransferase activity by said at least one of TA-R or TA-H.
42. The method of claim 32, further comprising: reducing programmed death ligand 1 (PD-L1) expression in cancer cells by said at least one of TA-R or TA-H; and Blocking T cell-based immunity.