Treatment and prevention of agent-induced liver conditions or diseases

Abstract

This disclosure provides for the use of compound 1 or a pharmaceutically acceptable salt thereof for the prevention and / or treatment of said liver condition or disease in a subject exposed to an agent capable of inducing liver condition or disease.

Description

Treatment and prevention of agent-induced liver disorders or diseases The present invention relates to the treatment and prevention of an agent-induced liver disorder or disease. It is known that certain agents (including approved pharmaceuticals) induce liver disorders or diseases such as liver inflammation, hepatocyte necrosis, liver injury, liver fibrosis, cirrhosis, acute liver failure, alcoholic fatty liver, alcoholic steatohepatitis, alcoholic liver disease, and hepatocellular carcinoma. The agents include common household items such as acetaminophen (APAP) and beverage alcohol. Acetaminophen toxicity is a leading cause of liver transplantation worldwide and results in hospitalizations, emergency room visits, and deaths. Alcoholic liver disease is the most common chronic liver disease and a leading cause of death worldwide. There are few treatment options for alcoholic liver disease and alcohol-induced liver disorders and diseases such as alcohol-induced hepatitis other than abstinence from alcohol and brief exposure to corticosteroids. Other agents that cause liver injury include small molecule drugs, biologic drugs, traditional Chinese medicines, natural medicines, and dietary supplements. The increasing use of herbs and dietary supplements is associated with an increase in herb- and dietary supplement-induced hepatotoxicity. US 6,583,265 discloses Compound 1: Compound 1 This compound was characterized in Example 27 of patent US 6,583,265, which includes hundreds of named compounds having modifications at different positions around the ring. However, no biological test data or specific uses of this compound or related analogs were described. Compound 1 is also disclosed in WO 2019 / 0169572 for the treatment or prevention of acute or chronic inflammatory disorders such as acute kidney injury, ischemia-reperfusion injury, or chronic or acute pancreatitis. Compound 1 is further disclosed in WO 2021 / 068957 for the prevention and / or treatment of kidney disorders or diseases induced by nephrotoxic drugs or endogenous nephrotoxins in a subject. WO 2019 / 0169572 and WO 2021 / 068957 do not disclose the use of Compound 1 in the prevention and / or treatment of the liver disorders or diseases in a subject exposed to an agent capable of inducing liver disorders or diseases. Accordingly, an object of the present disclosure is to provide novel treatment and prevention of liver disorders or diseases associated with or induced by exposure to one or more agents (e.g., induced by exposure to alcohol such as beverage alcohol), as well as protection of the liver of a subject receiving pharmaceutical treatment. Additional objects of the present disclosure will become apparent based on the following description of the examples and claims. In a first aspect, the present disclosure relates to Compound 1 or a pharmaceutically acceptable salt thereof, Compound 1 For use in the prevention and / or treatment of said liver disorder or disease in a subject exposed to an agent capable of inducing a liver disorder or disease. In another aspect, there is provided the use of Compound 1 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention and / or treatment of said liver disorder or disease in a subject exposed to an agent (i.e., a drug or other agent) capable of inducing a liver disorder or disease. In yet another aspect, the present disclosure provides a method for the prevention and / or treatment of said liver disorder or disease in a subject exposed to an agent capable of inducing a liver disorder or disease, the method comprising administering Compound 1 or a pharmaceutically acceptable salt thereof to the subject. In another aspect, the agent is acetaminophen (APAP) or alcohol. In a first aspect, the present disclosure relates to Compound 1 or a pharmaceutically acceptable salt thereof, Compound 1 For use in the prevention and / or treatment of said liver disorder or disease in a subject exposed to an agent capable of inducing a liver disorder or disease. Compound 1 is a cyclosporin A derivative substituted at position 3 (sarcosine, originally called N-methylglycine) with an N,N-dimethylaminoethoxy residue, and its synthesis and preparation have been described, for example, in WO2019 / 0169572. Compound 1 as depicted above may be referred to by one of its chemical names as [( R)-2’(2-dimethylaminoethoxy)-Sar] 3 Cyclosporin A. It should be understood herein that Compound 1 as described in the context of the present disclosure may refer to its enantiomers, diastereomers or racemates as well as its polymorphs, hydrates or complexes in addition to any pharmaceutically acceptable salts thereof. In an alternative and optional embodiment, Compound 1 may be provided as a mixture of the ( R) and ( S) stereoisomers at the 3-sarcosine position. Also included are the uses of optically pure stereoisomers of Compound 1 and the uses of combinations of its stereoisomers. The phrase "optically pure", which is interchangeable with the term "stereochemically pure", refers to a compound having a level of stereochemical purity recognized by those skilled in the art based on conventional methods used to determine stereochemistry and stereochemical purity. In another optional embodiment, Compound 1 or a pharmaceutically acceptable salt thereof may be provided as an isotope, for example, in the case where one or more of its atoms are replaced by an isotope such as 13 C) or by deuterium. As used herein, the term "agent" includes a compound or substance or mixture of compounds or substances capable of damaging, impairing or reducing liver function. Such compounds or substances include active pharmaceutical ingredients and / or pharmacological or diagnostic active compounds or mixtures of compounds, which can be used in medical or therapeutic applications for the prevention, diagnosis, stabilization, treatment or control of a condition, disorder or disease. An agent can be provided or administered to a subject as a pharmaceutical or drug dosage form comprising one or more agents and one or more non-pharmacologically active excipients or carriers. Other agents include small molecule drugs, biopharmaceuticals, traditional Chinese medicines, herbal medicines, natural medicines and dietary supplements. As understood herein, the phrase "exposure to an agent" or similar phrases can refer to a subject being exposed to an agent during the course of treating a condition, symptom or disease, wherein one or more doses of the agent are administered to the subject for therapeutic or diagnostic purposes, such as any one or combination of the agents as defined in various embodiments herein. The phrase "exposure to an agent" as used herein also includes any unintentional exposure of a subject to an agent, such as but not limited to accidental exposure (e.g., from a needlestick injury), or environmental / accidental circumstances (e.g., any physical or long-term exposure to an agent). The phrase also includes intentional exposure to an agent, such as drinking an agent, particularly in the case where a subject drinks a beverage (e.g., an alcoholic beverage). In one embodiment, the agent is an alcohol. The alcohol can be any organic compound containing one or more alcohol moieties that may cause a liver condition or disease upon exposure, such as methanol, ethanol, propanol, isopropanol, butanol, isobutanol, etc. Mixtures of alcohols are also contemplated. In a specific embodiment, the agent is a beverage alcohol, particularly ethanol. In another embodiment, the agent is a therapeutic agent. In a specific embodiment, the therapeutic agent is selected from analgesics, antipyretics, anesthetics, non-steroidal anti-inflammatory drugs, antimicrobials, antibiotics, antifungals, antivirals, antiretrovirals, HIV therapies, hypoglycemic agents, hypolipidemic agents, herbal medicines, traditional Chinese medicine drugs, anti-cancer drugs, anti-tuberculosis drugs and cardiac drugs. In a specific embodiment, the agent is the analgesic acetaminophen (APAP). In some embodiments, the therapeutic agent is a traditional Chinese medicine drug. Such traditional Chinese medicine drugs include herbs or drugs derived from animals, minerals or other substances. In some embodiments, the traditional Chinese medicine drug is selected from Polygonum multiflorum Thunb., Chinese name Heshouwu, Tripterygium wilfordii Hook. f., Chinese name Leigongteng, Bupleurum chinense DC., Chinese name Heshouwu), Tripterygium wilfordii Hook. f., Chinese name Leigongteng), Bupleurum chinense DC., Chinese name Bupleurum chinense DC., Chinese name Bupleurum), Epimedium ( Epimedium brevicornum Maxim., Chinese name is Yinyanghuo), Silybum marianum ( Silybum marianum (L.) Gaertn., Chinese name is Shuifeiji), Senna leaf ( Cassia acutifolia Delile, Chinese name is Fanxieye), Buckthorn ( Rhamnus purshiana DC. (cascara), Chinese name is Shuli), Star anise (Anisi Stellati Fructus, Chinese name is Bajiao), Sanguisorba officinalis (Radix Sanguisorbae, Chinese name is Diyu), Gardenia (Fructus Gardeniae, Chinese name is Zhizi), Chinese gallnut (Galla Chinensis, Chinese name is Wubeizi), Pomegranate peel (Cortex Granati, Chinese name is Shiliupi), Terminalia chebula (Chebulae Fructus, Chinese name is Hezi), Acorus tatarinowii (Rhizoma Acori tatarinowii, Chinese name is Shichangpu), Fennel (Fructus Foeniculi, Chinese name is Xiaohuixiang), Cinnamon bark (Cortex Cinnamomi, Chinese name is Guipi), Aristolochia fruit (Fructus Aristolochiae, Chinese name is Madouling), Akebia quinata (Caulis Akebiae, Chinese name is Mutong), Albizia julibrissin (Cortex Albiziae, Chinese name is Hehuanpi), Strychnos nux-vomica (Semen Strychni, Chinese name is Maqianzi), Alisma orientale (Rhizoma Alismatis, Chinese name is Zexie), Folium Sennae (Chinese name is Fanxieye), Semen Cassiae (Chinese name is Juemingzi), Herba Chenopodii (Chinese name is Tujinjie), Folium Clerodendri (Chinese name is Chouwutong), Radix Dioscoreae bulbifera (Chinese name is Huangdu), Omoto Nipponlily (Chinese name is Wannianqing), Herba Ephedrae (Chinese name is Mahuang), Herba Gynurae (Chinese name is Jusanqi), Semen Hydnocarpi Hainanensis (Chinese name is Dafengzi), Folium Ilexi pubescensi (Chinese name is Maodongqing), Fructus Trichosanthis (Chinese name is Gualou), Fructus Meliaceae (Chinese name is Kulianzi), Semen Myristicae (Chinese name is Roudoukou), Herba Papaveri somniferi (Chinese name is Yingsu), Radix Phytolaccae (Chinese name is Shanglu), Radix Polygoni cuspidati (Chinese name is Huzhang), Radix Polygoni multiflori (Chinese name is Heshouwu), Rhubarb (Chinese name is Dahuang), Semen Ricini (Chinese name is Bimazi), Salvia miltiorrhiza (Radix et Rhizoma Salviae miltiorrhizae, Chinese for Danshen), Scutellaria baicalensis (Radix Scutellariae, Chinese for Huangqin), Senecio scandens (Herba Senecioe scandensi, Chinese for Qianniguang), Scutellaria barbata (Herba Scutellariae Barbatae, Chinese for Banzhilian), Stephania tetrandra (Radix Stephaniae tetrandrae, Chinese for Hanfangji), Eugenia caryophyllata (Flos Syzygii aromatici, Chinese for Dingxiang), Taxillus chinensis (Herba Taxilli, Chinese for Sangjisheng), Tripterygium wilfordii (Radix et Rhizoma Tripterygii, Chinese for Leigongteng), Typha orientalis (Herba Typhae, Chinese for Xiangpu), Valeriana officinalis (Radix Valerian, Chinese for Xiecao), Xanthium sibiricum (Fructus Xanthii, Chinese for Cangerzi), Zhuanggu Guanjie Pills, Baichi Pills, Liushen Pills, Shiduqing Pills, Xuedu Pills, Zhuifeng Tougu Pills, Xiaokechuan Pills, Tianma Pills, Minor Bupleurum Decoction, Major Bupleurum Decoction, Gegen Decoction, Dahuang Mudanpi Decoction, Compound Qingdai Capsules, Vitiligo Capsules, Zhuanggu Shenjin Capsules, Di'ao Xinxuekang Capsules, Xiaoying Tablets, Xiaoke Tablets, Guxian Tablets, Zengshengping Tablets, Niuhuang Jiedu Tablets, Kunmingshanhaitang Tablets, Baifukang Granules, Compound Danshen Injection, Ganji Powder, Fangfeng Tongsheng Powder, Aconitum kusnezoffii (Radix Aconiti Kusnezoffii), Radix Aconiti penduli, Rhizoma Arisaematis, Flos Daturae, Rhizoma Typhonium, Radix Aconiti Lateralis, Rhizoma Pinellia, Semen Nut-vomitive, Herba Euphorbia, Radix euphorbiae lantu, Garcinia, Leptochloa, Radix Rhododendroni molli, Semen Hyoscyami, Croton, Venenum Bufonis, cantharidin, Huechys sanguinea, arsenic, arsenolite, arsenic stone, realgar, calomel, Hydrargyri oxydum Rubrum, mercury, aconitine, febrifugine B, reserpiline, vincristine, cardiac glycoside, cyanogenic glycoside, saponin, bulbifera, toxin fruit, Croton tiglium, Ricinus communis, abrinjatropha, Trichosanthes kirilowii, Scolopendra subspinipes, snake venom, Vipera russelli siamensis, Melia toosendan, Euphorbia pekinensis, Coriaria nepalensis Thunb. leaves, Artemisia absinthium L., galls, skin, Ilex purpurea Hassk., cinnabar, realgar, calomel, lead monoxide, alum, minium, Garcinia Garcinia, Illicium henryi, Hydnocarpus Hydnocarpus, Pinellia ternata Pinellia ternata, Daphne odora Thunb., momordica acid, Asarum Asarum, Rutaceae, Mentha haplocalyx Briq., Asarum forbesii Asarum forbesii, Moschus, Gramineae and any mixture or combination thereof. Compound 1 or a pharmaceutically acceptable salt thereof can be used to prevent and / or treat the liver disorder or disease in a subject exposed to an agent capable of inducing a liver disorder or disease. In some embodiments, the liver disorder or disease to be prevented and / or treated is a hepatotoxic disorder or disease. The liver disorder or disease can be the result of direct toxicity of the agent, an immune-mediated mechanism, or a combination of direct toxicity and immune-mediated mechanisms of the agent. In some embodiments, the immune-mediated mechanism is an inflammatory response. In certain embodiments, the hepatotoxic disorder or disease is selected from toxic hepatitis, toxin-induced hepatitis, drug-induced hepatitis, toxin-induced liver necrosis, drug-induced liver necrosis, toxin-induced liver fibrosis, drug-induced liver fibrosis, toxin-induced liver granuloma, drug-induced liver granuloma, toxic liver disease, toxin-induced liver disease, drug-induced liver disease, toxic liver disease with hepatitis, toxin-induced liver disease with hepatitis, drug-induced liver disease with hepatitis, toxin-induced liver injury, drug-induced liver injury, hepatogenic poisoning, toxic liver disease with cholestasis, or a combination thereof. In some embodiments, the liver disorder or disease is an acute or chronic liver disorder or disease. In certain embodiments, the liver disorder or disease is an acute disorder or disease. In other certain embodiments, the liver disorder or disease is a chronic disorder or disease. In certain embodiments, the liver disorder or disease is a liver disorder or disease caused by exposure to acetaminophen (also known as N-acetyl-p-aminophenol, APAP, paracetamol, and Tylenol®). Exposure to acetaminophen can lead to dose-related hepatocyte necrosis and / or acute liver failure. Acetaminophen overdose can be intentional or unintentional. The toxicity is characterized as "acute" or "ultra-acute", causing abdominal pain and nausea about 12 to 24 hours after overdose. The levels of transaminases such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) rapidly increase to elevated levels. As the overdose progresses, the subject may experience other severe symptoms such as hyperammonemia, lethargy, stupor, coma, lactic acidosis, cerebral edema, brainstem herniation, and vascular collapse. In patients with acute liver failure, other organs such as the kidneys may fail. Centrilobular hepatocyte necrosis is a prominent indicator of acetaminophen injury. Acetaminophen overdose is usually treated with N-acetylcysteine (NAC). In another specific embodiment, the liver disorder or disease is a liver disorder or disease caused by exposure to alcohol. Alcoholic liver disease typically progresses from alcoholic fatty liver (AFL, also known as steatosis) to alcoholic steatohepatitis (ASH) characterized by liver inflammation. Chronic ASH may ultimately lead to more severe liver disorders, including fibrosis, cirrhosis, necrosis (especially focal necrosis), and in some cases hepatocellular carcinoma (HCC). In addition, severe ASH (with or without cirrhosis) may lead to alcoholic hepatitis, which is an acute manifestation of ALD and is associated with liver failure and high mortality. In some embodiments, the liver disorder or disease associated with exposure to alcohol is non-alcoholic fatty liver disease, alcoholic liver disease, alcoholic fatty liver disease (steatosis), alcoholic steatohepatitis, liver inflammation, alcoholic hepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, or any combination thereof. In some embodiments, Compound 1 is administered to a subject to treat or prevent an alcohol-induced disorder or disease. In a specific embodiment, Compound 1 reduces the non-alcoholic fatty liver disease activity score (NAS) of the subject relative to an untreated subject. Since the non-alcoholic fatty liver disease (NAFLD) activity score ("NAS") method (which was originally developed to measure changes in NAFLD) can be used to score the characteristics of alcoholic liver disease ("ALD"), the NAS score can be used to determine the therapeutic or preventive efficacy of Compound 1 with respect to ALD. In another specific embodiment, Compound 1 effectively reduces the damage to the liver caused by excessive alcohol intake, as revealed by a reduction in Oil Red O liver staining of the subject relative to an untreated subject. In some embodiments, the subject has a pre-existing disorder or disease that, when exposed to an agent, increases the subject's risk of developing a liver disorder or disease. In some embodiments, the agent induces oxidative stress in the liver. In some embodiments, Compound 1 reduces oxidative stress in the liver of the subject relative to an untreated subject. In a specific embodiment, Compound 1 reduces the presence of oxidative stress biomarkers selected from CAT, SOD, NRF2, iNOS, or any combination thereof relative to an untreated subject. In some embodiments, the agent induces necrosis of the liver. In some embodiments, Compound 1 reduces necrosis of the liver of the subject relative to an untreated subject. In a specific embodiment, Compound 1 reduces the presence of necrosis biomarkers selected from BCL-2, BAX, or a combination thereof relative to an untreated subject. In another specific embodiment, the necrosis of the liver is centrilobular necrosis of the liver. In yet another specific embodiment, the necrosis of the liver is focal necrosis of the liver. In some embodiments, the agent induces liver inflammation. In some embodiments, Compound 1 reduces liver inflammation relative to untreated subjects. In certain embodiments, Compound 1 reduces the presence of inflammatory biomarkers selected from p38 MAPK, NF-κB p65, TNF-α, IL-1β, IL-6, and IL-10. In another specific embodiment, Compound 1 reduces the presence of inflammatory biomarkers selected from TNF-α, IL-1β, and IL-6. In some embodiments, the agent induces an elevation of the ALT (alanine transaminase) and AST (aspartate transaminase) biomarkers. In some embodiments, Compound 1 reduces the elevation of the ALT and AST biomarkers relative to untreated subjects. As used herein, the term "treating" or "treatment", which may be used interchangeably with the term "therapy", refers to a therapeutic intervention capable of achieving a cure, amelioration, remission, control, progression control, or progression prevention of a disease or disorder or symptoms associated with the disease or disorder. As understood herein, the term "prevention", which may be used interchangeably with the term "prophylaxis", refers to the use of a compound or composition to prevent the occurrence of a disease, disorder, or symptom, or to significantly reduce the likelihood of the occurrence of a disease, disorder, or symptom, as well as to prevent, for example, a further recurrence of a disease, disorder, or related symptom. The meaning of the term also includes preventing the progression of a disease, disorder, or related symptom after an initial improvement of the disease, disorder, or related symptom or after the initial elimination of the cause of the disease, disorder, or related symptom. It is also understood that any one or combination of the uses and treatment or prevention methods described herein includes administering a pharmacologically effective amount of Compound 1 to a subject in need thereof. A pharmacologically effective amount refers to an amount, dose, concentration, or strength of a compound or compound equivalent that is capable of or can produce or facilitate a desired pharmacological effect related to treatment and / or prevention. The term "pharmacologically effective amount" may also be used interchangeably with the term "therapeutically effective amount". As understood herein, the term "subject" may be used interchangeably with the term "patient". In a preferred embodiment, the subject is a human subject. In an optional embodiment, the subject may be other animals, such as other mammals. In an optional embodiment, the present invention may also be applied, for example, to domestic animals or other veterinary subjects, particularly mammals such as cats, dogs, primates, horses, cattle, and pigs. In one embodiment, Compound 1 or a pharmaceutically acceptable salt thereof can be repeatedly administered (e.g., more than once) to a subject during the course of its prescribed treatment. Thus, a dose of Compound 1 can be administered within the time period between successive doses of the agent. Optionally, more than one dose of Compound 1 can be administered within the time period between successive doses of the agent. As used herein, unless otherwise indicated by a time, time interval, or amount indication before or after, the term "dose" or "dosage" by itself refers to a single or unit dose of Compound 1 or a pharmaceutically acceptable salt thereof or an agent or medicament. For example, a "daily dose" or "dose per day" refers to the total amount of Compound 1 or an agent or medicament administered within a time period of one day (24 hours). If only one dose is administered once a day, the daily dose can include only one dose, but it can also be the total amount based on the sum of multiple unit doses administered within a day, e.g., if more than one unit dose is administered at two or more time intervals within a day. The interval between doses can be, for example, two doses administered approximately every 12 hours, or three doses administered approximately every 8 hours. Also as used herein, a dose of Compound 1 refers to a unit dose of Compound 1 or a pharmaceutically acceptable salt thereof, but it can also apply to a medicament or composition or dosage form containing the unit dose of Compound 1 or a pharmaceutically acceptable salt thereof. In another embodiment, Compound 1 or a pharmaceutically acceptable salt thereof is administered to a subject (preferably a human subject) at a dose of about 0.001 to 5 mg / kg or at a dose of about 0.001 to 10 mg / kg. Optionally, Compound 1 can be administered to a subject (preferably a human subject) at a dose of about 0.1 to 5 mg / kg or 0.1 to 10 mg / kg. The amount of the dose refers to a single dose. During the course of treatment, a single dose can be administered more than once. If any pharmaceutically acceptable salt of Compound 1 is described herein, the amount of the dose refers to the Compound 1 equivalent. In addition, a single dose of Compound 1 can be administered to a subject by administering a composition or medicament provided in a pharmaceutically acceptable dosage form and containing a certain dose of Compound 1. In some embodiments, Compound 1 or a pharmaceutically acceptable salt thereof is administered to a subject (preferably a human subject) within a few hours (in some cases within one hour) after exposure to an agent. In other embodiments, Compound 1 or a pharmaceutically acceptable salt thereof is administered to a subject (preferably a human subject) within a few weeks after exposure to an agent (in some cases within six to ten weeks after exposure), especially when the agent is alcohol and the subject has been drinking alcohol chronically. As used herein, the term "about" when associated with an attribute or value, such as a dosage amount, includes the exact attribute or precise value, as well as any attribute or value that is generally considered to fall within the normal or acceptable range of variability associated with the technical field and the method of measuring or determining the attribute or value. The term permits any variation that would, in conventional practice, permit the product being evaluated to be considered bioequivalent in a mammal to the claimed product at the same strength or dosage. The use of Compound 1 or a pharmaceutically acceptable salt thereof, and a method of treatment or prophylaxis, as described in any one of the embodiments herein, are also provided in the context of the present disclosure for the manufacture or preparation of a medicament or pharmaceutical composition adapted for and prescribed for said use or method of treatment or prophylaxis. The pharmaceutically acceptable salts of Compound 1 are salts that retain their biological properties and are non-toxic and compatible with pharmaceutical use. The salts of the present invention can be produced by the addition of an acid to Compound 1. The resulting acid addition salts include those formed with the following acids: acetic acid, 2,2-dichloroacetic acid, citric acid, lactic acid, mandelic acid, glycolic acid, adipic acid, alginic acid, arylsulfonic acids (e.g., benzenesulfonic acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonic acid, and p-toluenesulfonic acid), ascorbic acid (e.g., L-ascorbic acid), L-aspartic acid, benzoic acid, 4-acetamidobenzoic acid, butyric acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, mucic acid, gentisic acid, glucoheptonic acid, gluconic acid (e.g., D-gluconic acid), glucuronic acid (e.g., D-glucuronic acid), glutamic acid (e.g., L-glutamic acid), α-ketoglutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, hydroxyethanesulfonic acid, lactic acid (e.g., (+)-L-lactic acid and (±)-DL-lactic acid), lactobionic acid, maleic acid, malic acid (e.g., (-)-L-malic acid), (±)-DL-mandelic acid, metaphosphoric acid, methanesulfonic acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, propionic acid, L-pyroglutamic acid, salicylic acid, 4-aminosalicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, tannic acid, tartaric acid (e.g., (+)-L-tartaric acid), thiocyanic acid, undecylenic acid, and valeric acid. In particular, the acid addition salts include those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, metaphosphoric acid, nitric acid, and sulfuric acid; and those derived from organic acids such as tartaric acid, acetic acid, citric acid, malic acid, lactic acid, fumaric acid, benzoic acid, glycolic acid, gluconic acid, succinic acid, and arylsulfonic acids. Compound 1 or a pharmaceutically acceptable salt thereof can be administered enterally or parenterally to a subject. In one embodiment, Compound 1 or a composition or agent comprising said Compound 1 is suitable for parenteral administration or is administered parenterally, such as by intravenous injection, or by subcutaneous or intramuscular injection, or by intravenous or subcutaneous infusion. In an alternative embodiment, Compound 1 or a composition or agent comprising Compound 1 is suitable for enteral (e.g., oral) administration, or is administered enterally (e.g., orally) to a subject. The present invention may also relate to an agent or a pharmaceutical composition, said agent or pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof according to any one or combination of the embodiments described above and one or more pharmaceutically acceptable excipients. The agent or pharmaceutical composition comprising said Compound 1 can be formulated into a dosage form suitable for or adapted for injection or infusion by any of the above administration methods. Alternatively, for oral administration, the agent or pharmaceutical composition comprising Compound 1 can be provided in a dosage form suitable for or adapted for oral administration (such as but not limited to tablets, capsules, gel caps or films). The agent or pharmaceutical composition can be used according to any of the treatment or prevention methods or uses described herein. In one embodiment in which Compound 1 is formulated into a dosage form suitable for or adapted for injection or infusion, the formulation can be provided in the form of a clear solution, or as a lyophilized or freeze-dried powder, from which a clear solution can be obtained by reconstitution in a solvent or solution suitable for (i.e., formulated for) reconstitution. In one embodiment, the reconstitution solvent can comprise a solubilizer and / or a surfactant. In a specific embodiment, the reconstitution solution can comprise polysorbate (e.g., polysorbate 80 or Tween 80); further optionally, the solvent has a pH between 3.5 and 4.5, or a pH between 4.2 and 4.5. In another embodiment, the agent or pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof can further comprise polysorbate. In one embodiment, the composition is a clear aqueous solution having a pH between about 3.5 and about 4.5. In another embodiment, the solution has a pH between about 4.2 and about 4.5. In yet another embodiment, the composition comprising Compound 1 or its salt further comprises polysorbate and optionally one or more additional excipients, such as wherein the excipient is an acid (e.g., an organic acid) and / or one or more buffers. In one embodiment, the polysorbate (e.g., polyoxyethylene sorbitan monoester) is polysorbate 80 or Tween 80 (polyoxyethylene sorbitan monooleate). In one embodiment, the composition comprises or consists of: an effective amount of Compound 1 or its salt, polysorbate, acetic acid and acetate (e.g., sodium acetate). In another embodiment, Compound 1 is formulated with a suitable acid. For example, Compound 1 can be formulated with an acid selected from succinic acid, L - malic acid, or phosphoric acid. In yet another embodiment, a composition comprising Compound 1 can further comprise a solubilizer and / or a surfactant (such as polyethylene glycol (e.g., PEG 400) or polysorbate (e.g., Tween 80)). In a specific embodiment, a composition comprising Compound 1 can further comprise an acid (e.g., succinic acid, L - malic acid, phosphoric acid, or acetic acid) and a surfactant and / or a solubilizer (such as polyethylene glycol (e.g., PEG 400) or polysorbate (e.g., Tween 80)). In one embodiment, the composition can be suitable for or adapted for bolus injection and can be provided in the form of a clear aqueous solution having a pH between about 5.4 and about 5.6. Compositions suitable for injection or infusion are generally in the form of a solution, which means that the formulation components (including the active ingredient) must be completely dissolved (dissolved or solubilized). At the time of administration, or optionally, if the composition is stored as a solution, during storage, the formation or presence of a micellar phase or any other type of phase separation of any of the components or the active ingredient is not preferred. In one embodiment, a composition according to the present disclosure as described herein and comprising Compound 1 or a salt thereof is in the form of a clear solution. Preferably, the composition is in the form of a stable and clear solution, for example, stable for at least 1 hour or at least 15 hours at room temperature (or under refrigeration, such as at 0 °C). The stability of the solution can be determined, for example, by visual inspection (e.g., for phase separation or other visible changes) or alternatively based on turbidity detector measurements. Optionally, an agent or pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof can further comprise a medicament, i.e., Compound 1 can be co - formulated with another medicament as a single composition or dosage form. In another aspect, the present invention can also relate to a kit comprising a composition containing Compound 1 or a pharmaceutically acceptable salt thereof and optionally instructions for administering Compound 1 or a salt thereof for any of the methods or uses described herein. The following list of numbered items are examples included in the present disclosure: 1. Use of Compound 1 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention and / or treatment of a liver disorder or disease in a subject exposed to an agent capable of inducing the liver disorder or disease Compound 1. 2. The use according to item 1, wherein the liver disorder or disease is a hepatotoxic disorder or disease. 3. Use according to item 2, wherein the hepatotoxic disorder or disease is selected from toxic hepatitis, toxin-induced hepatitis, drug-induced hepatitis, toxin-induced liver necrosis, drug-induced liver necrosis, toxin-induced liver fibrosis, drug-induced liver fibrosis, toxin-induced liver granuloma, drug-induced liver granuloma, toxic liver disease, toxin-induced liver disease, drug-induced liver disease, toxic liver disease with hepatitis, toxin-induced liver disease with hepatitis, drug-induced liver disease with hepatitis, toxin-induced liver injury, drug-induced liver injury, hepatogenic poisoning, toxic liver disease with cholestasis or a combination thereof. 4. Use according to any one of items 1 to 3, wherein the liver disorder or disease is an acute or chronic liver disorder or disease. 5. Use according to any one of items 1 to 4, wherein the liver disorder or disease is an acute liver disorder or disease. 6. Use according to any one of items 1 to 4, wherein the liver disorder or disease is a chronic liver disorder or disease. 7. Use according to any one of items 1 to 6, wherein the liver disorder or disease is the result of the direct toxicity of the agent, an immune-mediated mechanism, or a combination of the direct toxicity and immune-mediated mechanism of the agent. 8. Use according to item 7, wherein the immune-mediated mechanism is an inflammatory reaction. 9. Use according to any one of items 1 to 8, wherein the agent is an alcohol. 10. Use according to item 9, wherein the alcohol is a beverage alcohol. 11. Use according to any one of items 9 to 10, wherein the alcohol is ethanol. 12. Use according to any one of items 9 to 11, wherein compound 1 reduces the non-alcoholic fatty liver disease activity score of the subject relative to an untreated subject. 13. Use according to any one of items 9 to 12, wherein compound 1 reduces Oil Red O liver staining in the subject relative to an untreated subject. 14. Use according to any one of items 9 to 13, wherein the liver disorder or disease is non-alcoholic fatty liver disease, alcoholic liver disease, alcoholic fatty liver disease (steatosis), alcoholic steatohepatitis, liver inflammation, alcoholic hepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, or any combination thereof. 15. Use according to any one of items 1 to 8, wherein the agent is a therapeutic agent. 16. The use according to item 15, wherein the therapeutic agent is selected from analgesics, antipyretics, anesthetics, non-steroidal anti-inflammatory drugs, antimicrobials, antibiotics, antifungals, antivirals, antiretrovirals, HIV therapies, hypoglycemic agents, hypolipidemic agents, herbal medicines, traditional Chinese medicines, anti-cancer drugs, anti-tuberculosis drugs, and cardiac drugs. 17. The use according to item 15 or 16, wherein the therapeutic agent is paracetamol. 18. The use according to any one of the preceding items, wherein the subject has a pre-existing condition or disease, and when exposed to the agent, the pre-existing condition or disease increases the risk of the subject developing a liver condition or disease. 19. The use according to any one of the preceding items, wherein the agent induces oxidative stress in the liver. 20. The use according to item 19, wherein compound 1 reduces the oxidative stress in the liver of the subject relative to an untreated subject. 21. The use according to item 20, wherein compound 1 reduces the presence of oxidative stress biomarkers selected from CAT, SOD, NRF2, iNOS, or any combination thereof in the liver of the subject relative to an untreated subject. 22. The use according to any one of the preceding items, wherein the agent induces necrosis of the liver. 23. The use according to item 22, wherein compound 1 reduces the necrosis of the liver of the subject relative to an untreated subject. 24. The use according to item 23, wherein compound 1 reduces the presence of necrosis biomarkers selected from BCL-2, BAX, or a combination thereof in the liver of the subject relative to an untreated subject. 25. The use according to any one of items 22 to 24, wherein the necrosis of the liver is centrilobular necrosis of the liver. 26. The use according to any one of items 22 to 25, wherein the necrosis of the liver is focal necrosis of the liver. 27. The use according to any one of the preceding items, wherein the agent induces inflammation of the liver. 28. The use according to item 27, wherein compound 1 reduces the inflammation of the liver of the subject relative to an untreated subject. 29. The use according to item 28, wherein compound 1 reduces the presence of inflammation biomarkers selected from p38 MAPK, NF-κB p65, TNF-α, IL-1β, IL-6, and IL-10. 30. The use according to item 29, wherein Compound 1 reduces the presence of inflammatory biomarkers selected from TNF-α, IL-1β, and IL-6. 31. The use according to any one of the preceding items, wherein the agent induces an increase in ALT and AST biomarkers. 32. The use according to item 31, wherein Compound 1 reduces the increase in ALT and AST biomarkers relative to untreated subjects. 33. The use according to any one of the preceding items, wherein Compound 1 is administered at a dose of about 0.001 to about 10 mg / kg, about 0.1 to about 10 mg / kg, or about 5 mg / kg to about 10 mg / kg. 34. The use according to any one of the preceding items, wherein the subject is a human subject. 35. The use according to any one of the preceding items, wherein the agent is formulated for administration by injection or infusion, preferably by subcutaneous, intramuscular, or intravenous injection, or by intravenous or subcutaneous infusion. 36. The use according to any one of the preceding items, wherein the agent is formulated for administration by injection or infusion, preferably by intravenous injection or infusion. 37. Compound 1 or a pharmaceutically acceptable salt thereof, Compound 1 for use in the prevention and / or treatment of said liver disorder or disease in a subject exposed to an agent capable of inducing a liver disorder or disease. 38. The compound for use in said use according to item 37, wherein the liver disorder or disease is a hepatotoxic disorder or disease. 39. The compound for use in said use according to item 38, wherein the hepatotoxic disorder or disease is selected from toxic hepatitis, toxin-induced hepatitis, drug-induced hepatitis, toxin-induced liver necrosis, drug-induced liver necrosis, toxin-induced liver fibrosis, drug-induced liver fibrosis, toxin-induced liver granuloma, drug-induced liver granuloma, toxic liver disease, toxin-induced liver disease, drug-induced liver disease, toxic liver disease with hepatitis, toxin-induced liver disease with hepatitis, drug-induced liver disease with hepatitis, toxin-induced liver injury, drug-induced liver injury, hepatogenic poisoning, toxic liver disease with cholestasis, or a combination thereof. 40. The compound for use in said use according to any one of items 37 to 39, wherein the liver disorder or disease is an acute or chronic liver disorder or disease. 41. The compound for use in said use according to any one of items 37 to 40, wherein the liver disorder or disease is an acute liver disorder or disease. 42. The compound for the use according to any one of items 37 to 40, wherein the liver disorder or disease is a chronic liver disorder or disease. 43. The compound for the use according to any one of items 37 to 42, wherein the liver disorder or disease is the result of the direct toxicity of the agent, an immune-mediated mechanism, or a combination of the direct toxicity and immune-mediated mechanism of the agent. 44. The compound for the use according to item 43, wherein the immune-mediated mechanism is an inflammatory response. 45. The compound for the use according to any one of items 37 to 44, wherein the agent is an alcohol. 46. The compound for the use according to item 45, wherein the alcohol is a beverage alcohol. 47. The compound for the use according to any one of items 45 to 46, wherein the alcohol is ethanol. 48. The compound for the use according to any one of items 45 to 47, wherein, relative to an untreated subject, Compound 1 reduces the non-alcoholic fatty liver disease activity score of the subject. 49. The compound for the use according to any one of items 45 to 48, wherein, relative to an untreated subject, Compound 1 reduces the Oil Red O liver staining of the subject. 50. The compound for the use according to any one of items 45 to 49, wherein the liver disorder or disease is non-alcoholic fatty liver disease, alcoholic liver disease, alcoholic fatty liver disease (steatosis), alcoholic steatohepatitis, liver inflammation, alcoholic hepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, or any combination thereof. 51. The compound for the use according to any one of items 37 to 44, wherein the agent is a therapeutic agent. 52. The compound for the use according to item 51, wherein the therapeutic agent is selected from analgesics, antipyretics, anesthetics, non-steroidal anti-inflammatory drugs, antimicrobials, antibiotics, antifungals, antivirals, antiretrovirals, HIV therapies, hypoglycemic agents, hypolipidemic agents, herbal medicines, traditional Chinese medicines, anticancer drugs, antituberculosis drugs, and cardiac drugs. 53. The compound for the use according to item 51 or 52, wherein the therapeutic agent is acetaminophen. 54. The compound for the use according to any one of the preceding items, wherein the subject has a pre-existing disorder or disease that, when exposed to the agent, increases the risk of the subject developing a liver disorder or disease. 55. A compound for the use according to any one of the preceding items, wherein the agent induces oxidative stress in the liver. 56. A compound for the use according to item 55, wherein compound 1 reduces oxidative stress in the liver of the subject relative to an untreated subject. 57. A compound for the use according to item 56, wherein compound 1 reduces the presence of oxidative stress biomarkers selected from CAT, SOD, NRF2, iNOS, or any combination thereof in the liver of the subject relative to an untreated subject. 58. A compound for the use according to any one of the preceding items, wherein the agent induces necrosis of the liver. 59. A compound for the use according to item 58, wherein compound 1 reduces necrosis of the liver of the subject relative to an untreated subject. 60. A compound for the use according to item 59, wherein compound 1 reduces the presence of necrosis biomarkers selected from BCL-2, BAX, or a combination thereof in the liver of the subject relative to an untreated subject. 61. A compound for the use according to any one of items 58 to 60, wherein the necrosis of the liver is centrilobular necrosis of the liver. 62. A compound for the use according to any one of items 58 to 61, wherein the necrosis of the liver is focal necrosis of the liver. 63. A compound for the use according to any one of the preceding items, wherein the agent induces inflammation of the liver. 64. A compound for the use according to item 63, wherein compound 1 reduces inflammation of the liver of the subject relative to an untreated subject. 65. A compound for the use according to item 64, wherein compound 1 reduces the presence of inflammation biomarkers selected from p38 MAPK, NF-κB p65, TNF-α, IL-1β, IL-6, and IL-10. 66. A compound for the use according to item 65, wherein compound 1 reduces the presence of inflammation biomarkers selected from TNF-α, IL-1β, and IL-6. 67. A compound for the use according to any one of the preceding items, wherein the agent induces an increase in ALT and AST biomarkers. 68. A compound for the use according to item 67, wherein compound 1 reduces the increase in ALT and AST biomarkers relative to an untreated subject. 69. The compound for the use according to any one of the preceding items, wherein Compound 1 is administered at a dose of about 0.001 to about 10 mg / kg, about 0.1 to about 10 mg / kg, or about 5 mg / kg to about 10 mg / kg. 70. The compound for the use according to any one of the preceding items, wherein the subject is a human subject. 71. The compound for the use according to any one of the preceding items, wherein the compound is formulated for administration by injection or infusion, preferably by subcutaneous, intramuscular or intravenous injection, or by intravenous or subcutaneous infusion. 72. The compound for the use according to any one of the preceding items, wherein the compound is formulated for administration by injection or infusion, preferably by intravenous injection or infusion. 73. A method for preventing and / or treating the liver disorder or disease in a subject exposed to an agent capable of inducing a liver disorder or disease, the method comprising administering Compound 1 or a pharmaceutically acceptable salt thereof Compound 1. 74. The method according to item 73, wherein the liver disorder or disease is a hepatotoxic disorder or disease. 75. The method according to item 74, wherein the hepatotoxic disorder or disease is selected from toxic hepatitis, toxin-induced hepatitis, drug-induced hepatitis, toxin-induced liver necrosis, drug-induced liver necrosis, toxin-induced liver fibrosis, drug-induced liver fibrosis, toxin-induced liver granuloma, drug-induced liver granuloma, toxic liver disease, toxin-induced liver disease, drug-induced liver disease, toxic liver disease with hepatitis, toxin-induced liver disease with hepatitis, drug-induced liver disease with hepatitis, toxin-induced liver injury, drug-induced liver injury, hepatogenic poisoning, toxic liver disease with cholestasis, or a combination thereof. 76. The method according to any one of items 73 to 75, wherein the liver disorder or disease is an acute or chronic liver disorder or disease. 77. The method according to any one of items 73 to 76, wherein the liver disorder or disease is an acute liver disorder or disease. 78. The method according to any one of items 73 to 76, wherein the liver disorder or disease is a chronic liver disorder or disease. 79. The method according to any one of items 73 to 78, wherein the liver disorder or disease is the result of the direct toxicity of the agent, an immune-mediated mechanism, or a combination of the direct toxicity and immune-mediated mechanism of the agent. 80. The method according to item 79, wherein the immune-mediated mechanism is an inflammatory reaction. 81. The method according to any one of items 73 to 80, wherein the agent is an alcohol. 82. The method according to item 81, wherein the alcohol is a beverage alcohol. 83. The method according to any one of items 81 to 82, wherein the alcohol is ethanol. 84. The method according to any one of items 81 to 83, wherein Compound 1 reduces the non-alcoholic fatty liver disease activity score of the subject relative to an untreated subject. 85. The method according to any one of items 81 to 84, wherein Compound 1 reduces Oil Red O liver staining in the subject relative to an untreated subject. 86. The method according to any one of items 81 to 85, wherein the liver disorder or disease is non-alcoholic fatty liver disease, alcoholic liver disease, alcoholic fatty liver disease (steatosis), alcoholic steatohepatitis, liver inflammation, alcoholic hepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, or any combination thereof. 87. The method according to any one of items 73 to 80, wherein the agent is a therapeutic agent. 88. The method according to item 87, wherein the therapeutic agent is selected from analgesics, antipyretics, anesthetics, non-steroidal anti-inflammatory drugs, antimicrobials, antibiotics, antifungals, antivirals, antiretrovirals, HIV therapies, hypoglycemic agents, hypolipidemic agents, herbal medicines, traditional Chinese medicines, anticancer drugs, antituberculosis drugs, and cardiac drugs. 89. The method according to item 87 or 88, wherein the therapeutic agent is paracetamol. 90. The method according to any one of the preceding items, wherein the subject has a pre-existing disorder or disease that, when exposed to the agent, increases the subject's risk of developing a liver disorder or disease. 91. The method according to any one of the preceding items, wherein the agent induces oxidative stress in the liver. 92. The method according to item 91, wherein Compound 1 reduces oxidative stress in the liver of the subject relative to an untreated subject. 93. The method according to item 92, wherein Compound 1 reduces the presence of oxidative stress biomarkers selected from CAT, SOD, NRF2, iNOS, or any combination thereof in the subject relative to an untreated subject. 94. The method according to any one of the preceding items, wherein the agent induces necrosis of the liver. 95. The method according to item 94, wherein, relative to an untreated subject, compound 1 reduces necrosis of the liver of the subject. 96. The method according to item 95, wherein, relative to an untreated subject, compound 1 reduces the presence of necrosis biomarkers selected from BCL-2, BAX, or a combination thereof. 97. The method according to any one of items 94 to 96, wherein the necrosis of the liver is centrilobular necrosis of the liver. 98. The method according to any one of items 94 to 97, wherein the necrosis of the liver is focal necrosis of the liver. 99. The method according to any one of the preceding items, wherein the agent induces inflammation of the liver. 100. The method according to item 99, wherein, relative to an untreated subject, compound 1 reduces the inflammation of the liver of the subject. 101. The method according to item 100, wherein compound 1 reduces the presence of inflammation biomarkers selected from p38 MAPK, NF-κB p65, TNF-α, IL-1β, IL-6, and IL-10. 102. The method according to item 101, wherein compound 1 reduces the presence of inflammation biomarkers selected from TNF-α, IL-1β, and IL-6. 103. The method according to any one of the preceding items, wherein the agent induces an increase in ALT and AST biomarkers. 104. The method according to item 103, wherein, relative to an untreated subject, compound 1 reduces the increase in ALT and AST biomarkers. 105. The method according to any one of the preceding items, wherein compound 1 is administered at a dose of about 0.001 to about 10 mg / kg, about 0.1 to about 10 mg / kg, or about 5 mg / kg to about 10 mg / kg. 106. The method according to any one of the preceding items, wherein the subject is a human subject. 107. The method according to any one of the preceding items, wherein the compound or a pharmaceutically acceptable salt thereof is formulated for administration by injection or infusion, preferably by subcutaneous, intramuscular, or intravenous injection, or by intravenous or subcutaneous infusion. 108. The method according to any one of the preceding items, wherein the compound or a pharmaceutically acceptable salt thereof is formulated for administration by injection or infusion, preferably by intravenous injection or infusion. The following examples are used to illustrate the present invention. However, it should not be construed as limiting the scope of the present invention. Examples Example 1 - Acetaminophen-induced mouse liver injury model C57BL / 6J wild-type mice were purchased from the Guangdong Medical Animal Centre (Guangzhou, China). Male mice (n = 8, 8 weeks old) were randomly assigned to different treatment groups. Mice were acclimatized to their environment for 1 week before the experiment. Before acetaminophen (APAP) administration, animals were fasted overnight but allowed water. APAP (Sigma Aldrich) was dissolved in warm phosphate-buffered saline (PBS; 55 ºC), cooled to 37 ºC before injection, and administered intraperitoneally at a dose of 300 mg / kg after 15 hours of starvation. For each experiment, compound 1 was freshly prepared at 20 mg / ml in sterile 0.9% saline. For each experiment, N-acetylcysteine (NAC, Sigma Aldrich) was freshly prepared at 20 mg / ml in 0.9% saline. At 1 hour after APAP administration, PBS (control group), compound 1 (10 mg / kg, 5 mg / kg, 2.5 mg / kg, 1 mg / kg) or NAC (150 mg / kg) was injected intravenously into the tail vein of the mice. In the control group, mice were injected with the phosphate-buffered saline vehicle (labeled "control (Ctrl)" in the figure), and in the vigilance group, mice were injected with compound 1 (labeled "v-compound 1-10 mg" in the figure). In both the control group and the vigilance group, APAP was not administered. There were 8 mice in each group. Mice were sacrificed at 6 and 24 hours after APAP administration. Blood samples and livers were harvested for serum ALT (alanine transaminase) and AST (aspartate transaminase) as well as histology. Serum ALT and AST in the serum samples were detected using an alanine transaminase assay kit (S03030) and an aspartate transaminase assay kit (S03040) and an automatic clinical chemistry analyzer (Chemray 800) (from Rayto). All liver sections were stained with hematoxylin and eosin (H&E) stain. The necrotic area was measured and expressed as the percentage of necrotic tissue in the entire liver section area. All animal procedures were approved by the Laboratory Animals Ethics Committee of Jinan University (Guangzhou, China). Results Six hours after APAP administration, compound 1 at 5 mg / kg and 10 mg / kg levels showed hepatoprotection, as shown in Figure 1. Compared to APAP administration alone, the 5 mg / kg and 10 mg / kg compound 1 levels showed reduced necrotic area. Similarly, compared to APAP administration alone, six hours after APAP administration, in the presence of compound 1 at 5 mg / kg and 10 mg / kg, the ALT and AST biomarker levels were reduced, as shown in Figure 2. In addition, ELISA results six hours after APAP administration showed a reduction in inflammatory biomarkers (TNF-α, IL-1β, and IL-6) at 5 mg / kg and 10 mg / kg compound 1 levels, as shown in Figure 3. Similar to the results six hours after APAP administration, 24 hours after APAP administration, compound 1 at 5 mg / kg and 10 mg / kg levels showed hepatoprotection, as shown in Figure 4. Compared to APAP administration alone, the 5 mg / kg and 10 mg / kg compound 1 levels showed reduced necrotic area. Similarly, compared to APAP administration alone, 24 hours after APAP administration, in the presence of compound 1 at 5 mg / kg and 10 mg / kg, the ALT and AST biomarker levels were reduced, as shown in Figure 5. Finally, ELISA results 24 hours after APAP administration showed a reduction in inflammatory biomarkers (TNF-α, IL-1β, and IL-6) at 5 mg / kg and 10 mg / kg compound 1 levels, as shown in Figure 6. Example 2 - Alcohol-Induced Liver Injury in Mice C57BL / 6J wild-type mice were purchased from the Guangdong Provincial Medical Animal Center (Guangzhou, China). Male mice (n = 7, 8 weeks old) were randomly assigned to different treatment groups. Initially, the mice were fed ad libitum a controlled Lieber-DeCarli diet (TP4030C, Trophic Animal Feed High-Tech Co., Ltd, China) for 5 days to acclimatize them to the liquid diet. Subsequently, the ethanol-fed group was allowed to freely consume an ethanol diet (TP4030D, Trophic) containing 5% (vol / vol) ethanol for 8 weeks. Long-term (8 weeks) plus multiple binge drinking (E8w + nB): The mice were fed the ethanol Lieber-DeCarli diet as described above for 8 weeks and were treated twice a week during the 8-week feeding period by intragastric administration (5 g / kg ethanol). The mice were euthanized 9 h after intragastric administration. The control mice were pair-fed an isocaloric control liquid diet for 8 weeks (P8w), then intragastrically administered an isocaloric liquid dextrin-maltose (control) without exposure to alcohol. There were 7 mice in each group. For each experiment, compound 1 was freshly prepared at 20 mg / ml in sterile 0.9% saline and administered intraperitoneally daily (10 mg / kg) for the last two weeks. Since mice do not eat after binge drinking, in order to compare with these groups, E8w mice and pair-fed mice were starved at 7:00 am and sacrificed after 9 hours. Blood samples and livers were harvested for serum ALT and AST as well as histology. All liver sections were stained by H&E and Oil Red O staining. The characteristics of alcoholic liver disease (「ALD」) were scored according to the non-alcoholic fatty liver disease (「NAFLD」) activity score (「NAS」), which was originally developed to measure changes in NAFLD during treatment trials, but is also applicable to ALD. The ALD score for each group was calculated according to the standard procedure. Oil Red O is a fat-soluble azo dye used to stain fats, especially neutral triglycerides, lipids and lipoproteins in tissues and cells. When tissue sections are placed in the dye solution, the dye leaves the dye solution and dissolves in the lipids (such as lipid droplets) in the tissue, staining the lipid droplets in the tissue red. The quantification of Oil Red O 「a.v.」 means subjective quantity, that is, 「arbitrary value」. ImageJ, an image quantification software, was used to select the Oil Red-stained areas in liver sections and quantify the areas of lipid droplets in the sections. Results Compared with untreated E8w + nB mice, compound 1 at a daily dose of 10 mg / kg for the last two weeks (weeks 7 and 8) reduced the ALD score from approximately 4 to approximately 2, as shown in Figure 7. The ALD score was calculated from the weighted sum of hepatocyte steatosis (0 to 3), lobular inflammation (0 to 3) and hepatocyte ballooning (0 to 2). ALD ≥ 5 can be diagnosed as non-alcoholic steatohepatitis (「NASH」), ALD < 3 can rule out NASH, and ALD (3 to 4) indicates that NASH is possible. As shown by the reduction in Oil Red O liver staining, compound 1 also reduced liver lipid accumulation, as shown in Figure 8. None Figure 1 depicts the effect of compound 1 administration on the necrotic area (%) of the liver 6 h after acetaminophen (APAP) administration, as described in Example 1. Plotted from left to right on the x-axis are: control group (no APAP administered, black circles); alert group (no APAP administered, 10 mg / kg compound 1 administered, black squares); APAP group (APAP administered, black triangles); compound 1-1 mg group (APAP administered, 1 mg / kg compound 1 administered, inverted black triangles); compound 1-2.5 mg group (APAP administered, 2.5 mg / kg compound 1 administered, open circles); compound 1-5 mg group (APAP administered, 5 mg / kg compound 1 administered, open squares); compound 1-10 mg group (APAP administered, 10 mg / kg compound 1 administered, open triangles); and positive control group (APAP administered, 150 mg / kg N-acetylcysteine "NAC" administered, inverted open triangles). At 6 h after APAP administration, 5 mg / kg and 10 mg / kg compound 1 levels showed hepatoprotection. Figure 2 depicts the effect of compound 1 administration on the serum ALT (alanine transaminase) and AST (aspartate transaminase) biomarker levels of the liver 6 h after acetaminophen (APAP) administration, as described in Example 1. Plotted from left to right on the x-axis are: control group (no APAP administered, black circles); alert group (no APAP administered, 10 mg / kg compound 1 administered, black squares); APAP group (APAP administered, black triangles); compound 1-1 mg group (APAP administered, 1 mg / kg compound 1 administered, inverted black triangles); compound 1-2.5 mg group (APAP administered, 2.5 mg / kg compound 1 administered, open circles); compound 1-5 mg group (APAP administered, 5 mg / kg compound 1 administered, open squares); compound 1-10 mg group (APAP administered, 10 mg / kg compound 1 administered, open triangles); and positive control group (APAP administered, 150 mg / kg N-acetylcysteine "NAC" administered, inverted open triangles). *** refers to P in the range of 0 to 0.001, based on one-way ANOVA; Tukey's multiple comparison test. At 6 h after APAP administration, all compound 1 levels showed decreased ALT and AST biomarker levels. Figure 3 depicts the effect of compound 1 administration on the TNF-α (tumor necrosis factor α), IL-1β (interleukin-1β), and IL-6 (interleukin-6) inflammatory biomarker levels of the liver 6 h after acetaminophen (APAP) administration, as described in Example 1.Plotted from left to right on the x-axis are: control group (not administered APAP, black circles); pre-alert group (not administered APAP, administered 10 mg / kg of Compound 1, black squares); APAP group (administered APAP, black triangles); Compound 1-1 mg group (administered APAP, administered 1 mg / kg of Compound 1, inverted black triangles); Compound 1-2.5 mg group (administered APAP, administered 2.5 mg / kg of Compound 1, open circles); Compound 1-5 mg group (administered APAP, administered 5 mg / kg of Compound 1, open squares); Compound 1-10 mg group (administered APAP, administered 10 mg / kg of Compound 1, open triangles); and positive control group (administered APAP, administered 150 mg / kg of N-acetylcysteine "NAC", inverted open triangles). * indicates P in the range of 0.01 to 0.05, ** indicates P in the range of 0.001 to 0.01, and *** indicates P in the range of 0 to 0.001, based on one-way ANOVA; Tukey's multiple comparison test. At 6 hours after APAP administration, 2.5 mg / kg, 5 mg / kg, and 10 mg / kg of Compound 1 levels showed decreased levels of TNF-α, IL-1β, and / or IL-6 inflammatory biomarkers. Figure 4 depicts the effect of Compound 1 administration on the necrotic area (%) of the liver at 24 h after acetaminophen (APAP) administration, as described in Example 1. Plotted from left to right on the x-axis are: control group (not administered APAP, black circles); pre-alert group (not administered APAP, administered 10 mg / kg of Compound 1, black squares); APAP group (administered APAP, black triangles); Compound 1-1 mg group (administered APAP, administered 1 mg / kg of Compound 1, inverted black triangles); Compound 1-2.5 mg group (administered APAP, administered 2.5 mg / kg of Compound 1, open circles); Compound 1-5 mg group (administered APAP, administered 5 mg / kg of Compound 1, open squares); Compound 1-10 mg group (administered APAP, administered 10 mg / kg of Compound 1, open triangles); and positive control group (administered APAP, administered 150 mg / kg of N-acetylcysteine "NAC", inverted open triangles). ** indicates P in the range of 0.001 to 0.01, based on one-way ANOVA; Tukey's multiple comparison test. At 24 hours after APAP administration, 5 mg / kg and 10 mg / kg of Compound 1 levels showed hepatoprotection. Figure 5 depicts the effect of Compound 1 administration on the serum ALT (alanine transaminase) and AST (aspartate transaminase) biomarker levels of the liver at 24 h after acetaminophen (APAP) administration, as described in Example 1.Plotted from left to right on the x-axis are: control group (not administered APAP, black circles); pre-alert group (not administered APAP, administered 10 mg / kg of Compound 1, black squares); APAP group (administered APAP, black triangles); Compound 1-1 mg group (administered APAP, administered 1 mg / kg of Compound 1, inverted black triangles); Compound 1-2.5 mg group (administered APAP, administered 2.5 mg / kg of Compound 1, open circles); Compound 1-5 mg group (administered APAP, administered 5 mg / kg of Compound 1, open squares); Compound 1-10 mg group (administered APAP, administered 10 mg / kg of Compound 1, open triangles); and positive control group (administered APAP, administered 150 mg / kg of N-acetylcysteine "NAC", inverted open triangles). * indicates P in the range of 0.01 to 0.05, ** indicates P in the range of 0.001 to 0.01, and *** indicates P in the range of 0 to 0.001, based on one-way ANOVA; Tukey's multiple comparison test. At 24 hours after APAP administration, all Compound 1 levels showed decreased ALT and AST biomarker levels. Figure 6 depicts the effect of Compound 1 administration on the hepatic TNF-α, IL-1β, and IL-6 inflammatory biomarker levels at 24 h after acetaminophen (APAP) administration, as described in Example 1. Plotted from left to right on the x-axis are: control group (not administered APAP, black circles); pre-alert group (not administered APAP, administered 10 mg / kg of Compound 1, black squares); APAP group (administered APAP, black triangles); Compound 1-1 mg group (administered APAP, administered 1 mg / kg of Compound 1, inverted black triangles); Compound 1-2.5 mg group (administered APAP, administered 2.5 mg / kg of Compound 1, open circles); Compound 1-5 mg group (administered APAP, administered 5 mg / kg of Compound 1, open squares); Compound 1-10 mg group (administered APAP, administered 10 mg / kg of Compound 1, open triangles); and positive control group (administered APAP, administered 150 mg / kg of N-acetylcysteine "NAC", inverted open triangles). * indicates P in the range of 0.01 to 0.05, ** indicates P in the range of 0.001 to 0.01, and *** indicates P in the range of 0 to 0.001, based on one-way ANOVA; Tukey's multiple comparison test. At 24 hours after APAP administration, all Compound 1 levels showed decreased TNF-α, IL-1β, and / or IL-6 inflammatory biomarker levels. Figure 7 depicts the effect of Compound 1 on alcoholic liver disease ("ALD"), as described in Example 2.The characteristics of ALD were scored according to the Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (「NAS」), which was originally developed to measure changes in NAFLD during treatment trials, but is also applicable to Alcoholic Liver Disease (「ALD」). Plotted from left to right on the x-axis are: the control group (not administered alcohol, black squares), the ALD group (administered alcohol for 8 weeks plus binge, black triangles), and the compound 1-w7 group (administered alcohol for 8 weeks plus binge, administered 10 mg / kg of compound 1 at week 7, inverted black triangles). Treatment with 10 mg / kg of compound 1 after 7 weeks reduced the ALD score compared to the untreated ALD group. Figure 8 depicts the effect of compound 1 on Alcoholic Liver Disease (「ALD」) using Oil Red O staining, as described in Example 2. Plotted on the y-axis is the quantification of Oil Red O (a.v.) (a.v., 「arbitrary value」, see Example 2). Plotted from left to right on the x-axis are: the control group of pair-fed mice (not administered alcohol, black circles), the ALD group (administered alcohol for 8 weeks plus binge, black squares), and the compound 1-w7 group (administered alcohol for 8 weeks plus binge, administered 10 mg / kg of compound 1 at week 7, black triangles). *** refers to P in the range of 0 to 0.001, based on one-way ANOVA; Tukey's multiple comparison test. Treatment with 10 mg / kg of compound 1 after 7 weeks reduced hepatic lipid accumulation compared to the untreated ALD group. Figure 9 depicts the effect of compound 1 administration on the serum ALT (alanine transaminase) and AST (aspartate transaminase) biomarker levels in the liver in an Alcoholic Fatty Liver Disease (「ALD」) model, as described in Example 2. Plotted from left to right on the x-axis are: the control group (not administered alcohol, black circles), the ALD group (administered alcohol for 8 weeks plus binge, black squares), and the compound 1-w7 group (administered alcohol for 8 weeks plus binge, administered 10 mg / kg of compound 1 at week 7, black triangles). *** refers to P in the range of 0 to 0.001, based on one-way ANOVA; Tukey's multiple comparison test. Treatment with 10 mg / kg of compound 1 after 7 weeks reduced the ALT and AST levels compared to untreated ALD. None.

Claims

1. Use of a compound 1 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention and / or treatment of a subject exposed to an agent capable of inducing a liver condition or disease, wherein the agent is an alcohol or acetaminophen.

2. The use as described in claim 1, wherein the liver condition or disease is a hepatotoxic condition or disease.

3. The use as described in claim 2, wherein the hepatotoxic condition or disease is selected from toxin-induced hepatitis, drug-induced hepatitis, toxin-induced liver necrosis, drug-induced liver necrosis, toxin-induced liver fibrosis, drug-induced liver fibrosis, toxin-induced hepatic granuloma, drug-induced hepatic granuloma, toxin-induced liver injury, drug-induced liver injury, hepatogenic poisoning, cholestasis, or a combination thereof.

4. The use as claimed in any one of claims 1 to 3, wherein the liver condition or disease is an acute or chronic liver condition or disease.

5. The use as described in claim 4, wherein the liver condition or disease is an acute liver condition or disease.

6. The use as described in claim 4, wherein the liver condition or disease is a chronic liver condition or disease.

7. The use as claimed in claim 1, wherein the liver condition or disease is the result of direct toxicity of the agent, an immune-mediated mechanism, or a combination of direct toxicity of the agent and an immune-mediated mechanism.

8. The use as described in claim 7, wherein the immune-mediated mechanism is an inflammatory response.

9. The use as claimed in claim 1, wherein, relative to an untreated subject, compound 1 reduces the subject's non-alcoholic fatty liver disease activity score.

10. The use as claimed in claim 1, wherein compound 1 reduces Oil Red O liver staining in said subject relative to untreated subject.

11. The use as described in claim 1, wherein the agent is a therapeutic agent.

12. The use as described in claim 11, wherein the therapeutic agent is selected from analgesics, antipyretics, anesthetics, nonsteroidal anti-inflammatory drugs, antimicrobials, antibiotics, antifungals, antivirals, antiretroviral drugs, HIV therapy, hypoglycemic agents, lipid-lowering agents, herbal medicines, traditional Chinese medicines, anticancer drugs, antituberculosis drugs, and cardiac drugs.

13. The use as claimed in claim 1, wherein the subject has a pre-existing condition or disease that, upon exposure to the agent, increases the risk of the subject developing a liver condition or disease.

14. The use as claimed in claim 1, wherein the agent induces oxidative stress in the liver.

15. The use as claimed in claim 14, wherein compound 1 reduces oxidative stress in the liver of the subject relative to an untreated subject.

16. The use as claimed in claim 15, wherein, relative to an untreated subject, compound 1 reduces the presence of oxidative stress biomarkers selected from CAT, SOD, NRF2, iNOS, or any combination thereof.

17. The use as claimed in claim 1, wherein the agent induces liver necrosis.

18. The use as described in claim 17, wherein compound 1 reduces liver necrosis in the subject relative to an untreated subject.

19. The use as claimed in claim 18, wherein, relative to an untreated subject, compound 1 reduces the presence of necrotic biomarkers selected from BCL-2, BAX, or combinations thereof.

20. The use as described in claim 17, wherein the necrosis of the liver is the necrosis of the central lobules of the liver.

21. The use as described in claim 17, wherein the necrosis of the liver is focal necrosis of the liver.

22. The use as claimed in claim 1, wherein the agent induces inflammation of the liver.

23. The use as described in claim 22, wherein compound 1 reduces inflammation of the liver of the subject relative to an untreated subject.

24. The use as claimed in claim 23, wherein compound 1 reduces the presence of inflammatory biomarkers selected from p38 MAPK, NF-κB p65, TNF-α, IL-1β, IL-6 and IL-10.

25. The use as claimed in claim 24, wherein compound 1 reduces the presence of inflammatory biomarkers selected from TNF-α, IL-1β and IL-6.

26. The use as claimed in claim 1, wherein the agent induces an increase in ALT and AST biomarkers.

27. The use as described in claim 26, wherein compound 1 reduces the elevation of ALT and AST biomarkers relative to untreated subjects.

28. The use as claimed in claim 1, wherein compound 1 is administered at a dose of 0.001 to 10 mg / kg, 0.1 to 10 mg / kg or 5 mg / kg to 10 mg / kg.

29. The use as described in claim 1, wherein the subject is a human subject.

30. The use as claimed in claim 1, wherein the agent is formulated for administration by injection or infusion.

31. The use as claimed in claim 30, wherein the agent is formulated for administration by subcutaneous, intramuscular or intravenous injection, or by intravenous or subcutaneous infusion.

32. The use as claimed in claim 31, wherein the agent is formulated for administration by intravenous injection or infusion.

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