STAT3 inhibitors for use in the treatment of cancer

Abstract

Provided herein, in some embodiments, are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a STAT3 inhibitor.

Description

STAT3 INHIBITORS FOR USE IN THE TREATMENT OF CANCERCROSS-REFERENCE

[0001] This application claims priority to U.S. Provisional Application Number 63 / 559,468 filed February 29, 2024, which is incorporated herein by reference in its entirety.SUMMARY

[0002] Disclosed herein, in some embodiments, are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0003] In some embodiments, the compound of Formula (I) is N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, N-(3, 1 '-Dihydroxy-[l,2']binaphthalenyl- 4 '-yl)-4-m ethoxy -benzenesulfonamide, N-(4,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4- methoxy -benzenesulfonamide, N-(5,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, N-(6,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, N-(7,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, N-(8,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, 4-Bromo-N-(l,6'-dihydroxy-[2,2']binaphthalenyl-4-yl)- benzenesulfonamide, or 4-Bromo-N-[4-hydroxy-3-(lH-[l,2,4]triazol-3-ylsulfanyl)- naphthalen-l-yl]-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.

[0004] In some embodiments, the compound of Formula (I) is N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, having the following structure:or a pharmaceutically acceptable salt thereof.

[0005] Further disclosed herein, in some embodiments, are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (II):or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0006] Further disclosed herein, in some embodiments, are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject as effective amount of a compound of Formula (V):or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0007] Other objects and advantages will become apparent to those skilled in the art from a consideration of the ensuing Detailed Description, Examples, and Claims.DETAILED DESCRIPTION

[0008] In some embodiments, the present disclosure provides methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or pharmaceutically acceptable salts thereof.Definitions

[0009] As used herein the specification, “a” or “an” means one or more. As used herein, when used in conjunction with the word "comprising", the words “a” or “an” means one or more than one. As used herein “another” means at least a second or more. Still further, the terms “having”, “including”, “containing” and “comprising” are interchangeable and one of skill in the art is cognizant that these terms are open ended terms. Some embodiments of the disclosure consist of or consist essentially of one or more elements, method steps, and / or methods of the disclosure. It is contemplated that any method, compound, or composition described herein can be implemented with respect to any other method, compound, or composition described herein.

[0010] About" and "approximately" shall generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given value or range of values.

[0011] As used herein, “pharmaceutically acceptable salt” refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, Berge et cd.. describes pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences (1977) 66: 1-19. Pharmaceutically acceptable salts of the compounds of this disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, di gluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy- ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate,stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like.

[0012] As used herein, “pharmaceutically acceptable excipient” refers to any substance in a pharmaceutical formulation other than the active pharmaceutical ingredient(s). Exemplary pharmaceutical excipients include those that aid the manufacturing process; protect, support or enhance stability; increase bioavailability; or increase patient acceptability. They may also assist in product identification or enhance the overall safety or function of the product during storage or use.

[0013] As used herein, a “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle-aged adult or senior adult)) and / or a non-human animal, e.g., a mammal such as primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In some embodiments, the subject is a human. In some embodiments, the subject is a non- human animal. The terms “human,” “patient,” “subject,” and “individual” are used interchangeably herein. None of these terms require the active supervision of medical personnel.

[0014] Disease, disorder, and condition are used interchangeably herein.

[0015] As used herein, and unless otherwise specified, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a subject is suffering from the specified disease, disorder or condition, which reduces the severity of the disease, disorder or condition, or reverses or slows the progression of the disease, disorder or condition (also “therapeutic treatment”).

[0016] In general, the “effective amount” of a compound refers to an amount sufficient to elicit the desired biological response. As will be appreciated by those of ordinary skill in this art, the effective amount of a compound of the disclosure may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, weight, health, and condition of the subject. A “therapeutically effective amount” of a compound is an amount sufficient to provide a therapeutic benefit (e.g., treating, preventing, and / or ameliorating cancer in a subject, or inhibiting protein-protein interactions mediated by an SH2 domain in a subject, at a reasonable benefit / risk ratio applicable to any medical treatment) in the treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition. A therapeutically effective amount of a compound meansan amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment of the disease, disorder or condition. The term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of disease or condition, or enhances the therapeutic efficacy of another therapeutic agent. A “prophylactically effective amount” of a compound is an amount sufficient to prevent a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or prevent its recurrence. A prophylactically effective amount of a compound means an amount of a therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the disease, disorder or condition. The term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent. A “prophylactic treatment” contemplates an action that occurs before a subject begins to suffer from the specified disease, disorder or condition.

[0017] The term “inhibitor” as used herein, for example with respect to STAT3 inhibitors, refers to one or more molecules that interfere at least in part with the activity of STAT3 to perform one or more activities, including the ability of STAT3 to bind to a molecule, protein, and / or the ability to be phosphorylated (e.g., activated).

[0018] As used herein, “characterized by the presence of’ e.g., a mutant p53 protein refers to being positive for one or more mutant p53 proteins or mutations in the tumor protein 53 gene (TP53), which can be detected, for example, by genetic testing (e.g., TP53 genetic testing) based on a sample from the subject. For example, a TP53 genetic testing employs a sample (e.g., blood sample) from the subject to evaluate changes in TP53. Other methods used to detect mutant p53 proteins or mutations in TP53 include, but are not limited to, direct DNA sequencing or mRNA from tumor tissue or bone marrow. In some embodiments, the presence of a mutant p53 protein is a biomarker in a subject for cancer. For example, the subject characterized by a presence of a mutant p53 protein does not have cancer or has not been diagnosed with cancer. In some embodiments, the presence of a mutant p53 protein is a predictive marker of the survival of a subject having cancer. The status of p53 protein may be altered by various factors, including but not limited to, medication and environment.

[0019] The following are definitions of terms used in the present specification. The initial definition provided for a group or term herein applies to that group or term throughout the present specification individually or as part of another group, unless otherwise indicated.Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0020] The term “alkyl” refers to a straight or branched chain alkane (hydrocarbon) radical containing from 1 to 12 carbon atoms, preferably 1 to 6 carbon atoms. Exemplary “alkyl” groups include methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, isobutyl pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, decyl, undecyl, dodecyl, and the like. The term “(C1-C4) alkyl” refers to a straight or branched chain alkane (hydrocarbon) radical containing from 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, and isobutyl. “Substituted alkyl” refers to an alkyl group substituted with one or more substituents, preferably 1 to 4 substituents, at any available point of attachment. Exemplary substituents include but are not limited to one or more of the following groups: hydrogen, halogen (e.g., a single halogen substituent or multiple halo substituents forming, in the latter case, groups such as CF3 or an alkyl group bearing CCI3), cyano, nitro, oxo (i.e., =0), CF3, OCF3, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, aryl, Ora, Sra, S(=O)Re, S(=O)2Re, P(=O)2Re, S(=O)2Ore, P(=O)2Ore, NRbRc, NRbS(=O)2Re, NRbP(=O)2Re, S(=O)2NRbRc, P(=O)2NRbRc, C(=O)Ord, C(=O)Ra, C(=O)NRbRc, OC(=O)Ra, OC(=O)NRbRc, NRbC(=O)Ore, NRdC(=O)NRbRc, NRdS(=O)2NRbRc, NRdP(=O)2NRbRc, NRbC(=O)Ra, or NRbP(=O)2Re, wherein each occurrence of Ra is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; each occurrence of Rb, Rc, and Rd is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle; and each occurrence of Re is independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl. In the aforementioned exemplary substituents, groups such as alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkenyl, heterocycle, and aryl can themselves be optionally substituted.

[0021] The term “alkenyl” refers to a straight or branched chain hydrocarbon radical containing from 2 to 12 carbon atoms and at least one carbon-carbon double bond. Exemplary such groups include ethenyl or allyl. The term “C2-C6 alkenyl” refers to a straight or branched chain hydrocarbon radical containing from 2 to 6 carbon atoms and at least one carbon-carbon double bond, such as ethylenyl, propenyl, 2-propenyl, (E)-but-2-enyl, (Z)-but- 2-enyl, 2-methy(E)-but-2-enyl, 2-methy(Z)-but-2-enyl, 2,3-dimethy-but-2-enyl, (Z)-pent-2- enyl, (E)-pent-l-enyl, (Z)-hex-l-enyl, (E)-pent-2-enyl, (Z)-hex -2-enyl, (E)-hex-2-enyl, (Z)- hex-l-enyl, (E)-hex-l-enyl, (Z)-hex-3-enyl, (E)-hex-3-enyl, and (E)-hex-l,3-dienyl. “Substituted alkenyl” refers to an alkenyl group substituted with one or more substituents,preferably 1 to 4 substituents, at any available point of attachment. Exemplary substituents include but are not limited to one or more of the following groups: hydrogen, halogen (e.g., a single halogen substituent or multiple halo substituents forming, in the latter case, groups such as CF3 or an alkyl group bearing CCI3), cyano, nitro, oxo (i.e., =0), CF3, OCF3, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, aryl, ORa, SRa, S(=O)Re, S(=0)2Re, P(=O)2Re, S(=O)2oRe, P(=O)2ORe, NRbRc, NRbS(=O)2Re, NRbP(=O)2Re, S(=O)2NRbRc, P(=O)2NrbRc, C(=O)ORd, C(=0)Ra, C(=0)NRbRc, 0C(=0)Ra, 0C(=0)NRbRc, NRbC(=0)0Re, NRdC(=O)NRbRc, NRdS(=O)2NRbRc, NRdP(=O)2NRbRc, NRbC(=0)Ra, or NRbP(=O)2Re, wherein each occurrence of Ra is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; each occurrence of Rb, Rc, and Rd is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle; and each occurrence of Re is independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl. The exemplary substituents can themselves be optionally substituted.

[0022] The term “alkynyl” refers to a straight or branched chain hydrocarbon radical containing from 2 to 12 carbon atoms and at least one carbon to carbon triple bond. Exemplary such groups include ethynyl. The term “C2-Ce alkynyl” refers to a straight or branched chain hydrocarbon radical containing from 2 to 6 carbon atoms and at least one carbon-carbon triple bond, such as ethynyl, prop-l-ynyl, prop-2-ynyl, but-l-ynyl, but-2-ynyl, pent-l-ynyl, pent-2 -ynyl, hex-l-ynyl, hex-2-ynyl, or hex-3-ynyl. “Substituted alkynyl” refers to an alkynyl group substituted with one or more substituents, preferably 1 to 4 substituents, at any available point of attachment. Exemplary substituents include but are not limited to one or more of the following groups: hydrogen, halogen (e.g., a single halogen substituent or multiple halo substituents forming, in the latter case, groups such as CF3 or an alkyl group bearing CCI3), cyano, nitro, oxo (i.e., =0), CF3, OCF3, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, aryl, ORa, SRa, S(=O)Re, S(=O)2Re, P(=O)2Re, S(=O)2oRe, P(=O)2ORe, NRbRc, NRbS(=O)2Re, NRbP(=O)2Re, S(=O)2NRbRc, P(=O)2NrbRc, C(=O)ORd, C(=O)Ra, C(=O)NRbRc, OC(=O)Ra, OC(=O)NRbRc, NRbC(=O)ORe, NRdC(=O)NRbRc, NRdS(=O)2NRbRc, NRdP(=O)2NRbRc, NRbC(=O)Ra, or NRbP(=O)2Re, wherein each occurrence of Ra is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; each occurrence of Rb, Rc and Rd is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said Rb and Rc, together with the N to which they are bonded optionally form a heterocycle; and each occurrence of Re isindependently alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl. The exemplary substituents can themselves be optionally substituted.

[0023] The term “cycloalkyl” refers to a fully-saturated cyclic hydrocarbon group containing from 1 to 4 rings and 3 to 8 carbons per ring. “C3-C7 cycloalkyl” refers to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl. “Substituted cycloalkyl” refers to a cycloalkyl group substituted with one or more substituents, preferably 1 to 4 substituents, at any available point of attachment. Exemplary substituents include but are not limited to one or more of the following groups: hydrogen, halogen (e.g., a single halogen substituent or multiple halo substituents forming, in the latter case, groups such as CF3 or an alkyl group bearing CCI3), cyano, nitro, oxo (i.e., =0), CF3, OCF3, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, aryl, ORa, SRa, S(=O)Re, S(=O)2Re, P(=O)2Re, S(=O)2oRe, P(=O)2ORe, NRbRc, NRbS(=O)2Re, NRbP(=O)2Re, S(=O)2NRbRc, P(=O)2NrbRc, C(=O)ORd, C(=O)Ra, C(=O)NRbRc, OC(=O)Ra, OC(=O)NRbRc, NRbC(=O)ORe, NRdC(=O)NRbRc, NRdS(=O)2NRbRc, NRdP(=O)2NRbRc, NRbC(=O)Ra, or NRbP(=O)2Re, wherein each occurrence of Ra is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; each occurrence of Rb, Rc, and Rd is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle; and each occurrence of Re is independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl. The exemplary substituents can themselves be optionally substituted. Exemplary substituents also include spiro-attached or fused cyclic substituents, especially spiro-attached cycloalkyl, spiro-attached cycloalkenyl, spiro-attached heterocycle (excluding heteroaryl), fused cycloalkyl, fused cycloalkenyl, fused heterocycle, or fused aryl, where the aforementioned cycloalkyl, cycloalkenyl, heterocycle, and aryl substituents can themselves be optionally substituted.

[0024] The term “cycloalkenyl” refers to a partially unsaturated cyclic hydrocarbon group containing 1 to 4 rings and 3 to 8 carbons per ring. Exemplary such groups include cyclobutenyl, cyclopentenyl, cyclohexenyl, etc. “Substituted cycloalkenyl” refers to a cycloalkenyl group substituted with one more substituents, preferably 1 to 4 substituents, at any available point of attachment. Exemplary substituents include but are not limited to one or more of the following groups: hydrogen, halogen (e.g., a single halogen substituent or multiple halo substituents forming, in the latter case, groups such as CF3 or an alkyl group bearing CCI3), cyano, nitro, oxo (i.e., =0), CF3, OCF3, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, aryl, ORa, SRa, S(=O)Re, S(=O)2Re, P(=O)2Re, S(=O)2oRe,P(=O)2ORe, NRbRc, NRbS(=O)2Re, NRbP(=O)2Re, S(=O)2NRbRc, P(=O)2NrbRc, C(=O)ORd, C(=O)Ra, C(=O)NRbRc, OC(=O)Ra, OC(=O)NRbRc, NRbC(=O)ORe, NRdC(=O)NRbRc, NRdS(=O)2NRbRc, NRdP(=O)2NRbRc, NRbC(=O)Ra, or NRbP(=O)2Re, wherein each occurrence of Ra is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; each occurrence of Rb, Rc, and Rd is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle; and each occurrence of Re is independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl. The exemplary substituents can themselves be optionally substituted. Exemplary substituents also include spiro-attached or fused cyclic substituents, especially spiro-attached cycloalkyl, spiro-attached cycloalkenyl, spiro-attached heterocycle (excluding heteroaryl), fused cycloalkyl, fused cycloalkenyl, fused heterocycle, or fused aryl, where the aforementioned cycloalkyl, cycloalkenyl, heterocycle, and aryl substituents can themselves be optionally substituted.

[0025] The term “aryl” refers to cyclic, aromatic hydrocarbon groups that have 1 to 5 aromatic rings, especially monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. Where containing two or more aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group may be joined at a single point (e.g., biphenyl), or fused (e.g., naphthyl, phenanthrenyl, and the like). “Substituted aryl” refers to an aryl group substituted by one or more substituents, preferably 1 to 3 substituents, at any available point of attachment. Exemplary substituents include but are not limited to one or more of the following groups: hydrogen, halogen (e.g., a single halogen substituent or multiple halo substituents forming, in the latter case, groups such as CF3 or an alkyl group bearing CCI3), cyano, nitro, oxo (i.e., =0), CF3, OCF3, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, aryl, ORa, SRa, S(=O)Re, S(=O)2Re, P(=O)2Re, S(=O)2oRe, P(=O)2ORe, NRbRc, NRbS(=O)2Re, NRbP(=O)2Re, S(=O)2NRbRc, P(=O)2NrbRc, C(=O)ORd, C(=O)Ra, C(=O)NRbRc, OC(=O)Ra, OC(=O)NRbRc, NRbC(=O)ORe, NRdC(=O)NRbRc, NRdS(=O)2NRbRc, NRdP(=O)2NRbRc, NRbC(=O)Ra, or NRbP(=O)2Re, wherein each occurrence of Ra is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; each occurrence of Rb, Rc, and Rd is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle; and each occurrence of Re is independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl. The exemplary substituents can themselves be optionally substituted. Exemplary substituents also include fused cyclic groups, especiallyfused cycloalkyl, fused cycloalkenyl, fused heterocycle, or fused aryl, where the aforementioned cycloalkyl, cycloalkenyl, heterocycle, and aryl substituents can themselves be optionally substituted.

[0026] The term “carbocycle” refers to a fully saturated or partially saturated cyclic hydrocarbon group containing from 1 to 4 rings and 3 to 8 carbons per ring, or cyclic, aromatic hydrocarbon groups that have 1 to 5 aromatic rings, especially monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. The term “carbocycle” encompasses cycloalkyl, cycloalkenyl, cycloalkynyl, and aryl as defined hereinabove. The term “substituted carbocycle” refers to carbocycle or carbocyclic groups substituted with one or more substituents, preferably 1 to 4 substituents, at any available point of attachment. Exemplary substituents include, but are not limited to, those described above for substituted cycloalkyl, substituted cycloalkenyl, substituted cycloalkynyl, and substituted aryl. Exemplary substituents also include spiro-attached or fused cyclic substituents at any available point or points of attachment, especially spiro-attached cycloalkyl, spiro-attached cycloalkenyl, spiro-attached heterocycle (excluding heteroaryl), fused cycloalkyl, fused cycloalkenyl, fused heterocycle, or fused aryl, where the aforementioned cycloalkyl, cycloalkenyl, heterocycle, and aryl substituents can themselves be optionally substituted.

[0027] The terms “heterocycle” and “heterocyclic” refer to fully saturated, or partially or fully unsaturated, including aromatic (i.e., “heteroaryl”) cyclic groups (for example, 4 to 7 membered monocyclic, 7 to 11 membered bicyclic, or 8 to 16 membered tricyclic ring systems) which have at least one heteroatom in at least one carbon atom-containing ring. Each ring of the heterocyclic group containing a heteroatom may have 1, 2, 3, or 4 heteroatoms selected from nitrogen atoms, oxygen atoms, and / or sulfur atoms, where the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quatemized. (The term “heteroarylium” refers to a heteroaryl group bearing a quaternary nitrogen atom and thus a positive charge.) The heterocyclic group may be attached to the remainder of the molecule at any heteroatom or carbon atom of the ring or ring system. Exemplary monocyclic heterocyclic groups include azetidinyl, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, furyl, tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2- oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, hexahydrodiazepinyl, 4-piperidonyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, triazolyl, tetrazolyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinylsulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and tetrahydro- 1,1 -di oxothienyl, and the like. Exemplary bicyclic heterocyclic groups include indolyl, isoindolyl, benzothiazolyl, benzoxazolyl, benzoxadiazolyl, benzothienyl, benzo[d][l,3]dioxolyl, 2,3- dihydrobenzo[b][l,4]dioxinyl, quinuclidinyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, benzofurazanyl, chromonyl, coumarinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrol opyridyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl], or furo[2,3-b]pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), triazinylazepinyl, tetrahydroquinolinyl, and the like. Exemplary tricyclic heterocyclic groups include carbazolyl, benzidolyl, phenanthrolinyl, acridinyl, phenanthridinyl, xanthenyl, and the like.

[0028] Substituted heterocycle” and “substituted heterocyclic” (such as “substituted heteroaryl”) refer to heterocycle or heterocyclic groups substituted with one or more substituents, preferably 1 to 4 substituents, at any available point of attachment. Exemplary substituents include but are not limited to one or more of the following groups: hydrogen, halogen (e.g., a single halogen substituent or multiple halo substituents forming, in the latter case, groups such as CF3 or an alkyl group bearing CCI3), cyano, nitro, oxo (i.e., =0), CF3, OCF3, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, aryl, ORa, SRa, S(=O)Re, S(=O)2Re, P(=O)2Re, S(=O)2oRe, P(=O)2ORe, NRbRc, NRbS(=O)2Re, NRbP(=O)2Re, S(=O)2NRbRc, P(=O)2NrbRc, C(=O)ORd, C(=O)Ra, C(=O)NRbRc, OC(=O)Ra, OC(=O)NRbRc, NRbC(=O)ORe, NRdC(=O)NRbRc, NRdS(=O)2NRbRc, NRdP(=O)2NRbRc, NRbC(=O)Ra, or NRbP(=O)2Re, wherein each occurrence of Ra is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; each occurrence of Rb, Rc, and Rd is independently hydrogen, alkyl, cycloalkyl, heterocycle, aryl, or said Rb and Rc together with the N to which they are bonded optionally form a heterocycle; and each occurrence of Re is independently alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl. The exemplary substituents can themselves be optionally substituted. Exemplary substituents also include spiro-attached or fused cyclic substituents at any available point or points of attachment, especially spiro-attached cycloalkyl, spiro-attached cycloalkenyl, spiro-attached heterocycle (excluding heteroaryl), fused cycloalkyl, fused cycloalkenyl, fused heterocycle, or fused aryl, where the aforementioned cycloalkyl, cycloalkenyl, heterocycle, and aryl substituents can themselves be optionally substituted.

[0029] The term “alkylamino” refers to a group having the structure -NHR’, wherein R’ is hydrogen, alkyl or substituted alkyl, or cycloalkyl or substituted cyclolalkyl, as defined herein. Examples of alkylamino groups include, but are not limited to, methylamino, ethylamino, n-propylamino, iso-propylamino, cyclopropylamino, n-butylamino, tertbutylamino, neopentylamino, n-pentylamino, hexylamino, cyclohexylamino, and the like.

[0030] The term “dialkylamino” refers to a group having the structure -NRR’, wherein R and R’ are each independently alkyl or substituted alkyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cyclolalkenyl, aryl or substituted aryl, or heterocylyl or substituted heterocyclyl, as defined herein. R and R’ may be the same or different in a dialkyamino moiety. Examples of dialkylamino groups include, but are not limited to, dimethylamino, methyl ethylamino, diethylamino, methylpropylamino, di(n-propyl)amino, di(iso-propyl)amino, di(cyclopropyl)amino, di(n-butyl)amino, di(tert-butyl)amino, di(neopentyl)amino, di(n-pentyl)amino, di(hexyl)amino, di(cyclohexyl)amino, and the like. In some embodiments, R and R’ are linked to form a cyclic structure. The resulting cyclic structure may be aromatic or non-aromatic. Examples of cyclic diaminoalkyl groups include, but are not limited to, aziridinyl, pyrrolidinyl, piperidinyl, morpholinyl, pyrrolyl, imidazolyl, 1,3,4-trianolyl, and tetrazolyl.

[0031] The terms “halogen” or “halo” refer to chlorine, bromine, fluorine, or iodine.

[0032] Unless otherwise indicated, any heteroatom with unsatisfied valences is assumed to have hydrogen atoms sufficient to satisfy the valences.

[0033] Compounds of the present disclosure, and salts or solvates thereof, in some embodiments, exist in their tautomeric form (for example, as an amide or imino ether). All such tautomeric forms are contemplated herein as part of the present disclosure.

[0034] All stereoisomers of the present compounds (for example, those which may exist due to asymmetric carbons on various substituents), including enantiomeric forms and diastereomeric forms, are contemplated within the scope of this disclosure. Individual stereoisomers of the compounds of the disclosure may, for example, be substantially free of other isomers (e.g., as a pure or substantially pure optical isomer having a specified activity), or may be admixed, for example, as racemates or with all other, or other selected, stereoisomers. The chiral centers of the present disclosure, in some embodiments, have the S or R configuration as defined by the International Union of Pure and Applied Chemistry (IUPAC) 1974 Recommendations. The racemic forms can be resolved by physical methods, such as, for example, fractional crystallization, separation or crystallization of diastereomeric derivatives, or separation by chiral column chromatography. The individual optical isomerscan be obtained from the racemates by any suitable method, including without limitation, conventional methods, such as, for example, salt formation with an optically active acid followed by crystallization.

[0035] Compounds of the present disclosure are, subsequent to their preparation, preferably isolated and purified to obtain a composition containing an amount by weight equal to or greater than 90%, for example, equal to greater than 95%, equal to or greater than 99% of the compounds (“substantially pure” compounds), which is then used or formulated as described herein. Such “substantially pure” compounds of the present disclosure are also contemplated herein as part of the present disclosure.

[0036] All configurational isomers of the compounds of the present disclosure are contemplated, either in admixture or in pure or substantially pure form. The definition of compounds of the present disclosure embraces both cis (Z) and trans (E) alkene isomers, as well as cis and trans isomers of cyclic hydrocarbon or heterocyclic rings.

[0037] Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this disclosure, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in “Organic Chemistry,” Thomas Sorrell, University Science Books, Sausalito (1999), the entire contents of which are incorporated herein by reference.

[0038] Certain compounds of the present disclosure, in some embodiments, exist in particular geometric or stereoisomeric forms. The present disclosure contemplates all such compounds, including cis- and trans-i somers, R- and S-enantiomers, diastereomers, (d)- isomers, (l)-isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the disclosure. Additional asymmetric carbon atoms, in some embodiments, are present in a substituent such as an alkyl group. All such isomers, as well as mixtures thereof, are intended to be included in this disclosure.

[0039] Isomeric mixtures containing any of a variety of isomer ratios, in some embodiments, are utilized in accordance with the present disclosure. For example, where only two isomers are combined, mixtures containing 50:50, 60:40, 70:30, 80:20, 90: 10, 95:5, 96:4, 97:3, 98:2, 99: 1, or 100:0 isomer ratios are all contemplated by the present disclosure. Those of ordinary skill in the art will readily appreciate that analogous ratios are contemplated for more complex isomer mixtures.

[0040] The present disclosure also includes isotopically-labeled compounds, which are identical to the compounds disclosed herein, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds of the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, and chlorine, such as 2H, 3H, 13C, 11C, 14C, 15N, 180, 170, 3 IP, 32P, 35S, 18F, and 36C1, respectively. Compounds of the present disclosure, or an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, which contain the aforementioned isotopes and / or other isotopes of other atoms are within the scope of this disclosure. Certain isotopically-labeled compounds of the present disclosure, for example those into which radioactive isotopes such as 3H and 14C are incorporated, are useful in drug and / or substrate tissue distribution assays. Tritiated, i.e., 3H, and carbon-14, i.e., 14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., 2H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and hence may be preferred in some circumstances. Isotopically labeled compounds can generally be prepared by carrying out the procedures disclosed in the Schemes and / or in the Examples below, by substituting a readily- available isotopically labeled reagent for a non-isotopically labeled reagent.

[0041] If, for instance, a particular enantiomer of a compound of the present disclosure is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers.

[0042] It will be appreciated that the compounds, as described herein, in some embodiments, are substituted with any number of substituents or functional moieties. In general, the term “substituted” whether preceded by the term “optionally” or not, and substituents contained in formulas of this disclosure, refer to the replacement of hydrogen radicals in a given structure with the radical of a specified substituent. When more than one position in any given structure, in some embodiments, are substituted with more than onesubstituent selected from a specified group, the substituent is either the same or different at every position. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic, substituents of organic compounds. For purposes of this disclosure, heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valencies of the heteroatoms. Furthermore, this disclosure is not intended to be limited in any manner by the permissible substituents of organic compounds. Combinations of substituents and variables envisioned by this disclosure are preferably those that result in the formation of stable compounds useful in the treatment, for example, of infectious diseases or proliferative disorders. The term “stable,” as used herein, preferably refers to compounds which possess stability sufficient to allow manufacture and which maintain the integrity of the compound for a sufficient period of time to be detected and preferably for a sufficient period of time to be useful for the purposes detailed herein.P53

[0043] TP53 is located on the short arm of human chromosome 17 (17p 13.1) and comprises 11 exons, 10 introns and 393 amino acid residues. The TP53 gene, which encodes the p53 protein, is an important regulator of the cell cycle; however, mutations in TP53 are prevalent in cancers. Exemplary mutations in TP53 include, missense mutations, where a single amino acid is substituted within the DNA binding domain of TP53, for example, at six hot-spot codons (R175, G245, R248, R249, R273, R282), insertion mutations, deletion mutations, and nonsense mutations. Mutations affecting p53 function include loss of function and gain of function.

[0044] Loss of p53 function by mutation is prevalent in cancers. For example, functional loss of p53 results in reactive oxygen species accumulation, which disrupts SHP2 activity and induces EGFR, thereby promoting persistent STAT3 activation. Gain of function mutant p53 interacts with a chaperone such as heat shock protein (HSP90) to form a stable complex that prevents it from degradation and further promotes STAT3 activity. Thus, both loss of function and gain of function p53 mutations may lead to STAT3 activation. Mutant p53 proteins not only lose their tumor suppressive activities but often gain additional oncogenic functions that endow cells with growth and survival advantages. Though the TP53mutational spectrum differs between tumors, mutant p53 is associated with poorer prognosis in malignant tumors. Expression of mutant p53 is negatively correlated with overall survival of cancer patients in several cancers, including breast cancer, pancreatic cancer, hepatobiliary cancer, bone cancer, non-small cell lung cancer, and thyroid cancer. The methods provided herein, in some embodiments, result in clinical benefits in cancer patients (e.g., patients with HCC) identified as having a mutant p53 protein.

[0045] Conversely, wild type TP53 is able to reduce tyrosine phosphorylation of STAT3, and thus prevent STAT3 activation. On the other hand, mutant TP53 induces persistent STAT3 activation. Therefore, activated STAT3 may be preferentially present in cells with p53 mutations.

[0046] Wild type p53 has an amino acid sequence according to any one of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID. NO. 4, SEQ ID NO. 5, SEQ ID. NO. 6, SEQ. ID NO 7, SEQ ID NO. 8, and SEQ ID NO. 9. Any protein with a variance in the amino acid sequence of any of the aforementioned wild type p53 protein sequences is considered a mutant p53 protein.

[0047] In some embodiments, the mutant p53 protein is associated with a TP53 gene mutation selected from the group consisting of E2, K120, V143M, A159D, C176F, R196P, C229, C242S, R249S, C275G, R282G, E3, C124, V143A, A161D, C176Y, V197G, Y234H, C242, P250L, C275Y, R282W, Q5, Y126, Q144, Y163N, C176S, E198, Y234C, C242W, I255F, C275F, R282P, S6, S127P, L145Q, Y163H, C176, G199, Y234, G244S, L257Q, C275S, R282Q, Ell, S127T, L145P, Y163D, C176W, G199E, Y236D, G244C, L257P, C275, R283H, Q16, S127F, W146, Y163C, P177S, L201, Y236H, G244R, E258, C275W, R283P, E17, S127Y, D148, Y163S, P177H, E204, Y236N, G244D, E258K, A276P, E285, S20, S127C, P151T, Y163, P177R, Y205D, Y236C, G244V, D259Y, C277Y, E285K, W23, K132, P151S, K164, H179N, Y205S, Y236S, G244A, D259V, C277F, E285V, K24, K132Q, P151A, K164E, H179Y, Y205C, Y236, G245S, N263, C277, E286, E28, K132E, P151R, Q165, H179R, Y205, M237I, G245R, L265P, P278T, E286K, L35, K132R, P151H, S166, H179L, L206, C238R, G245C, G266, P278S, E286Q, Q38, K132M, P152S, Q167, H179Q, R209, C238Y, G245D, G266R, P278A, E286G, L43, K132T, P152L, H168Y, H179, R213, C238F, G245V, G266E, P278H, E286V, E51, K132N, G154V, H168R, E180, R213Q, C238, G245A, G266V, P278L, E286A, Q52, M133K, T155P, H168P, C182, R213L, N239D, M246V, R267W, P278R, E286D, W53, C135R, T155N, H168L, S183, H214R, N239S, M246L, R267P, G279E, E287, E56, C135S, R156P, E171, S183, S2151, N239, M246R, F270C, R280, N288D, E62, C135G, V157F, V173M, QI 92, V216M, S240G, N247I, E271, R280G, K291, R65, C135Y, V157L, V173L, H193Y, V216L, S241T, N247T, V272M, R280T, K292, E68, C135F, V157D, V173G, H193D, V216E, S241A, R248W, R273C, R280K, E294, W91, C135S, V157G, V173E, H193N, V216G, S241P, R248G, R273S, R2801, E298, S94, C135, V157A, R175G, H193L, Y220N, S241F, R248Q, R273G, R280S, K305, Q100, C135W, R158G, R175C, H193P, Y220H, S241C, R248L, R273H, D281N, R306, K101, Q136, R158S, R175H, H193R, Y220D, S241Y, R248P, R273L, D281Y, R337C, Y103, A138P, R158P, R175L, L194F, Y220C, C242S, R249W, R273P, D281H, Q104, A138G, R158H, R175P, L194R, Y220S, C242R, R249G, V274F, D281G, Y107,KI 39, R158L, C176R, I195F, Y220, C242G, R249M, V274A, D281V, R110L, C141Y, A159P, C176S, I195T, E221, C242Y, R249K, C275R, D281A, LI 14, C141, A159V, C176G, R196, E224, C242F, R249T, C275S, and D281E, and any combination thereof.

[0048] In some embodiments, the mutant p53 protein is associated with a TP53 gene mutation in R175, G245, R248, R249, R273, or R282, or any combination thereof.

[0049] In some embodiments, the mutant p53 protein is associated with a loss of function of p53.

[0050] In some embodiments, the mutant p53 protein is associated with a gain of function of p53.STAT 3 Inhibitors

[0051] Provided herein, in certain embodiments, are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein X is selected from the group consisting of hydrogen, phenylsulfanyl, hydroxy -naphthal enyl, quinolin-8-ylsulfanyl, triazol-3-yl sulfanyl, and benzothiazol-2-ylsulfanyl; and Yis selected from the group consisting of hydrogen, methyl, chloro, bromo, methoxy, ethoxy, tert-butyl, nitro, methyl ester, acetamide, 1,4 di oxine, fluoro, trifluoro methoxy, acetyl, trifluoro methyl, propyl, cyclohexene, methoxy-phenoxy, chloro phenoxy, tolyloxy, and phenoxy.

[0052] In some embodiments, the compound of Formula (I) is N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, N-(3, 1 '-Dihydroxy-[l,2']binaphthalenyl- 4 '-yl)-4-m ethoxy -benzenesulfonamide, N-(4,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4- methoxy -benzenesulfonamide, N-(5,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, N-(6,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, N-(7,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, N-(8,l'-Dihydroxy-[l,2']binaphthalenyl-4'-yl)-4-methoxy- benzenesulfonamide, 4-Bromo-N-(l,6'-dihydroxy-[2,2']binaphthalenyl-4-yl)-benzenesulfonamide, or 4-Bromo-N-[4-hydroxy-3-(lH-[l,2,4]triazol-3-ylsulfanyl)- naphthalen-l-yl]-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.

[0053] In some embodiments, the compound of Formula (I) is N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, having the following structure:(also referred to herein as TTI-101), or a pharmaceutically acceptable salt thereof.

[0054] In some embodiments, disclosed herein are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (II):or a pharmaceutically acceptable salt thereof, wherein each occurrence of Ri is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRbRc, NRbC(=O)Rc, C(=O)NRbRc, NRbC(=O)ORc, OC(=O)NRbRc, NRaC(=O)NRbRc, alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle; m is 0, 1, 2, 3, or 4; each occurrence of R2 is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRbRc, NRbC(=O)Rc, C(=O)NRbRc, NRbC(=O)ORc, OC(=O)NRbRc, NRaC(=O)NRbRc, alkyl, alkenyl, cycloalkyl, cycloalkenyl, optionally substituted aryl, optionally substituted aryloxyl, or optionally substituted heterocycle; n2 is 0, 1, 2, 3, 4, or 5;R.3 is hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, OC(=O)Ra, alkyl, alkenyl, cycloalkyl, or optionally substituted aryl or heteroaryl;R4 is hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, NRbRc, OC(=O)Ra, alkyl, alkenyl, or cycloalkyl; each occurrence of Rs, Re, and R7 is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRbRc, NRbC(=O)Rc, C(=O)NRbRc, NRbC(=O)ORc, OC(=O)NRbRc, NRaC(=O)NRbRc, alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle; ns is 0, 1, 2, 3, or 4; and each occurrence of Ra, Rb, and Rc is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; or said Rb and Rc together with the nitrogen atom to which they are bonded optionally form a heterocycle comprising 1-4 heteroatoms.

[0055] In some embodiments of Formula (II), each occurrence of Ri is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, or SRa. In some embodiments of Formula (II), each occurrence of Ri is independently C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRaRb, NRbC(=O)Ra, C(=O)NRbRc, NRbC(=O)ORa, OC(=O)NRbRc, or NRaC(=O)NRbRc. In some embodiments of Formula (II), each occurrence of Ri is independently alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle. In some embodiments of Formula (II), Ri is hydrogen.

[0056] In some embodiments of Formula (II), m is 0, 1, or 2. In some embodiments of Formula (II), m is 1. In some embodiments of Formula (II), m is 0.

[0057] In some embodiments of Formula (II), each occurrence of R2 is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, or SRa. In some embodiments of Formula (II), each occurrence of R2 is independently C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRaRb, NRbC(=O)Ra, C(=O)NRbRc, NRbC(=O)ORa, OC(=O)NRbRc, or NRaC(=O)NRbRc. In some embodiments of Formula (II), each occurrence of R2 is independently alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle. In some embodiments of Formula (II), R2 is hydrogen.

[0058] In some embodiments of Formula (II), is 0, 1, or 2. In some embodiments of Formula (II), m is 1. In some embodiments of Formula (II), is 0.

[0059] In some embodiments of Formula (II), R3 is hydrogen, halogen, cyano, nitro, or CF3. In some embodiments of Formula (II), R3 is OCF3, ORa, SRa, or OC(=O)Ra. In some embodiments of Formula (II), R3 is alkyl, alkenyl, or cycloalkyl. In some embodiments of Formula (II), R3 is hydrogen.

[0060] In some embodiments of Formula (II), R4 is hydrogen, halogen, cyano, nitro, or ORa. In some embodiments of Formula (II), R4 is OCF3, SRa, or OC(=O)Ra. In some embodiments of Formula (II), R4 is alkyl, alkenyl, or cycloalkyl. In some embodiments of Formula (II), R4is OH. In some embodiments of Formula (II), R4 is OMe.

[0061] In some embodiments of Formula (II), Rs, Re, and R7 are each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, and CF3. In some embodiments of Formula (II), Rs, Re, and R7 are each independently selected from the group consisting of OCF3, ORa, and SRa. In some embodiments of Formula (II), Rs, Re, and R7 are each independently selected from the group consisting of OCF3 and ORa. In some embodiments of Formula (II), Rs, Re, and R7 are each independently selected from the group consisting of C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRaRb, NRbC(=O)Ra, C(=O)NRbRc, NRbC(=O)ORa, OC(=O)NRbRc, and NRaC(=O)NRbRc. In some embodiments of Formula (II), Rs, Re, and R7 are each independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, optionally substituted aryl, and optionally substituted heterocycle. In some embodiments of Formula (II), each occurrence of Rs, Re, and R7 is hydrogen.

[0062] In some embodiments of Formula (II), n3 is 0, 1, or 2. In some embodiments of Formula (II), n3 is 1. In some embodiments of Formula (II), n3 is 0.

[0063] In some embodiments of Formula (II), each occurrence of Ra is independently hydrogen, alkyl, heterocycle, or aryl. In some embodiments of Formula (II), each occurrence of Ra is independently hydrogen or alkyl. In some embodiments of Formula (II), each occurrence of Rb and Rc is independently hydrogen, alkyl, heterocycle, or aryl. In some embodiments of Formula (II), each occurrence of Rb and Rc is independently hydrogen or alkyl. In some embodiments of Formula (II), Rb and Rc together with the nitrogen atom to which they are bonded optionally form a heterocycle comprising 1-4 heteroatoms each selected from the group consisting of N, O, and S.

[0064] In some embodiments, the compound of Formula (II) is a compound of Formula (III):or a pharmaceutically acceptable salt thereof.

[0065] In some embodiments of Formula (III), R2 is H, OH, alkyl, alkoxy, halogen,NRbRc, CF3, OCF3, or CN. In some embodiments of Formula (III), R2 is NH2, OH, OMe, OEt, OCH2CH2CH3, or OCH(CH3)2. In some embodiments of Formula (III), R2 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, tert-butyl, F, Cl, Br, CF3, nitro, methoxy, ethoxy, OCF3, -C(=O)Me, -C(=O)OMe, -NHC(=O)Me, 1,4-dioxanyl, cyclohexanyl, cyclohexenyl, phenoxy, 2-methoxyphenoxy, 3-methoxyphenoxy, 4- methoxyphenoxy, 2-chlorophenoxy, 3 -chlorophenoxy, 4-chlorophenoxy, 2-m ethylphenoxy, 3 -methylphenoxy, and 4-methylphenoxy. In some embodiments of Formula (III), R2 is OMe.

[0066] In some embodiments of Formula (III), R3 is H, OH, alkyl, alkoxy, or halogen. In some embodiments of Formula (III), R3 is H.

[0067] In some embodiments of Formula (III), R4 is H, alkyl, OH, NH2, alkoxy, halogen, CF3, or CN. In some embodiments of Formula (III), R4 is H, OH, or alkoxy. In some embodiments of Formula (III), R4 is OH. In some embodiments of Formula (III), R4is OMe.

[0068] In some embodiments, the compound of Formula (III) is a compound of Formula (IV):or a pharmaceutically acceptable salt thereof.

[0069] In some embodiments, the compound of Formula (II) is a compound selected from Examples of compounds shown in Table A, or a pharmaceutically acceptable salt thereof.Table A. Selected compounds of Formula (II), where m, n2, and m are independently 1 or 2.

[0070] In some embodiments, the compound of Formula (III) is a compound selected from Examples of compounds shown in Table B, or a pharmaceutically acceptable salt thereof.Table B. Selected compounds of Formula (III).

[0071] In another aspect, provided herein are methods of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (V):or a pharmaceutically acceptable salt or a solvate thereof, whereinA is halo, Ci-4alkyl, Ci-4alkoxy, Ci-4haloalkyl, or Ci-4haloalkoxy;R1, R2, and R3are each independently H, C(=O)NRARB, P(=O)(OH)(RC), or Ci- 4alkylene-O-P(=O)(OH)(Rc); orR1and R2together form:provided that R1, R2and R3are not simultaneously H;RAis H or Ci-4alkyl;RBis Ci-6alkylene-N(H)(Ci-ealkyl), Ci-ealkylene-(5-8 membered heterocyclyl), Ci- ealkylene-C(=O)OH optionally substituted with amine, Ci-4alkyl, or benzyl;Rcis Ci-4alkyl or hydroxy; and n is an integer 0, 1, 2, or 3.

[0072] In some embodiments, R3is H. In other embodiments, R3is C(=O)NRARB. In some embodiments, R3is P(=O)(OH)(RC). In some embodiments, R3is Ci-4alkylene-O- P(=O)(OH)(RC). In some embodiments, R3is H or C(=O)NRARB. In some embodiments, R3is H or C(=O)NRARBwherein RAis H and RBis Ci-ealkylene-C(=O)OH optionally substituted with amine.

[0073] In some embodiments, R1is H. In other embodiments, R1is C(=O)NRARB. In some embodiments, R1is P(=O)(OH)(RC). In some embodiments, R1is Ci-4alkylene-O- P(=O)(OH)(RC). In some embodiments, R1is H, C(=O)NRARB, or P(=O)(OH)(RC). In some embodiments, R1is H, C(=O)NRARBwherein RAis H or methyl and RBis Ci-ealkylene- N(H)(Ci-4alkyl), Ci-ealkylene-C(=O)OH optionally substituted with amine, or Ci-ealkylene- (5-6 membered heterocyclyl), or P(=O)(OH)2. In some embodiments, R1is H, C(=O)NRARBwherein RAis H or methyl and RBis C2-ealkylene-N(H)(Ci-4alkyl), C2-6alkylene-C(=O)OH optionally substituted with amine, or C2-ealkylene-(5- membered heterocyclyl), or P(=O)(OH)2.

[0074] In some embodiments, R2is H. In other embodiments, R2is C(=O)NRARB. In some embodiments, R2is P(=O)(OH)(RC). In some embodiments, R2is Ci-4alkylene-O- P(=O)(OH)(RC). In some embodiments, R2is H, C(=O)NRARB, or P(=O)(OH)(RC). In some embodiments, R2is H, C(=O)NRARBwherein RAis H or methyl and RBis Ci-ealkylene- N(H)(Ci-4alkyl), Ci-6alkylene-C(=O)OH optionally substituted with amine, or Ci-ealkylene- (5-6 membered heterocyclyl), or P(=O)(OH)2. In some embodiments, R2is H, C(=O)NRARBwherein RAis H or methyl and RBis C2-ealkylene-N(H)(Ci-4alkyl), C2-6alkylene-C(=O)OHoptionally substituted with amine, or C2-ealkylene-(5- membered heterocyclyl), or P(=0)(0H)2.

[0075] In some embodiments, R1and R2together form:. In some embodiments, R1and R2together form:wherein Rcis OH.

[0076] In some embodiments, RAis H or methyl. In some embodiments, RAis H. In some embodiments, RAis methyl.

[0077] In some embodiments, RBis Ci-6alkylene-N(H)(Ci-ealkyl). In some embodiments, RBis Ci-4alkylene-N(H)(Ci-ealkyl). In some embodiments, RBis C2-4alkylene- N(H)(Ci-ealkyl). In some embodiments, RBis CH2CH2N(H)(Ci-ealkyl). In some embodiments, RBis CH2CH2CH2N(H)(Ci-ealkyl). In some embodiments, RBis CH2CH2N(H)(CH3). In some embodiments, RBis CH2CH2CH2N(H)(CH3).

[0078] In some embodiments, RBis Ci-ealkylene-(5-8 membered heterocyclyl). In some embodiments, RBis Ci-4alkylene-(5-8 membered heterocyclyl). In some embodiments, RBis Ci-2alkylene-(5-8 membered heterocyclyl). In some embodiments, RBis Ci-ealkylene- (5-8 membered heterocyclyl). In some embodiments, RBis Ci-4alkylene-(5-6 membered heterocyclyl). In some embodiments, RBis Ci-2alkylene-(5-6 membered heterocyclyl). In some embodiments, RBis Ci-6alkylene-(5-membered heterocyclyl). In some embodiments, RBis Ci-4alkylene-(5-membered heterocyclyl). In some embodiments, RBis Ci-2alkylene-(5- membered heterocyclyl). In some embodiments, RBis Ci-4alkylene-(5-8 membered N- containing heterocyclyl). In some embodiments, RBis Ci-4alkylene-(5-6 membered N- containing heterocyclyl). In some embodiments, RBis Ci-4alkylene-(5-membered N- containing heterocyclyl). In some embodiments, RBis Ci-2alkylene-(5-membered heterocyclyl). In some embodiments, RBis Ci-2alkylene-(5-8 membered N-containing heterocyclyl). In some embodiments, RBis Ci-2alkylene-(5-6 membered N-containing heterocyclyl). In some embodiments, RBis Ci-2alkylene-(5-membered N-containing heterocyclyl).

[0079] In some embodiments, RBis Ci-6alkylene-C(=O)OH optionally substituted with amine, Ci-4alkyl, or benzyl. In some embodiments, RBis Ci-6alkylene-C(=O)OHsubstituted with amine. In some embodiments, RBis Ci-4alkylene-C(=O)OH substituted with amine. In some embodiments, RBis C2-6alkylene-C(=O)OH substituted with amine. In some embodiments, RBis C2-4alkylene-C(=O)OH substituted with amine.

[0080] In some embodiments, Rcis Ci-4alkyl. In some embodiments, Rcis methyl. In other embodiments, Rcis hydroxy.

[0081] In some embodiments, A is halo, Ci-4alkyl, Ci-4alkoxy, Ci-4haloalkyl, or Ci- 4haloalkoxy. In some embodiments, A is halo, Ci-4alkyl, or Ci-4alkoxy. In some embodiments, A is Ci-4alkoxy. In some embodiments, A is methoxy.

[0082] In some embodiments, n is 0, 1, or 2. In some embodiments, n is 0 or 1. In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2.

[0083] In some embodiments, the compound is a compound of Formula (V-A):(V-A), or a pharmaceutically acceptable salt or a solvate thereof.

[0084] In some embodiments, the compound is a compound of Formula (V-B):or a pharmaceutically acceptable salt or a solvate thereof.

[0085] In some embodiments, the compound is a compound of Formula (V-C):(V-C), or a pharmaceutically acceptable salt or a solvate thereof.

[0086] In some embodiments, the compound is a compound of Formula (V-D):(V-D), or a pharmaceutically acceptable salt or a solvate thereof.

[0087] In some embodiments, the compound is a compound of Formula (V-E):(V-E), or a pharmaceutically acceptable salt or a solvate thereof.

[0088] In some embodiments, the compound is a compound of Formula (V-F):or a pharmaceutically acceptable salt or a solvate thereof.

[0089] In some embodiments, the compound is a compound of Formula (V-G):(V-G), or a pharmaceutically acceptable salt or a solvate thereof.

[0090] In some embodiments, the compound is a compound of Formula (V-H):(V-H), or a pharmaceutically acceptable salt or a solvate thereof.

[0091] In some embodiments, the compound is a compound of Formula (V-I):or a pharmaceutically acceptable salt or a solvate thereof.

[0092] In some embodiments, the compound is a compound of Formula (V-J):(V-J), or a pharmaceutically acceptable salt or a solvate thereof.

[0093] In some embodiments, the compound is a compound of Formula (V-K):(V-K), or a pharmaceutically acceptable salt or a solvate thereof.

[0094] In some embodiments, the compound is a compound of Formula (V-L):(V-L), or a pharmaceutically acceptable salt or a solvate thereof.

[0095] In some embodiments, the compound of Formula (V) is:thereof.Cancers

[0096] In some embodiments, the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, kidney cancer, testicular cancer,colon cancer, rectal cancer, gastric cancer, esophageal cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, bone cancer, spleen cancer, gall bladder cancer, brain cancer, pancreatic cancer, stomach cancer, anal cancer, multiple myeloma, post-transplant lymphoproliferative disease, restenosis, myelodysplastic syndrome, leukemia, lymphoma, and acute myelogenous leukemia. In some embodiments, the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, testicular cancer, colon cancer, rectal cancer, gastric cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, stomach cancer, and leukemia. In some embodiments, the cancer is liver cancer. In some embodiments, the liver cancer is selected from the group consisting of hepatocellular carcinoma, fibrolamellar carcinoma, bile duct cancer, angiosarcoma, and hepatoblastoma. In some embodiments, the liver cancer is hepatocellular carcinoma. In some embodiments, the cancer is breast cancer. In some embodiments, the breast cancer is identified as hormone receptor (HR)-positive. In some embodiments, the breast cancer is identified as human epidermal growth factor receptor 2 (HER2)-negative .

[0097] In some embodiments, the subject has been administered one or more prior cancer therapies. In some embodiments, the subject is refractory to the one or more prior cancer therapies.

[0098] In some embodiments, the prior cancer therapy is an immune checkpoint inhibitor, including but not limited to PD-1 inhibitors, PD-L1 inhibitors, PD-L2 inhibitors, and CTLA-4 inhibitors. Exemplary immune checkpoint inhibitors include, but are not limited to, pembrolizumab, nivolumab, atezolizumab, durvalumab, and tremelimumab, and pharmaceutically acceptable salts thereof, or any combination thereof. In some embodiments, the prior cancer therapy is a protein kinase inhibitor, including but not limited to ALX inhibitors, RO SI inhibitors, TYRO3 inhibitors, MER inhibitors, TRKB inhibitors, TIE2 inhibitors, VEGFR inhibitors, PDGFR inhibitors, RAF inhibitors, MEK inhibitors, ERK inhibitors, MET inhibitors, KIT inhibitors, FLT3 inhibitors, FGFR inhibitors, and RET inhibitors. In some embodiments, the protein kinase inhibitor inhibits more than one protein kinase. Exemplary protein kinase inhibitors include, but are not limited to, sorafenib, lenvatinib, bevacizumab, ramucirumab, cabozantinib, infigratinib, pemigatinib, regorafenib, and pharmaceutically acceptable salts thereof, or any combination thereof. In some embodiments, the prior cancer therapy is selected from the group consisting of sorafenib, pembrolizumab, nivolumab, lenvatinib, and bevacizumab.

[0099] In some embodiments, the cancer has progressed from, or the subject was intolerant to, a prior first line cancer therapy. In some embodiments, the cancer has progressed from, or the subject was intolerant to, a prior second line cancer therapy. In some embodiments, the cancer has progressed from, or the subject was intolerant to, a prior third line cancer therapy.[000100] In some embodiments, the cancer is treatment naive (has not been previously administered a cancer therapy).Combinations[000101] The phrase, "in combination with," and the terms "co-administration," "coadministering," or "co-providing", as used herein in the context of the administration of a compound described herein (e.g., a compound of Formula (I) or Formula (II)) and another agent or therapy, means that two (or more) different compounds, agents, or therapies are delivered to the subject during the course of the subject's affliction with the cancer, e.g., two (or more) different compounds, agents, or therapies are delivered to the subject after the subject has been diagnosed with the cancer and before the cancer has been cured or eliminated or treatment has ceased for other reasons.[000102] In some embodiments, the delivery of one compound, agent, or therapy is still occurring when the delivery of the second begins, so that there is overlap in terms of administration. This is sometimes referred to herein as "simultaneous" or "concurrent delivery." In other embodiments, the delivery of one compound, agent, or therapy ends before the delivery of the other compound, agent, or therapy begins. In some embodiments of either case, the treatment (e.g., administration of compound, composition, or therapy) is more effective because of combined administration. For example, the second compound, agent, or therapy is more effective, e.g., an equivalent effect is seen with less of the second compound, agent, or therapy, or the second compound, agent, or therapy reduces symptoms to a greater extent, than would be seen if the second compound, agent, or therapy were administered in the absence of the first compound, agent, or therapy, or the analogous situation is seen with the first compound, agent, or therapy. In some embodiments, delivery is such that the reduction in a symptom, or other parameter related to the disorder is greater than what would be observed with one compound, agent, or therapy delivered in the absence of the other. The effect of the two compounds or therapies can be partially additive, wholly additive, or greaterthan additive (e.g., synergistic). The delivery can be such that the first compound, agent, or therapy delivered is still detectable when the second is delivered.[000103] In some embodiments, the first compound, agent, or therapy and second compound, agent, or therapy can be administered simultaneously (e.g., at the same time), in the same or in separate compositions, or sequentially. Sequential administration refers to administration of one compound, agent, or therapy before (e.g., immediately before, less than 5, 10, 15, 30, 45, 60 minutes; 1 , 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 48, 72, 96 or more hours; 4, 5, 6, 7, 8, 9 or more days; 1 , 2, 3, 4, 5, 6, 7, 8 or more weeks before) administration of an additional, e.g., secondary, compound, agent, or therapy. The order of administration of the first and secondary compound, agent, or therapy can also be reversed.[000104] In some embodiments, the methods described herein further comprise administering to the subject one or more additional agent.[000105] In some embodiments, the additional agent is selected from the group consisting of an angiogenesis inhibitor, an anti-PD-1 antibody, and an anti-PD-Ll antibody, or a combination thereof.[000106] Exemplary anti-PD-1 antibodies include, but are not limited to, cemiplimab, nivolumab, pembrolizumab, pidilizumab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, sasanlimab, retifanlimab, tebotelimab, ABBV-181, AK104, AK105, BCD-100, BI-754091, CBT-501, CC-90006, GLS-010, HLX10, IBI-308, JNJ-3283, JS001, LZM009, MEDI0680 (AMP-514), REGN-2810, SHR-1210, Sym021, TSR-042, and XmAb20717. In some embodiments, the anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, and pidilizumab. In some embodiments, the anti-PD-1 antibody is pembrolizumab.[000107] Exemplary anti-PD-Ll antibodies include, but are not limited to, atezolizumab, avelumab, durvalumab, envafolimab, FS118, BCD-135, BGB-A333, BGBA- 317, CBT-502, CK-301, CS1001, FAZ053, MDX-1105, MSB2311, SHR-1316, M7824, LY3415244, CA-170, and CX-072. In some embodiments, the anti-PD-Ll antibody is selected from the group consisting of atezolizumab, avelumab, durvalumab, and envafolimab. In some embodiments, the anti-PD-Ll antibody is atezolizumab.[000108] Exemplary angiogenesis inhibitors include, but are not limited to, bevacizumab, sorafenib, sunitinib, nilotinib, pazopanib, dasatinib, regorafenib, cabozantinib, lenvatinib, ponatinib, ziv-aflibercept, axitinib, tivozanib, everolimus, lenalidomide, thalidomide, vandetanib, orvandetanib, and ramucirumab. In some embodiments, the angiogenesis inhibitor is bevacizumab.[000109] In some embodiments, the additional agent is selected from the group consisting of a cyclin-dependent kinase (CDK) inhibitor (e.g., CDK4 / 6 inhibitor), an aromatase inhibitor, and hormone therapy, or a combination thereof.[000110] Exemplary cyclin-dependent kinase inhibitors include, but are not limited to, palbociclib, ribociclib, abemaciclib, roniciclib, trilaciclib, lerociclib, milciclib, TQB3303, GLR2007, SHR-6390, PF-06873600, XZP-3287, ON-123300, ETH-155008, HEC-80797, JS-104, PF-07220060, RMC-4550, and SRX-3177, and pharmaceutically acceptable salts thereof. In some embodiments, the cyclin-dependent kinase inhibitor is palbociclib or ribociclib.[000111] Exemplary aromatase inhibitors include, but are not limited to, letrozole, anastrozole, exemestane, and testalactone, and pharmaceutically acceptable salts thereof. [000112] Exemplary hormone therapy includes, but are limited to, elacestrant, fulvestrant, goserelin, leuprolide, megestrol, tamoxifen, and toremifene, and pharmaceutically acceptable salts thereof.Administration, Dosages, and Formulations[000113] The compounds of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V- D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or pharmaceutically acceptable salts thereof are administered orally, parenterally, topically, rectally, or via an implanted reservoir, preferably by oral administration. In some cases, the pH of a composition (e.g., pharmaceutical composition) comprising a compound of Formula (I), (II), (III), (IV), (V), (V- A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof is adjusted with pharmaceutically acceptable acids, bases or buffers to enhance the stability or efficacy of the composition.[000114] In some embodiments, the subject is administered a composition (e.g., pharmaceutical composition) comprising a compound of Formula (I), (II), (III), (IV), (V), (V- A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof orally. In some embodiments the composition (e.g., pharmaceutical composition) is orally administered in any orally acceptable dosage form including, but not limited to, liqui-gel tablets or capsules, syrups, emulsions and aqueous suspensions. Liqui-gels, in some embodiments, include gelatins, plasticisers, and / or opacifiers, as needed to achieve a suitable consistency and in some embodiments, are coated with enteric coatings that are approved for use, e.g., shellacs. Additional thickening agents, for example gums, e.g., xanthum gum, starches, e.g., corn starch, or glutens in someembodiments be added to achieve a desired consistency of the composition (e.g., pharmaceutical composition) when used as an oral dosage. If desired, certain sweetening and / or flavoring and / or coloring agents, in some embodiments, are added.[000115] In some embodiments, the subject is administered a composition (e.g., pharmaceutical composition) comprising a compound of Formula (I), (II), (III), (IV), (V), (V- A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof in a form suitable for oral administration such as a tablet, capsule, pill, powder, sustained release formulations, solution, and suspension. The composition (e.g., pharmaceutical composition), in some embodiments, is in unit dosage forms suitable for single administration of precise dosages. Pharmaceutical compositions, in some embodiments, comprise, in addition to a compound as described herein a pharmaceutically acceptable carrier, and optionally further comprise one or more pharmaceutically acceptable excipients, such as, for example, stabilizers, diluents, binders, and lubricants. In addition, the tablet, in some embodiments, include other medicinal or pharmaceutical agents, carriers, and or adjuvants.[000116] The dosage vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. Lower or higher doses than those recited above may be required. Specific dosage and treatment regimens for any particular subject will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health status, sex, diet, time of administration, rate of excretion, drug combination, the severity and course of the disease, condition or symptoms, the subject's disposition to the disease, condition or symptoms, and the judgment of the treating physician. A course of therapy can comprise one or more separate administrations of a compound as described herein.[000117] In some embodiments, about 1 mg / kg / day to about 100 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V- G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 1 mg / kg / day to about 90 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V- F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 1 mg / kg / day to about 80 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptablesalt thereof, is administered to the subject. In some embodiments, about 1 mg / kg / day to about 70 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V- D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 1 mg / kg / day to about 60 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V- A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 1 mg / kg / day to about 50 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 5 mg / kg / day to about 50 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 5 mg / kg / day to about 40 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V- G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 5 mg / kg / day to about 30 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V- F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 5 mg / kg / day to about 8 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 10 mg / kg / day to about 15 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V- C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 20 mg / kg / day to about 30 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V- A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 0.5 mg / kg / dose to about 25 mg / kg / dose of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 2.5 mg / kg / dose to about 15 mg / kg / dose of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H),(V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 2.5 mg / kg / day to about 4 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V- G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 5 mg / kg / day to about 7.5 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V- F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject. In some embodiments, about 10 mg / kg / day to about 15 mg / kg / day of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject.[000118] In some embodiments, the subject is dosed twice daily of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof. In some embodiments, the subject is dosed twice daily of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, at about 1.6 mg / kg / dose. In some embodiments, the subject is dosed twice daily of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, at about 3.2 mg / kg / dose. In some embodiments, the subject is dosed twice daily of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, at about 6.4 mg / kg / dose. In some embodiments, the subject is dosed twice daily of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, at about 12.8 mg / kg / dose.[000119] In some embodiments, about 100 mg to about 5000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 200 mg to about 5000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 200 mg to about 4000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H),(V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 200 mg to about 3000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 200 mg to about 2000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 200 mg to about 1000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 200 mg to about 800 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg to about 5000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg to about 4000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg to about 3000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg to about 2000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg to about 1600 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg to about 1400 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg to about 1200 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered tothe subject per day. In some embodiments, about 600 mg to about 1000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1000 mg to about 5000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V- G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1000 mg to about 4000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V- F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1000 mg to about 3000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1000 mg to about 2000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1000 mg to about 1600 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1400 mg to about 5000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1400 mg to about 4000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1400 mg to about 3000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1400 mg to about 2000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.[000120] In some embodiments, about 400 mg to about 1600 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H),(V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 400 mg to about 800 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 800 mg to about 1200 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1200 mg to about 1600 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V- G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.[000121] In some embodiments, about 100 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 200 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 300 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 400 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 500 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 600 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 700 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 800 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or apharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 900 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V- B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1100 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1200 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1300 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1400 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1500 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1600 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1700 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1800 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 1900 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In someembodiments, about 2000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 2200 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 2400 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 2600 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 2800 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day. In some embodiments, about 3000 mg of the compound of Formula (I), (II), (III), (IV), (V), (V-A), (V-B), (V-C), (V-D), (V-E), (V-F), (V-G), (V-H), (V-I), (V-J), (V-K), or (V-L), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.[000122] In some embodiments, the compound of Formula (I) is N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, and the N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide is administered orally to the subject as a composition comprising: a. a therapeutically effective amount of N-(l ',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide or a pharmaceutically acceptable salt thereof; b. an emulsifier (e.g., glyceride); c. a solubilizer; d. a polyethylene glycol (PEG); and e. a surfactant; and optionally, f. an antioxidant.[000123] In some embodiments, the composition comprises: a. a therapeutically effective amount of N-(l ',2-dihydroxy-l,2'-binaphthalen- 4'-yl)-4-methoxybenzenesulfonamide or a pharmaceutically acceptable salt thereof;b. an emulsifier (e.g., glyceride), the emulsifier being present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'- yl)-4-methoxybenzenesulfonamide to the emulsifier of about 1 : 1 to about 1 :2 (e.g., about 1 : 1.5); c. a solubilizer, the solubilizer being present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to solubilizer of about 1 : 1 to about 1 :5 (e.g., about 1 :2 to about 1 :4, e.g., about 1 :3); d. a polyethylene glycol (PEG), the polyethylene glycol being present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'- yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 :2 to about 1 :6 (e.g., about 1 :3 to about 1 :5, e.g., about 1 :4); e. a surfactant, the surfactant being present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to surfactant of about 2: 1 to about 1 :2 (e.g., about 1 : 1 to about 1 :2, e.g., about 1 : 1, e.g., about 1 :2, e.g. about 1 : 1.2); and f. an antioxidant, the antioxidant being present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to antioxidant of about 10: 1 to about 30: 1 (e.g., about 15: 1 to about 25: 1, e.g., about 20: 1).[000124] In some embodiments, the emulsifier is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the emulsifier of about 1 : 1. In some embodiments, the emulsifier is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the emulsifier of about 1 :2. In some embodiments, the emulsifier is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to the emulsifier of about 1:3. In some embodiments, the emulsifier is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the emulsifier of about 1 :4. In some embodiments, the emulsifier is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the emulsifier of about 1 :5. In some embodiments, the emulsifier is present in the composition in a weight ratio of N- (l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the emulsifier ofabout 1 :6. In some embodiments, the emulsifier is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the emulsifier of about 1 :7. In some embodiments, the emulsifier is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the emulsifier of about 1 : 1.5.[000125] In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 : 1. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :2. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to solubilizer of about 1 :3. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :4. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :5. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :4. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :6. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :4. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to solubilizer of about 1 :7. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :4. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :8. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :4. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 :9. In some embodiments, the solubilizer is present in the composition ina weight ratio of N-(l\2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1:10. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to solubilizer of about 1 : 11. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1:12. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 : 13. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 : 14. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1:15. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to solubilizer of about 1:16. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1:17. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 : 18. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1 : 19. In some embodiments, the solubilizer is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to solubilizer of about 1:20.[000126] In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1:1. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to polyethylene glycol of about 1:2. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1:3. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1:4. In some embodiments, the polyethylene glycol is present in thecomposition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to polyethylene glycol of about 1 :4.2. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy- l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 :5. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 :6. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to polyethylene glycol of about 1 :7. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 :8. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 :9. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to polyethylene glycol of about 1 : 10. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 : 11. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l ',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 : 12. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to polyethylene glycol of about 1 : 13. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 : 14. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l ',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 : 15. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to polyethylene glycol of about 1 : 16. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 : 17. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l ',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethyleneglycol of about 1 : 18. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to polyethylene glycol of about 1 : 19. In some embodiments, the polyethylene glycol is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to polyethylene glycol of about 1 :20. [000127] In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 4: 1. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 3: 1. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to surfactant of about 2: 1. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)- 4-methoxybenzenesulfonamide to surfactant of about 1 : 1. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 1 : 1.2. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 1 :2. In some embodiments, the surfactant is present in the composition in a weight ratio of N- (l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 1 :3. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 1 :4. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 1 :5. In some embodiments, the surfactant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to surfactant of about 1 :6.[000128] In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 2: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to antioxidant of about 3 : 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 4: 1. In someembodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 5: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 6: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 7: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to antioxidant of about 8: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 9: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 10: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 11 : 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 12: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to antioxidant of about 13: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 14: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 15 : 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 16: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 17: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to antioxidant of about 18: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 18.4: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-1, 2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 19: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 20: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 21 : 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to antioxidant of about 22: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 23: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 24: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 25: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 26: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide to antioxidant of about 27: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 28: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 29: 1. In some embodiments, the antioxidant is present in the composition in a weight ratio of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to antioxidant of about 30: 1.[000129] In some embodiments, the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide is present in the composition in a concentration of at least 50 mg / g (e.g., at least 60 mg / g, at least 70 mg / g, at least 80 mg / g, or at least 90 mg / g) (e.g., excluding the mass of a capsule shell). In some embodiments, the N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide is present in the composition in a concentration of at least 50 mg / g. In some embodiments, the N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide is present in the composition in a concentration of at least 60 mg / g. In some embodiments, the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide is present in the composition in a concentration of at least 70 mg / g. In some embodiments, the N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide is present in the composition in a concentration of at least 80 mg / g. In some embodiments, the N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide is present in the composition in a concentration of at least 90 mg / g.[000130] In some embodiments, the emulsifier is a glyceride emulsifier. In some embodiments, the emulsifier comprises optionally polyglycolyzed medium- and / or long- chain mono-, di-, and / or tri-glyceride(s). In some embodiments, the emulsifier comprises a medium-chain mono-glyceride. In some embodiments, the emulsifier comprises a polyglycolyzed medium-chain mono-glyceride. In some embodiments, the emulsifier comprises a long-chain mono-glyceride. In some embodiments, the emulsifier comprises a polyglycolyzed long-chain mono-glyceride. In some embodiments, the emulsifier comprises a medium-chain di-glyceride. In some embodiments, the emulsifier comprises a polyglycolyzed medium-chain di-glyceride. In some embodiments, the emulsifier comprises a long-chain di-glyceride. In some embodiments, the emulsifier comprises a polyglycolyzed long-chain di-glyceride. In some embodiments, the emulsifier comprises a medium-chain triglyceride. In some embodiments, the emulsifier comprises a polyglycolyzed medium-chain tri-glyceride. In some embodiments, the emulsifier comprises a long-chain tri-glyceride. In some embodiments, the emulsifier comprises a polyglycolyzed long-chain tri-glyceride.[000131] In some embodiments, the emulsifier is Labrasol®. In some embodiments, the emulsifier is Capmul® MCM. In some embodiments, the emulsifier is Capmul® MCM EP. In some embodiments, the emulsifier is Capmul® C8 EP. In some embodiments, the emulsifier is Capryol® 90.[000132] In some embodiments, the solubilizer is a polyoxyl castor oil or a vitamin E polyethylene glycol succinate (TPGS). In some embodiments, the solubilizer is a polyoxyl castor oil. In some embodiments, the solubilizer is a vitamin E polyethylene glycol succinate. In some embodiments, the surfactant is Kolliphor® RH 40. In some embodiments, the solubilizer is Vitamin E TPGS.[000133] In some embodiments, the polyethylene glycol (PEG) has an average molecular weight of about 200 to about 1000 (e.g., about 500 to about 700, or about 550 to about 650, or about 600). In some embodiments, the polyethylene glycol (PEG) has an average molecular weight of about 200 to 1000. In some embodiments, the polyethylene glycol (PEG) has an average molecular weight of about 500 to 700. In some embodiments,the polyethylene glycol (PEG) has an average molecular weight of about 550 to 650. In some embodiments, the polyethylene glycol (PEG) has an average molecular weight of about 600. [000134] In some embodiments, the polyethylene glycol (PEG) is PEG200. In some embodiments, the polyethylene glycol (PEG) is PEG300. In some embodiments, the polyethylene glycol (PEG) is PEG400. In some embodiments, the polyethylene glycol (PEG) is PEG500. In some embodiments, the polyethylene glycol (PEG) is PEG600. In some embodiments, the polyethylene glycol (PEG) is PEG700. In some embodiments, the polyethylene glycol (PEG) is PEG800. In some embodiments, the polyethylene glycol (PEG) is PEG900. In some embodiments, the polyethylene glycol (PEG) is PEG1000.[000135] In some embodiments, the surfactant is polysorbate (e.g., polysorbate 20). In some embodiments, the surfactant is polysorbate 20. In some embodiments, the surfactant is polysorbate 40. In some embodiments, the surfactant is polysorbate 60. In some embodiments, the surfactant is polysorbate 80.[000136] In some embodiments, the antioxidant is vitamin E. In some embodiments, the antioxidant is ascorbyl palmitate. In some embodiments, the antioxidant is butylated hydroxytoluene. In some embodiments, the antioxidant is triethyl citrate. In some embodiments, the antioxidant is citric acid.[000137] In some embodiments, the composition further comprises a co-solvent (e.g., Transcutol®). In some embodiments, the composition further comprises Transcutol® HP. [000138] In some embodiments, the methods described herein contemplate administering to the subject an oral dosage form comprising the composition as described herein contained within a capsule.[000139] In some embodiments, the compound of Formula (I) is N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, and the N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, is orally administered to the subject as a composition comprising: a solid amorphous dispersion comprising: a) a therapeutically effective amount of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide, or a pharmaceutically acceptable salt thereof; and b) a polymer excipient.[000140] In some embodiments, the composition further comprises a crystallization inhibiting polymer. In some embodiments, the composition further comprises at least one of: diluent or filler, disintegrant, or lubricant.[000141] In some embodiments, the composition comprises: a) a solid amorphous dispersion comprising:i) an effective amount of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide, or a pharmaceutically acceptable salt thereof (e.g., at least 150 mg of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide, or a pharmaceutically acceptable salt thereof); and ii) a polymer excipient in an amount of about 15-25% w / w of the composition; b) a crystallization inhibiting polymer in an amount of about 15-25% w / w of the composition; c) a diluent or filler in an amount of about 20-35% of the composition; d) a disintegrant in an amount of about 3-8% w / w of the composition; and e) a lubricant in an amount of about 1-3% w / w of the composition.[000142] In some embodiments, the polymer excipient is one or more celluloses or derivatives thereof (e.g., microcrystalline cellulose, carboxymethylcellulose, hydroxypropyl methylcellulose (HPMC) or hypromellose, hydroxypropyl methylcellulose acetate succinate (HPMCAS) or hypromellose acetate succinate (e g., HPMCAS-LG, HPMCAS-MG, HPMCAS-HG), HPMC phthalate (HPMCP) (e.g, HPMCP -HP55, HPMCP - HP55S), Methocel™ (e.g, Methocel™ E3 (e.g, Methocel™ E3LV))), hydroxypropyl cellulose, hydroxy ethylcellulose, ethylcellulose, and cellulose acetate phthalate), polyacrylates (e.g, polymethacrylates (e.g, copolymers comprising methacrylic acid and methyl methacrylate, copolymers comprising methacrylic acid and ethyl acrylate, copolymer comprising N,N- dimethylaminoethyl methacrylate, methylmethacrylate, and butylmethacrylate (e.g, Eudragit®, (e.g, Eduragit® EPO, Eudragit® L30 D-55, Eudragit® L100, Eudragit® L100- 55)))), polyvinyl pyrrolidones (PVP), polyvinyl pyrrolidone vinyl acetates (PVPVA), other copolymers (e.g, copolymers comprising polyethylene glycol, polyvinylcaprolactam, and polyvinylacetate (e.g, polyvinyl acetate phthalate (PVAP); polyvinyl caprolactam - polyvinyl acetate - polyethylene glycol graft copolymer)) (e.g, Soluplus®), or copolymers comprising vinyl acetate and N-vinyl-2-pyrrolidone (e.g, Plasdone™ (e.g, Plasdone™ S630 (e.g, Plasdone™ S630 Ultra)), or mixtures thereof.[000143] In some embodiments, the polymer excipient is selected from: hydroxypropyl methylcellulose (HPMC), a copolymer comprising methacrylic acid, a copolymer comprising vinyl acetate, and N-vinyl-2-pyrrolidone, and combinations thereof.[000144] In some embodiments, the polymer excipient is hydroxypropyl methylcellulose acetate succinate (HPMC AS). In some embodiments, the HPMC AS is HPMC AS L grade (HPMC AS-L).[000145] In some embodiments, the polymer excipient is a copolymer comprising methacrylic acid and ethyl acrylate, a copolymer comprising methacrylic acid and methyl methacrylate, or a copolymer comprising N,N-dimethylaminoethyl methacrylate, methylmethacrylate, and butylmethacrylate. In some embodiments, the polymer excipient is a copolymer comprising methacrylic acid and ethyl acrylate. In some embodiments, the polymer excipient is a copolymer of about 1.4: 1 to about 1 : 1.4 methacrylic acid and ethyl acrylate. In some embodiments, the polymer excipient is a copolymer of about 1.2: 1 to about 1 : 1.2 methacrylic acid and ethyl acrylate. In some embodiments, the polymer excipient is a copolymer of 1 : 1 methacrylic acid and ethylacrylate.[000146] The polymer excipient, in some embodiments, also act as a crystallization inhibitor, which helps slow or inhibit crystallization of TTI-101 when it is released from the formulation in the GI tract or mediates supersaturation stabilization (e.g. , stabilization of a supersaturated solution).[000147] In some embodiments, the solid amorphous dispersion comprises about 40% w / w to about 80% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 40% w / w to about 70% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'- yl)-4-methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 40% w / w to about 60% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'- yl)-4-methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 45% w / w to about 55% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'- yl)-4-methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 40% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 45% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 50% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 55% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 60% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 65% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersioncomprises about 70% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 75% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the solid amorphous dispersion comprises about 80% w / w of the N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide.[000148] In some embodiments, the solid amorphous dispersion comprises about 40% w / w to about 80% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises In some embodiments, the solid amorphous dispersion comprises about 40% w / w to about 70% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 40% w / w to about 60% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 45% w / w to about 55% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 40% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 45% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 50% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 55% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 60% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 65% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 70% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 75% w / w of the polymer excipient. In some embodiments, the solid amorphous dispersion comprises about 80% w / w of the polymer excipient.[000149] In some embodiments, the solid amorphous dispersion further comprises an antioxidant.[000150] In some embodiments, the antioxidant is vitamin E. In some embodiments, the antioxidant is ascorbyl palmitate. In some embodiments, the antioxidant is butylated hydroxytoluene. In some embodiments, the antioxidant is triethyl citrate. In some embodiments, the antioxidant is citric acid. In some embodiments, the antioxidant is ascorbic acid.[000151] In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.05 to about 5% (e.g., about 0.1 to about 3%, about 0.2 toabout 1%). In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.05%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.1%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.2%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.3%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.4%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.5%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.6%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.7%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.8%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 0.9%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 1%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 2%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 3%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 4%. In some embodiments, the antioxidant is present in the solid amorphous dispersion in a% w / w of about 5%.[000152] In some embodiments, the solid amorphous dispersion further comprises a surfactant.[000153] In some embodiments, the surfactant is a copolymer comprising polyoxypropylene and polyoxyethylene, polyoxyl 40 hydrogenated castor oil, or a water- soluble derivative of natural Vitamin E (e.g., D-a-tocopheryl polyethylene glycol succinate (vitamin E TPGS)). In some embodiments, the surfactant is pol oxamer 188, pol oxamer 407, Kolliphor® RH40, or vitamin E TPGS.[000154] In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 0.01 to about 10%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 0.01 to about 5%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 0.1 to about 5%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 0.5 to about 5%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 1 to about 5%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about1%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 2%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 3%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 4%. In some embodiments, the surfactant is present in the solid amorphous dispersion in a% w / w of about 5%.[000155] In some embodiments, the composition comprises about 5% w / w to about 50% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 5% w / w to about 40% w / w of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 10% w / w to about 40% w / w of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 15% w / w to about 40% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)- 4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 20% w / w to about 40% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 5% w / w to about 30% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 10% w / w to about 30% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 20% w / w to about 35% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 25% w / w to about 35% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 15% w / w to about 30% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 15% w / w to about 25% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 20% w / w to about 25% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 25% w / w to about 30% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide.[000156] In some embodiments, the composition comprises about 5% w / w of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 10% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 15% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 20% w / w of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 25% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 30% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 35% w / w of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 40% w / w of N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide.[000157] In some embodiments, the composition comprises about 5% w / w to about 50% w / w of the polymer excipient. In some embodiments, the composition comprises about 5% w / w to about 40% w / w of the polymer excipient. In some embodiments, the composition comprises about 10% w / w to about 40% w / w of the polymer excipient. In some embodiments, the composition comprises about 15% w / w to about 40% w / w of the polymer excipient. In some embodiments, the composition comprises about 20% w / w to about 40% w / w of the polymer excipient. In some embodiments, the composition comprises about 5% w / w to about 30% w / w of the polymer excipient. In some embodiments, the composition comprises about 10% w / w to about 30% w / w of the polymer excipient. In some embodiments, the composition comprises about 20% w / w to about 35% w / w of the polymer excipient. In some embodiments, the composition comprises about 25% w / w to about 35% w / w of the polymer excipient. In some embodiments, the composition comprises about 15% w / w to about 30% w / w of the polymer excipient. In some embodiments, the composition comprises about 15% w / w to about 25% w / w of the polymer excipient. In some embodiments, the composition comprises about 20% w / w to about 25% w / w of the polymer excipient. In some embodiments, the composition comprises about 25% w / w to about 30% w / w of the polymer excipient.[000158] In some embodiments, the composition comprises about 5% w / w of the polymer excipient. In some embodiments, the composition comprises about 10% w / w of the polymer excipient. In some embodiments, the composition comprises about 15% w / w of the polymer excipient. In some embodiments, the composition comprises about 20% w / w of the polymer excipient. In some embodiments, the composition comprises about 25% w / w of the polymer excipient. In some embodiments, the composition comprises about 30% w / w of thepolymer excipient. In some embodiments, the composition comprises about 35% w / w of the polymer excipient. In some embodiments, the composition comprises about 40% w / w of the polymer excipient.[000159] In some embodiments, the composition comprises 1:1 in w / w % of N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the polymer excipient. In some embodiments, the composition comprises 1:1.5 in w / w % of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the polymer excipient. In some embodiments, the composition comprises 1.5:1 in w / w % of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the polymer excipient. In some embodiments, the composition comprises 1:2 in w / w % of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the polymer excipient. In some embodiments, the composition comprises 2:1 in w / w % of N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide to the polymer excipient.[000160] Examples of crystallization inhibiting polymers include, but are not limited to, celluloses and derivatives thereof (e.g., microcrystalline cellulose, carboxymethylcellulose, hydroxypropyl methylcellulose (HPMC) or hypromellose, hydroxypropyl methylcellulose acetate succinate (HPMCAS) or hypromellose acetate succinate (e.g., HPMCAS-LG, HPMCAS-MG, HPMCAS-HG, HPMCAS-LF, HPMCAS-LMP), HPMC phthalate (HPMCP) (e.g., HPMCP -HP55, HPMCP - HP55S), Methocel™ (e.g, Methocel™ E3 (e.g, Methocel™ E3LV)), hydroxypropyl cellulose, hydroxyethylcellulose, ethylcellulose, and cellulose acetate phthalate).[000161] In some embodiments, the crystallization inhibiting polymer is a methyl cellulose or HPMC. In some embodiments, the crystallization inhibiting polymer is HPMC. In some embodiments, the crystallization inhibiting polymer is HPMCAS (e.g., HPMCAS- LF, HPMCAS-LMP).[000162] In some embodiments, the composition comprises about 1% w / w to about 40% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 5% w / w to about 40% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 10% w / w to about 40% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 5% w / w to about 30% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 15% w / w to about 35% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 10% w / w to about 30% w / w of the crystallization inhibiting polymer. In some embodiments, the compositioncomprises about 15% w / w to about 40% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 20% w / w to about 40% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 5% w / w to about 30% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 10% w / w to about 30% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 15% w / w to about 30% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 15% w / w to about 25% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 20% w / w to about 30% w / w of the crystallization inhibiting polymer.[000163] In some embodiments, the composition comprises about 1% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 2% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 3% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 4% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 5% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 10% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 15% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 20% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 25% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 30% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 35% w / w of the crystallization inhibiting polymer. In some embodiments, the composition comprises about 40% w / w of the crystallization inhibiting polymer.[000164] In some embodiments, when the selected crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 20% to about 60% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 20% to about 50% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 30% to about 60% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibitingpolymer for the composition is the same as the polymer excipient, the composition comprises about 30% to about 50% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 40% to about 60% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 40% to about 50% w / w of the crystallization inhibiting polymer / polymer excipient.[000165] In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 20% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 30% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 40% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 50% w / w of the crystallization inhibiting polymer / polymer excipient. In some embodiments, when the crystallization inhibiting polymer for the composition is the same as the polymer excipient, the composition comprises about 60% w / w of the crystallization inhibiting polymer / polymer excipient.[000166] In some embodiments, the composition comprises at least 100 mg of a N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 110 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 120 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 130 mg of a N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 140 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 150 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 160 mg of a N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 170 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 180 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 190 mg of a N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 200 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 300 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 400 mg of a N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises at least 500 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide.[000167] In some embodiments, the composition comprises about 200 mg of a N-(l',2- dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 250 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 300 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 350 mg of a N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 400 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4- methoxybenzenesulfonamide. In some embodiments, the composition comprises about 450 mg of a N-(l',2-dihydroxy-l,2'-binaphthalen-4'-yl)-4-methoxybenzenesulfonamide. In some embodiments, the composition comprises about 500 mg of a N-(l',2-dihydroxy-l,2'- binaphthalen-4'-yl)-4-methoxybenzenesulfonamide.[000168] In some embodiments, the composition further comprises at least one additional component. Said component can be intra-granular or extra-granular components that improve processability of the tablet manufacture (e.g., processability of roller compaction, tablet compression and film coating). The additional components can also impart good powder flow and compression characteristics to the material being compressed. Desirable characteristics of the additional components can include high-compressibility so as to allow for strong tablets to be made at low compression forces; good powder flow properties that can improve the powder flow of other excipients in the composition; and cohesiveness, for example to prevent a tablet from crumbling during processing, shipping, and handling. Other components which give physical characteristics to a finished tablet are coloring and flavoring agents (e.g., in the case of chewable tablets). Examples of additionalcomponents are described, for example, in the Handbook of Pharmaceutical Excipients (5thedition), Edited by Raymond C Rowe, Paul J. Sheskey, and Sian C. Owen; Publisher: Pharmaceutical Press.[000169] In some embodiments, the additional components include, but are not limited to, diluents, binders, fillers, disintegrants, surfactants, lubricants, flavoring agents, and colors. The additional component can serve multiple functions. For example, a diluent, in some embodiments, also serve as a filler. As another example, a surfactant, in some embodiments, also serve as a lubricant.[000170] In some embodiments, diluents or fillers are added, for example, to increase the bulk weight of the blend resulting in a practical size for compression. Diluents or fillers that, in some embodiments, are used include one or more of calcium salts such as calcium phosphate dibasic and sugars such as lactose, sucrose, dextrose, microcrystalline cellulose, mannitol, and maltodextrin. Examples of pharmaceutically acceptable fillers and pharmaceutically acceptable diluents include, but are not limited to, confectioner's sugar, compressible sugar, dextrates, dextrin, dextrose, lactose, mannitol, microcrystalline cellulose, powdered cellulose, sorbitol, sucrose and talc. In some embodiments, the diluent or filler is microcrystalline cellulose, which can be manufactured by the controlled hydrolysis of alphacellulose. In some embodiments, suitable microcrystalline cellulose has an average particle size of from about 20 nm to about 200 nm. Suitable microcrystalline cellulose includes Avicel PH 101, Avicel PH 102, Avicel PH 103, Avicel PH 105 and Avicel PH 200. In some embodiments, the diluent or filler is silicified microcrystalline cellulose, such as ProSolv® SMCC 50 or ProSolv® SMCC HD 90. In some embodiments, the diluent or filler is lactose. In some embodiments, the diluent or filler is a mixture of two or more diluents or fillers. In some embodiments, the diluent or filler is microcrystalline cellulose, silicified microcrystalline cellulose, or powdered cellulose, or a mixture thereof.[000171] In some embodiments, the amount of diluent or filler employed in the composition is from about 5% to about 50% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 5% to about 40% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 5% to about 30% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 5% to about 25% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 5% to about 20% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 5% to about 15% w / w. In some embodiments, the amount of diluent or filler employed in thecomposition is from about 5% to about 10% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 10% to about 50% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 10% to about 40% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 10% to about 30% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 10% to about 20% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 15% to about 40% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 15% to about 35% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 15% to about 30% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 15% to about 20% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 20% to about 50% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 20% to about 40% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 20% to about 35% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 5% to about 20% w / w. In some embodiments, the amount of diluent or filler employed in the composition is from about 20% to about 30% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 5% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 10% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 15% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 20% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 25% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 30% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 35% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 40% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 45% w / w. In some embodiments, the amount of diluent or filler employed in the composition is about 50% w / w.[000172] In some embodiments, the composition further includes a lubricant. Lubricants are typically added to prevent the tableting materials from clumping together and from stick to the tablet punches, minimize friction during tablet compression, and to allow for removal of the compressed tablet from the die. Such lubricants are included in the final tablet mix inamounts usually less than 5 by weight per weight of a composition. Examples of lubricants include, but are not limited to, colloidal silica, magnesium trisilicate, talc, magnesium carbonate, stearic acid, magnesium oxide, glycerylbehaptate, polyethylene glycol, ethylene oxide polymers, sodium lauryl sulphate, magnesium stearate, aluminum stearate, calcium stearate, sodium stearyl fumarate, stearic acid, magnesium lauryl stearate, and mixtures of magnesium stearate with sodium lauryl sulphate. In some embodiments, the lubricant is sodium lauryl sulfate or sodium stearyl fumarate, or a mixture thereof. In some embodiments, the lubricant is a mixture of two or more lubricants.[000173] In some embodiments, the amount of lubricant employed in the composition is from about 0.01 to about 5.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.01 to about 4.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.01 to about 3.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.1 to about 3.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.01 to about 2.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.05 to about 2.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.1 to about 2.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.01 to about 1.5% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.05 to about 1.5% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.1 to about 1.5% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.5 to about 4.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.5 to about 3.5% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.5 to about 3.0 w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.5 to about 2.5% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.5 to about 2.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 0.5 to 1.5% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 1.0 to about 3.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 1.0 to about 2.5% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 1.0 to about 2.0% w / w. In some embodiments, the amount of lubricant employed in the composition is from about 1.5 to about 2.0% w / w. In some embodiments, the amount of lubricantemployed in the composition is from about 0.5 to 1.0% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.1% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.2% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.3% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.4% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.5% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.6% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.7% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.8% w / w. In some embodiments, the amount of lubricant employed in the composition is about 0.9% w / w. In some embodiments, the amount of lubricant employed in the composition is about 1.0% w / w. In some embodiments, the amount of lubricant employed in the composition is about 1.5% w / w. In some embodiments, the amount of lubricant employed in the composition is about 1.8% w / w. In some embodiments, the amount of lubricant employed in the composition is about 2.0% w / w. In some embodiments, the amount of lubricant employed in the composition is about 2.5% w / w.[000174] In some embodiments, glidants are added, for example, to improve tablet powder’s flowability by reducing interparticle friction and cohesion. Examples of glidants include magnesium stearate, magnesium carbonate, silica (e.g., colloidal silicon dioxide (such as the grades sold as Aerosil)), starch and talc. Glidants, in some embodiments, are present in the composition at an amount of from 0.01 to about 5% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.01 to about 4.0% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.01 to about 3.0% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.01 to about 2.0% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.05 to about 2.0% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.1 to about 2.0% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.01 to about 1.5% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.05 to about 1.5% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.1 to about 1.5% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.5 to 1.5% w / w. In some embodiments, the amount of glidant employed in the composition is from about 0.5 to 1.0% w / w. In some embodiments, the amount of glidant employed in the composition is about0.1% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.2% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.3% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.4% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.5% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.6% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.7% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.8% w / w. In some embodiments, the amount of glidant employed in the composition is about 0.9% w / w. In some embodiments, the amount of glidant employed in the composition is about 1.0% w / w. In some embodiments, the amount of glidant employed in the composition is about 2.0% w / w.[000175] In some embodiments, a tablet disintegrant is present in the composition at an amount, for example, to expedite dissolution (e.g., increase the rate of tablet disintegration). Disintegrants are excipients which can oppose the physical forces of particle bonding in a tablet when the dosage form is placed in an aqueous environment. Disintegrants include starch derivatives and salts of carboxymethylcellulose. Examples of pharmaceutically acceptable disintegrants include, but are not limited to, starches, e.g., sodium starch glycolate, pregelatinized starch; clays; celluloses; alginates; gums; cross-linked polymers, e.g., crosslinked polyvinyl pyrrolidone (e.g., polyvinyl polypyrrolidone, PVPP, crospovidone, crospolividone), cross-linked calcium carboxymethylcellulose and cross-linked sodium carboxymethylcellulose (sodium croscarmellose); and polysaccharides. In some embodiments, the disintegrant is a mixture of two or more disintegrants.[000176] Generally the amount of disintegrant can be from 0.1 to about 25% w / w of the composition. In some embodiments, the amount of disintegrant is from about 1% to about 15% w / w of the composition. In some embodiments, the amount of disintegrant is from about 1% to about 10% w / w of the composition. In some embodiments, the amount of disintegrant is from about 1% to about 8% w / w of the composition. In some embodiments, the amount of disintegrant is from about 5% to about 10% w / w of the composition. In some embodiments, the amount of disintegrant is from about 3% to about 10% w / w of the composition. In some embodiments, the amount of disintegrant is from about 3% to about 8% w / w of the composition. In some embodiments, the amount of disintegrant is from about 5% to about 10% w / w of the composition. In some embodiments, the amount of disintegrant is from about 5% to about 15% w / w of the composition. In some embodiments, the amount of disintegrant is from about 1% to about 5% w / w of the composition. In some embodiments, the amount ofdisintegrant is about 1% w / w of the composition. In some embodiments, the amount of disintegrant is about 2% w / w of the composition. In some embodiments, the amount of disintegrant is about 3% w / w of the composition. In some embodiments, the amount of disintegrant is about 4% w / w of the composition. In some embodiments, the amount of disintegrant is about 5% w / w. In some embodiments, the amount of disintegrant is about 6% w / w of the composition. In some embodiments, the amount of disintegrant is about 7% w / w of the composition. In some embodiments, the amount of disintegrant is about 8% w / w of the composition. In some embodiments, the amount of disintegrant is about 9% w / w of the composition. In some embodiments, the amount of disintegrant is about 10% w / w of the composition. In some embodiments, the amount of disintegrant is about 15% w / w of the composition.[000177] In some embodiments, the methods described herein contemplate administering to the subject an oral dosage form comprising the composition as described herein in the form of a tablet.[000178] In some embodiments, a composition is set forth as in Table C or Table D (e.g., wherein the total wt. % in the composition does not exceed 100%).Table C: Exemplary CompositionsTable D: Exemplary Compositions[000179] Tablets, in some embodiments, are plain, film, sugar coated, bisected, embossed, layered, and / or sustained-release. They can be made in a variety of sizes, shapes, and colors. Tablets, in some embodiments, are swallowed, chewed, or dissolved in the buccal cavity or beneath the tongue.[000180] In some embodiments, the tablet is coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action, protect tablet ingredients from deterioration, make large or unpleasant-tasking tablets easier to swallow, or to protect from the acid conditions of the stomach. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer that serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol, and cellulose acetate.[000181] In some embodiments, the tablet is polymer-coated.[000182] In some embodiments, the tablet is coated with Opadry® EZ white.[000183] Components of an exemplary 200 mg tablet comprising TTI-101 is shown in Table E.Table E: Example 200 mg TTI-101 Tablet Formulation[000184] In some embodiments, the compositions described herein is administered as a suspension in a pharmaceutically acceptable carrier (e.g., after, optionally, crushing the compositions or solid oral dosage forms into fine powder for the suspension). In some embodiments, the suspension is administered orally. In some embodiments, the suspension is administered via a feeding tube (e.g., via percutaneous endoscopic gastronomy (PEG) tube or G tube). PEG allows for a feeding tube to be place through the abdominal wall and into the stomach, allowing the composition to be put directly into the stomach, bypassing the mouth and esophagus.EXAMPLESExample 1. Safety and efficacy of TTI-101 in cancer patients with p53 mutation.[000185] This study evaluates the safety and efficacy of TTI-101 in advanced solid tumors, such as liver cancer. TTI-101 was administered twice daily at doses of 1.6 (Cohort 1; n=4), 3.2 (Cohort 2; n=3), or 6.4 mg / kg / dose (Cohort 3; n=8) of a Labrasol / PEG400formulation (60:40 %v / v) or 6.4 mg / kg / dose (Cohort 3a; n=37) or 12.8 mg / kg / dose (Cohort 4; n=10) of oral capsule formulation (composition comprising TTI-101 at a concentration of 92 mg / g in a mixture of Kolliphor RH 40 (PEG-40 hydrogenated castor oil), PEG600, Polysorbate 20, Labrasol, and citric acid). Alternatively, TTI-101 was administered twice daily at 6.4mg / kg / dose (Cohort 5; n=7) of oral tablet formulation (comprising 200 mg of TTI- 101).[000186] Preliminary data demonstrates among 10 evaluable participants with HCC and known p53 status treated with TTI-101 as monotherapy, after two 28-day cycles of TTI-101 treatment, 6 of 7 participants with mutant p53 showed clinical benefit (4 of 7 showed stable disease; remaining 2 of 7 showed partial response). On the other hand, 0 of 3 participants with wild type p53 showed clinical benefit (3 of 3 showed progressive disease).[000187] In the phase lb / 2 study, the safety and efficacy of treatment with TTI-101 will be evaluated as monotherapy (cohort A), in combination with pembrolizumab (cohort B), or in combination with atezolizumab + bevacizumab (cohort C), in male and female participants with locally advanced or metastatic, and unresectable HCC. In cohort A, TTI-101 will be administered as a single agent in participants who have recently demonstrated objective progression on up to 3 prior lines of systemic antitumor drug therapy. In cohort B, TTI-101 will be administered in combination with pembrolizumab in participants who have recently demonstrated objective progression following at least 3 months of first-line anti-PD-1 or anti- PD-L1 monotherapy or combination therapy. In cohort C, TTI-101 will be administered in combination with atezolizumab and bevacizumab in participants who were treatment-naive. [000188] TTI-101 will be administered as a 200 mg spray-dried dispersion (SDD) tablets. Exemplary doses are: 400 mg / day (e.g., 2 tablets / day, taken as 1 tablet am / 1 tablet pm orally), 800 mg / day (e.g., 4 tablets / day, taken as 2 tablets am / 2 tablets pm orally), 1200 mg / day (e.g., 6 tablets / day, taken as 3 tablets am / 3 tablets pm orally), and 1600 mg / day (e.g., 8 tablets / day, taken as 4 tablets am / 4 tablets pm orally). In cohort B, pembrolizumab will be administered as an IV infusion, e.g., 400 mg every 6 weeks or 200 mg every 3 weeks (physician’s choice). In cohort C, atezolizumab will be administered as sequential IV infusion, e.g., 1200 mg atezolizumab followed by 15 mg / kg bevacizumab on the same day every 3 weeks. If a dose-limiting toxicity (DLT) is observed in >2 participants at the 800 mg / day dose in phase lb, the dose will be de-escalated to 400 mg / day.[000189] In another phase lb / 2 study, the safety and efficacy of treatment with TTI-101 will be evaluated when combined with palbociclib (or ribociclib) and an aromatase inhibitor(Al) or fulvestrant to participants with breast cancer (e.g., hormone-receptor-positive (HR+) human epidermal receptor 2-negative (HER2)-palbociclib-resistant breast cancer.[000190] TTI-101 will be administered as a 200 mg spray-dried dispersion (SDD) tablets. Exemplary doses are: 400 mg / day (e.g., 2 tablets / day, taken as 1 tablet am / 1 tablet pm orally), 800 mg / day (e.g., 4 tablets / day, taken as 2 tablets am / 2 tablets pm orally), 1200 mg / day (e.g., 6 tablets / day, taken as 3 tablets am / 3 tablets pm orally), and 1600 mg / day (e.g., 8 tablets / day, taken as 4 tablets am / 4 tablets pm orally). Palbociclib will be administered as an oral capsule, e.g., 125 mg, 100 mg, or 75 mg per day (e.g., 21 days every 28 day cycle), ribociclib will be administered as an oral tablet, e.g., 200 mg, 400 mg, or 600 mg per day (e.g., 21 days every 28 days cycle), and aromatase inhibitor will be administered as an oral tablet. Fulvestrant will be administered as an oral tablet.

Claims

CLAIMS1. A method of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (I):or a pharmaceutically acceptable salt thereof, whereinX is selected from the group consisting of hydrogen, phenylsulfanyl, hydroxy - naphthalenyl, quinolin-8-ylsulfanyl, triazol-3-yl sulfanyl, and benzothiazol-2- yl sulfanyl; andYis selected from the group consisting of hydrogen, methyl, chloro, bromo, methoxy, ethoxy, tert-butyl, nitro, methyl ester, acetamide, 1,4 di oxine, fluoro, trifluoro methoxy, acetyl, trifluoro methyl, propyl, cyclohexene, methoxy-phenoxy, chloro phenoxy, tolyloxy, and phenoxy.

2. The method of claim 1, wherein the compound of Formula (I) is:or a pharmaceutically acceptable salt thereof.

3. The method of claim 1, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, kidney cancer, testicular cancer, colon cancer, rectal cancer, gastric cancer, esophageal cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, bone cancer, spleen cancer, gall bladder cancer, brain cancer, pancreatic cancer, stomachcancer, anal cancer, multiple myeloma, post-transplant lymphoproliferative disease, restenosis, myelodysplastic syndrome, leukemia, lymphoma, and acute myelogenous leukemia4. The method of claim 3, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, testicular cancer, colon cancer, rectal cancer, gastric cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, stomach cancer, and leukemia.

5. The method of claim 4, wherein the liver cancer is selected from the group consisting of hepatocellular carcinoma, fibrolamellar carcinoma, bile duct cancer, angiosarcoma, and hepatoblastoma.

6. The method of claim 5, wherein the liver cancer is hepatocellular carcinoma.

7. The method of claim 1, wherein the subject has not been administered a prior cancer therapy.

8. The method of claim 1, wherein the subject has been administered one or more prior cancer therapy.

9. The method of claim 8, wherein the prior cancer therapy selected from the group consisting of sorafenib, pembrolizumab, nivolumab, lenvatinib, bevacizumab, atezolizumab, ramucirumab, cabozantinib, infigratinib, pemigatinib, regorafenib, tremelimumab, and durvalumab, and pharmaceutically acceptable salts thereof, or any combination thereof.

10. The method of claim 9, wherein the prior cancer therapy is selected from the group consisting of sorafenib, pembrolizumab, nivolumab, lenvatinib, and bevacizumab.

11. The method of claim 1, wherein the cancer has progressed from, or the subject was intolerant to, a prior first line cancer therapy.

12. The method of claim 1, wherein the cancer has progressed from, or the subject was intolerant to, a prior second line cancer therapy.

13. The method of claim 1, wherein the cancer has progressed from, or the subject was intolerant to, a prior third line cancer therapy.

14. The method of claim 1, wherein about 1 mg / kg / day to about 50 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

15. The method of claim 14, wherein about 5 mg / kg / day to about 30 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

16. The method of claim 14, wherein about 5 mg / kg / day to about 8 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

17. The method of claim 14, wherein about 10 mg / kg / day to about 15 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

18. The method of claim 14, wherein about 20 mg / kg / day to about 30 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

19. The method of claim 1, wherein about 0.5 mg / kg / dose to about 25 mg / kg / dose of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

20. The method of claim 19, wherein about 2.5 mg / kg / dose to about 15 mg / kg / dose of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

21. The method of claim 19, wherein about 2.5 mg / kg / day to about 4 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

22. The method of claim 19, wherein about 5 mg / kg / day to about 7.5 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

23. The method of claim 19, wherein about 10 mg / kg / day to about 15 mg / kg / day of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject.

24. The method of any one of claims 14-23, wherein the subject is dosed twice daily of the compound of Formula (I), or a pharmaceutically acceptable salt thereof.

25. The method of claim 1, wherein the subject is dosed twice daily of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, at about 1.6 mg / kg / dose.

26. The method of claim 1, wherein the subject is dosed twice daily of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, at about 3.2 mg / kg / dose.

27. The method of claim 1, wherein the subject is dosed twice daily of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, at about 6.4 mg / kg / dose.

28. The method of claim 1, wherein the subject is dosed twice daily of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, at about 12.8 mg / kg / dose.

29. The method of claim 1, wherein about 200 mg to about 2000 mg of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.

30. The method of claim 29, wherein about 400 mg of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.

31. The method of claim 29, wherein about 800 mg of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.

32. The method of claim 29, wherein about 1200 mg of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.

33. The method of claim 29, wherein about 1600 mg of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.

34. The method of claim 1, further comprising administering to the subject one or more additional agent.

35. The method of claim 34, wherein the additional agent is selected from the group consisting of an angiogenesis inhibitor, an anti-PD-1 antibody, and an anti-PD-Ll antibody, or a combination thereof.

36. The method of claim 35, wherein the additional agent is an anti-PD-1 antibody selected from the group consisting of cemiplimab, nivolumab, pembrolizumab, pidilizumab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, sasanlimab, retifanlimab, tebotelimab, ABBV-181, AK104, AK105, BCD-100, BI-754091, CBT-501, CC-90006, GLS-010, HLX10, IBI-308, JNJ-3283, JSOO1, LZM009, MEDI0680 (AMP-514), REGN-2810, SHR-1210, Sym021, TSR- 042, and XmAb20717,37. The method of claim 36, wherein the anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, and pidilizumab.

38. The method of claim 36, wherein the anti-PD-1 antibody is pembrolizumab.

39. The method of claim 35, wherein the additional agent is an anti-PD-Ll antibody selected from the group consisting of atezolizumab, avelumab, durvalumab, envafolimab, FS118, BCD-135, BGB-A333, BGBA-317, CBT-502, CK-301, CS1001, FAZ053, MDX-1105, MSB2311, SHR-1316, M7824, LY3415244, CA-170, and CX-072.

40. The method of claim 39, wherein the anti-PD-Ll antibody is selected from the group consisting of atezolizumab, avelumab, durvalumab, and envafolimab.

41. The method of claim 39, wherein the anti-PD-Ll antibody is atezolizumab.

42. The method of claim 35, wherein the additional agent is an angiogenesis inhibitor selected from the group consisting of bevacizumab, sorafenib, sunitinib, nilotinib, pazopanib, dasatinib, regorafenib, cabozantinib, lenvatinib, ponatinib, ziv-aflibercept, axitinib, tivozanib, everolimus, lenalidomide, thalidomide, vandetanib, orvandetanib, and ramucirumab.

43. The method of claim 42, wherein the angiogenesis inhibitor is bevacizumab.

44. The method of claim 34, wherein the additional agent is selected from the group consisting of a cyclin-dependent kinase inhibitor, an aromatase inhibitor, and hormone therapy, or a combination thereof.

45. The method of claim 44, wherein the additional agent is a cyclin-dependent kinase inhibitor selected from the group consisting of palbociclib, ribociclib, abemaciclib, roniciclib, trilaciclib, lerociclib, milciclib, TQB3303, GLR2007, SHR-6390, PF- 06873600, XZP-3287, ON-123300, ETH-155008, HEC-80797, JS-104, PF-07220060, RMC-4550, and SRX-3177, and pharmaceutically acceptable salts thereof.

46. The method of claim 45, wherein the cyclin-dependent kinase inhibitor is palbociclib or ribociclib.

47. The method of claim 44, wherein the additional agent is an aromatase inhibitor selected from the group consisting of letrozole, anastrozole, exemestane, and testalactone, and pharmaceutically acceptable salts thereof.

48. The method of claim 44, wherein the additional agent is hormone therapy selected from the group consisting of elacestrant, fulvestrant, goserelin, leuprolide, megestrol, tamoxifen, and toremifene, and pharmaceutically acceptable salts thereof.

49. The method of claim 1, wherein the mutant p53 protein is associated with a TP53 gene mutation selected from the group consisting of E2, K120, V143M, A159D, C176F, R196P, C229, C242S, R249S, C275G, R282G, E3, C124, V143A, A161D, C176Y, V197G, Y234H, C242, P250L, C275Y, R282W, Q5, Y126, Q144, Y163N, C176S, E198, Y234C, C242W, I255F, C275F, R282P, S6, S127P, L145Q, Y163H, C176, G199, Y234, G244S, L257Q, C275S, R282Q, Ell, S127T, L145P, Y163D, C176W, G199E, Y236D, G244C, L257P, C275, R283H, Q16, S127F, W146, Y163C, P177S, L201, Y236H, G244R, E258, C275W, R283P, E17, S127Y, D148, Y163S, P177H, E204, Y236N, G244D, E258K, A276P, E285, S20, S127C, P151T, Y163, P177R, Y205D, Y236C, G244V, D259Y, C277Y, E285K, W23, K132, P151S, K164, H179N, Y205S, Y236S, G244A, D259V, C277F, E285V, K24, K132Q, P151A, K164E, H179Y, Y205C, Y236, G245S, N263, C277, E286, E28, K132E, P151R, Q165, H179R, Y205, M237I, G245R, L265P, P278T, E286K, L35, K132R, P151H, S166, H179L, L206, C238R, G245C, G266, P278S, E286Q, Q38, K132M, P152S, Q167, H179Q, R209, C238Y, G245D, G266R, P278A, E286G, L43, K132T, P152L,H168Y, H179, R213, C238F, G245V, G266E, P278H, E286V, E51, K132N, G154V, H168R, E180, R213Q, C238, G245A, G266V, P278L, E286A, Q52, M133K, T155P, H168P, C182, R213L, N239D, M246V, R267W, P278R, E286D, W53, C135R, T155N, H168L, S183, H214R, N239S, M246L, R267P, G279E, E287, E56, C135S, R156P, E171, S183, S2151, N239, M246R, F270C, R280, N288D, E62, C135G, V157F, V173M, QI 92, V216M, S240G, N247I, E271, R280G, K291, R65, C135Y, V157L, V173L, H193Y, V216L, S241T, N247T, V272M, R280T, K292, E68, C135F, V157D, V173G, H193D, V216E, S241A, R248W, R273C, R280K, E294, W91, C135S, V157G, V173E, H193N, V216G, S241P, R248G, R273S, R2801, E298, S94, C135, V157A, R175G, H193L, Y220N, S241F, R248Q, R273G, R280S, K305, Q100, C135W, R158G, R175C, H193P, Y220H, S241C, R248L, R273H, D281N, R306, K1O1, Q136, R158S, R175H, H193R, Y220D, S241Y, R248P, R273L, D281Y, R337C, Y1O3, A138P, R158P, R175L, L194F, Y220C, C242S, R249W, R273P, D281H, Q104, A138G, R158H, R175P, L194R, Y220S, C242R, R249G, V274F, D281G, Y107, K139, R158L, C176R, I195F, Y220, C242G, R249M, V274A, D281V, R110L, C141Y, A159P, C176S, I195T, E221, C242Y, R249K, C275R, D281A, LI 14, C141, A159V, C176G, R196, E224, C242F, R249T, C275S, D281E, and any combination thereof.

50. The method of claim 49, wherein the mutant p53 protein is associated with loss of function of p53.

51. The method of claim 49, wherein the mutant p53 protein is associated with gain of function of p53.

52. A method of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (II):or a pharmaceutically acceptable salt thereof, wherein each occurrence of Ri is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRbRc, NRbC(=O)Rc, C(=O)NRbRc, NRbC(=O)ORc, OC(=O)NRbRc, NRaC(=O)NRbRc, alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle; m is 0, 1, 2, 3, or 4; each occurrence of R2 is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRbRc, NRbC(=O)Rc, C(=O)NRbRc, NRbC(=O)ORc, OC(=O)NRbRc, NRaC(=O)NRbRc, alkyl, alkenyl, cycloalkyl, cycloalkenyl, optionally substituted aryl, optionally substituted aryloxyl, or optionally substituted heterocycle; n2 is 0, 1, 2, 3, 4, or 5;R3 is hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, OC(=O)Ra, alkyl, alkenyl, cycloalkyl, or optionally substituted aryl or heteroaryl;R4 is hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, NRbRc, OC(=O)Ra, alkyl, alkenyl, or cycloalkyl; each occurrence of Rs, Re, and R7 is independently hydrogen, halogen, cyano, nitro, CF3, OCF3, ORa, SRa, C(=O)Ra, OC(=O)Ra, C(=O)ORa, NRbRc, NRbC(=O)Rc, C(=O)NRbRc, NRbC(=O)ORc, OC(=O)NRbRc, NRaC(=O)NRbRc, alkyl, alkenyl, cycloalkyl, optionally substituted aryl, or optionally substituted heterocycle; n3 is 0, 1, 2, 3, or 4; and each occurrence of Ra, Rb, and Rc is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocycle, or aryl; or said Rb and Rc together with the nitrogen atom to which they are bonded optionally form a heterocycle comprising 1-4 heteroatoms.

53. The method of claim 52, wherein the compound of Formula (II) is a compound of Formula (III):or a pharmaceutically acceptable salt thereof.

54. The method of claim 53, wherein the compound of Formula (III) is a compound of Formula (IV):or a pharmaceutically acceptable salt thereof.

55. The method of claim 52, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, kidney cancer, testicular cancer, colon cancer, rectal cancer, gastric cancer, esophageal cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, bone cancer, spleen cancer, gall bladder cancer, brain cancer, pancreatic cancer, stomach cancer, anal cancer, multiple myeloma, post-transplant lymphoproliferative disease, restenosis, myelodysplastic syndrome, leukemia, lymphoma, and acute myelogenous leukemia56. The method of claim 55, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, testicular cancer, colon cancer, rectal cancer, gastric cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, stomach cancer, and leukemia.

57. The method of claim 56, wherein the liver cancer is selected from the group consisting of hepatocellular carcinoma, fibrolamellar carcinoma, bile duct cancer, angiosarcoma, and hepatoblastoma.

58. The method of claim 57, wherein the liver cancer is hepatocellular carcinoma.

59. The method of claim 52, wherein the subject has not been administered a prior cancer therapy.

60. The method of claim 52, wherein the subject has been administered one or more prior cancer therapy.

61. The method of claim 60, wherein the prior cancer therapy selected from the group consisting of sorafenib, pembrolizumab, nivolumab, lenvatinib, bevacizumab, atezolizumab, ramucirumab, cabozantinib, infigratinib, pemigatinib, regorafenib, tremelimumab, and durvalumab, and pharmaceutically acceptable salts thereof, or any combination thereof.

62. The method of claim 61, wherein the prior cancer therapy is selected from the group consisting of sorafenib, pembrolizumab, nivolumab, lenvatinib, and bevacizumab.

63. The method of claim 52, wherein the cancer has progressed from, or the subject was intolerant to, a prior first line cancer therapy.

64. The method of claim 52, wherein the cancer has progressed from, or the subject was intolerant to, a prior second line cancer therapy.

65. The method of claim 52, wherein the cancer has progressed from, or the subject was intolerant to, a prior third line cancer therapy.

66. The method of claim 52, wherein about 1 mg / kg / day to about 50 mg / kg / day of the compound of Formula (II), or a pharmaceutically acceptable salt thereof, is administered to the subject.

67. The method of claim 52, wherein about 0.5 mg / kg / dose to about 25 mg / kg / dose of the compound of Formula (II), or a pharmaceutically acceptable salt thereof, is administered to the subject.

68. The method of claim 52, wherein about 200 mg to about 2000 mg of the compound of Formula (II), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.

69. The method of claim 52, further comprising administering to the subject one or more additional agent.

70. The method of claim 69, wherein the additional agent is selected from the group consisting of an angiogenesis inhibitor, an anti-PD-1 antibody, and an anti-PD-Ll antibody, or a combination thereof.

71. The method of claim 70, wherein the additional agent is an anti-PD-1 antibody selected from the group consisting of cemiplimab, nivolumab, pembrolizumab, pidilizumab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, sasanlimab, retifanlimab, tebotelimab, ABBV-181, AK104, AK105, BCD-100, BI-754091, CBT-501, CC-90006, GLS-010, HLX10, IBI-308, JNJ-3283, JS001, LZM009, MEDI0680 (AMP-514), REGN-2810, SHR-1210, Sym021, TSR- 042, and XmAb20717.

72. The method of claim 71, wherein the anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, and pidilizumab.

73. The method of claim 71, wherein the anti-PD-1 antibody is pembrolizumab.

74. The method of claim 70, wherein the additional agent is an anti-PD-Ll antibody selected from the group consisting of atezolizumab, avelumab, durvalumab, envafolimab, FS118, BCD-135, BGB-A333, BGBA-317, CBT-502, CK-301, CS1001, FAZ053, MDX-1105, MSB2311, SHR-1316, M7824, LY3415244, CA-170, and CX-072.

75. The method of claim 74, wherein the anti-PD-Ll antibody is selected from the group consisting of atezolizumab, avelumab, durvalumab, and envafolimab.

76. The method of claim 74, wherein the anti-PD-Ll antibody is atezolizumab.

77. The method of claim 70, wherein the additional agent is an angiogenesis inhibitor selected from the group consisting of bevacizumab, sorafenib, sunitinib, nilotinib, pazopanib, dasatinib, regorafenib, cabozantinib, lenvatinib, ponatinib, ziv-aflibercept, axitinib, tivozanib, everolimus, lenalidomide, thalidomide, vandetanib, orvandetanib, and ramucirumab.

78. The method of claim 77, wherein the angiogenesis inhibitor is bevacizumab.

79. The method of claim 69, wherein the additional agent is selected from the group consisting of a cyclin-dependent kinase inhibitor, an aromatase inhibitor, and hormone therapy, or a combination thereof.

80. The method of claim 79, wherein the additional agent is a cyclin-dependent kinase inhibitor selected from the group consisting of palbociclib, ribociclib, abemaciclib, roniciclib, trilaciclib, lerociclib, milciclib, TQB3303, GLR2007, SHR-6390, PF- 06873600, XZP-3287, ON-123300, ETH-155008, HEC-80797, JS-104, PF-07220060, RMC-4550, and SRX-3177, and pharmaceutically acceptable salts thereof.

81. The method of claim 80, wherein the cyclin-dependent kinase inhibitor is palbociclib or ribociclib, or pharmaceutically acceptable salts thereof.

82. The method of claim 79, wherein the additional agent is an aromatase inhibitor selected from the group consisting of letrozole, anastrozole, exemestane, and testalactone, and pharmaceutically acceptable salts thereof.

83. The method of claim 79, wherein the additional agent is hormone therapy selected from the group consisting of elacestrant, fulvestrant, goserelin, leuprolide, megestrol, tamoxifen, and toremifene, and pharmaceutically acceptable salts thereof.

84. The method of claim 52, wherein the mutant p53 protein is associated with a TP53 gene mutation selected from the group consisting of E2, K120, V143M, A159D, C176F, R196P, C229, C242S, R249S, C275G, R282G, E3, C124, V143A, A161D, C176Y, V197G, Y234H, C242, P250L, C275Y, R282W, Q5, Y126, Q144, Y163N, C176S, E198, Y234C, C242W, I255F, C275F, R282P, S6, S127P, L145Q, Y163H, C176, G199, Y234, G244S, L257Q, C275S, R282Q, Ell, S127T, L145P, Y163D, C176W, G199E, Y236D, G244C, L257P, C275, R283H, Q16, S127F, W146, Y163C, P177S, L201, Y236H, G244R, E258, C275W, R283P, E17, S127Y, D148, Y163S, P177H, E204, Y236N, G244D, E258K, A276P, E285, S20, S127C, P151T, Y163, P177R, Y205D, Y236C, G244V, D259Y, C277Y, E285K, W23, K132, P151S, K164, H179N, Y205S, Y236S, G244A, D259V, C277F, E285V, K24, K132Q, P151A, K164E, H179Y, Y205C, Y236, G245S, N263, C277, E286, E28, K132E, P151R, Q165, H179R, Y205, M237I, G245R, L265P, P278T, E286K, L35, K132R, P151H, S166, H179L, L206, C238R, G245C, G266, P278S, E286Q, Q38, K132M, P152S, Q167, H179Q, R209, C238Y, G245D, G266R, P278A, E286G, L43, K132T, P152L,H168Y, H179, R213, C238F, G245V, G266E, P278H, E286V, E51, K132N, G154V, H168R, E180, R213Q, C238, G245A, G266V, P278L, E286A, Q52, M133K, T155P, H168P, C182, R213L, N239D, M246V, R267W, P278R, E286D, W53, C135R, T155N, H168L, S183, H214R, N239S, M246L, R267P, G279E, E287, E56, C135S, R156P, E171, S183, S2151, N239, M246R, F270C, R280, N288D, E62, C135G, V157F, V173M, QI 92, V216M, S240G, N247I, E271, R280G, K291, R65, C135Y, V157L, V173L, H193Y, V216L, S241T, N247T, V272M, R280T, K292, E68, C135F, V157D, V173G, H193D, V216E, S241A, R248W, R273C, R280K, E294, W91, C135S, V157G, V173E, H193N, V216G, S241P, R248G, R273S, R2801, E298, S94, C135, V157A, R175G, H193L, Y220N, S241F, R248Q, R273G, R280S, K305, Q100, C135W, R158G, R175C, H193P, Y220H, S241C, R248L, R273H, D281N, R306, K1O1, Q136, R158S, R175H, H193R, Y220D, S241Y, R248P, R273L, D281Y, R337C, Y1O3, A138P, R158P, R175L, L194F, Y220C, C242S, R249W, R273P, D281H, Q104, A138G, R158H, R175P, L194R, Y220S, C242R, R249G, V274F, D281G, Y107, K139, R158L, C176R, I195F, Y220, C242G, R249M, V274A, D281V, R110L, C141Y, A159P, C176S, I195T, E221, C242Y, R249K, C275R, D281A, LI 14, C141, A159V, C176G, R196, E224, C242F, R249T, C275S, D281E, and any combination thereof.

85. The method of claim 84, wherein the mutant p53 protein is associated with loss of function of p53.

86. The method of claim 84, wherein the mutant p53 protein is associated with gain of function of p53.

87. A method of treating a cancer characterized by the presence of a mutant p53 protein in a subject in need thereof, comprising administering to the subject an effective amount of a compound of Formula (V):or a pharmaceutically acceptable salt or a solvate thereof, whereinA is halo, Ci-4alkyl, Ci-4alkoxy, Ci-4haloalkyl, or Ci-4haloalkoxy;R1, R2, and R3are each independently H, C(=O)NRARB, P(=O)(OH)(RC), or Ci-4alkylene-O-P(=O)(OH)(Rc); orR1and R2together form:provided that R1, R2and R3are not simultaneously H;RAis H or Ci-4alkyl;RBis Ci-6alkylene-N(H)(Ci-ealkyl), Ci-ealkylene-(5-8 membered heterocyclyl), Ci- ealkylene-C(=O)OH optionally substituted with amine, Ci-4alkyl, or benzyl;Rcis Ci-4alkyl or hydroxy; and n is an integer 0, 1, 2, or 3.

88. A method of claim 87, wherein the compound of Formula (V) is:r pharmaceutically acceptable salts or solvates thereof.

89. The method of claim 87, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, kidney cancer, testicular cancer, colon cancer, rectal cancer, gastric cancer, esophageal cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, bone cancer, spleen cancer, gall bladder cancer, brain cancer, pancreatic cancer, stomach cancer, anal cancer, multiple myeloma, post-transplant lymphoproliferative disease, restenosis, myelodysplastic syndrome, leukemia, lymphoma, and acute myelogenous leukemia90. The method of claim 89, wherein the cancer is selected from the group consisting of liver cancer, lung cancer, head and neck cancer, breast cancer, testicular cancer, colon cancer, rectal cancer, gastric cancer, skin cancer, malignant melanoma, prostate cancer, ovarian cancer, cervical cancer, stomach cancer, and leukemia.

91. The method of claim 90, wherein the liver cancer is selected from the group consisting of hepatocellular carcinoma, fibrolamellar carcinoma, bile duct cancer, angiosarcoma, and hepatoblastoma.

92. The method of claim 91, wherein the liver cancer is hepatocellular carcinoma.

93. The method of claim 87, wherein the subject has not been administered a prior cancer therapy.

94. The method of claim 87, wherein the subject has been administered one or more prior cancer therapy.

95. The method of claim 94, wherein the prior cancer therapy selected from the group consisting of sorafenib, pembrolizumab, nivolumab, lenvatinib, bevacizumab, atezolizumab, ramucirumab, cabozantinib, infigratinib, pemigatinib, regorafenib,tremelimumab, and durvalumab, and pharmaceutically acceptable salts thereof, or any combination thereof.

96. The method of claim 95, wherein the prior cancer therapy is selected from the group consisting of sorafenib, pembrolizumab, nivolumab, lenvatinib, and bevacizumab.

97. The method of claim 87, wherein the cancer has progressed from, or the subject was intolerant to, a prior first line cancer therapy.

98. The method of claim 87, wherein the cancer has progressed from, or the subject was intolerant to, a prior second line cancer therapy.

99. The method of claim 87, wherein the cancer has progressed from, or the subject was intolerant to, a prior third line cancer therapy.

100. The method of claim 87, wherein about 1 mg / kg / day to about 50 mg / kg / day of the compound of Formula (V), or a pharmaceutically acceptable salt thereof, is administered to the subject.

101. The method of claim 87, wherein about 0.5 mg / kg / dose to about 25 mg / kg / dose of the compound of Formula (V), or a pharmaceutically acceptable salt thereof, is administered to the subject.

102. The method of claim 87, wherein about 200 mg to about 2000 mg of the compound of Formula (V), or a pharmaceutically acceptable salt thereof, is administered to the subject per day.

103. The method of claim 87, further comprising administering to the subject one or more additional agent.

104. The method of claim 103, wherein the additional agent is selected from the group consisting of an angiogenesis inhibitor, an anti-PD-1 antibody, and an anti-PD- L1 antibody, or a combination thereof.

105. The method of claim 104, wherein the additional agent is an anti-PD-1 antibody selected from the group consisting of cemiplimab, nivolumab, pembrolizumab, pidilizumab, spartalizumab, camrelizumab, sintilimab, tislelizumab, toripalimab, dostarlimab, sasanlimab, retifanlimab, tebotelimab, ABBV-181, AK104,AK105, BCD-100, BL754091, CBT-501, CC-90006, GLS-010, HLX10, IBL308, JNJ-3283, JS001, LZM009, MEDI0680 (AMP-514), REGN-2810, SHR-1210, Sym021, TSR-042, and XmAb20717,106. The method of claim 105, wherein the anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, and pidilizumab.

107. The method of claim 105, wherein the anti-PD-1 antibody is pembrolizumab.

108. The method of claim 104, wherein the additional agent is an anti-PD-Ll antibody selected from the group consisting of atezolizumab, avelumab, durvalumab, envafolimab, FS118, BCD-135, BGB-A333, BGBA-317, CBT-502, CK-301, CS1001, FAZ053, MDX-1105, MSB2311, SHR-1316, M7824, LY3415244, CA-170, and CX-072.

109. The method of claim 108, wherein the anti-PD-Ll antibody is selected from the group consisting of atezolizumab, avelumab, durvalumab, and envafolimab.

110. The method of claim 108, wherein the anti-PD-Ll antibody is atezolizumab.

111. The method of claim 104, wherein the additional agent is an angiogenesis inhibitor selected from the group consisting of bevacizumab, sorafenib, sunitinib, nilotinib, pazopanib, dasatinib, regorafenib, cabozantinib, lenvatinib, ponatinib, ziv- aflibercept, axitinib, tivozanib, everolimus, lenalidomide, thalidomide, vandetanib, orvandetanib, and ramucirumab.

112. The method of claim 111, wherein the angiogenesis inhibitor is bevacizumab.

113. The method of claim 103, wherein the additional agent is selected from the group consisting of a cyclin-dependent kinase inhibitor, an aromatase inhibitor, and hormone therapy, or a combination thereof.

114. The method of claim 113, wherein the additional agent is a cyclin-dependent kinase inhibitor selected from the group consisting of palbociclib, ribociclib, abemaciclib, roniciclib, trilaciclib, lerociclib, milciclib, TQB3303, GLR2007, SHR- 6390, PF-06873600, XZP-3287, ON-123300, ETH-155008, HEC-80797, JS-104, PF- 07220060, RMC-4550, and SRX-3177, and pharmaceutically acceptable salts thereof.

115. The method of claim 114, wherein the cyclin-dependent kinase inhibitor is palbociclib or ribociclib, or pharmaceutically acceptable salts thereof.

116. The method of claim 113, wherein the additional agent is an aromatase inhibitor selected from the group consisting of letrozole, anastrozole, exemestane, and testalactone, and pharmaceutically acceptable salts thereof.

117. The method of claim 113, wherein the additional agent is hormone therapy selected from the group consisting of elacestrant, fulvestrant, goserelin, leuprolide, megestrol, tamoxifen, and toremifene, and pharmaceutically acceptable salts thereof.

118. The method of claim 87, wherein the mutant p53 protein is associated with a TP53 gene mutation selected from the group consisting of E2, K120, V143M, A159D, C176F, R196P, C229, C242S, R249S, C275G, R282G, E3, C124, V143A, A161D, C176Y, V197G, Y234H, C242, P250L, C275Y, R282W, Q5, Y126, Q144, Y163N, C176S, E198, Y234C, C242W, I255F, C275F, R282P, S6, S127P, L145Q, Y163H, C176, G199, Y234, G244S, L257Q, C275S, R282Q, Ell, S127T, L145P, Y163D, C176W, G199E, Y236D, G244C, L257P, C275, R283H, Q16, S127F, W146, Y163C, P177S, L201, Y236H, G244R, E258, C275W, R283P, E17, S127Y, D148, Y163S, P177H, E204, Y236N, G244D, E258K, A276P, E285, S20, S127C, P151T, Y163, P177R, Y205D, Y236C, G244V, D259Y, C277Y, E285K, W23, K132, P151S, K164, H179N, Y205S, Y236S, G244A, D259V, C277F, E285V, K24, K132Q, P151A, K164E, H179Y, Y205C, Y236, G245S, N263, C277, E286, E28, K132E, P151R, Q165, H179R, Y205, M237I, G245R, L265P, P278T, E286K, L35, K132R, P151H, S166, H179L, L206, C238R, G245C, G266, P278S, E286Q, Q38, K132M, P152S, Q167, H179Q, R209, C238Y, G245D, G266R, P278A, E286G, L43, K132T, P152L, H168Y, H179, R213, C238F, G245V, G266E, P278H, E286V, E51, K132N, G154V, H168R, E180, R213Q, C238, G245A, G266V, P278L, E286A, Q52, M133K, T155P, H168P, C182, R213L, N239D, M246V, R267W, P278R, E286D, W53, C135R, T155N, H168L, S183, H214R, N239S, M246L, R267P, G279E, E287, E56, C135S, R156P, E171, S183, S2151, N239, M246R, F270C, R280, N288D, E62, C135G, V157F, V173M, QI 92, V216M, S240G, N247I, E271, R280G, K291, R65, C135Y, V157L, V173L, H193Y, V216L, S241T, N247T, V272M, R280T, K292, E68, C135F, V157D, V173G, H193D, V216E, S241A, R248W, R273C, R280K, E294, W91, C135S, V157G, V173E, H193N, V216G, S241P, R248G, R273S, R2801, E298,S94, C135, V157A, R175G, H193L, Y220N, S241F, R248Q, R273G, R280S, K305, Q100, C135W, R158G, R175C, H193P, Y220H, S241C, R248L, R273H, D281N, R306, K1O1, Q136, R158S, R175H, H193R, Y220D, S241Y, R248P, R273L, D281Y, R337C, Y1O3, A138P, R158P, R175L, L194F, Y220C, C242S, R249W, R273P, D281H, Q104, A138G, R158H, R175P, L194R, Y220S, C242R, R249G, V274F, D281G, Y107, K139, R158L, C176R, I195F, Y220, C242G, R249M, V274A, D281V, R110L, C141Y, A159P, C176S, I195T, E221, C242Y, R249K, C275R, D281A, LI 14, C141, A159V, C176G, R196, E224, C242F, R249T, C275S, D281E, and any combination thereof.

119. The method of claim 118, wherein the mutant p53 protein is associated with loss of function of p53.

120. The method of claim 118, wherein the mutant p53 protein is associated with gain of function of p53.