COMPOSITIONS FOR USE IN SRC KINASE INHIBITION AND THE TREATMENT AND PREVENTION OF ASSOCIATED DISORDERS

Abstract

The present invention comprises compounds and compositions that inhibit Src kinase and methods for treating or preventing disorders associated with it. In some embodiments, the invention comprises compositions and combinations of agents that act simultaneously to inhibit the growth of cancer cells, and in particular, the compositions and combinations can be used for the treatment of cancer.

Description

COMPOSITIONS FOR USE FOR THE INHIBITION OF SRC KINASE AND THE TREATMENT AND PREVENTION OF ASSOCIATED DISORDERS CROSS REFERENCE TO RELATED REQUESTS The present application claims the benefit of US provisional patent application Ν.θ62 / 901 540, filed on September 17, 2019, which is incorporated herein in its entirety by this reference in its entirety. FIELD OF THE INVENTION The present invention comprises compounds and compositions that inhibit Src kinase and methods for treating or preventing disorders associated therewith. In some embodiments, the invention comprises compositions and combinations of agents that act simultaneously to inhibit the growth of cancer cells and, in particular, the compositions and combinations can be used for the treatment of cancer. BACKGROUND OF THE INVENTION The National Cancer Institute has estimated that in the United States alone, 1 in 3 people will develop cancer during their lifetime. The widespread occurrence of this disease underscores the need for improved anticancer regimens for the treatment of malignancies. Vernonia cinerea (Asteracea family), also commonly called Sahadevi, is a species native to tropical Asia and Africa. This branching herb is approximately 0.5 to 3 feet tall and is found throughout India. Different parts of the plant, such as stems, seeds, leaves, roots and flowers, have been mentioned in ancient texts and alternative medicines. Several studies from the Asian subcontinent have reported the use of Sahadevi as an anthelmintic, antibacterial, antiviral, antifungal, anti-inflammatory, diuretic and stomachic. Phytochemical screening of the whole plant extract revealed the presence of triterpene compounds such as beta amyrin acetate, lupeol acetate; sterols such as beta-sitosterol, stigmasterol and alpha-spinasterol, and phenolic resins. Recently, the antitumor activity of the plant extract has also been established. However, the identification of biologically active compounds responsible for antitumor activity has been difficult to achieve. The inventors have identified the active compound and certain derivatives responsible for the anti-tumor activity of crude extract of Sahadevi by using various extraction and bioanalytical tools. DIGEST OF THE INVENTION The invention generally encompasses compounds that inhibit a specific tyrosine kinase (i.e., Src kinase) and compositions that include such compounds, as well as frncacn / zznz / q / υιλι combinations of such compositions with known anticancer drugs for treating and preventing cancer. . In another embodiment, the invention encompasses methods of using the compositions, including active compounds or derivatives and metabolites thereof, in any disease condition in which the activity of Src tyrosine kinase or Src family kinases has been implicated ( SFK), for example, but not limited to, the development, maintenance, progression and metastatic spread of cancers. In certain embodiments, the compound and compositions are effective against human cancer and tumor cells, including, but not limited to, those associated with chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL). ), breast cancer (e.g. triple negative, HER2+, etc.), and colon cancer. In one embodiment, the compounds of the invention include compounds of the following structure: frncacn / zznz / q / υιλι Formula I where X is O or S; Ri is a hydrogen, or a substituted or unsubstituted substituent including, but not limited to, lower alkyl, a lower alkenyl, a lower alkynyl, -(CH2)mR7, (CH2)m-OH, -(CH2)m- Olower alkyl, -(CH2)m-O-lower alkyl, -(CH2)n-O-(CH2)m-R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl , -(CH2)n-S-(CH2)m-R7 each of R2-Re is independently a hydrogen, a hydroxyl, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an amino, a nitro, an azido , a sulfate, a sulfonate, a sulfonamide, -(CH2)mR7, (CH2)m-OH, -(CH2)m-O-lower alkyl, -(CH2)m-O-lower alkyl, -(CH2)nO-(CH2) m-R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl, (CH2)n-S-(CH2)m-R7 R7 represents, for each occurrence, hydrogen, hydroxyl or a substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, benzyl, cycloalkyl, cycloalkenyl or heterocycle; and wherein each occurrence of m is independently an integer from 1 to 9, and each occurrence of n is independently an integer from 1 to 9; or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diasteromer, a racemate or a pharmaceutically acceptable mixture thereof. In another embodiment, the compounds of the invention include compounds of the following structure: hncQQn / zznz / q / υιλι where X is O or S; Ri is a hydrogen, or a substituted or unsubstituted substituent including, but not limited to, lower alkyl, a lower alkenyl, a lower alkynyl, -(CH2)mR7, (CH2)m-OH, -(CH2)m- Olower alkyl, -(CH2)m-O-lower alkyl, -(CH2)n-O-(CH2)m-R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl , -(CH2)n-S-(CH2)m-R7 each of R2-Re is independently a hydrogen, a hydroxyl, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an amino, a nitro, an azido, a sulfate, a sulfonate, a sulfonamide, -(CH2)mR7, (CH2)m-OH, -(CH2)m-O-lower alkyl, -(CH2)m-O-lower alkyl, -(CH2)n-O-(CH2)m -R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl, (CH2)n-S-(CH2)m-R7 each of R7, Rs and Rg independently represents, for each occurrence, hydrogen, hydroxyl or a substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, benzyl, cycloalkyl, cycloalkenyl or heterocycle; and where each occurrence of m and n is independently an integer from 1 to 9, and each occurrence of z is independently an integer from 1 to 9; or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diasteromer, a racemate or a pharmaceutically acceptable mixture thereof. In another embodiment, the compounds of the invention include compounds of the following structure: frncacn / zznz / q / υιλι Formula III Ri is a hydrogen, or a substituted or unsubstituted substituent including, but not limited to, lower alkyl, a lower alkenyl, a lower alkynyl, -(CH2)mR7, -(CH2)m-OH, (CH2)m( =X)XR7, -(CH2)m(=X)R7, -(CH2)m-X-lower alkyl, -(CH2)m-X-lower alkyl, -(CH2)n-X(CH2)m-R7, -(CH2) m-XR7where X is O or S; each of R2, Rs and Re is independently a hydrogen, a hydroxyl, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an amino, a nitro, an azido, a sulfate, a sulfonate, a sulfonamide, - (CH2)mR7, (CH2)m-OH, -(CH2)m-O-lower alkyl, -(CH2)m-O-lower alkyl, -(CH2)n-O-(CH2)m-R7, -(CH2)m-SH , -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl, (CH2)n-S-(CH2)m-R7 R'7 represents, for each occurrence, hydrogen, hydroxyl or a substituted or unsubstituted alkyl, acyl, alkenyl, aryl, aralkyl, benzyl, cycloalkyl, cycloalkenyl or heterocycle; and wherein each occurrence of m is independently an integer from 1 to 9, and each occurrence of n is independently an integer from 1 to 9; or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diasteromer, a racemate or a pharmaceutically acceptable mixture thereof. In certain embodiments, Ri is a straight chain or branched alkyl having six or fewer carbon atoms (e.g., O-Ce for straight chain, C3-C6 for branched chain), and in another embodiment, a straight chain or branched alkyl has four or fewer carbon atoms. The present invention relates to a method of treating or preventing cancer by administering a composition that includes a compound of Formula (I) or (II) or a (III) pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate, to a subject in need thereof, where administration of the composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, results in one or more of the following: prevention of the proliferation of cancer cells by accumulation of cells in one or more phases of the cell cycle (for example, G1, G1 / S, G2 / M), or induction of cellular senescence, or promotion of tumor cell differentiation; promotion of cell death in cancer cells via cytotoxicity, necrosis or apoptosis, without a significant amount of cell death in normal cells, antitumor activity in animals with a therapeutic index of at least 2. As used herein, the "index therapeutic" is the maximum tolerated dose divided by the effective dose. In certain embodiments, the invention encompasses methods of modulating a Src kinase that comprise the administration of a following structure: frncacn / zznz / q / υιλι where X is O or S; Ri is a hydrogen, or a substituted or unsubstituted substituent including, but not limited to, lower alkyl, a lower alkenyl, a lower alkynyl, -(CH2)mR7, (CH2)m-OH, -(CH2)m- Olower alkyl, -(CH2)m-O-lower alkyl, -(CH2)n-O-(CH2)m-R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl , -(CH2)n-S-(CH2)rr1-R7 each of R2-Re is independently a hydrogen, a hydroxyl, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an amino, a nitro, an azido , a sulfate, a sulfonate, a sulfonamide, -(CH2)mR7, (CH2)m-OH, -(CH2)m-O-lower alkyl, -(CH2)m-O-lower alkyl, -(CH2)n-O-(CH2) m-R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl, (CH2)n-S-(CH2)m-R7 each of R7, Re and R9 independently represents , for each occurrence, hydrogen, hydroxyl or a substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, benzyl, cycloalkyl, cycloalkenyl or heterocycle; and where each occurrence of m and n is independently an integer from 1 to 9, and each occurrence of z is independently an integer from 1 to 9; or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diasteromer, a racemate or a pharmaceutically acceptable mixture thereof. In certain embodiments, each of Rs and R4 is -OH. In certain embodiments, each of R2 and R3 is -OH. In certain embodiments, z is 2 and each of Rs and R9 is -H. In certain embodiments, z is 2; each of R1, R2, R5, Re, Rs and R9-H; and R3 and R4 are each -OH. In certain embodiments, X is O. In certain embodiments, each of Ri, R2, R3, Re, Rs and R9 is -H; each of R4 and Rs is -OH; X is O; and Z is 2. In certain embodiments, the compound of formula II has the following structure: hncQQn / zznz / q / υιλι Exemplary compound E05 or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diasteromer, a racemate or a pharmaceutically acceptable mixture thereof. In certain embodiments, the compound of formula II is a prodrug of the following structure: Formula IV wherein R1 comprises esters, including ethyl esters, morpholinoethanol esters, acetate, dialkylamine acetates, formates, phosphates, sulfates and benzoate derivatives; carbamates including Ν,Ν-dimethylaminocarbonyl hydroxy functional groups, and N-acyl derivatives. The invention also encompasses prodrugs of the formula: Formula IV hncQQn / zznz / q / υιλι where Ri comprises esters, including alkyl esters, morpholinoethanol esters, acetate, dialkylamine acetates, formates, phosphates, sulfates and benzoate derivatives; carbamates including Ν,Ν-dimethylaminocarbonyl hydroxy functional groups, and N-acyl derivatives. In other embodiments, the invention encompasses methods of treating cancer, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), breast cancer and colon cancer, comprising the administration of a following structure: Formula II where X is O or S; Ri is a hydrogen, or a substituted or unsubstituted substituent including, but not limited to, lower alkyl, a lower alkenyl, a lower alkynyl, -(CH2)mR7, (CH2)m-OH, -(CH2)m- Olower alkyl, -(CH2)m-O-lower alkyl, -(CH2)n-O-(CH2)m-R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl , -(CH2)n-S-(CH2)m-R7 each of R2-Re is independently a hydrogen, a hydroxyl, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an amino, a nitro, an azido , a sulfate, a sulfonate, a sulfonamide, -(CH2)mR7, (CH2)m-OH, -(CH2)m-O-lower alkyl, -(CH2)m-O-lower alkyl, -(CH2)nO-(CH2) m-R7, -(CH2)m-SH, -(CH2)m-S-lower alkyl, -(CH2)m-S-lower alkyl, (CH2)n-S-(CH2)m-R7 each of R7, Rs and R9 independently represents , for each occurrence, hydrogen, hydroxyl or a substituted or unsubstituted alkyl, alkenyl, aryl, aralkyl, benzyl, cycloalkyl, cycloalkenyl or heterocycle; and where each occurrence of m and n is independently an integer from 1 to 9, and each occurrence of z is independently an integer from 1 to 9; or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diasteromer, a racemate or a pharmaceutically acceptable mixture thereof. In certain embodiments, each of R3 and R4 is -OH. In certain embodiments, each of R2 and R3 is -OH. In certain embodiments, z is 2 and each of Rs and R9 is -H. In certain embodiments, z is 2; each of R1, R2, R5, Re, Rs and R9-H; and R3 and R4 are each -OH. In certain embodiments, X is O. In certain embodiments, each of R1, R2, R3, Re, Rs and R9 is -H; each of R4 and Rs is -OH; X is O; and Z is 2. In certain embodiments, the compound of formula II has the following structure: frncacn / zznz / q / υιλι Exemplary compound E05 or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diasteromer, a racemate or a pharmaceutically acceptable mixture thereof. In certain embodiments, the compound of formula II is a prodrug of the following structure: Formula IV frncacn / zznz / q / υιλι wherein R1 comprises esters, including ethyl esters, morpholinoethanol esters, acetate, dialkylamine acetates, formates, phosphates, sulfates and benzoate derivatives; carbamates including Ν,Ν-dimethylaminocarbonyl hydroxy functional groups, and N-acyl derivatives. In certain embodiments, the invention further encompasses the administration of one or more additional therapeutic agents comprising antineoplastic agents or chemotherapeutic agents. One skilled in the art may refer to general reference texts for detailed descriptions of known techniques discussed herein or equivalent techniques. These texts include Ausubel et al., Current Protocols in Molecular Biology, John Wiley and Sons, Inc. (2005); Sambrook et al., Molecular Cloning, A Laboratory Manual (3rd edition), Coid Spring Harbor Press, Coid Spring Harbor, N.Y. (2000); Coligan et al., Current Protocols in Immunology, John Wiley & Sons, N.Y.; Enna et al., Current Protocols in Pharmacology, John Wiley & Sons, N.Y.; Fingí et al., The Pharmacological Basis of Therapeutics (1975), Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 18th edition (1990). Of course, these texts may also be referred to when making or using an aspect of the invention. The present invention provides effective therapeutic methods for modulating tumor growth or metastasis in which a combination of agents is employed. The methods of the present invention provide advantages such as greater overall efficacy, for example, to achieve synergy or avoid antagonism, and allow, when desired, a reduction in the amount of one or more of the individual agents used with a reduction concomitant side effects. Furthermore, when the tumor to be treated does not respond optimally to a given antineoplastic agent, the use of current methods of combination therapy may provide effective treatment. As used herein, the phrase "effective amount" of a compound or pharmaceutical composition refers to an amount sufficient to modulate tumor growth or metastasis in an animal, especially a human, including, but not limited to , decreasing tumor growth or size or preventing tumor formation in an animal lacking any tumor formation prior to administration, i.e., prophylactic administration. As used in this document, the terms "tumor", "tumor growth" or "tumor tissue" can be used interchangeably and refer to an abnormal growth of tissue resulting from the progressive uncontrolled multiplication of cells and that does not fulfill any physiological function. . A solid tumor can be malignant, for example, tend to metastasize and be life-threatening, or benign. Examples of solid tumors that can be treated or prevented according to a method of the present invention include sarcomas and carcinomas such as, but not limited to: fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangioosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, colorectal cancer, gastric cancer, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, liver metastases, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, carcinoma of thyroid such as anaplastic thyroid cancer, Wilms tumor, cervical cancer, testicular tumor, lung carcinoma such as small cell lung carcinoma and non-small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma and retinoblastoma. Furthermore, tumors comprising dysproliferative changes (such as metaplasias and dysplasias) can be treated or prevented with a pharmaceutical composition or method of the present invention in epithelial tissues such as those of the cervix, colon, esophagus and lung. Therefore, the present invention provides for the treatment of conditions known or suspected of prior progression to neoplasia or cancer, in particular, where non-neoplastic cell growth has occurred consisting of hyperplasia, metaplasia or, more particularly, dysplasia (for review of such abnormal growth conditions, see Robbins and Angelí, 1976, Basic Pathology, 2nd ed., W.B. Saunders Co., Philadelphia, pp. 68-79). Hyperplasia is a form of controlled cell proliferation that involves an increase in the number of cells in a tissue or organ, without significant alteration in structure or function. For example, endometrial hyperplasia often precedes endometrial cancer. Metaplasia is a form of controlled cell growth in which one type of adult or fully differentiated cell replaces another type of adult cell. Metaplasia can occur in epithelial or connective tissue cells. Atypical metaplasia involves a somewhat disordered metaplastic epithelium. Dysplasia is often a precursor to cancer, frncacn / zznz / q / υιλι and is found mainly in the epithelia; It is the most disordered form of non-neoplastic cell growth, which involves a loss in individual cellular uniformity and in the architectural orientation of the cells. Dysplastic cells often have abnormally large and deeply stained nuclei, and exhibit pleomorphism. Dysplasia characteristically occurs where chronic irritation or inflammation exists, and is often found in the cervix, respiratory tract, oral cavity, and gallbladder. See a review of such disorders in Fishman et al, 1985, Medicine, 2nd ed., J.B. Lippincott Co., Philadelphia. The present invention covers the treatment and / or prevention of various types of leukemia. Leukemia is a cancer of the early blood-forming cells. Most often, leukemia is a cancer of the white blood cells, but some leukemias begin in other types of blood cells. There are several types of leukemia, which are mainly divided based on whether the leukemia is acute (fast growing) or chronic (slower growing), and whether it begins in myeloid cells or lymphoid cells. Different types of leukemia have different treatment options and outlooks. Acute lymphocytic (or lymphoblastic) leukemia is sometimes called ALL. It begins in the bone marrow where blood cells are produced. It is more common in children than in adults. Acute myeloid leukemia is also called acute myelocytic leukemia, acute myelogenous leukemia, acute granulocytic leukemia, acute nonlymphocytic leukemia, or sometimes simply AML. It is more common in older people. Chronic lymphocytic leukemia (CLL) is a type of cancer that begins in white blood cells (called lymphocytes) in the bone marrow. CLL primarily affects older adults and accounts for approximately one-third of all leukemias. Chronic myeloid leukemia (CML) is also known as chronic myelogenous leukemia. It is a type of cancer that begins in the blood-forming cells of the bone marrow and invades the blood. About 15% of leukemias in adults are CML. Chronic myelomonocytic leukemia (CMML) is a type of cancer that begins in the blood-forming cells of the bone marrow and invades the blood. It mainly affects older adults. Current methods can, for example, be carried out using a single pharmaceutical composition comprising both an Aur-A inhibitor and a Src inhibitor (dasatinib) (when administration must be simultaneous) or using two or more separate pharmaceutical compositions. comprising the Src inhibitor and dasatinib (when administration must be simultaneous or sequential). The phrase "pharmaceutically acceptable" refers to entities and molecular compositions that are physiologically tolerable and preferably do not produce an allergic or similar reaction, such as gastric discomfort, dizziness and the like, when administered to a human being. A pharmaceutical composition of the present invention may be administered by any suitable route, for example, by injection, oral, pulmonary, nasal or other forms of administration. frncacn / zznz / q / υιλι In general, pharmaceutical compositions contemplated to be within the scope of the invention comprise, among other things, pharmaceutically acceptable diluents, preservatives, solubilizers, emulsifiers, adjuvants or vehicles. Such compositions may include diluents of different buffer content (e.g., Tris-HCI, acetate, phosphate), pH, and ionic strength; additives such as detergents and solubilizing agents (e.g. Tween 80, polysorbate 80), antioxidants (e.g. ascorbic acid, sodium metabisulfite), preservatives (e.g. thimersol, benzyl alcohol) and thickening substances (e.g. lactose, mannitol ); incorporation of the material in particle preparations of polymeric compounds such as polylactic acid, polyglycolic acid, etc., or in liposomes. Such compositions can influence the physical state, stability, in vivo release rate and in vivo clearance rate of the components of a pharmaceutical composition of the present invention. See, for example, Remington's Pharmaceutical Sciences, 18th ed. (1990, Mack Publishing Co., Easton, Pa. 18042), pages 14351712, which are incorporated herein by this reference. A pharmaceutical composition of the present invention may be prepared, for example, in liquid form, or may be in dry powder, such as the lyophilized form. Particular methods of administering such compositions are described below. The present invention relates to methods of modulating tumor growth and metastasis comprising the administration of an Aur-A inhibitor as listed above and at least one Src inhibitor, preferably dasatinib. The agents of the invention may be administered separately (e.g., they may be formulated and administered separately), or in combination as a pharmaceutical composition of the present invention. Administration can be achieved by any suitable route, such as parenterally, transmucosally, for example, orally, nasally or rectally, or transdermally. Preferably, administration is parenteral, for example by intravenous injection. Alternative means of administration also include, but are not limited to, intraarteriolar, intramuscular, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial administration, or by injection into the tumor(s) being treated or into tissues surrounding the tumor(s). In another embodiment, a pharmaceutical composition of the present invention may be administered in a controlled release system, such as using an intravenous infusion, an implantable osmotic pump, a transdermal patch, liposomes, or other modes of administration. In a particular embodiment, a pump may be used [see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989)]. In another embodiment, polymeric materials can be used [see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Press: Boca Raton, Florida. (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smolen and Ball (eds.), frncacn / zznz / q / υιλι Wiley: New York (1984); Ranger and Peppas, J. Macromol. Sci. Rev. Macromol. Chem. 23:61 (1983); see also Levy et al., Science 228:190 (1985); During et al., Ann. Neurol. 25:351 (1989); Howard et al., J. Neurosurg. 71:105 (1989)]. In yet another embodiment, a controlled release system can be placed in close proximity to the target tissues of the animal, thus requiring only a fraction of the systemic dose [see, for example, Goodson, in Medical Applications of Controlled Release, supra, vol . 2, pp. 115-138 (1984)]. In particular, a controlled release device can be introduced into an animal near the site of inappropriate immune activation or a tumor. Other controlled release systems are discussed in the review by Langer [Science 249:15271533 (1990)]. BRIEF DESCRIPTION OF THE FIGURES FIGURE 1 illustrates and exemplifies the modality of a chromatographic profile of the fractions identified in the initial capture stage. FIGURE 2 illustrates and exemplifies the modality of a chromatographic profile of the fractions identified in the intermediate stage. FIGURE 3 illustrates and exemplifies the modality of a chromatographic profile of the fractions identified in the finishing stage. FIGURE 4 illustrates and exemplifies the modality of a chromatographic profile of the fractions identified in the desalting stage. One embodiment of a proton (1H) NMR profile of the purified compound E05 is illustrated and exemplified in FIGURE 5. One embodiment of a carbon (13C) NMR profile of the purified compound E05 is illustrated and exemplified in FIGURE 6. An embodiment of a distortion-free enhancement profile by polarization transfer (DEPT) of the purified compound E05 is illustrated and exemplified in FIGURE 7. An embodiment of an infrared (IR) profile of the purified compound E05 is illustrated and exemplified in FIGURE 8. One embodiment of an LC-MS spectrum of the purified compound E05 is illustrated and exemplified in FIGURE 9a. One embodiment of an MS spectrum of the purified compound E05 is illustrated and exemplified in FIGURE 9b. An embodiment of an ORTEP view of compound E05 (3-(3,4-dihydroxyphenyl)propaneic acid) showing the atom numbering scheme is illustrated and exemplified in FIGURE 10, the displacement ellipsoids being They are drawn at the 50% probability level and the H atoms are shown as small spheres with arbitrary radii. A modality of an antiproliferative activity frncacn / zznz / q / υιλι induced by the water-soluble fraction of Sahadevi in ​​different cell lines is illustrated and exemplified in FIGURE 11. An embodiment of the antiproliferative activity of the pure compound (E05) in the colon cancer cell line, HCT116, is illustrated and exemplified in FIGURE 12. A dose-dependent response can be observed after treatment with the pure compound. An embodiment of the antiproliferative activity of the pure compound (E05) in the breast cancer cell line, BT-474, is illustrated and exemplified in FIGURE 13. A dose-dependent response can be observed after treatment with the pure compound. One embodiment of a comparison of IC50 values ​​between synthetic E05 and the SRC kinase inhibitor Bosutinib in F-36E cells is illustrated and exemplified in FIGURE 14. An embodiment of the IC50 value of synthetic E05 in the triple negative breast cancer cell line, MDA-MB-468, is illustrated and exemplified in FIGURE 15. One embodiment of a comparison of antiproliferative activity between synthetic E05 and lapatinib in the triple negative breast cancer cell line, MDA-MB-468, is illustrated and exemplified in FIGURE 16. An embodiment of the efficacy of exemplary compound E05 in the murine xenograft model of triple negative breast cancer is illustrated and exemplified in FIGURE 17. An embodiment of the average plasma concentration versus time profile of small molecules following oral gavage administration of the small molecule dose formulation in male Sprague Dawley rats (dose: 10 mg) is illustrated and exemplified in FIGURE 18. / kg; G3) DETAILED DESCRIPTION OF THE INVENTION As used herein, the term "cycloalkyl" refers to a monoring or multiring system (e.g., fused, bridged, or spiro rings) of optionally substituted unsaturated or saturated nonaromatic hydrocarbons having from 3 to 30 carbon atoms. (e.g. C3-C10). Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl and adamantyl. The term "heterocycloalkyl" refers to a saturated or non-aromatic 3- to 8-membered monocyclic, 7- to 12-membered bicyclic (fused, bridged, or spiro) or 11 to 14-membered (fused, bridged, or spiro rings) ring system. unsaturated having one or more heteroatoms (such as O, N, S or Se), unless otherwise specified. Examples of heterocycloalkyl groups include, but are not limited to, piperidinyl, piperazinyl, pyrrolidinyl, dioxanyl, tetrahydrofuranyl, isoindolinyl, indolinyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isoxazolidinyl, traizolidinyl, tetrahydrofuranyl, oxiranyl, azetidinyl, oxetanyl, tietanyl, 1,2 , 3,6-tetrahydropyridinyl, tetrahydropyranyl, dihydropyranyl, pyranyl, morpholinyl, 1,4-diazepanyl, 1,4-oxazepanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2,5frncacn / zznz / q / υιλι diazabic cyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, 2,6-diazaspiro[3.3]heptanyl, 1,4dioxa-8-azaspiro[4.5]decanyl and the like . The term "optionally substituted alkyl" refers to an alkyl or unsubstituted alkyl having designated substituents that replace one or more hydrogen atoms on one or more carbons of the hydrocarbon backbone. Such substituents may include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, amino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro , trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl or an aromatic or heteroaromatic moiety. An "arylalkyl" or "aralkyl" moiety is an alkyl substituted with an aryl (for example, phenylmethyl(benzyl)). An "alkylaryl" moiety is an aryl substituted with an alkyl (e.g., methylphenyl). "Alkenyl" includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but containing at least one double bond. For example, the term "alkenyl" includes straight chain alkenyl groups (e.g., ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl) and branched alkenyl groups. In certain embodiments, a straight or branched chain alkenyl group has six or fewer carbon atoms in its main chain (e.g., O-Ce for straight chain, C3-C6 for branched chain). The term "C2-C6" includes alkenyl groups containing two to six carbon atoms. The term "C3-C6" includes alkenyl groups containing three to six carbon atoms. The term "optionally substituted alkenyl" refers to an alkenyl or unsubstituted alkenyl having designated substituents that replace one or more hydrogen atoms on one or more carbon atoms of the hydrocarbon backbone. Such substituents may include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, amino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro , trifluoromethyl, cyano, heterocyclyl, alkylaryl or an aromatic or heteroaromatic moiety. frncacn / zznz / q / υιλι "Alkynyl" includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but containing at least one triple bond. For example, "alkynyl" includes straight chain alkynyl groups (e.g., ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptinyl, octynyl, nonyl, decynyl) and branched alkynyl groups. In certain embodiments, a straight or branched chain alkynyl group has six or fewer carbon atoms in its main chain (e.g., C2-Ce for straight chain, C3-C6 for branched chain). The term "C2-C6" includes alkynyl groups containing two to six carbon atoms. The term "C3-C6" includes alkynyl groups containing three to six carbon atoms. The term "optionally substituted alkynyl" refers to an alkynyl or unsubstituted alkynyl having designated substituents that replace one or more hydrogen atoms on one or more carbon atoms of the hydrocarbon backbone. Such substituents may include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, amino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro , trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl or an aromatic or heteroaromatic moiety. Other optionally substituted moieties (such as cycloalkyl, heterocycloalkyl, aryl, or optionally substituted heteroaryl) include both unsubstituted moieties and moieties having one or more of the designated substituents. For example, substituted heterocycloalkyl includes those substituted by one or more alkyl groups, such as 2,2,6,6-tetramethyl-piperidinyl and 2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridinyl. "Aryl" includes groups with aromaticity, including "conjugated" or multicyclic systems with at least one aromatic ring and do not contain any heteroatoms in the ring structure. Examples include phenyl, benzyl, 1,2,3,4-tetrahydronaphthalenyl, etc. "Heteroaryl" groups are aryl groups, as defined above, except that they have one to four heteroatoms in the ring structure, and may also be called "aryl heterocycles" or "heteroaromatic compounds." As used herein, the term "heteroaryl" is intended to include a stable 5-, 6-, or 7-membered monocyclic or 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic heterocyclic ring consisting of carbon atoms. and one or more heteroatoms, for example, 1, 1 to 2, 1 to 3, 1 to 4, 1 to 5 or 1 to 6 heteroatoms, or, for example, 1, 2, 3, 4, 5 or 6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen and sulfur. The nitrogen atom may be substituted or unsubstituted (i.e., N or NR, where R is H or other substituents, as defined). The nitrogen frncacn / zznz / q / υιλι and sulfur heteroatoms may be optionally oxidized (i.e., N.fwdarw.O and S(O).sub.p, where p=1 or 2). It should be noted that the total number of S and O atoms in the aromatic heterocycle is not more than 1. Examples of heteroaryl groups include pyrrole, furan, thiophene, thiazole, isothiazole, imidazole, triazole, tetrazole, pyrazole, oxazole, isoxazole, pyridine , pyrazine, pyridazine, pyrimidine and the like. Furthermore, the terms "aryl" and "heteroaryl" include multicyclic aryl and heteroaryl groups, for example, tricyclic, bicyclic, for example, naphthalene, benzoxazole, benzodioxazole, benzothiazole, benzoimidazole, benzothiophene, methylenedioxyphenyl, quinoline, isoquinoline, naphthyridine, indole, benzofuran, purine, benzofuran, desazapurine, indolizine. In the case of multicyclic aromatic rings, only one of the rings must be aromatic (e.g., 2,3-dihydroindole), although all rings can be aromatic (e.g., quinoline). The second ring can also be fused or bridged. The cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring can be substituted at one or more positions of the ring (for example, the heteroatom such as N or carbon that forms the ring) with the substituents described above, for example, alkyl, alkenyl, alkynyl, halogen phosphate , amino (including alkylamine , dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, amino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro, trifluoromethyl , cyano, azido, heterocyclyl, alkyladyl, or an aromatic or heteroaromatic moiety. Aryl and heteroaryl groups can also be fused or bridged with non-aromatic alicyclic or heterocyclic rings to form a multicyclic system (e.g., tetralin, methylenedioxyphenyl). As used herein, "carbocycle" or "carbocyclic ring" is intended to include any stable monocyclic, bicyclic or tricyclic ring having the specified number of carbons, any of which may be saturated, unsaturated or aromatic. A carbocycle includes cycloalkyl and aryl. For example, a C.sub.3-C.sub.14 carbocycle is intended to include a monocyclic, bicyclic or tricyclic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 carbon atoms. Examples of carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctadienyl, fluorenyl, phenyl, naphthyl, indanyl, adamantyl and tetrahydronaphthyl. Bridged rings are also included in the definition of carbocycle, including, for example, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, and [2.2.2]bicyclooctane. A bridged ring occurs when one or more hncQQn / zznz / q / υιλι carbon atoms bridge two non-adjacent carbon atoms. In one embodiment, the bridging rings are one or two carbon atoms. It is observed that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents mentioned for the ring may also be present on the bridge. Also included are fused rings (e.g., naphthyl, tetrahydronaphthyl) and spiro. As used herein, "heterocycle" or "heterocyclic group" includes any ring structure (saturated, unsaturated or aromatic) that contains at least one ring heteroatom (e.g., N, O or S). Heterocycle includes heterocycloalkyl and heteroaryl. Examples of heterocycles include, but are not limited to, morpholine, pyrrolidine, tetrahydrothiophene, piperidine, piperazine, oxetane, pyran, tetrahydropyran, azetidine and tetrahydrofuran. Examples of heterocyclic groups include, but are not limited to, acridinyl, azocynyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4a H-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1Hindazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, ¡soindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl , 1 ,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazol5(4H)-one, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxatinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridoxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrole yl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4thiadiazolyl, 1,2, 5-thiadiazolyl, 1,3,4-thiadiazolyl, thiantrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5- triazolyl, 1,3,4-triazolyl and xanthenyl. When any variable (for example, R2) occurs more than once in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at each other occurrence. So, for example, if a group is shown to be substituted by 0 to 2 R.sub.1 residues, then the group may optionally be substituted by up to two residues R.sub.1 and R.sub.1 at each occurrence. selects regardless of the definition of R.sub.1. Additionally, combinations of substituents or variables are permissible, but only if such combinations result in stable compounds. frncacn / zznz / q / υιλι The terms "hydroxy" or "hydroxyl" include groups with an -OH. As used herein, "halo" or "halogen" refers to fluorine, chlorine, bromine and iodine. The term "perhalogenated" generally refers to a moiety where all hydrogen atoms are replaced by halogen atoms. The terms "haloalkyl" or "haloalkoxy" refer to an alkyl or alkoxyl substituted with one or more halogen atoms. The term "carbonyl" includes compounds and moieties containing a carbon connected with a double bond to an oxygen atom. Examples of carbonyl-containing moieties include, but are not limited to, aldehydes, ketones, carboxylic acids, amides, esters, anhydrides, etc. The term "carboxyl" refers to -COOH or its Oí-Ce alkyl ester. "Acyl" includes parts containing the acyl radical (R-C(O)-) or a carbonyl group. A "substituted acyl" includes acyl groups where one or more of the hydrogen atoms are replaced, for example, with alkyl groups, alkynyl groups, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonate, phosphinate, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, amino, sulfhydryl, alkylthio , arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl or an aromatic or heteroaromatic moiety. The terms "alkoxy" or "alkoxyl" include substituted and unsubstituted alkyl, alkenyl and alkyl groups covalently bonded to an oxygen atom. Examples of alkoxy groups or alkoxyl radicals include, but are not limited to, methoxy, ethoxy, isopropyloxy, propoxy, butoxy and pentoxy groups. Examples of substituted alkoxy groups include halogenated alkoxy groups. The alkoxy groups may be substituted with groups such as alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylminocarbonyl, alkylthiocarbonyl, alkoxy, phosphate, phosphonate, phosphinate, amino (including alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, amino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonate, sulfamoyl, sulfonamido, nitro , trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl or aromatic or heteroaromatic residues. Examples of halogen-substituted alkoxy groups include, but are not limited to, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy and trichloromethoxy. The terms "ether" or "alkoxy" include compounds or moieties containing an oxygen bonded to two carbon atoms or heteroatoms. For example, the term includes "alkoxyalkyl", which refers to an alkyl, alkenyl or alkynyl group covalently bonded to an oxygen atom that frncacn / zznz / q / υιλι is covalently bonded to an alkyl group. The term "ester" includes compounds or moieties containing a carbon or heteroatom bonded to an oxygen atom that is bonded to the carbon of a carbonyl group. The term "ester" includes alkoxycarboxy groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, etc. As used herein, "amine" or "amino" refers to substituted or unsubstituted -NH.sub.2. "Alkylamino" includes groups of compounds where the NH.sub.2 nitrogen is attached to at least one alkyl group. Examples of alkylamine groups include benzylamino, methylamino, ethylamino, phenethylamino, etc. "Dialkylamino" includes groups where the nitrogen of -NH.sub.2 is attached to at least two additional alkyl groups. Examples of dialkylamino groups include, but are not limited to, dimethylamino and diethylamino. "Arylamino" and "diarylamino" include groups where the nitrogen is attached to at least one or two aryl groups, respectively. "Aminoaryl" and "aminoaryloxy" refer to aryl and aryloxy substituted with amino. "Alkylarylamino", "alkylaminaryl" or "arylaminoalkyl" refers to an amino group that is linked to at least one alkyl group and at least one aryl group. "Alcaminoalkyl" refers to an alkyl, alkenyl or alkynyl group attached to a nitrogen atom that is also attached to an alkyl group. "Acylamine" includes groups where nitrogen is attached to an acyl group. Examples of acylamino include, but are not limited to, alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido groups. The terms "amide" or "aminocarboxy" include compounds or moieties containing a nitrogen atom that is bonded to the carbon of a carbonyl or thiocarbonyl group. The term includes "alkaminocarboxy" groups which include alkyl, alkenyl or alkynyl groups attached to an amino group that is attached to the carbon of a carbonyl or thiocarbonyl group. It also includes "arylaminocarboxy" groups which include aryl or heteroaryl moieties attached to an amino group that is attached to the carbon of a carbonyl or thiocarbonyl group. The terms "alkylaminocarboxy", "alkenylaminocarboxy", "alkynylaminocarboxy" and "arylaminocarboxy" include moieties wherein the alkyl, alkenyl, alkynyl and aryl moieties, respectively, are bonded to a nitrogen atom which, in turn, is bonded to carbon. of a carbonyl group. Amides can be substituted by substituents such as straight chain alkyl, branched alkyl, cycloalkyl, aryl, heteroary or heterocycle. The substituents on the amide groups may be further substituted. Compounds of the present invention containing nitrogens can be converted to N-oxides by treatment with an oxidizing agent (e.g., 3-chloroperoxybenzoic acid (mCPBA) or hydrogen peroxides) to provide other compounds of the present invention. Therefore, all nitrogen-containing compounds shown and claimed, where valency and structure permit, are considered to include both the compound as shown and its N-oxide derivative (which may be designated as N.fwdarw.O or N.sup.-ι—O.sup.-). Furthermore, in other cases, the nitrogens in the compounds of the present invention can be converted to N-hydroxy or N-alkoxy compounds. For example, N-hydroxy compounds can be prepared by oxidation of the parent amine by an oxidizing agent such as m-CPBA. All nitrogen-containing compounds illustrated and claimed are also considered, where valency and structure permit, to cover both the compound as shown and its N-hydroxy (i.e., N-OH) and N-alkoxy ( i.e., N-OR, where R is Ci-Ce alkyl, CrCe alkenyl, Ci-Ce alkynyl, a 3- to 14-membered carbocycle or a 3- to 14-membered heterocycle). Herein, the structural formula of the compounds of Formula (I) or (II) represents a certain isomer for convenience in some cases, but the present invention includes all isomers, such as geometric isomers, optical isomers based on a asymmetric carbon, stereoisomers, tautomers and the like. Additionally, a crystal polymorphism may be present for compounds represented by the formula. It is noted that any crystalline form, mixture of crystalline form, or anhydride or hydrate thereof is included within the scope of the present invention. Likewise, the so-called metabolite that is produced by degradation of the present compound in vivo is included in the scope of the present invention. It should be understood that the structures and other compounds discussed in this invention include all atropic isomers thereof. "Atropic isomers" are a type of stereoisomer in which the atoms of two isomers are arranged differently in space. Atropic isomers owe their existence to a restricted rotation caused by the hindrance of the rotation of large groups around a central bond. Such atropic isomers typically exist as a mixture, however, as a result of recent advances in chromatography techniques, it has been possible to separate mixtures of two atropic isomers in selected cases. A "tautomer" is one of two or more structural isomers that exist in equilibrium and is easily converted from one isomeric form to another. This conversion results in the formal migration of a hydrogen atom accompanied by a change of adjacent conjugated double bonds. Tautomers exist as a mixture of a tautomeric set in solution. In solutions where tautomerization is possible, a chemical equilibrium of the tautomers will be achieved. The exact ratio of tautomers depends on several factors, including temperature, solvent, and pH. The concept of tautomers that are interconvertible by tautomerizations is called tautomerism. The terms "crystalline polymorphs", "polymorphs" or "crystalline forms" mean crystalline structures in which a compound (or a salt or solvate thereof) can be crystallized into different crystal packing arrangements, all of which have the same composition. frncacn / zznz / q / υιλι elementary. Different crystal forms generally have different X-ray diffraction patterns, infrared spectrum, melting points, density hardness, crystal form, optical and electrical properties, stability and solubility. Recrystallization solvent, crystallization rate, storage temperature, and other factors can cause one crystal form to dominate. Crystalline polymorphs of compounds can be prepared by crystallization under different conditions. The term "compounds of the invention" includes compounds of Formula (I), (II), (III) or (IV) disclosed herein and includes the compounds themselves, as well as their salts, their esters, their solvates and their prodrugs, if applicable. A salt, for example, can form between an anion and a positively charged group (e.g., amino) in an aryl- or heteroaryl-substituted benzene compound. Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate and acetate (for example, trifluoroacetate). The term "pharmaceutically acceptable anion" refers to an anion suitable for forming a pharmaceutically acceptable salt. Similarly, a salt can also form between a cation and a negatively charged group (e.g., carboxylate) in an aryl- or heteroaryl-substituted benzene compound. Suitable cations include sodium ions, potassium ions, magnesium ions, calcium ions and an ammonium cation such as tetramethylammonium ion. Aryl- or heteroaryl-substituted benzene compounds also include those salts containing quaternary nitrogen atoms. In the salt form, it is understood that the ratio of the compound to the cation or anion of the salt may be 1:1, or any ratio other than 1:1, for example, 3:1, 2:1, 1 :2 or 1:3. Examples of prodrugs include esters and other pharmaceutically acceptable derivatives, which, upon administration to a subject, are capable of providing active aryl- or heteroaryl-substituted benzene compounds. Furthermore, the compounds of the present invention, for example, salts of the compounds, can exist in hydrated or non-hydrated (anhydrous) form or as solvates with other solvent molecules. Non-limiting examples of hydrates include monohydrates, dihydrates, etc. Non-limiting examples of solvates include ethanol solvates, acetone solvates, etc. "Solvate" means solvent addition forms containing stoichiometric or non-stoichiometric amounts of solvent. Some compounds have a tendency to trap a fixed molar ratio of solvent molecules in the crystalline solid state, thus forming a solvate. If the solvent is water, the solvate formed is a hydrate; and if the solvent is alcohol, the solvate formed is an alcoholate. Hydrates are formed by the combination of one or more frncacn / zznz / q / υιλι water molecules with a molecule of the substance in which water retains its molecular state as H2O. As used herein, the term "analog" refers to a chemical compound that is structurally similar to another, but differs slightly in composition (such as in the replacement of an atom with an atom of a different element or in the presence of a particular functional group, or the replacement of one functional group by another functional group). Therefore, an analogue is a compound that is similar or comparable in function and appearance, but not in structure or origin, to the reference compound. As defined herein, the term "derivative" refers to compounds that have a common core structure and are replaced by various groups as described herein. For example, all compounds represented by Formulas (I) and (II) are benzene compounds substituted by aryl or heteroaryl, and have Formulas (I) and (II) as a common nucleus. The term "bioisostere" refers to a compound resulting from the exchange of one atom or group of atoms with another broadly similar atom or group of atoms. The goal of a bioisostere replacement is to create a new compound with similar biological properties to the parent compound. Bioisostere replacement can have a physicochemical or topological basis. Examples of carboxylic acid bioisosteres include, but are not limited to, acylsulfonimides, tetrazoles, sulfonates, and phosphonates. See, for example, Patani and LaVoie, Chem. Rev. 96, 3147-3176, 1996. The present invention is intended to include all isotopes of atoms that occur in the compounds present. Isotopes include those atoms that have the same atomic number, but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include C-13 and C-14. The inhibition is a moderate inhibition compared to an adequate control. In one embodiment, the inhibition is at least 10 percent inhibition compared to an adequate control. That is, the rate of enzyme activity or the amount of product with the inhibitor is less than or equal to 90 percent of the corresponding rate or amount produced without the inhibitor. In various other embodiments, the inhibition is at least 20, 25, 30, 40, 50, 60, 70, 75, 80, 90 or 95 percent inhibition compared to a suitable control. In one embodiment, the inhibition is at least 99 percent inhibition compared to an adequate control. That is, the rate of enzyme activity or the amount of product with the inhibitor is less than or equal to 1 percent of the corresponding rate or amount produced without the inhibitor. The term "composition of the invention" comprises a compound of Formula (I) or (II), (III), or (IV), or a pharmaceutically acceptable salt thereof, as well as its esters, its solvates and its prodrugs, if corresponds. frncacn / zznz / q / υιλι The present invention provides for the administration of a compound of Formula (I), (II), (III), or (IV) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents or a pharmaceutically acceptable salt thereof, such as coformulation or as separate formulations, in which the administration of formulations is simultaneous, sequential or alternately. In certain embodiments, the other therapeutic agents may be an agent that is recognized in the art as useful in treating the disease or condition being treated with the composition of the present invention. In another embodiment, the other therapeutic agent may be an agent that is recognized in the art as useful for treating the disease or condition being treated with the composition of the present invention. In one aspect, the other therapeutic agents may be an agent that imparts a beneficial attribute to the composition of the present invention (for example, an agent that affects the viscosity of the composition). The beneficial attribute to the composition of the present invention includes, but is not limited to, the pharmacokinetic or pharmacodynamic influence resulting from the combination of a compound of Formula (I), (II), (III) or (IV) and one or more therapeutic agents. For example, one or more therapeutic agents may be antineoplastic agents or chemotherapeutic agents. For example, one or more therapeutic agents may be glucocorticoids. For example, one or more therapeutic agents can be selected from prednisone, prednisolone, cyclophosphamide, vincristine, doxorubicin, mafosfamide, cisplatin, AraC, everolimus, decitabine, dexamethasone or functional analogues, derivatives, prodrugs and metabolites thereof. In another aspect, the other therapeutic agent may be prednisone or its active metabolite, prednisolone. COMBINATIONS OF THE INVENTION A composition of the present invention comprises a compound of Formula (I), (II), (III) or (IV), or a pharmaceutically acceptable salt thereof, and one or more additional therapeutic agents, or a pharmaceutically acceptable salt thereof. . The present invention provides for the administration of a compound of Formula (I), (II), (III), or (IV) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents or a pharmaceutically acceptable salt thereof, such as coformulation or as separate formulations, in which the administration of formulations is simultaneous, sequential or alternately. In certain embodiments, the other therapeutic agents may be an agent that is recognized in the art as useful in treating the disease or condition being treated with the composition of the present invention. In another embodiment, the other therapeutic agent may be an agent that is recognized in the art as useful for treating the disease or condition being treated with the composition of the present invention. In one aspect, the other therapeutic agents may be an agent that imparts a beneficial attribute to the composition of the present invention (for example, an agent that affects the viscosity of the composition). The beneficial attribute to the composition of frncacn / zznz / q / υιλι of the present invention includes, but is not limited to, the pharmacokinetic or pharmacodynamic influence resulting from the combination of a compound of Formula (I), (II), (III) or (IV) and one or more therapeutic agents. For example, one or more therapeutic agents may be antineoplastic agents or chemotherapeutic agents. For example, one or more therapeutic agents may be glucocorticoids. For example, one or more therapeutic agents can be selected from prednisone, prednisolone, cyclophosphamide, vincristine, doxorubicin, mafosfamide, cisplatin, AraC, everolimus, decitabine, dexamethasone or functional analogues, derivatives, prodrugs and metabolites thereof. In another aspect, the other therapeutic agent may be prednisone or its active metabolite, prednisolone. The therapeutic agents set forth below are for illustrative purposes and are not intended to be limiting. The present invention includes at least one other therapeutic agent selected from the following lists. The present invention may include more than one therapeutic agent, for example, two, three, four or five other therapeutic agents, such that the composition of the present invention can fulfill its intended function. In one embodiment, the other therapeutic agent is an antineoplastic agent. In one embodiment, the antineoplastic agent is selected from the group consisting of chemotherapeutic compounds (such as 2CdA, 5-FU, 6-mercaptopurine, 6-TG, Abraxane™, Accutane®, actinomycin-D, Adriamycin®, Alimta®, retinoic acid trans, amethopterin, Ara-C, azacitadine, BCNU, Blenoxane®, Camptosar®, CeeNU®, clofarabine, Clolar™, Cytoxan®, daunorubicin hydrochloride, DaunoXome®, Dacogen®, DIC, Doxil®, Ellence®, Eloxatin®, Emcyt®, etoposide phosphate, Fludara®, FUDR®, Gemzar®, Gleevec®, hexamethylmelamine, Hycamtin®, Hydrea®, Idamycin®, Ifex®, ixabepilone, Ixempra®, L-asparaginase, Leukeran®, Ara-C liposomal, L-PAM, Lysodren, Matulane®, Mitracin, Mitomycin-C, Myleran®, Navelbine®, Neutrexin®, Nilotinib, Nipent®, Nitrogen Mustard, Novantrone®, Oncaspar®, Panretin®, Paraplatin®, Platinol®, Prolifeprospane 20 with carmustine implant, Sandostatin®, Targretin®, Tasigna®, Taxotere®, Temodar®, TESPA, Trisenox®, Valstar®, Velban®, Vidaza™, vincristine sulfate, VM 26, Xeloda® and Zanosar®); biological compounds (such as alpha interfered, Bacillus Calmette-Guerin, Bexxar®, Campath®, Ergamisol®, Erlotinib, Herceptin®, interleukin 2, Iressa®, lenalidomide, Mylotarg®, Ontak®, Pegasys®, Revlimid®, Rituxan®, Tarceva ™, Thalomid®, Tykerb®, Velcade® and Zevalin™); corticost raid es, (such as dexamethasone sodium phosphate, DeltaSone® and Delta-Cortef®); hormonal therapies (such as Arimidex®, Aromasin®, Casodex®, Cytadren®, Eligard®, Eulexin®, Evista®, Faslodex®, Femara®, Halotestin®, Megace®, Nilandron®, Nolvadex®, Plenaxis™ and Zoladex®); and radiopharmaceutical compounds (such as lodotope®, Metastron®, Phosphocol® and Samarium SM-153). In another embodiment, the other therapeutic agent is a chemotherapeutic agent (also hncQQn / zznz / q / υιλι known as antineoplastic agent or antiproliferative agent), selected from the group including an alkylating agent; an antibiotic; an antimetabolite; a detoxifying agent; an interferon; a polyclonal or monoclonal antibody; an EGFR inhibitor; a HER2 inhibitor; a histone deacetylase inhibitor; a hormone; a mitotic inhibitor; an MTOR inhibitor; a multikinase inhibitor; a serine / threonine kinase inhibitor; tyrosine kinase inhibitors; a VEGF / VEGFR inhibitor; a taxane or taxane derivative, an aromatase inhibitor, an anthracycline, a microtubule-targeting drug, a topoisomerase toxic drug, an inhibitor of a molecular target or enzyme (for example, a kinase or a protein methyltransferase), a cytidine analog drug or any chemotherapeutic, antineoplastic or antiproliferative agent listed at www.cancer.org / docroot / cdg / cdg_0.asp. Examples of alkylating agents include, but are not limited to, cyclophosphamide (Cytoxan; Neosar); chlorambucil (Leukeran); melphalan (Alkeran); carmustine (BiCNU); busulfan (Busulfex); lomustine (CeeNU); dacarbazine (DTIC-Dome); oxaliplatin (Eloxatina); carmustine (Gliadel); ifosfamide (Ifex); mechlorethamine (Mustargen); busulfan (Myleran); carboplatin (Paraplatin); cisplatin (CDDP; Platinol); temozolomide (Temodar); .sub.thiotepa (Thioplex); .sub.bendamustine(Treanda); or .sub.streptozocin (Zanosar). Examples of antimetabolites include, but are not limited to, fluorouracil (Adrucil); capecitabine (Xeloda); hydroxyurea (Hydrea); mercaptopurine (Purinethol); pemetrexed (Alimta); fludarabine (Fludara); nelarabine (Arranon); cladribine (Cladribine Novaplus); clofarabine (Clolar); cytarabine (Cytosar-U); decitabine (Dacogen); liposomal cytarabine (DepoCyt); hydroxyurea (Droxia); pralatrexate (Folotyn); floxuridine (FUDR); gemcitabine (Gemzar); cladribine (Leustatin); fludarabine (Oforta); methotrexate (MTX; Rheumatrex); methotrexate (Trexall); thioguanine (Tabloid); TS-1 or cytarabine (Tarabina PFS). Examples of detoxifying agents include, but are not limited to, amifostine (Ethyol) or .sub.mesna (Mesnex). Examples of interferons include, but are not limited to, interferon alfa-2b (Intron A) or interferon alfa-2a (Roferon-A). Examples of polyclonal or monoclonal antibodies include, but are not limited to, rastuzumab (Herceptin); ofatumumab (Arzerra); bevacizumab (Avastin); rituximab (Rituxan); cetuximab (Erbitux); panitumumab (Vectibix); tositumomab / iodine131 tositumomab (Bexxar); alemtuzumab (Campath); ibritumomab (Zevalin; ln-111; Y-90 Zevalin); .sub.gemtuzumab (Mylotarg); .sub.eculizumab (Soliris) ordosumab. Examples of EGFR inhibitors include, but are not limited to, gefitinib (Iressa); lapatinib (Tykerb); cetuximab (Erbitux); erlotinib (Tarceva); panitumumab (Vectibix); PKI-166; canertinib (CI-1033); matuzumab (Emd7200) or EKB-569. frncacn / zznz / q / υιλι Examples of HER2 inhibitors include, but are not limited to, trastuzumab (Herceptin); lapatinib (Tykerb) or AC-480. Histone deacetylase inhibitors include, but are not limited to, vorinostat (Zolinza). Examples of hormones include, but are not limited to, tamoxifen (Soltamox; Nolvadex); raloxifene (Evista); megestrol (Megace); leuprolide (Lupron; Lupron Depot; Eligard; Viadur); fulvestrant (Faslodex); letrozole (Femara); Triptorelin (Trelstar LA; Trelstar Depot); exemestane (Aromasin); goserelin (Zoladex); bicalutamide (Casodex); anastrozole (Arimidex); fluoxymesterone (Androxy; Halotestin); medroxyprogesterone (Provera; Depo-Provera); estramustine (Emcyt); flutamide (Eulexin); toremifene (Fareston); .sub.degarelix(Firmagon); .sub.nilutamide (Nilandron), .sub.abarelix (Plenaxis); or testolactone (Teslac). Examples of mitotic inhibitors include, but are not limited to, paclitaxel (Taxol; Onxol; Abraxane); docetaxel (Taxotere); vincristine (Oncovin; Vincasar PFS); vinblastine (Velban); etoposide (Toposar; Etopofos; VePesid); teniposide (Vumon); ixabepuone (Ixempra); nocodazole; epopolione; .sub.vinorelbine (Navelbine); camptothecin (CPT); .sub.irinotecan (Camptosar); topotecan (Hycamtin); amsacrine or lamellarin D (LAM-D). Examples of MTOR inhibitors include, but are not limited to, everolimus (Afinitor) or temsirolimus (Torisel); rapamuna, ridaforolimus or AP23573. Examples of VEGFNEGFR inhibitors include, but are not limited to, bev.sub.acizumab (Avastin); .sub.sorafenib (Nexavar); .sub.sunitinib (Sutent); ranibizumab; pegaptanib; or vandetinib. Examples of microtubule-targeting drugs include, but are not limited to, paclitaxel, docetaxel, vincristine, vinblastine, nocodazole, epothilones, and navelbine. Examples of topoisomerase toxic drugs include, but are not limited to, teniposide, etoposide, adriamycin, camptothecin, daunorubicin, dactinomycin, mitoxantrone, amsacrine, epirubicin, and idarubicin. Examples of taxanes or taxane derivatives include, but are not limited to, paclitaxel and docetaxol. Examples of general chemotherapeutic, antineoplastic and antiproliferative agents include, but are not limited to, altretamine (Hexalen); isotretinoin (Accutane; Amnesteem; Claravis; Sotret); tretinoin (Vesanoid); azacitidine (Vidaza); bortezomib (Velcade) asparaginase (Elspar); levamisole (Ergamisol); mitotane (Lysodren); procarbazine (Matulane); pegaspargase (Oncaspar); denileukin diftitox (Ontak), porfimer (Photofrin); .sub.aldesleukin (Proleukin); lenalidomide (Revlimid); bexarotene (Targretin); thalidomide (Thalomid); temsirolimus (Torisel); arsenic trioxide (Trisenox); verteporfin (Visudyne); mimosine (Leukenol); (1M tegafur-0.4M 5-chloro-2,4dihydroxypyrimidine-1M potassium oxonate), or lovastatin. In another aspect, the other therapeutic agent is a chemotherapeutic agent or a frncacn / zznz / q / υιλι cytokine such as G-CSF (granulocyte colony stimulating factor). In yet another aspect, the other therapeutic agents may be standard chemotherapy combinations such as, but not limited to, CMF (cyclophosphamide, methotrexate and 5-fluorouracil), CAF (cyclophosphamide, adriamycin and 5-fluorouracil), AC (adriamycin and cyclophosphamide), FEC (5-fluorouracil, epirubicin and cyclophosphamide), ACT or ATC (adriamycin, cyclophosphamide and paclitaxel), rituximab, Xeloda (capecitabine), cisplatin (CDDP), carboplatin, TS-1 (tegafur, gimestat and otastat potassium in a molar ratio of 1:0.4:1), camptothecin 11 (CPT-11, irinotecan or Camptosar™), CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone), R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone or prednisolone) or CMFP (cyclophosphamide, methotrexate, 5-fluorouracil and prednisone). In another aspect, the other therapeutic agents may be an inhibitor of an enzyme, such as a receptor or a non-receptor kinase. Receptor and non-receptor kinases are, for example, tyrosine kinases or serine / threonine kinases. The kinase inhibitors described herein are small molecules, polynucleic acids, polypeptides or antibodies. Examples of kinase inhibitors include, but are not limited to, Bevacizumab (targets VEGF), BIBW 2992 (targets EGFR and Erb2), Cetuximab / Erbitux (targets Erb1), Imatinib / Gleevic (targets Bcr-Abl), Trastuzumab (targets Erb2), Gefitinib / lressa (targets EGFR), Ranibizumab (targets VEGF), Pegaptanib (targets VEGF), Erlotinib / Tarceva (targets Erb1), Nilotinib (targets targets Bcr-Abl), Lapatinib (targets Erb1 and Erb2 / Her2), GW-572016 / lapatinib ditosylate (targets HER2 / Erb2), Panitumumab / Vectibix (targets EGFR), Vandetinib (targets RET / VEGFR), E7080 (has multiple targets including RET and VEGFR), Herceptin (targets HER2 / Erb2), PKI-166 (targets EGFR), Canertinib / CI-1033 (targets EGFR), Sunitinib / SU11464 / Sutent (targets EGFR and FLT3), Matuzumab / Emd7200 (targets EGFR), EKB-569 (targets EGFR), Zd6474 (targets EGFR and VEGFR), PKC-412 (targets VEGR and FLT3), Vatalanib / Ptk787 / ZK222584 (targets VEGR), CEP-701 (targets FLT3), SU5614 (targets FLT3), MLN518 (targets FLT3), XL999 (targets FLT3), VX-322 (targeting FLT3), Azd0530 (targeting SRC), BMS-354825 (targeting SRC), SKI-606 (targeting SRC), CP-690 (targeting JAK), AG- 490 (targets JAK), WHI-P154 (targets JAK), WHI-P131 (targets JAK), sorafenib / Nexavar (targets RAF kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR- .beta., KIT, FLT-3 and RET), Dasatinib / Sprycel (BCR / ABL and Src), AC-220 (targets Flt3), AC-480 (targets all HER proteins, panHER), Motesanib diphosphate (targets VEGF1-3, PDGFR, and c-kit), Denosumab (targets RANKL, inhibits SRC), AMG888 (targets HER3), and AP24534 (has multiple targets including Flt3). Examples of serine / threonine kinase inhibitors include, but are not limited to, Rapamune (targets, Rapamune (targets mTOR / FRAP1), Deforolimus (targets mTOR), frncacn / zznz / q / υιλι Certican / Everolimus (targets mTOR / FRAP1), AP23573 (targets mTORJFRAPI), Eril / Fasudil hydrochloride (targets RHO), Flavopiridol (targets CDK), Selic¡cl¡b / CYC202 / Roscov¡trine (targets CDK), SNS-032 / BMS-387032 (targets CDK), Ruboxistaurin (targets PKC), Pkc412 (targets PKC), Bryostatin (targets PKC), KAI-9803 (targets PKC), targets PKC), SF1126 (targets PI3K), VX-680 (targets Aurora kinase), Azd1152 (targets Aurora kinase), Arry-142886 / AZD6244 (targets MAP / MEK), SCIO-469 (targets MAP / MEK), GW681323 (targets MAP / MEK), CC-401 (targets JNK), CEP-1347 (targets JNK), and PD 332991 (targets CDK). Examples of tyrosine kinase inhibitors include, but are not limited to, erlotinib (Tarceva); gefitinib (Iressa); imatinib (Gleevec); sorafenib (Nexavar); sunitinib (Sutent); trastuzumab (Herceptin); bevacizumab (Avastin); rituximab (Rituxan); lapatinib (Tykerb); cetuximab (Erbitux); panitumumab (Vectibix); everolimus (Afinitor); alemtuzumab (Campath), .sub.gemtuzumab (Mylotarg); .sub.temsimlimus (Torisel), .sub.pazopanib (Votrient); .sub.dasatinib (Sprycel); .sub.niotinib (Tasigna), vatalanib (Ptk787; ZK222584); CEP-701; SU5614; MLN518, XL999; VX-322; Azd0530; BMS-354825; SKI-606 CP-690; AG-490; WHI-P154; WHI-P131; AC-220; or AMG888. The present invention provides methods for combination therapy in which a composition comprising a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents are administered to a subject in need of treatment. for an illness or cancer. Combination therapy can also be administered to cancer cells to inhibit proliferation or induce cell death. In one aspect, a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, is administered prior to administration of the composition of the present invention comprising a compound of Formula (I), or a salt pharmaceutically acceptable thereof, and one or more therapeutic agents. In one aspect, a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, is administered prior to the administration of one or more therapeutic agents, so that the other therapeutic agents are administered in a single composition. or in two or more compositions, for example, administered simultaneously, sequentially or alternately. In one embodiment, a composition of the present invention includes a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, and one or more antineoplastic agents, for example, CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone or prednisolone) or R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone or prednisolone). In one embodiment, a composition of the present invention includes a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, and prednisone or prednisolone. The methods of the present invention include combination therapy of administering a compound of Formula (I) or (II), or a pharmaceutically acceptable salt thereof, and antineoplastic agents, wherein the antineoplastic agents are CHOP, R-CHOP, prednisone or prednisolone. hncQQn / zznz / q / υιλι In certain embodiments, the combined therapy is intended to comprise the administration of these therapeutic agents sequentially, that is, where each therapeutic agent is administered at a different time, as well as the administration of these therapeutic agents, or at least two of them. therapeutic agents, substantially simultaneously. Simultaneous administration can be achieved, for example, by administering to the subject a single capsule having a fixed ratio of each therapeutic agent or in multiple individual capsules for each of the therapeutic agents. Sequential or substantially simultaneous administration of each therapeutic agent may be effected by any appropriate route, including, but not limited to, oral routes, intravenous routes, intramuscular routes, and direct absorption through mucous membrane tissues. The therapeutic agent may be administered by the same route or by different routes. For example, a first therapeutic agent of the selected combination may be administered by intravenous injection, while the other therapeutic agents of the combination may be administered orally. Alternatively, for example, both therapeutic agents can be administered orally or both therapeutic agents can be administered by intravenous injection. The therapeutic agents can also be administered alternately. In certain aspects of the invention, the combination therapies presented in the present invention may result in a synergistic effect in the treatment of a disease or cancer. A “synergistic effect” is defined as when the effectiveness of a combination of therapeutic agents is greater than the sum of the effects of any of the agents administered alone. A synergistic effect may also be an effect that cannot be achieved by administering any of the compounds or other therapeutic agents as single agents. The synergistic effect may include, but is not limited to, an effect of cancer treatment by reducing tumor size, inhibiting tumor growth, or increasing subject survival. The synergistic effect may also include reducing cancer cell viability, inducing cancer cell death, and inhibiting or slowing cancer cell growth. In certain aspects of the invention, "combination therapy" also encompasses the administration of the therapeutic agents described above in additional combination with other biologically active ingredients and non-pharmacological therapies (for example, surgery or radiation therapy). Where the combination therapy also comprises a non-pharmacological treatment, the non-pharmacological treatment may be carried out at any appropriate time, provided that a beneficial effect is achieved from the coercion of the combination of the therapeutic agents and the non-pharmacological treatment. For example, in appropriate cases, the beneficial effect is still achieved when the non-pharmacological treatment is temporarily removed from the administration of the therapeutic agents, perhaps for days or even weeks. In another aspect, a composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, analog or derivative, may be administered in combination with radiotherapy. Radiotherapy may also be administered in combination with a composition of the present invention and another chemotherapeutic agent described herein as part of a multi-agent therapy. COMPOSITIONS OF THE INVENTION The present invention also provides pharmaceutical compositions comprising a compound of Formula (I), (II), (III) or (IV), or pharmaceutically acceptable salts thereof, admixed with suitable pharmaceutical vehicles or excipients at doses to treat or prevent a disease. or condition as described herein. In one aspect, the present invention also provides pharmaceutical compositions comprising any compound of Formula (I) or (II), or pharmaceutically acceptable salts thereof, mixed with pharmaceutically acceptable carriers or excipients in doses to treat or prevent such a disease or condition. as described herein. In another aspect, the present invention also provides pharmaceutical compositions comprising compounds of Formula (I), (II), (III) or (IV), or pharmaceutically acceptable salts thereof, admixed with pharmaceutically suitable vehicles or excipients at doses to treat or prevent a disease or condition as described herein. The pharmaceutical compositions of the present invention may also be administered in combination with other therapeutic agents or therapeutic modalities simultaneously, sequentially or alternately. The mixtures of compositions of the present invention may also be administered to the patient as a simple mixture or in appropriately formulated pharmaceutical compositions. For example, one aspect of the invention relates to a pharmaceutical composition comprising a therapeutically effective dose of an SRC inhibitor of Formula (I), (II), (III) or (IV), or a salt, hydrate, enantiomer or pharmaceutically acceptable stereoisomer thereof; one or more therapeutic agents, and a pharmaceutically acceptable diluent or carrier. A "pharmaceutical composition" is a formulation containing the compounds of Formula (I), (II), (III) or (IV) in a form suitable for administration to a subject. In one embodiment, the pharmaceutical composition is in bulk or unit dose form. The unit dosage form is any of a variety of forms, including, for example, a capsule, an intravenous bag, a tablet, a single pump in an aerosol inhaler, or a vial. The amount of active ingredient (for example, a formulation of the described compound or a salt, hydrate, solvate or isomer thereof) in a unit dose of the composition is an effective amount and varies depending on the particular treatment involved. One skilled in the art will appreciate that it is sometimes necessary to make routine variations to the dosage depending on the age and condition of the patient. The dose will also depend on the route of administration. A variety of routes are contemplated, including oral, pulmonary, rectal, parenteral, transdermal, subcutaneous, intravenous, intramuscular, intraperitoneal, inhalatory, buccal, sublingual, intrapleural, intrathecal, intranasal and the like. Dosage forms for topical or transdermal administration of a compound of this invention include powders, aerosols, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. In one embodiment, the active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and with any preservative, buffer or propellant that is required. As used herein, the term "pharmaceutically acceptable" refers to those compounds, anions, cations, materials, compositions, vehicles or dosage forms that, in medical judgment, are suitable for use in contact with human tissues. and animals without causing excessive toxicity, irritation, allergic response or other problem or complication, with a reasonable corresponding risk-benefit ratio. "Pharmaceutically acceptable excipient" means an excipient that is useful for preparing a pharmaceutical composition that is generally safe, non-toxic and neither biological nor undesirable, and includes an excipient that is acceptable for veterinary use and human pharmaceutical use. A "pharmaceutically acceptable excipient", as used in the specification and claims, includes both one and more than one such excipient. A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral administration, for example, intravenous, intradermal, subcutaneous, oral (for example, inhalation), transdermal (topical), and transmucosal. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application may include the following components: a sterile diluent such as water for injection, saline, nonvolatile oils, polyethylene glycols, glycerin, propylene glycol, or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates, and tonicity-adjusting agents such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation may be contained in ampoules, disposable syringes, or multiple-dose vials made of glass or plastic. A composition of the invention can be administered to a subject in many of the well-known methods currently used for chemotherapeutic treatment. For example, for the treatment of cancers, a compound of the invention may be injected directly into tumors, injected into the bloodstream or body cavities, or taken orally, or long-acting frncacn / zznz / q / υιλι may be administered every 3 to 4 days, every week or once every two weeks, depending on the half-life and clearance rate of the particular formulation. Pharmaceutical compositions containing active compounds of the present invention may be manufactured in a manner that is generally known, for example, by conventional mixing, dissolving, granulating, coating, leviating, emulsifying, encapsulating, trapping or lyophilizing processes. Pharmaceutical compositions may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers comprising excipients or auxiliaries that facilitate processing of the active compounds into preparations that can be used pharmaceutically. Of course, the appropriate formulation depends on the chosen route of administration. Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (when soluble in water) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable vehicles include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.), or phosphate-buffered saline (PBS). In such cases, the composition should be sterile and fluid to the extent that it can be easily drawn into a syringe. It must be stable under the conditions of manufacture and storage and preferably, it must be preserved against the contaminating action of microorganisms, such as bacteria and fungi. The carrier may be a solvent or a dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol and the like) and suitable mixtures thereof. Adequate fluidity can be maintained, for example, by the use of a coating such as lecithin, by maintaining the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol and sorbitol, and sodium chloride in the composition. Prolonged absorption of injectable compositions can be caused by the inclusion in the composition of an absorption retarding agent, for example, aluminum monostearate and gelatin. Sterile injectable solutions may be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients listed herein, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle containing a basic dispersion medium and the other necessary ingredients of those mentioned above. In the case of sterile powders for the preparation of sterile injectable solutions, one method of preparation is vacuum drying and lyophilization, which produces a powder of the active ingredient plus any desired additional ingredients from a previously sterile filtered solution of it. Oral compositions generally include an inert diluent or a pharmaceutically acceptable edible carrier. They can also be contained in gelatin capsules or tablets. For the purpose of oral therapeutic administration, the active compound may be incorporated with excipients and used in the form of tablets, lozenges or capsules. Oral compositions can also be prepared using a liquid carrier for use as a mouthwash, wherein the compound in the liquid carrier is applied orally and shaken and expectorated or swallowed. Pharmaceutically compatible binding agents or adjuvant materials may be included as part of the composition. Tablets, pills, capsules, lozenges and the like may contain any of the following ingredients or compounds of a similar nature: a binder, such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient, such as starch or lactose; a disintegrating agent, such as alginic acid, Primogel or corn starch; a lubricant, such as magnesium stearate or Sterotes; a glidant, such as a colloidal silicon dioxide; a sweetening agent, such as sucrose or saccharin; or a flavoring agent, such as mint, methyl salicylate or orange. For administration by inhalation, the compounds are administered as an aerosol from a pressurized container or dispenser, containing a suitable propellant, for example, a gas such as carbon dioxide, or a nebulizer. Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts and fusidic acid derivatives. Transmucosal administration can be achieved through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, gels or creams as is generally known in the art. Active compounds can be prepared with pharmaceutically acceptable carriers that will protect the compound from rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable and biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters and polylactic acid. Methods for preparing such formulations will be apparent to those skilled in the art. Materials can also be obtained commercially from Alza Corporation and Nova frncacn / zznz / q / υιλι Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeting infected cells with monoclonal antibodies against viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in US Patent No. 4,522,811. It is especially advantageous to formulate oral or parenteral compositions in unit dosage form for ease of administration and dosage uniformity. "Unit dosage form" as used herein refers to physically discrete units suitable as unit doses for the subject to be treated; Each unit contains a predetermined amount of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The unit dosage forms of the invention are subject to and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect that is desired to be achieved. In therapeutic applications, doses of the SRC inhibitory compounds of formula (I), (II), (III) or (IV) described herein, other therapeutic agents described herein, compositions comprising a compound of formula ( I), (II), (III) or (IV) and optionally one or more therapeutic agents, or the pharmaceutical compositions used in accordance with the invention, vary depending on the agent, the age, weight and clinical condition of the recipient patient , and the experience and judgment of the physician or professional administering the therapy, among other factors that affect the dosage selected. In general, the dose should be sufficient to cause slowing and preferably regression of tumor growth and also preferably to cause complete regression of the cancer. Doses can range from about 0.01 mg / kg per day to about 5000 mg / kg per day. In preferred embodiments, doses may range from about 1 mg / kg per day to about 1000 mg / kg per day. In one aspect, the dose will be in the range of about 0.1 mg / day to about 50 g / day; about 0.1 mg / day to about 25 g / day; about 0.1 mg / day to about 10 g / day; about 0.1 mg to about 3 g / day; or about 0.1 mg to about 1 g / day, in single, divided, or continuous doses (dose that can be adjusted for the patient's weight in kg, body surface area in m2, and age in years). An effective amount of a pharmaceutical agent is that which provides an objectively identifiable improvement as noted by the physician or other qualified observer. For example, the regression of a tumor in a patient can be measured with reference to the diameter of a tumor. A decrease in the diameter of a tumor indicates regression. Regression is also indicated by the inability of tumors to recur after treatment has stopped. As used herein, the term "effective dosage form" refers to the amount of an active compound to produce the desired biological effect in a subject or cell. Pharmaceutical compositions may be included in a container, package or dispenser along with administration instructions. The composition of the present invention is capable of forming salts. The composition of the present invention is capable of forming more than one salt per molecule, for example, one, two, three. All of these forms are also contemplated within the scope of the claimed invention. As used herein, "pharmaceutically acceptable salts" refer to derivatives of the compounds of the present invention in which the parent compound is modified to produce acidic or basic salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, alkali or organic salts of acidic residues such as carboxylic acids and the like. Pharmaceutically acceptable salts include non-toxic conventional salts or quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such non-toxic conventional salts include, but are not limited to, those derived from inorganic and organic acids selected from 2-acetoxybenzoic, 2-hydroxyethane sulfonic, acetic, ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric, aedetic, disulfonic ethane acids. , 1,2-ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycoliarsanilic, hexyloresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodic, hydroxymallelic, hydroxynaphtonic, isetionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methanesulfonic , nafolic, nitric, oxalic, pamoic, pantothenic, phenylacetic, phosphoric, polygalachronic, propionic, salicylic, stearic, subacetic, succinic, sulfamic, sulfanilic, sulfuric, tannic, tartaric, toluene sulfonic and the common amino acids, e.g., glycine, alanine , phenylalanine, arginine, etc. Other examples of pharmaceutically acceptable salts include hexanoic acid, cyclopentane propionic acid, pyruvic acid, malonic acid, 3-(4-hydroxybenzo¡l)benzo¡ic acid, cinnamic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4- toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo-[2.2.2]-oct-2-ene-1-carboxylic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, muconic acid and the like. The present invention also encompasses salts formed when an acidic proton present in the parent compound is replaced by a metal ion, for example, an alkali metal ion, an alkaline earth ion or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine and the like. It should be understood that all references to pharmaceutically acceptable salts include solvent addition forms (solvates) or crystalline forms (polymorphs), as defined herein, of the same salt. frncacn / zznz / q / υιλι The composition of the present invention may also be prepared as esters, for example, pharmaceutically acceptable esters. For example, a carboxylic acid function group in a compound of Formula (I), (II), (III) or (IV) can be converted to its corresponding ester, for example, a methyl, ethyl or other ester. Additionally, an alcohol group in a compound can be converted to its corresponding ester, for example, acetate, propionate, or other ester. The composition of the present invention may also be prepared as prodrugs, for example, pharmaceutically acceptable prodrugs. The term "prodrug" refers to any compound that releases an active parent drug in vivo. Since prodrugs are known to improve numerous desirable qualities of pharmaceutical products (e.g., solubility, bioavailability, manufacturing, etc.), the compounds of the present invention can be administered in prodrug form. Therefore, it is intended that the present invention comprises prodrugs of the currently claimed compounds, methods of administration thereof and compositions containing them. "Prodrugs" are intended to include any covalently linked carrier that releases an active parent drug of the present invention in vivo when said prodrug is administered to a subject. The prodrugs in the present invention are prepared by modifying the functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of the present invention in which a hydroxy, amino, sulfhydryl, carboxy or carbonyl group is attached to any group that can be cleaved in vivo to form a free hydroxyl, free amino, free sulfhydryl, free carboxy or free carbonyl group. , respectively. Examples of prodrugs include, but are not limited to, esters (e.g., acetate, dialkylaminoacetates, formates, phosphates, sulfates and benzoate derivatives) and carbamates (e.g., N, N-dimethylaminocarbonyl) of hydroxy functional groups, esters (e.g. ethyl esters, morpholinoethanol esters) of carboxyl functional groups, N-acyl derivatives (e.g. N-acetyl bases), N-Mannich bases, Schiff bases and enaminones of amino functional groups, oximes, acetals, ketals and esters of ketone and aldehyde functional groups in the section of compounds of the invention, and the like. See Bundegaard, H., Design of Products, p. 1-92, Elesevier, New York-Oxford (1985). The agents or compounds, or pharmaceutically acceptable salts or derivatives thereof, are administered by oral, nasal, transdermal, pulmonary, inhalation, buccal, sublingual, intraperitoneal, subcutaneous, intramuscular, intravenous, rectal, intrapleural, intrathecal and parenteral routes. In some embodiments, the compound is administered orally. One skilled in the art will recognize the advantages of certain routes of administration. The dosage regimen using the compounds of the present invention is selected according to various factors including the type, species, age, weight, sex and medical condition of the patient, severity of the condition to be treated, the route of administration, the patient's kidney and liver function, and the particular compound, or salt thereof, used. A physician or veterinarian skilled in the art can easily determine and prescribe the effective amount of the drug necessary to prevent, counteract or stop the progression of the condition. Techniques for the formulation and administration of the disclosed compounds of the invention can be found in Remington: the Science and Practice of Pharmacy, 19th edition, Mack Publishing Co., Easton, Pennsylvania (1995). In one embodiment, the compounds described herein, and pharmaceutically acceptable salts thereof, are used in pharmaceutical preparations in combination with a pharmaceutically acceptable carrier or diluent. In one embodiment, suitable pharmaceutically acceptable carriers include, but are not limited to, inert solid diluents or fillers and sterile organic or aqueous solutions. The compounds will be present in such pharmaceutical compositions in amounts sufficient to provide the desired dosage amount in the range described herein. All percentages and ratios used in this document, unless otherwise indicated, are expressed by weight. Other characteristics and advantages of the present invention emerge from the different examples. The examples provided illustrate different components and methodology useful in the practice of the present invention. The examples do not limit the claimed invention. Based on the present disclosure, one skilled in the art can identify and employ other components and methodology useful in practicing the present invention. The present invention provides compositions and methods for the treatment of conditions and diseases whose course can be influenced by modulation of the methylation state of histones or other proteins, wherein said methylation state is mediated at least in part by SRC activity. Modulation of histone methylation status can, in turn, influence the expression level of methylation-activated target genes or methylation-suppressed target genes. The method includes administering, to a subject in need of such treatment, a therapeutically effective amount of a composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, to a subject in need of such treatment. . Based at least on the fact that abnormal histone methylation has been found to be associated with certain cancers and precancerous conditions, one method of treating the cancer or precancerous condition with a mutant SRC in a subject is to administer to the subject that requires a therapeutically effective amount of a compound that inhibits methylation. In a modulation, a method of treating cancer or a precancerous condition in a subject consists of administering to the subject in need thereof a therapeutically effective amount of a compound that inhibits the conversion of unmethylated H3-K27 into Monomethylated H3-K27 (H3-K27me1). In a modulation, a method of treating cancer or a precancerous condition in a subject consists of administering to the subject in need thereof a therapeutically effective amount of a compound that inhibits the conversion of monomethylated H3-K27 (H3-K27me1) to H3-K27 dimethylated (H3-K27me2). In a modulation, a method of treating cancer or a precancerous condition in a subject consists of administering to the subject in need thereof a therapeutically effective amount of a compound that inhibits the conversion of H3-K27me2 to trimethylated H3-K27 (H3-K27me3). . In a modulation, a method of treating cancer or a precancerous condition in a subject consists of administering to the subject in need thereof a therapeutically effective amount of a compound that inhibits the conversion of H3-K27me1 to H3-K27me2 and the conversion of H3- K27me2 on H3-K27me3 It is important to note that disease-specific increases in methylation can occur in chromatin at key genomic loci in the absence of a global increase in cellular levels of protein or histone methylation. For example, it is possible that aberrant hypermethylation in key disease-relevant genes occurs in a context of global histone or protein hypomethylation. Methylation modulators can be used to modulate cell proliferation in general. For example, in some cases overproliferation can be reduced with agents that decrease methylation, while underproliferation can be stimulated with agents that increase methylation. Consequently, diseases that can be treated include hyperproliferative diseases, such as benign cell growth and malignant cell growth (cancer). The disorder in which SRC-mediated protein methylation plays a role may be cancer, a cell proliferative disorder, or a precancerous condition. The present invention further provides the use of a composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, to a subject in need of said treatment for the preparation of a medicament useful for the treatment of cancer. . Examples of cancers that can be treated include lymphomas, including non-Hodgkin's lymphoma, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL); melanoma; and leukemia, including CML. Example of precancerous condition includes myelodysplastic syndrome (MDS; formerly known as preleukemia). Generally, compounds that are modulators of methylation can be used to modulate cell proliferation in general. For example, in some cases overproliferation can be reduced with agents that decrease methylation, while underproliferation can be stimulated with agents that increase methylation. Accordingly, frncacn / zznz / q / υιλι diseases that can be treated with the compounds of the invention include hyperproliferative diseases, such as benign cell growth and malignant cell growth. As used herein, a "subject in need" is a subject who has a disorder in which the SRC-mediated protein plays a role, or a subject who has an increased risk of developing such a disorder relative to the population. in general. A subject who needs it may have a precancerous condition. Preferably, a subject in need has cancer. A "subject" includes a mammal. The mammal may be, for example, any mammal, for example, a human, primate, bird, mouse, rat, fowl, dog, cat, cow, horse, goat, camel, sheep or pig. Preferably, the mammal is a human. The subject of the present invention includes any human subject who has been diagnosed with, has symptoms of, or is at risk of developing a cancer or precancerous condition. The subject of the present invention includes any human subject that expresses a mutant SRC. For example, a mutant SRC comprises one or more mutations, where the mutation is a substitution, a point mutation, a switching mutation, an amino acid mutation, a deletion, an insertion, or any other SRC mutation described herein. A subject who needs it may have resistant cancer. A "resistant cancer" means a cancer that does not respond to treatment. Cancer may be resistant at the beginning of treatment or may become resistant during treatment. In some embodiments, the subject in need has cancer recurrence after remission in the most recent treatment. In some embodiments, the subject in need received all known effective therapies for the treatment of cancer and did not have a positive result for any of them. In some modalities, the subject in need received at least one prior therapy. In certain modalities, the prior therapy is a monotherapy. In certain embodiments, the prior therapy is a combination therapy. In some embodiments, a subject in need may have a secondary cancer as a result of prior therapy. A "secondary cancer" means cancer that arises due to or as a consequence of previous carcinogenic therapies, such as chemotherapy. The subject may also exhibit resistance to histone methyltransferase SRC inhibitors or any other therapeutic agent. The invention also presents a method for selecting a combination therapy for a subject having cancer. The method includes the steps of: detecting one or more SRC mutations described herein in a sample from the subject and selecting, based on the presence of one or more SRC mutations, a combination therapy for the treatment of cancer. In one embodiment, the therapy includes administering to the subject a composition of the invention. In one embodiment, the method further includes administering to the subject a therapeutically effective amount of a frncacn / zznz / q / υιλι composition of the invention. An SRC mutation can be detected using any suitable method known in the art. Additional methods are described in US Patent Publication 20130040906, which is incorporated herein by this reference in its entirety. The methods and uses described herein may include steps to detect one or more SRC mutations described herein in a sample from a subject in need thereof before or after administration of a composition of the invention (for example, a composition comprising a compound of Formula (I), (II), (III) or (IV), or pharmaceutically acceptable salts thereof, and one or more therapeutic agents) to the subject. The presence of one or more SRC mutations described here in the sample tested indicates that the subject responds to the combination therapy of the invention. The present invention provides personalized cancer medication, treatment or management for a subject by genetic screening for one or more SRC mutations described herein in the subject. For example, the present invention provides methods of treating or alleviating a symptom of cancer or a precancerous condition in a subject in need thereof by determining the subject's responsiveness to a combination therapy and when the subject responds to the combination therapy, by administering to the subject a composition of the invention. Responsiveness is determined by obtaining a sample from the subject and detecting one or more SRC mutations described herein, and the presence of one or more SRC mutations described herein indicates that the subject is responsive. composition of the invention. Once a subject's responsiveness is determined, a therapeutically effective amount of a composition may be administered, for example, a composition comprising a compound of Formula (I), (II), (III) or (IV). , or pharmaceutically acceptable salts thereof, and one or more therapeutic agents. The therapeutically effective amount of a composition can be determined by one skilled in the art. As used herein, the term "responsiveness" is interchangeable with "responsive", "sensitive" and "sensitivity", and is understood to mean that a subject exhibits therapeutic responses when administered a composition of the invention, For example, the tumor cells or tumor tissues of the subject undergo apoptosis or necrosis, or show reduced growth, division or proliferation. This expression also means that a subject has or will have a greater probability, with respect to the general population, of presenting therapeutic responses when administered a composition of the invention, for example, the tumor cells or tumor tissues of the subject undergo apoptosis. or necrosis, or show reduced growth, division or proliferation. “Sample” means any biological sample derived from the subject, including, but not limited to, cells, tissue samples, body fluids (including, but not limited to, mucus, frncacn / zznz / q / υιλι blood, plasma, serum , urine, saliva and semen), tumor cells and tumor tissues. Preferably, the sample is selected from bone marrow, peripheral blood cells, blood, plasma and serum. Samples may be provided by the subject undergoing treatment or testing. Alternatively, samples may be obtained by the physician in accordance with routine practice in the art. CONDITIONS, DISORDERS OR DISEASES THAT CAN BE TREATED OR PREVENTED BY THE COMPOUNDS, COMPOSITIONS AND COMBINATIONS OF THE INVENTION As used herein, the term "cell proliferative disorder" refers to conditions in which unregulated or abnormal growth, or both, of cells can lead to the development of an unwanted condition or disease, which may or may not not be cancerous. Examples of cell proliferative disorders of the invention encompass a variety of conditions in which cell division is deregulated. Examples of cell proliferative disorders include, but are not limited to, neoplasms, benign tumors, malignant tumors, precancerous conditions, tumors in situ, encapsulated tumors, metastatic tumors, liquid tumors, solid tumors, immunological tumors, hematological tumors, cancers, carcinomas, leukemias, lymphomas, sarcomas and rapidly dividing cells. The term “rapidly dividing cell,” as used herein, is defined as any cell that divides at a rate that exceeds or is greater than that expected or observed among neighboring or juxtaposed cells within it. tissue. A cell proliferative disorder includes a precancer or precancerous condition. A cell proliferative disorder includes cancer. Preferably, the methods provided herein are used to treat or alleviate a cancer symptom. The term "cancer" includes solid tumors, as well as hematological tumors or malignancies. A "precancerous cell" is a cell that manifests a cell proliferative disorder that is a precancer or precancerous condition. A "cancer cell" is a cell that manifests a cell proliferative disorder that is a cancer. Any reproducible measurement means can be used to identify cancer cells or precancerous cells. Cancer cells or precancerous cells can be identified by histological grading or typing of a tissue sample (for example, a biopsy sample). Cancer cells or precancerous cells can be identified by using appropriate molecular markers. Exemplary non-cancerous conditions or disorders include, but are not limited to, rheumatoid arthritis; inflammation; autoimmune disease; lymphoproliferative conditions; acromegaly; rheumatoid spondylitis; osteoarthritis; gout, other arthritic conditions; sepsis; septic shock; endotoxic shock; gram-negative sepsis; toxic shock syndrome; asthma; frncacn / zznz / q / υιλι syndrome adult respiratory distress; chronic obstructive pulmonary disease; chronic lung inflammation; inflammatory bowel disease; Crohn's disease; psoriasis; eczema; ulcerative colitis; pancreatic fibrosis; liver fibrosis; acute and chronic kidney disease; irritable bowel syndrome; pyresis; restenosis; cerebral malaria; stroke and ischemic injury; neural trauma; Alzheimer disease; Huntington's disease; Parkinson's disease; acute and chronic pain; allergic rhinitis; allergic conjunctivitis; chronic heart failure; acute coronary syndrome; cachexia; malaria; leprosy; leishmaniasis; Lyme's desease; Reiter's syndrome; acute synovitis; muscle degeneration, bursitis; tendinitis; tenosynovitis; herniated, ruptured or prolapsed intervertebral disc syndrome; osteopetrosis; thrombosis; restenosis; silicosis; pulmonary sarcosis; bone resorption diseases, such as osteoporosis; graft versus host reaction; multiple sclerosis; lupus; fibromyalgia; AIDS and other viral diseases such as herpes zoster, herpes simplex I or II, influenza virus, and cytomegalovirus; and diabetes mellitus. Examples of cancers include, but are not limited to, adrenocortical carcinoma, AIDS-related cancers, AIDS-related lymphoma, anal cancer, anorectal cancer, anal canal cancer, appendix cancer, childhood cerebellar astrocytoma, childhood brain astrocytoma, carcinoma basal cell, skin cancer (non-melanoma), biliary cancer, extrahepatic bile duct cancer, intrahepatic bile duct cancer, bladder cancer, urinary bladder cancer, bone and joint cancer, osteosarcoma and malignant fibrous histiocytoma, brain cancer , brain tumor, brainstem glioma, cerebellar astrocytoma, cerebral astrocytoma / malignant glioma, ependymoma, medulloblastoma, supratentorial primitive neuroectodeimal tumors, visual glioma and hypothalamic glioma, breast cancer, bronchial adenomas / carcinoids, carcinoid tumor, gastrointestinal, systemic cancer nervous system, lymphoma of the nervous system, cancer of the central nervous system, lymphoma of the central nervous system, cervical cancer, childhood cancers, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorders, colon cancer, colorectal cancer, cutaneous lymphocytic lymphoma T, lymphoid neoplasia, mycosis fungoides, Seziary syndrome, endometrial cancer, esophageal cancer, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic bile duct cancer, eye cancer, intraocular melanoma, retinoblastoma, gallbladder cancer biliary, gastric (stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), germ cell tumor, ovarian germ cell tumor, gestational trophoblastic tumor glioma, head and neck cancer, hepatocellular (liver) cancer, lymphoma Hodgkin, hypopharyngeal cancer, intraocular melanoma, ocular cancer, islet cell tumors (endocrine pancreas), Kaposi sarcoma, kidney cancer, renal cancer, kidney cancer, laryngeal cancer, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, lip and oral cavity cancer, frncacn / zznz / q / υιλι liver cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, lymphoma related AIDS, non-Hodgkin's lymphoma, primary central nervous system lymphoma, Waldenstrom's macroglobulinemia, medulloblastoma, melanoma, infraocular (eye) melanoma, Merkel cell carcinoma, malignant mesothelioma, mesothelioma, metastatic squamous neck cancer, oral cancer, tongue, multiple endocrine neoplasia syndrome, mycosis fungoides, myelodysplastic syndromes, myelodysplastic / myeloproliferative diseases, chronic myelogenous leukemia, acute myeloid leukemia, multiple myeloma, chronic myeloproliferative disorders, nasopharyngeal cancer, neuroblastoma, oral cancer, oral cavity cancer, oropharyngeal cancer, ovarian cancer, epithelial ovarian cancer, ovarian tumor of low malignant potential, pancreatic cancer, islet cell pancreatic cancer, paranasal sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineoblastoma and supratentorial primitive neuroectodermal tumors, pituitary tumor, plasma cell neoplasia / multiple myeloma, pleuropulmonary blastoma, prostate cancer, cancer of the rectum, renal pelvis and ureter, transitional cell cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer , sarcoma family of tumors, Kaposi sarcoma, soft tissue sarcoma, uterine cancer, uterine sarcoma, skin cancer (non-melanoma), skin cancer (melanoma), Merkel cell skin carcinoma, small intestine cancer, soft tissue sarcoma, squamous cell carcinoma, stomach (gastric) cancer, supratentorial primitive neuroectodermal tumors, testicular cancer, throat cancer, thymoma, thymoma and thymic carcinoma, thyroid cancer, transitional cell cancer of the renal pelvis and the ureter and other urinary organs, gestational trophoblastic tumor, urethral cancer, uterine endometrial cancer, uterine sarcoma, uterine corpus cancer, vaginal cancer, vulvar cancer and Wilm's tumor. A “cell proliferative disorder of the hematologic system” is a cell proliferative disorder involving cells of the hematologic system. A cellular proliferative disorder of the hematologic system may include lymphoma, leukemia, myeloid neoplasms, mast cell neoplasms, myelodysplasia, benign monoclonal gammopathy, lymphomatoid granulomatosis, lymphomatoid papulosis, polycythemia vera, chronic myelocytic leukemia, agnogenic myeloid metaplasia, and essential thrombocythemia. A cell proliferative disorder of the hematologic system may include hyperplasia, dysplasia, and metaplasia of cells of the hematologic system. Preferably, the compositions of the present invention may be used to treat a cancer selected from the group consisting of a hematological cancer of the present invention or a hematological cell proliferative disorder of the present invention. A hematological cancer of the present invention may include multiple myeloma, lymphoma (includes Hodgkin's lymphoma, non-Hodgkin's lymphoma, childhood lymphomas, and lymphomas of lymphocytic and cutaneous origin), leukemia (includes childhood leukemia, frncacn / zznz / q / υιλι single cell leukemia). hairy cells, acute lymphocytic leukemia, acute myelocytic leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, chronic myelogenous leukemia and mast cell leukemia), myeloid neoplasms and mast cell neoplasms. A “cell proliferative disorder of the lung” is a cell proliferative disorder involving lung cells. Cell proliferative disorders of the lung can include all forms of cell proliferative disorders that affect lung cells. Cellular proliferative disorders of the lung may include lung cancer, a precancer or precancerous condition of the lung, benign growths or lesions of the lung and malignant growths or lesions of the lung, and metastatic lesions to tissues and organs of the body other than the lung. Preferably, the compositions of the present invention can be used to treat lung cancer or cell proliferative disorders of the lung. Lung cancer can include all forms of lung cancer. Lung cancer can include lung malignancies, carcinoma in situ, typical carcinoid tumors, and atypical carcinoid tumors. Lung cancer can include small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), squamous cell carcinoma, adenocarcinoma, small cell carcinoma, large cell carcinoma, adenosquamous cell carcinoma, and mesothelioma. Lung cancer can include cicatricial carcinoma, bronchioalveolar carcinoma, giant cell carcinoma, spindle cell carcinoma, and large cell neuroendocrine carcinoma. Lung cancer may include lung neoplasms with histological and ultrastructural heterogeneity (e.g., mixed cell types). Cell proliferative disorders of the lung can include all forms of cell proliferative disorders that affect lung cells. Cellular proliferative disorders of the lung may include lung cancer, precancerous conditions of the lung. Cellular proliferative disorders of the lung may include hyperplasia, metaplasia, and dysplasia of the lung. Cellular proliferative disorders of the lung may include asbestos-induced hyperplasia, squamous metaplasia, and benign reactive mesothelial metaplasia. Cellular proliferative disorders of the lung may include replacement of columnar epithelium with stratified squamous epithelium and mucosal dysplasia. People exposed to harmful inhaled environmental agents, such as cigarette smoke and asbestos, may be at increased risk of developing lung cell proliferative disorders. Previous lung diseases that may predispose individuals to the development of cell proliferative disorders of the lung may include chronic interstitial lung disease, necrotizing lung disease, scleroderma, rheumatoid disease, sarcoidosis, interstitial pneumonitis, tuberculosis, recurrent pneumonias, idiopathic pulmonary fibrosis, granulomata, asbestosis, fibrosing alveolitis and Hodgkin's disease. hncQQn / zznz / q / υιλι A “colon cell proliferative disorder” is a cell proliferative disorder involving colon cells. Preferably, the colonic cell proliferative disorder is colon cancer. Preferably, the compositions of the present invention can be used to treat colon cancer or colon cell proliferative disorders. Colon cancer can include all forms of colon cancer. Colon cancer can include sporadic and hereditary colon cancers. Colon cancer can include colon malignancies, carcinoma in situ, typical carcinoid tumors, and atypical carcinoid tumors. Colon cancer can include adenocarcinoma, squamous cell carcinoma, and adenosquamous cell carcinoma. Colon cancer may be associated with a hereditary syndrome selected from the group consisting of hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, Gardner syndrome, Peutz-Jeghers syndrome, Turcot syndrome, and juvenile polyposis. Colon cancer may be caused by a hereditary syndrome selected from the group consisting of hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, Gardner syndrome, Peutz-Jeghers syndrome, Turcot syndrome, and juvenile polyposis. Cell proliferative disorders of the colon can include all forms of cell proliferative disorders that affect colon cells. Cellular proliferative disorders of the colon may include colon cancer, precancerous conditions of the colon, adenomatous polyps of the colon, and metachronous lesions of the colon. A cell proliferative disorder of the colon may include adenoma. Colonic cell proliferative disorders can be characterized by colonic hyperplasia, metaplasia, and dysplasia. Previous colon diseases that may predispose individuals to the development of colonic cell proliferative disorders may include previous colon cancer. Current disease that may predispose people to the development of colonic cell proliferative disorders may include Crohn's disease and ulcerative colitis. A colonic cell proliferative disorder can be associated with a mutation in a gene selected from the group consisting of p53, ras, FAP and DCC. An individual may be at high risk of developing colonic cell proliferative disorder due to the presence of a mutation in a gene selected from the group consisting of p53, ras, FAP, and DCC. A “pancreatic cell proliferative disorder” is a cell proliferative disorder involving cells of the pancreas. Cell proliferative disorders of the pancreas can include all forms of cell proliferative disorders that affect the cells of the pancreas. Cellular proliferative disorders of the pancreas may include pancreatic cancer, a precancerous or precancerous condition of the pancreas, hyperplasia of the pancreas and dysplasia of the pancreas, benign growths or lesions of the pancreas and malignant growths or lesions of the pancreas, and metastatic lesions in tissues and organs of the pancreas. body other than the pancreas. Pancreatic cancer includes all forms of pancreatic cancer. Pancreatic cancer may include frncacn / zznz / q / υιλι ductal adenocarcinoma, adenocamous carcinoma, pleomorphic giant cell carcinoma, mucinous adenocarcinoma, osteoclast-like giant cell carcinoma, mucinous cystadenocarcinoma, acinar carcinoma, unclassified large cell carcinoma, small cell carcinoma, pancreatoblastoma, papillary neoplasia, mucinous cystadenoma, papillary cystic neoplasia and serous cystadenoma. Pancreatic cancer may also include pancreatic neoplasms with histological and ultrastructural heterogeneity (e.g., mixed cell types). A “prostate cell proliferative disorder” is a cell proliferative disorder involving prostate cells. Cell proliferative disorders of the prostate can include all forms of cell proliferative disorders that affect prostate cells. Cell proliferative disorders of the prostate may include prostate cancer, a precancer or precancerous condition of the prostate, benign growths or lesions of the prostate and malignant growths or lesions of the prostate, and metastatic lesions in tissues and organs of the body other than the prostate. Cellular proliferative disorders of the prostate may include hyperplasia, metaplasia, and dysplasia of the prostate. A “skin cell proliferative disorder” is a cell proliferative disorder involving skin cells. Skin cell proliferative disorders can include all forms of cell proliferative disorders that affect skin cells. Cellular proliferative disorders of the skin may include prostate cancer, a precancer or precancerous condition of the skin, benign growths or lesions of the skin and malignant growths or lesions of the skin, and metastatic lesions in tissues and organs of the body other than the skin. Cellular proliferative disorders of the skin may include skin hyperplasia, metaplasia, and dysplasia. An “ovarian cell proliferative disorder” is a cell proliferative disorder involving cells of the ovary. Ovarian cell proliferative disorders can include all forms of cell proliferative disorders that affect ovarian cells. Cell proliferative disorders of the ovary may include ovarian cancer, a precancer or precancerous condition of the ovary, benign growths or lesions of the ovary and malignant growths or lesions of the ovary, and metastatic lesions to tissues and organs of the body other than the ovary. Cellular proliferative disorders of the skin may include hyperplasia, metaplasia, and dysplasia of ovarian cells. A “breast cell proliferative disorder” is a cell proliferative disorder involving breast cells. Cell proliferative disorders of the breast can include all forms of cell proliferative disorders that affect breast cells. Cellular proliferative disorders of the breast may include breast cancer, a precancer or precancerous condition of the breast, benign growths or lesions of the breast, and malignant growths or lesions of the breast, and metastatic lesions. in tissues and organs of the body other than the breast. Cellular proliferative disorders of the breast may include hyperplasia, metaplasia, and dysplasia of the breast. A “breast cell proliferative disorder” may be a precancerous condition of the breast. The compositions of the present invention can be used to treat a precancerous condition of the breast. A precancerous condition of the breast may include atypical breast hyperplasia, ductal carcinoma in situ (DCIS), intraductal carcinoma, lobular carcinoma in situ (LCIS), lobular neoplasia, and stage 0 or grade 0 breast growth or lesion ( for example, stage 0 or grade 0 breast cancer, or carcinoma in situ). A precancerous condition of the breast can be staged according to the TNM classification scheme accepted by the American Joint Committee on Cancer (AJCC), where the primary tumor (T) has been assigned a stage of TO or Tis; and where the regional lymph nodes (N) have been assigned a stage of NO; and where the distant metastasis (M) has been assigned an MO stage. Breast cell proliferative disorder can be breast cancer. Preferably, the compositions of the present invention can be used to treat breast cancer. Pancreatic cancer includes all forms of breast cancer. Breast cancer can include primary epithelial breast cancers. Breast cancer can include cancers in which the breast is involved by other tumors such as lymphoma, sarcoma or melanoma. Breast cancer may include carcinoma of the breast, ductal carcinoma of the breast, lobular carcinoma of the breast, undifferentiated carcinoma of the breast, phyllodes cystosarcoma of the breast, angiosarcoma of the breast, and primary lymphoma of the breast. Breast cancer can include stage I, II, II, IIIB, CIN, and IV breast cancer. Ductal carcinoma of the breast may include invasive carcinoma, invasive carcinoma in situ with a predominant intraductal component, inflammatory breast cancer, and a ductal carcinoma of the breast with a histological type selected from the group consisting of comedo, mucinous (colloid), medullary, medullary with lymphatic, papillary, scirrhous and tubular infiltrate. Lobular carcinoma of the breast may include invasive lobular carcinoma with a predominant in situ component, invasive lobular carcinoma, and infiltrating lobular carcinoma. Breast cancer may include Paget's disease, Paget's disease with intraductal carcinoma, and Paget's disease with invasive ductal carcinoma. Breast cancer may include breast neoplasms with histological and ultrastructural heterogeneity (e.g., mixed cell types). Preferably, the compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, can be used to treat breast cancer. A breast cancer to be treated may include familial breast cancer. A breast cancer to be treated may include sporadic breast cancer. A breast cancer to be treated may occur in a male subject. A breast cancer to be treated may occur in a female subject. A breast cancer to be treated may occur in a premenopausal female subject or a postmenopausal female subject. A breast cancer to be treated may arise in a subject 30 years of age or older, or in a subject under 30 years of age. A breast cancer to be treated arises in a subject 50 years of age or older, or in a subject under 50 years of age. A breast cancer to be treated may arise in a subject 70 years of age or older, or in a subject under 70 years of age. A breast cancer to be treated can be typed to identify a familial or spontaneous mutation in BRCA1, BRCA2, or p53. A breast cancer to be treated can be typed as having an amplification of the HER2 / neu gene, as having overexpression of HER2 / neu, or as having a low, intermediate, or high level of HER2 / neu expression. A breast cancer to be treated can be typed for a marker selected from the group consisting of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2, Ki- 67, CA15-3, CA 27-29 and c-Met. A breast cancer to be treated can be typed as ER unknown, ER rich, or ER poor. A breast cancer to be treated can be typed as ER negative or ER positive. ER typing of a breast cancer can be performed by any reproducible means. ER typing of a breast cancer can be performed as set out in Onkologie 27: 175-179 (2004). A breast cancer to be treated can be typed as having unknown PR, PR-rich, or PR-poor. A breast cancer to be treated can be typed as PR-negative or PR-positive. A breast cancer to be treated can be typed as positive or negative for a receptor. A breast cancer to be treated may be typed as being associated with elevated blood levels of CA 15-3, or CA 27-29, or both. A breast cancer to be treated may include a localized tumor of the breast. A breast cancer to be treated may include a breast tumor that is associated with a negative sentinel lymph node (SLN) biopsy. A breast cancer to be treated may include a breast tumor that is associated with a positive sentinel lymph node (SLN) biopsy. A breast cancer to be treated may include a tumor of the breast that is associated with one or more positive axillary lymph nodes, where the axillary lymph nodes have been staged by any applicable method. A breast cancer to be treated may include a breast tumor that has been typed as having a node-negative status (e.g., node-negative) or a node-positive status (e.g., node-positive). A breast cancer to be treated may include a breast tumor with metastases to other locations in the body. A breast cancer to be treated can be classified as having metastasized to a location selected from the group consisting of bone, lung, liver, or brain. A breast cancer to be treated can be classified according to a selected characteristic of the frncacn / zznz / q / υιλι group consisting of metastatic, localized, regional, local-regional, locally advanced, distant, multicentric, bilateral, ipsilateral , contralateral, newly diagnosed, recurrent and inoperable. A compound or composition of the present invention, or a pharmaceutically acceptable salt, ester, prodrug, metabolite, polymorph or solvate thereof, can be used to treat or prevent a cell proliferative disorder of the breast, or to treat or prevent breast cancer. , in a subject who has a higher risk of developing breast cancer in relation to the general population. A subject with an increased risk of developing breast cancer relative to the general population is a female subject with a family history or personal history of breast cancer. A subject at increased risk of developing breast cancer relative to the general population is a female subject who has a spontaneous or germline mutation in BRCA1 or BRCA2, or both. A subject at increased risk of developing breast cancer relative to the general population is a female subject with a family history of breast cancer and who has a spontaneous or germline mutation in BRCA1 or BRCA2, or both. A subject with a higher risk of developing breast cancer relative to the general population is a woman who is over 30 years old, over 40 years old, over 50 years old, over 60 years old, over 70 years old, over 80 years or more than 90 years. A subject at increased risk of developing breast cancer relative to the general population is a subject with atypical hyperplasia of the breast, ductal carcinoma in situ (DCIS), intraductal carcinoma, lobular carcinoma in situ (LCIS), lobular neoplasia, and stage 0 or grade 0 breast growth or lesion (for example, stage 0 or grade 0 breast cancer, or carcinoma in situ). A breast cancer to be treated can be classified histologically according to the Scarff-Bloom-Richardson system, in which a breast tumor has been assigned a mitotic count score of 1.2 or 3; a nuclear pleiomorphism score of 1.2 or 3; a tubule formation score of 1, 2, or 3; and a total Scarff-BloomRichardson score between 3 and 9. A breast cancer to be treated may be assigned a tumor grade according to the International Consensus Panel on the Treatment of Breast Cancer selected from the group consisting of grade 1, grade 1 -2, grade 2, grade 2-3 or grade 3. A cancer to be treated can be staged according to the American Joint Committee on Cancer (AJCC) TNM staging system, where the tumor (T) has been assigned a stage of TX, T1, T1mic, T1a, T1b , T1c, T2, T3, T4, T4a, T4b, T4c or T4d; and where the regional lymph nodes (N) have been assigned a stage of NX, NO, N1, N2, N2a, N2b, N3, N3a, N3b or N3c; and where the distant metastasis (M) can be assigned a stage of MX, M0 or MI. A cancer to be treated may be staged according to an American Joint Committee on Cancer (AJCC) classification as Stage I, Stage I, Stage IIB, Stage II, Stage IIIB, Stage hncQQn / zznz / q / υιλι IIIC or Stage IV. A cancer to be treated may be assigned a grade according to an AJCC classification such as Grade GX (for example, the grade cannot be evaluated), Grade 1, Grade 2, Grade 3, or Grade 4. A cancer that to be treated can be staged according to an AJCC pathologic classification (pN) of pNX, pNO, PNO (I-), PNO (l+), PNO (mol-), PNO (mol+), PN1, PN1 (e ), PN1a, PN1b, PN1c, pN2, pN2a, pN2b, pN3, pN3a, pN3b or pN3c. A cancer to be treated may include a tumor that has been determined to be less than or equal to about 2 centimeters in diameter. A cancer to be treated may include a tumor that has been determined to be about 2 to about 5 centimeters in diameter. A cancer to be treated may include a tumor that has been determined to be greater than or equal to about 3 centimeters in diameter. A cancer to be treated may include a tumor that has been determined to be larger than about 5 centimeters in diameter. A cancer to be treated can be classified by microscopic appearance as well differentiated, moderately differentiated, poorly differentiated, or undifferentiated. A cancer to be treated can be classified by microscopic appearance with respect to mitotic count (e.g., amount of cell division) or nuclear pleiomorphism (e.g., change in cells). A cancer to be treated can be classified by microscopic appearance as being associated with areas of necrosis (for example, areas of dying or degenerating cells). A cancer to be treated can be classified as having an abnormal karyotype, having an abnormal number of chromosomes, or having one or more chromosomes that are abnormal in appearance. A cancer to be treated can be classified as aneuploid, triploid, tetraploid, or with an altered ploidy. A cancer to be treated can be classified as having a chromosomal translocation, or a deletion or duplication of an entire chromosome, or a region of deletion, duplication, or amplification of a portion of a chromosome. A cancer to be treated can be evaluated by DNA cytometry, flow cytometry, or image cytometry. A cancer to be treated can be typed as having 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% cells in the synthesis stage of cell division. (for example, in the S phase of cell division). A cancer to be treated can be typed as having a low S-phase fraction or a high S-phase fraction. As used herein, a “normal cell” is a cell that cannot be classified as part of a “cell proliferative disorder.” A normal cell lacks unregulated or abnormal growth, or both, which can lead to the development of an unwanted condition or disease. Preferably, a normal cell possesses normally functioning cell cycle checkpoint control mechanisms. As used herein, "contact with a cell" refers to a condition in which a compound or other composition of matter is in direct contact with a cell or is close enough to induce a desired biological effect in a cell. As used herein, "candidate compound" or "compound of the invention" refers to a compound of formula (I), (II), (III) or (IV) or a salt, ester, prodrug, metabolite , polymorph or pharmaceutically acceptable solvate thereof, which has been or will be evaluated in one or more in vitro or in vivo biological assays, in order to determine whether that compound is likely to provoke a desired biological or medical response in a cell, tissue , system, animal or human that is being investigated by a researcher or clinical professional. A candidate compound is a compound of the present invention, or a pharmaceutically acceptable salt, ester, prodrug, metabolite, polymorph or solvate. The biological or medical response may be cancer treatment. The biological or medical response may be the treatment or prevention of a cell proliferative disorder. In vitro or in vivo biological assays may include, but are not limited to, enzyme activity assays, electrophoretic mobility shift assays, reporter gene assays, in vitro cell viability assays, and the assays described herein. As used herein, "treating" or "treating" describes the management and care of a patient for the purpose of combating a disease, condition or disorder and includes the administration of a compound of the present invention, or a salt , prodrug, metabolite, polymorph or pharmaceutically acceptable solvate thereof, to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. A composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, may also be used to prevent a disease, condition or disorder. As used herein, "preventing" or "preventing" describes reducing or eliminating the occurrence of symptoms or complications of the disease, condition or disorder. As used herein, the term “alleviate” is intended to describe a process by which the severity of a sign or symptom of a disorder is decreased. It is important to note that a sign or symptom can be relieved without being eliminated. In a preferred embodiment, the administration of pharmaceutical compositions of the invention leads to the elimination of a sign or symptom, however, elimination is not required. Effective doses are expected to decrease the severity of a sign or symptom. For example, a sign or symptom of a disorder such as cancer, which can occur in multiple locations, is relieved if the severity of the cancer decreases in at least one of the multiple locations. As used herein, the term "severity" is intended to describe the potential of cancer to transform from a precancerous or benign state to a malignant state. Alternatively, or additionally, severity is intended to describe a stage of cancer, for example, according to the TNM system (accepted by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC)) or by other methods recognized in the art. Cancer stage refers to the extent or severity of the cancer, depending on factors such as the location of the primary tumor, the size of the tumor, the number of tumors, and lymph node involvement (spread of the cancer to the lymph nodes). Alternatively, or in addition, severity is intended to describe the grade of the tumor by methods recognized in the art (see, National Cancer Institute, www.cancer.gov). Tumor grade is a system used to classify cancer cells in terms of how abnormal they look under a microscope and how quickly the tumor is likely to grow and spread. Many factors are considered when determining tumor grade, including the structure and growth pattern of the cells. The specific factors used to determine tumor grade vary with each type of cancer. Severity also describes a histological grade, also called differentiation, which refers to how much the tumor cells look like normal cells of the same tissue type (see, National Cancer Institute, www.cancer.gov). Additionally, severity describes a nuclear grade, which refers to the size and shape of the nucleus in the tumor cells and the percentage of tumor cells that are dividing (see, National Cancer Institute, www.cancer.gov). In another aspect of the invention, severity describes the degree to which a tumor has secreted growth factors, degraded the extracellular matrix, become vascularized, lost adhesion to apposed tissues, or metastasized. Additionally, severity describes the number of locations to which a primary tumor has metastasized. Finally, severity includes the difficulty of treating tumors of different types and locations. For example, inoperable tumors, those cancers that have greater access to multiple body systems (hematological and immunological tumors), and those that are most resistant to traditional treatments are considered more serious. In these situations, prolonging the subject's life expectancy or reducing pain, decreasing the proportion of cancer cells or restricting cells to a system, and improving cancer stage, tumor grade, histological grade, or nuclear grade are considered relief of a sign or symptom of cancer. As used in this document, the term “symptom” is defined as an indication of illness, injury, or that something is wrong with the body. Symptoms are felt or noticed by the individual experiencing the symptom, but may not be easily noticed by others. Others are defined as non-health professionals. As used in this document, the term “sign” is defined as an indication of illness, injury, or that something is wrong with the body. But signs are defined as things that can be seen by a doctor, nurse, or other health care professional. Cancer is a group of diseases that can cause almost any sign or symptom. frncacn / zznz / q / υιλι Signs and symptoms will depend on where the cancer is located, the size of the cancer, and how much it affects nearby organs or structures. If a cancer spreads (metastasizes), then symptoms may appear in different parts of the body. The disorder in which SRC-mediated protein methylation plays a role may be a neurological disease. Therefore, the compound of this invention can also be used to treat neurological diseases such as epilepsy, schizophrenia, bipolar disorder or other psychological or psychiatric disorders, neuropathies, skeletal muscle atrophy and neurodegenerative diseases, for example, a neurodegenerative disease . Examples of neurodegenerative diseases include: Alzheimer's, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. Another class of neurodegenerative diseases includes diseases caused at least in part by polyglutamine aggregation. Diseases in this class include: Huntington's diseases, spinobulbar muscular atrophy (SBMA or Kennedy disease), dentatorrubropallidoluisian atrophy (DRPLA), spinocerebellar ataxia 1 (SCA1), spinocerebellar ataxia 2 (SCA2), Machado-Joseph m disease (MJD ; SCA3), spinocerebellar ataxia 6 (SCA6), spinocerebellar ataxia 7 (SCAT) and spinocerebellar ataxia 12 (SCA12). Any other disease in which epigenetic methylation, which is mediated by SRC, plays a role may be treatable or preventable using compositions and methods described herein. Cancer treatment can result in a reduction in the size of a tumor. A reduction in the size of a tumor may also be called "tumor regression." Preferably, after treatment, the size of the tumor is reduced by 5% or more relative to its size before treatment; more preferably, the size of the tumor is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and more preferably, reduced by more than 75% or more. The size of a tumor can be measured by any reproducible means of measurement. The size of a tumor can be measured as a tumor diameter. Cancer treatment can result in a reduction in tumor volume. Preferably, after treatment, the volume of the tumor is reduced by 5% or more relative to its size before treatment; more preferably, the tumor volume is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and more preferably, reduced by more than 75% or more. The volume of a tumor can be measured by any reproducible means of measurement. frncacn / zznz / q / υιλι Cancer treatment can result in a reduction in the number of tumors. Preferably, after treatment, the number of tumors is reduced by 5% or more relative to the number before treatment; more preferably, the number of tumors is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and more preferably, reduced by more than 75% or more. The number of tumors can be measured by any reproducible means of measurement. The number of tumors can be measured by counting tumors visible to the naked eye or under specific magnification. Preferably, the specified magnification is 2 times, 3 times, 4 times, 5 times, 10 times or 50 times. Cancer treatment may result in a decrease in the number of metastatic lesions in other tissues or organs distant from the primary tumor site. Preferably, after treatment, the number of metastatic lesions is reduced by 5% or more relative to the number before treatment; more preferably, the number of tumors is reduced by 10% or more; more preferably, reduced by 20% or more; more preferably, reduced by 30% or more; more preferably, reduced by 40% or more; even more preferably, reduced by 50% or more; and more preferably, reduced by more than 75% or more. The number of metastatic lesions can be measured by any reproducible means of measurement. The number of metastatic lesions can be measured by counting metastatic lesions with the naked eye or with specific magnification. Preferably, the specified magnification is 2 times, 3 times, 4 times, 5 times, 10 times or 50 times. Cancer treatment may result in an increase in the average survival time of a population of treated subjects compared to a population receiving vehicle alone. Preferably, the average survival time increases by more than 30 days; more preferably, more than 60 days; more preferably, more than 90 days; and more preferably, more than 120 days. An increase in the average survival time of a population can be measured by any reproducible means. An increase in the average survival time of a population can be measured, for example, by calculating for a population the average survival duration after initiation of treatment with an active compound. An increase in the average survival time of a population can be measured, for example, by calculating for a population the average duration of survival after completion of the first round of treatment with an active compound. Cancer treatment may result in an increase in the average survival time of a population of treated subjects compared to a population of untreated subjects. Preferably, the average survival time increases by more than 30 days; more frncacn / zznz / q / υιλι preferably more than 60 days; more preferably, more than 90 days; and more preferably, more than 120 days. An increase in the average survival time of a population can be measured by any reproducible means. An increase in the average survival time of a population can be measured, for example, by calculating for a population the average survival duration after initiation of treatment with an active compound. An increase in the average survival time of a population can be measured, for example, by calculating for a population the average duration of survival after completion of the first round of treatment with an active compound. Cancer treatment may result in an increase in the average survival time of a population of treated subjects compared to a population receiving monotherapy with a drug that is not a compound of the present invention, or a salt, prodrug, metabolite, analogue or pharmaceutically acceptable derivative thereof. Preferably, the average survival time increases by more than 30 days; more preferably, more than 60 days; more preferably, more than 90 days; and more preferably, more than 120 days. An increase in the average survival time of a population can be measured by any reproducible means. An increase in the average survival time of a population can be measured, for example, by calculating for a population the average survival duration after initiation of treatment with an active compound. An increase in the average survival time of a population can be measured, for example, by calculating for a population the average duration of survival after completion of the first round of treatment with an active compound. Cancer treatment may result in a reduction in the mortality rate of a population of treated subjects compared to a population receiving vehicle alone. Cancer treatment may result in a reduction in the mortality rate of a population of treated subjects compared to an untreated population. Cancer treatment may result in a reduction in the mortality rate of a population of treated subjects compared to a population receiving monotherapy with a drug that is not a compound of the present invention, or a salt, prodrug, metabolite, analog or pharmaceutically acceptable derivative thereof. Preferably, the mortality rate is reduced by more than 2%, more preferably by more than 5%, more preferably by more than 10% and more preferably by more than 25%. A decrease in the mortality rate of a population of treated subjects can be measured by any reproducible means. A decrease in the mortality rate of a population can be measured, for example, by calculating for a population the average number of disease-related deaths per unit of time after the start of treatment with an active compound. An increase in the mortality rate of a population can be measured, for example, by calculating for a population the number of disease-related deaths per unit of time after the end of the first round of treatment with an active compound. Cancer treatment may result in a decrease in the rate of tumor growth. Preferably, after treatment, the tumor growth rate is reduced by at least 5% relative to the number before treatment; more preferably, the tumor growth rate is reduced by at least 10%; more preferably, it is reduced by at least 20%; more preferably, it is reduced by at least 30%; more preferably, it is reduced by at least 40%; more preferably, it is reduced by at least 50%; even more preferably, it is reduced by at least 50%; and more preferably, it is reduced by at least 75%. Tumor growth rate can be measured by any reproducible measurement means. Tumor growth rate can be measured according to a change in tumor diameter per unit of time. Cancer treatment may result in a reduction in tumor recurrence. Preferably, after treatment, tumor regrowth is less than 5%; more preferably, the tumor regrowth is less than 10%; more preferably, less than 20%; more preferably, less than 30%; more preferably, less than 40%; more preferably, less than 50%; even more preferably, less than 50%; and more preferably, less than 75%. Tumor recurrence can be measured by any reproducible means of measurement. Tumor regrowth is measured, for example, by measuring an increase in the diameter of a tumor after a previous tumor shrinkage following treatment. A decrease in tumor regrowth is indicated by the inability of tumors to recur after treatment has stopped. Treatment or prevention of a cell proliferative disorder may result in a reduction in the rate of cell proliferation. Preferably, after treatment, the cell proliferation rate is reduced by at least 5%; more preferably, at least 10%; more preferably, at least 20%; more preferably, at least 30%; more preferably, at least 40%; more preferably, at least 50%; even more preferably, at least 50%; and more preferably, at least 75%. The cell proliferation rate can be measured by any reproducible measurement means. The rate of cell proliferation is measured, for example, by measuring the number of dividing cells in a tissue sample per unit of time. Treatment or prevention of a cell proliferative disorder may result in a reduction in the proportion of proliferating cells. Preferably, after treatment, the cell proliferation rate is reduced by at least 5%; more preferably, at least 10%; more preferably, at least 20%; more preferably, at least 30%; more preferably, at least 40%; more preferably, at least 50%; even more frncacn / zznz / q / υιλι preferably, at least by 50%; and more preferably, at least 75%. The proportion of proliferating cells can be measured by any reproducible measurement means. Preferably, the proportion of proliferating cells is measured, for example, by quantifying the number of dividing cells relative to the number of non-dividing cells in a tissue sample. The proportion of proliferating cells may be equivalent to the mitotic index. Treatment or prevention of a cell proliferative disorder may result in a decrease in the size of an area or zone of cell proliferation. Preferably, after treatment, the size of an area or zone of cell proliferation is reduced by at least 5% relative to its size before treatment; more preferably, it is reduced by at least 10%; more preferably, it is reduced by at least 20%; more preferably, it is reduced by at least 30%; more preferably, it is reduced by at least 40%; more preferably, it is reduced by at least 50%; even more preferably, it is reduced by at least 50%; and more preferably, it is reduced by at least 75%. The size of an area or zone of cell proliferation can be measured by any reproducible measuring means. The size of an area or zone of cell proliferation can be measured as a diameter or width of an area or zone of cell proliferation. Treatment or prevention of a cell proliferative disorder may result in a decrease in the number or proportion of cells that have an abnormal appearance or morphology. Preferably, after treatment, the number of cells having abnormal morphology is reduced by at least 5% relative to their size before treatment; more preferably, it is reduced by at least 10%; more preferably, it is reduced by at least 20%; more preferably, it is reduced by at least 30%; more preferably, it is reduced by at least 40%; more preferably, it is reduced by at least 50%; even more preferably, it is reduced by at least 50%; and more preferably, it is reduced by at least 75%. Abnormal cell appearance or morphology can be measured by any reproducible measurement means. Abnormal cell morphology can be measured by microscopy, for example using an inverted tissue culture microscope. Abnormal cellular morphology can take the form of nuclear pleiomorphism. As used herein, the term “selectively” means that it tends to occur more frequently in one population than in another population. The compared populations may be cellular populations. Preferably, a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, acts selectively on a cancerous or precancerous cell, but not on a normal cell. Preferably, a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, acts selectively to modulate a molecular target (e.g., a target protein methyltransferase), but does not modulate frncacn / zznz / q / υιλι significantly another molecular target (e.g., a non-target protein methyltransferase). The invention also provides a method of selectively inhibiting the activity of an enzyme, such as a protein methyltransferase. Preferably, an event occurs selectively in population A relative to population B if it occurs more than twice as frequently in population A compared to population B. An event occurs selectively if it occurs more than five times as frequently in population A. An event occurs selectively if it occurs more than ten times more frequently in population A; more preferably, more than fifty times; even more preferably, more than 100 times; and more preferably, more than 1000 times more frequently in population A compared to population B. For example, cell death would be said to occur selectively in cancer cells if it occurred more than twice as frequently in cancer cells compared with normal cells. In certain embodiments, a composition of the present invention (for example, a composition comprising any compound of Formula (I), (II), (III) or (IV) or pharmaceutically acceptable salt thereof), and one or more agents Therapeutic agents, such as prednisone, can modulate the activity of a molecular target (for example, a methyltransferase target protein). Modulation refers to stimulating or inhibiting an activity of a molecular target. Preferably, a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, modulates the activity of a molecular target if it stimulates or inhibits the activity of the molecular target by at least 2-fold relative to the activity of the molecular target under the same conditions, but lacking only the presence of said compound. More preferably, a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, modulates the activity of a molecular target if it stimulates or inhibits the activity of the molecular target by at least 5-fold, by at least 10 times, at least 20 times, at least 50 times, at least 100 times in relation to the activity of the molecular target under the same conditions, but lacking only the presence of said compound. The activity of a molecular target can be measured by any reproducible means. The activity of a molecular target can be measured in vitro or in vivo. For example, the activity of a molecular target can be measured in vitro by an enzyme activity assay or a DNA binding assay, or the activity of a molecular target can be measured in vivo by a reporter gene expression assay. A composition of the present invention does not significantly modulate the activity of a molecular target if the addition of the compound does not stimulate or inhibit the activity of the molecular target by more than 10% relative to the activity of the molecular target under the same conditions, but lacking only the presence of said compound. As used herein, the term "selective isoenzyme" means the preferential inhibition or stimulation of a first isoform of an enzyme compared to a second isoform of an enzyme (e.g., inhibition or preferential stimulation of a protein methyltransferase ¡sozyme alpha compared to a protein methyltransferase ¡sozyme beta). Preferably, a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, demonstrates a minimum of a fourfold differential, preferably, a tenfold differential, more preferably a fiftyfold differential, in the dose required to achieve a biological effect. Preferably, a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, demonstrates this differential over the entire range of inhibition and the differential is exemplified by IC50, i.e., 50% inhibition. , for a molecular target of interest. Administration of a composition of the present invention to a cell or subject in need thereof may result in the modulation (i.e., stimulation or inhibition) of a protein methyltransferase activity of interest. The administration of a compound of the invention, for example, a composition comprising any compound of formula (I), (II), (III) or (IV), or pharmaceutically acceptable salt thereof, and one or more therapeutic agents, such as prednisone, to a cell or subject in need results in the modulation (i.e., stimulation or inhibition) of an activity of an intracellular target (e.g., substrate). Various intracellular targets can be modulated with the compounds of the present invention, including, but not limited to, the methyltrasferase protein. Activation refers to placing a composition of matter (e.g., protein or nucleic acid) into a state suitable for carrying out a desired biological function. A composition of matter capable of being activated also has a non-activated state. An activated composition of matter may have an inhibitory or stimulating biological function, or both. Elevation refers to an increase in a desired biological activity of a composition of matter (e.g., a protein or a nucleic acid). Elevation can occur through an increase in the concentration of a composition of matter. As used herein, "a cell cycle checkpoint pathway" refers to a biochemical pathway that is involved in the modulation of a cell cycle checkpoint. A cell cycle checkpoint pathway may have stimulatory or inhibitory effects, or both, on one or more functions comprising a cell cycle checkpoint. A cell cycle checkpoint pathway is composed of at least two compositions of matter, preferably proteins, that contribute to the modulation of a cell cycle checkpoint. A cell cycle checkpoint pathway can be activated through activation of one or more members of the frncacn / zznz / q / υιλι cell cycle checkpoint pathway. Preferably, a cell cycle checkpoint pathway is a biochemical signaling pathway. As used herein, "cell cycle checkpoint regulator" refers to a composition of matter that can function, at least in part, in modulating a cell cycle checkpoint. A cell cycle checkpoint pathway regulator may have stimulatory or inhibitory effects, or both, on one or more functions comprising a cell cycle checkpoint. A cell cycle checkpoint regulator may be a protein or a non-protein. Treatment of cancer or a cell proliferative disorder may result in cell death, and preferably the cell death results in a decrease of at least 10% in the number of cells in a population. More preferably, cell death means a decrease of at least 20%; more preferably, a decrease of at least 30%; more preferably, a decrease of at least 40%; more preferably, a decrease of at least 50%; preferably, a decrease of at least 75%. The number of cells in a population can be measured by any reproducible means. A number of cells in a population can be measured by fluorescence activated cell sorting (FACS), immunofluorescence microscopy and light microscopy. Methods for measuring cell death are those shown in Li et al., Proc Nati Acad Sci U.S.A. 100(5): 2674-8, 2003. In one aspect, cell death occurs by apoptosis. Preferably, an effective amount of a composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, is not significantly cytotoxic to normal cells. A therapeutically effective amount of a compound is not significantly cytotoxic to normal cells if administration of the compound in a therapeutically effective amount does not induce cell death in more than 10% of normal cells. A therapeutically effective amount of a compound does not significantly affect the viability of normal cells if administration of the compound in a therapeutically effective amount does not induce cell death in more than 10% of normal cells. In one aspect, cell death occurs by apoptosis. Contact of a cell with a composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, can selectively induce or activate cell death in cancer cells. Administering to a subject in need thereof a compound of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, may selectively induce or activate cell death in cancer cells. Contact of a cell with a composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate of frncacn / zznz / q / υιλι thereof, can selectively induce cell death in one or more cells affected by a cell proliferative disorder. Preferably, administering to a subject in need thereof a composition of the present invention, or a pharmaceutically acceptable salt, prodrug, metabolite, polymorph or solvate thereof, selectively induces cell death in one or more cells affected by a cell proliferative disorder. The following examples are provided to illustrate certain embodiments of the invention. They are not intended to limit the invention in any way. It is intended that said modifications be included in the scope of the attached claims. EXPERIMENTATION AND RESULTS: 1. Isolation and purification process of the active component of Vernonia cinerea (Sahadevi): Plant material and sample preparation The freshly harvested whole Sahadevi plant was cut into pieces and washed thoroughly in water, followed by grinding in a mixer grinder to make an aqueous suspension. The suspension was filtered through a muslin cloth, followed by high-speed centrifugation (15,000 x g for 30 minutes) to remove any debris. The aqueous extract was subjected to chloroform treatment (1:1 v / v, 3 times) to separate chlorophyll and other organic components. A trace of chloroform was removed from the aqueous part by rotary evaporation. The aqueous part was subjected to ethanol precipitation by treating it with ice-cold 100% ethanol to precipitate proteins and nucleic acids. The trace ethanol was even further removed by rotary evaporation followed by lyophilization of the aqueous part in a lyophilizer. The raw powder was stored in an airtight container at room temperature. 50 g of crude Vernonia cinerea powder was added to 500 ml of Milli Q water and kept overnight with gentle stirring. The supernatant was decanted and dried in a lyophilizer. The water-soluble dry powder was used in the bioassay to verify its activity before further purification later. The dry powder of the water extract was resuspended in 500 ml of methanol and kept stirring for two hours at room temperature. The methanol extract was further dried. The activity of the dried methanol extract was further analyzed using a biological assay Process flow diagram The purification process flow along with the process parameters and the role of each step are illustrated below. frncacn / zznz / q / υιλι Process parameter Process step In-process tests • Resin: Capto adhere ImpRes Capture step (RP-HPLC chromatography of the fractions • Bed height: 15 cm ± 10% • Column diameter: 32 mm • Bed volume: ~ 120 mL • Residence time: ~ 4 min • Operating flow rate: ~30 mL / min • Balance buffer: 50 mM sodium acetate, pH 5.5 • Elution buffer 50 mM sodium acetate buffer, 300 mM NaCl pH 5.5 • Regeneration and sanitization solution: 1M NaOH solution, 2M NaCl solution • Column storage solution: ethanol 20 % or 10% NaOH. • Elution: Linear gradient with 0 to 50% elution buffer • Elution collection: For a 2 mm path length of the UV flow cell, collect the elution fraction from five column volumes of the 120 ml column after washing post multimodal loading) in elution • Resin: Puritas C18, 100Ao • Bed height: 25 cm • Column diameter: 50 mm • Bed volume: ~ 480 mi • Residence time: ~ 10 min • Operating flow rate: -48 mL / min • Equilibrium buffer: Acetic acid 0.1% Intermediate Step (PrepRPHPLC) RP-HPLC of the eluting fractions and bioassay after drying hncQQn / zznz / q / υιλι • Elution buffer: 0.1% acetic acid in 85% acetonitrile • Regeneration and sanitization solution: 90% ACN • Column storage solution: 60% ACN • Elution: Linear gradient with 0 to 100% elution buffer for lOOmin • Elution Collection: 1 min fractions, each collected after 34 min • Resin: ImpRes Capto adhere • Bed height: ~5 cm ± 10% • Column diameter: 11 mm • Bed volume: ~ 5 mi • Residence time: ~4 min • Operating flow rate: 1.25 ml_ / min • Equilibrium buffer: 50 mM sodium acetate, pH 5.5 • Elution buffer 50 mM sodium acetate buffer, 300 mM NaCl pH 5.5 • Solution solution regeneration and sanitization: 1M NaOH solution, 2M NaCl solution • Column storage solution: 20% ethanol or 10% NaOH. • Elution: Linear gradient with 0 to 33% elution buffer for 10 CV, followed by 33% to 50% elution buffer for 3CV. Finishing step (multimodal chromatography) hncQQn / zznz / q / υιλι • Elution Collection: For the 2 mm path length of the UV flow cell, the elution fraction of 1 ml each is collected from 20 mAu upstream to 20 mAu downstream. • Resin: PharmPrep® P 100 RP-18e (10pm) • Bed height: 15 cm • Column diameter: 4.6 mm • Bed volume: ~ 4.2 mi • Residence time: ~ 8 min • Operating flow rate: -0.5 mL / min • Equilibrium buffer: 0.1% acetic acid • Elution buffer: 0.1% acetic acid in 85% acetonitrile • Regeneration and sanitization solution: 90% ACN • Column storage solution: 60% ACN • Elution: Linear gradient with 0 to 15% elution buffer for 30 minutes, followed by 15% to 20% elution buffer for 40 minutes • Elution collection: Fractions of 0.5 min each collected after the post-gradient is stratified to 20 minutes . Desalination step (RP-HPLC) RP-HPLC of the eluting fractions and bioassay after drying Description of the purification process Chromatography 1 (Capture Step) The dried methanol extract was subjected to purification with ImpRes frncacn / zznz / q / υιλι Capto adhere resin (120 ml column volume) (Make, GE Healthcare) which has multimodal functionality in the mentioned process parameters. The resin was equilibrated with 50 mM sodium acetate at pH 5.5 and the methanol extract was resuspended in the same equilibration buffer and loaded onto the column at 4 min residence time. The column was washed further to remove unbound fractions and then eluted with a linear gradient using 50 mM sodium acetate containing 300 mM sodium chloride, pH 5.5. Fractions were collected and analyzed with RPHPLC and mass spectroscopy. The fractions were also analyzed for activity with the biological assay method. Chromatography 2 (Intermediate Step) Fractions containing bioactivity were pooled and subjected to purification with RP-HPLC chromatography. The Puritas C18 preparation column (PP18-05-100-250C) from Chromachemie was used for 2-step chromatography purification. The column was equilibrated with 0.1% acetic acid and the dry powder of the Chrom 1 elution group was resuspended in the same equilibration buffer and loaded onto the column at 10 min residence time. The column was washed further to remove unbound fractions and then eluted with a linear gradient using 0.1% acetic acid in 85% acetonitrile. The fractions were collected and analyzed by RP-HPLC, mass spectroscopy and by the biological assay method. Chromatography 3 (Finishing Step) The activity-containing fractions were further pooled and subjected to finishing step purification again with Capto adhere ImpRes (5 ml column volume) with the same buffer conditions and the linear gradient mentioned above (Chrom 1 step). The elution fractions were collected and pooled considering the highest purity according to analytical RP-HPLC, and then dried. Chromatography 4 (Desalination Step) The dried elution pool of Chrom 3 was resuspended and subjected to the desalting step using the PharmPrep® P 100 RP-18e column (10pm) from Merck. The column was equilibrated with 0.1% acetic acid and the dry powder of the Chrom 3 elution group was resuspended in the same equilibration buffer and loaded onto the column at approximately 8 min residence time. The column was additionally washed to remove salt fractions and then eluted with a linear gradient with 0.1% acetic acid in 85% acetonitrile. Fractions were collected and analyzed by RP-HPLC, mass spectroscopy, and biological assay. Characterization of active fractions: For structural elucidation, the active compound was analyzed by elemental analysis, 1H-NMR, 13C-NMR, distortion-free enhancement by polarization transfer (DEPT), infrared (IR) spectroscopy, LC-MS and X-ray crystallography. frncacn / zznz / q / υιλι Elemental analysis confirmed elements C, H and O only (C:57.62%, H:4.72%, rest O). The purified compound (E05) was analyzed by 1H NMR. The analysis revealed the presence of a benzene ring structure along with 2 OH groups, a COOH group, and a methylene group (Figure 5). The purified compound (E05) was analyzed by 13C NMR. The analysis confirmed the presence of 9 different carbon atoms (Figure 6). DEPT (Distortionless Enhancement by Polarization Transfer) showed the presence of 3 carbon atoms with an odd number of hydrogens and 2 carbon atoms with an even number of hydrogens (Figure 7) The pure fraction (E05) was subjected to LC-MS analysis. MS analysis revealed the main peak of 182 Dalton (Figure 9). X-ray crystallography: A suitable single crystal was selected for single crystal X-ray diffraction analysis using the Leica microscope. For X-ray crystallographic analysis, a specimen of the E-05 compound was used, approximate dimensions 0.238 mm x 0.214 mm x 0.087 mm. X-ray intensity data were measured on a Bruker D8 VENTURE Kappa Duo PHOTON II CPAD diffractometer equipped with Incotech multilayer mirror optics. Intensity measurements were carried out with the Mo microfocus sealed tube diffraction source (Mo-Κα = 0.71073 Á) at a temperature of 100(2) K. The X-ray generator operated at 50 kV and 1.4 mA. A preliminary set of cellular constants and an orientation matrix were calculated from three sets of 12 frames. Data were collected with scan width ω and φ of 0.5° at different settings of φ and ω with a frame time of 20 seconds keeping the sample-to-detector distance fixed at 4.00 cm. X-ray data collection was monitored by the APEX3 program (Bruker, 2016).1 The total exposure time was 5 hours. The frameworks were integrated with the Bruker SAINT Software package using a narrow framework algorithm. All data were corrected for polarization and Lorentzian absorption effects using the SAINT and SADABS programs. ShelX-97 was used for structure solution and full-matrix least squares refinement at F2.2. All hydrogen atoms were placed in geometrically idealized positions and constrained to assemble on their parent atoms. An ORTEP III3 view (Figure 10) of the compound was drawn with 50% probability shift ellipsoids and the H atoms are shown as small spheres of arbitrary radii. Single crystal analysis revealed that the unknown compound is 3-(3,4dihydroxyphenyl)propanoic acid. Table 1: Sample and crystalline data for the purified compound frncacn / zznz / q / υιλι Identification code E-05 Chemical formula C?HicO4 Formula weight 182 17 g mol Temperature 100(2)K Wavelength 0 71073 A Crystal size 0 087 x 0 214 x 0 238 mm Monocyclic crystal system Space group P2vc Dimensions of unit cell a = 11 3269(9)A a = 90: b = 5 5745(4) A / 3 = 109 283(3) c= 13 8497(9) A y = 90: Volume 825 43(10) A - Z 4 Density (calculated) 1 466 g cm3 Absorption coefficient 0 116 mm·' F(000) 384 frncacn / zznz / q / υιλι 3. In vitro biological assay using water soluble extract of Sahadevi, different fractions during purification, pure and synthetic compound, 3-(3,4-dihydroxy¡phenyl)propanoic acid The cell line F-36E (Riken, BRC , RCB0776) that was derived from a patient with erythroleukemia shows a complete dependence of growth on EPO (erythropoietin). For the present study, F-36E cells were used to measure the in vitro activity in the water-soluble plant extract, different fractions collected by analytical techniques, purified samples (E05) and with the synthetic compound [3-(3,4 -dihídroxípheníl)propanoico]. Cells were cultured and maintained in RPMI-1640 complete medium supplemented with 1 lU / ml EPO. For the assay, F-36E cells were plated in a 96-well plate, 10,000 cells / well. Cells were cultured overnight in RPMI 1640 containing 5% FBS and EPO. Cells were treated with water-soluble extract (200 μg / well) or with different fractions, purified compound or synthetic compound for 24 to 48 hours. Cells treated with EPO (1IU / ml) [EPO control] or without any growth factor (cell control) were used as control. Cell viability was measured using alamar blue cell viability reagent. The 96-well plate was read at an excitation wavelength of 530 nm and an emission wavelength of 590 nm. The relative fluorescence units obtained are directly proportional to the number of live cells. The antiproliferative activity of the synthetic compound [3-(3,4-dihydroxy¡phen¡l)propanoic acid] and Bosutinib was also tested using an F-36E bioassay. The values ​​obtained from different fractions were normalized to the cellular control value. The antiproliferative activity of Sahadevi extract was specific to leukemia cell lines, F-36E and TF-1 (erythroleukemia cell line). Cells treated with EPO or GMCSF were used as a control to normalize the value of cells treated with E05. Chinese hamster ovary (CHO) cells, squamous cell carcinoma cells (A431), and rat medullary thyroid carcinoma cells (6-23) showed no effect on extract treatment (Figure 11). A dose-dependent inhibition of the growth of the colon cancer cell line HCT116 and the breast cancer cell line BT474 could also be observed during E05 treatment (Figure 12 and Figure 13). The ICso values ​​are comparable between the two molecules (Figure 14). Kinase Inhibitor Screening Assay Promega kinase selectivity profiling systems were used to test the inhibitory activity of the purified compound against the broad panel of tyrosine kinases. Kinase selectivity assays were assembled in a 384-well plate using 1 μΙ of the purified compound (1 μΜ final concentration), 2 μΙ of each kinase working material, and 2 μΙ of the corresponding ATP / Substrate working material according to manufacturer's protocol, and kinase activity was quantified using the Promega ADP-Glo™ Kinase Assay. The assembled reaction with kinase and the corresponding ATP / Substrate without the purified compound was used as a positive control. Of the 16 tyrosine kinases, the activity of SRC kinase was found to be inhibited by the purified compound isolated from Sahadevi extract. In vitro bioassay with triple negative breast cancer cell line MDA-MB-468 cells, isolated from a pleural effusion of a patient with metastatic breast adenocarcinoma, are a triple-negative breast cancer (TNBC) cell line. The IC 50 value of E05 or lapatinib (Sigma) or structural analogs of E05 were evaluated in this cell line. Briefly, MDA-MB-468 cells (ATCC no. of testing). The plates were incubated at 37°C, 5% CO2, for 24 hours. E05 and analogues were diluted in the assay medium and added to the respective wells of the assay plate. The plates were further incubated at 37°C, in 5% CO2 for 24 hours. After incubation, cell viability was assessed using CelITiter-Glo® and luminescence of the plates was read using Cytation 5 (Biotek). The relative luminescence units (RLU) obtained were plotted as a function of concentration and EC50 values ​​were estimated using Graphpad Prism 5 software (Figure 15 and Table 2). frncacn / zznz / q / υιλι Table 2: Analysis of different structural analogues of E05 in MDA-MB-468 cells. The activity of E05 and structural analogs were evaluated in the TNBC cell line. E05 and E05_A and E05_E demonstrated cell killing activity in the TNBC cell line. frncacn / zznz / q / υιλι Compound Structure Π) of sample Activity (EC5(T 3 / 3.4-dihydroxyphenylJ propanoic acid C: O- ·<? E2? S6.23uM 3-(3,4-dihydroxyphenyl)-2propiomic acid (caffeic acid; 3-( 2,4-hydroxypheml) propionic 3-(3-hydroxyphenyl) propionic acid <:♦· or μΓ: EC5_A EC5_B EC5_C 122.: uM Inactive Inactive 3-(4-hydroxyphenyl) propionic acid (phoretic acid) Oh EC5_D Inactive 1, 2-Dihydroxyb enene (Catecolj OH QH E25_E 122 ' uM 3-hydroxy-4-methoxyben2oic acid (isovanilic acid) O - ~ OH H-.CO OH EC5_F Inactive 4-hydroxy-3-methoxybenzoic acid (vanillic acid; Acid 2, 4-dihydroxybenzoic acid O OH HO O • OH HO OH EC5_G EC5_H Inactive Inactive The antiproliferative activity of synthetic E05 was compared with that of lapatinib in the triple-negative breast cancer cell line, MDA-MB-468. MDA-MB-468 cells (ATCC #HTB-32) were seeded at a density of 5000 cells per well in a white 96-well plate (Costar cat. #3917) in DMEM medium supplemented with 10% FBS ( test medium). The plates were further incubated at 37°C, in 5% CO2, for 24 hours. E05 and Lapatinib were diluted in the assay medium and added to the respective wells of the assay plates. The plates were further incubated at 37°C, in 5% CO2, for 8 hours. After incubation, cell viability was assessed using CelITiter-Glo® and luminescence of the plates was read using Cytation 5 (Biotek). The relative luminescence units (RLU) obtained were plotted as a function of concentration and EC50 values ​​were estimated with Graphpad Prism 5 software. E05 showed stronger inhibition compared to lapatinib within 8 hours of incubation (Figure 16). E05 Xenograft Study in SCID Mice An efficacy study of E05 and positive control (5-Fluorouracil) was performed in a murine xenograft model of triple-negative breast cancer (MDA-MB-468). The dosage was carried out frncacn / zznz / q / υιλι according to the Table. 3. Table 3: Dosing pattern in different groups during the xenograft study Groups Group ID Treatment* Number of mice / group 1 Vehicle control Vehicle, oral, twice daily, for 6 weeks 10 2 Positive control (5-fluorouracil) i.p., 10 mg / kg, q2days, for 6 weeks 10 3 E05 Oral, twice a day (q12h), for 6 weeks (75 mg / kg) 10 4 E05 Oral, twice a day (q12h), for 6 weeks (200 mg / kg) 10 5 E05 Oral, twice a day day (q12h), for 6 weeks (500 mg / kg) 10 Female SCID (Severe Combined Immunodeficient) mice were used for this study. Approximately 5 χ 106 cells in 0.2 ml of FBS-free medium containing 50% Matrigel were injected into the subcutaneous tissue on the right flank of each mouse. Treatment with E05 or positive control was started when the average tumor volume reached -100 mm3. Tumor volume was measured periodically. A dose-dependent decrease in tumor volumes was observed for the test compound. E05 showed statistically significant efficacy in the triple negative breast cancer (TNBC) murine xenograft model (Figure 17). Animal toxicological study. A 7-day repeat dose range finding (DRF) study of E05 via rapid intravenous injection was carried out in Wistar rats. E05 did not produce any systemic toxicity up to the dose level of 500 mg / kg body weight when administered daily by rapid intravenous injection for 7 consecutive days. TABLE 4: Mortality and morbidity record of the study to determine the 7-day repeat dose interval of E05 through rapid intravenous injection in Wistar frncacn / zznz / q / υιλι rats Sex and group no. Total no. of rats Morbidity Mortality: No. % No. % Male G1 5 0 0 0 0 G2 5 0 0 0 0 G3 5 0 0 0 0 G4 5 0 0 0 0 Female G1 5 0 0 0 0 G2 5 0 0 0 0 G3 5 0 0 0 0 G4 5 0 0 0 0 Dose: G1 - 0; G2 -125; G3 - 250; G4 - 500 mg / kg body weight. A 7-day repeat dose interval determination (DRF) study of E05 via gavage was carried out in Wistar rats. In this DRF study, no mortality, morbidity, or clinical sign was observed during the treatment period. No treatment-related changes were observed in food consumption, organ weight, and relative organ weight of male and female rats in the treatment groups. Based on the results, it is concluded that E05 did not produce any toxicity up to the dose level of 1000 mg / kg body weight when administered orally, via gavage, for 7 consecutive days to Wistar rats. TABLE 5: Mortality and morbidity record of the dose interval determination study with repeated 7-day dosing of E05 through gavage feeding in Wistar rats Sex and group no. Total no. of rats Morbidity Mortality No. % No. % Male G1 5 0 0 0 0 G2 5 0 0 0 0 G3 5 0 0 0 0 G4 5 0 0 0 0 Female G1 5 0 0 0 0 G2 5 0 0 0 0 G3 5 0 0 0 0 G4 5 0 0 0 0 Dose: G1 - 0; G2 - 250; G3 - 500; G4 -1000 mg / kg body weight frncacn / zznz / q / υιλι A maximum tolerated dose (MTD) study was performed with E05. In the MTD study, the group of 3 male rats and 3 female rats were administered doses of 175 (group 1), 550 (group 2), 1750 (group 3), and 2000 (group 4) mg / kg body weight. In MTD, no mortality, morbidity or clinical sign was observed during the 72-h observation period after single administration of 175, 550, 1750 and 2000 mg / kg body weight of the test element, E05. TABLE 6: Mortality and morbidity record of the study of maximum tolerated dose of E05 through oral gavage in Wistar rats Sex and group No. Dose (mg / kg body weight) Number of rats Mortality on experimental day Mortality on experimental day 1 2 3 4 1 2 3 4 Male G1 175 3 0 0 0 0 0 0 0 0 0 G2 550 3 0 0 0 0 0 0 0 0 G3 1750 3 0 0 0 0 0 0 0 0 G4 2000 3 0 0 0 0 0 0 0 0 Female G1 175 3 0 0 0 0 0 0 0 0 G2 550 3 0 0 0 0 0 0 0 0 G3 1750 3 0 0 0 0 0 0 0 0 G4 2000 3 0 0 0 0 0 0 0 0 Pharmacokinetic Study of E05 in Male Sprague Dawley Rats A study was conducted to determine the pharmacokinetics of E05 following single oral administration (10 mg / kg) in male Sprague Dawley rats. After single oral gavage administration of the E05 dose formulation to male Sprague Dawley rats (dose: 10 mg / kg), the mean time to reach maximum plasma concentration (Tmax) was found to be 0.25 h, suggesting a rapid absorption rate. The exposure (Cmax and AUCIast) was found to be 306 ng / mL and 151 ng.h / mL, respectively. The absolute oral bioavailability of the small molecule was 80% (Figure 18). The scientific and patent literature referenced herein sets forth the knowledge that is available to those skilled in the art. All published and unpublished United States patents and United States patent applications cited herein are incorporated by this reference. All published foreign patents and patent applications cited herein are incorporated by this reference. All other references, documents, manuscripts and published scientific literature cited herein are incorporated by reference. While this invention has been particularly shown and described with reference to preferred embodiments thereof, those skilled in the art will understand that various changes in form and details may be made thereto without departing from the scope of the invention encompassed by the claims. attached.

Claims

1. A method of modulating an Src kinase comprising the administration of the following structure: frncacn / zznz / q / uili where X is OS;Ri is a hydrogen, or a substituted or unsubstituted substituent including, but not limited to, lower alkyl, lower alkenyl, lower alkynyl, -(CH2)mR7, (CH2)m-OH, -(CH2)m-O lower alkyl, -(CH2)mO lower alkyl, -(CH2)nO-(CH2)m-R7, -(CH2)m-SH, -(CH2)mS lower alkyl, -(CH2)mS lower alkyl, -(CH2)nS-(CH2)m-R7 each of R2-Re is independently a hydrogen, a hydroxyl, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an amino, a nitro, an azide, a sulfate, a sulfonate, a sulfonamido, -(CH2)mR7, (CH2)m-OH, -(CH2)mO lower alkyl, -(CH2)mO-lower alkyl, -(CH2)nO-(CH2)m-R7, -(CH2)m-SH, -(CH2)mS-lower alkyl, -(CH2)mS-lower alkyl, (CH2)nS-(CH2)m-R7 each of R?, Rs and R9 independently represents, for each occurrence, hydrogen, hydroxyl or an alkyl, alkenyl, aryl, aralkyl, benzyl, cycloalkyl, cycloalkenyl or substituted or unsubstituted heterocycle;and wherein each occurrence of m and n is independently an integer from 1 to 9, and each occurrence of z is independently an integer from 1 to 9; or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diastereomer, a racemate, or a pharmaceutically acceptable mixture thereof.

2. The method of claim 1, wherein each of R3 and R4 is -OH.

3. The method of claim 1, wherein each of R2 and R3 is -OH.

4. The method of claim 1, wherein z is 2 and each of Re and Rg is -H.

5. The method of claim 1, wherein z is 2; each of Ri, R2, Rs, Re, Rs and Rg is -H; and each of R3 and R4 is -OH.

6. The method of claim 1, wherein X is O.

7. The method of claim 1, wherein each of R1, R2, R3, Re, Rs and Rg is -H; each of R3 and R4 is -OH; X is O; and Z is 2.

8. The compound of claim 1, wherein the compound of formula has the following structure: hncQQn / zznz / q / υιλι or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diastereomer, a racemate or a pharmaceutically acceptable mixture thereof.

9. The method of claim 1, wherein the compound of formula II is a prodrug of the following structure: wherein R1 comprises esters, including ethyl esters, morpholinoethanol esters, acetate, dialkylamine acetates, formates, phosphates, sulfates and benzoate derivatives; carbamates including N,N-dimethylaminocarbonyl functional hydroxy groups, and N-acyl derivatives.

10. A prodrug of formula: frncacn / zznz / q / uili wherein Ri comprises esters, including ethyl esters, morpholinoethanol esters, acetate, dialkylamine acetates, formates, phosphates, sulfates and benzoate derivatives; carbamates including N,N-dimethylaminocarbonyl functional hydroxy groups, and N-acyl derivatives.

11. A method for treating chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), breast cancer, and colon cancer comprising the administration of the following structure: Formula II wherein X is O or S;Ri is a hydrogen, or a substituted or unsubstituted substituent including, but not limited to, lower alkyl, lower alkenyl, lower alkynyl, -(CH2)mR7, (CH2)m-OH, -(CH2)m-O lower alkyl, -(CH2)mO lower alkyl, -(CH2)nO-(CH2)m-R7, -(CH2)m-SH, -(CH2)mS lower alkyl, -(CH2)mS lower alkyl, -(CH2)nS-(CH2)m-R7 each of R2-Re is independently a hydrogen, a hydroxyl, a halogen, a lower alkyl, a lower alkenyl, a lower alkynyl, an amino, a nitro, an azide, a sulfate, a sulfonate, a sulfonamido, -(CH2)mR7, (CH2)m-OH, -(CH2)mO lower alkyl, -(CH2)mO-lower alkyl, -(CH2)nO-(CH2)m-R7, -(CH2)m-SH, -(CH2)mS-lower alkyl, -(CH2)mS-lower alkyl, (CH2)nS-(CH2)m-R7 each of R7, Rs and R9 independently represents, for each occurrence, hydrogen, hydroxyl or an alkyl, alkenyl, aryl, aralkyl, benzyl, cycloalkyl, cycloalkenyl or substituted or unsubstituted heterocycle;and wherein each occurrence of m and n is independently an integer from 1 to 9, and each occurrence of z is independently an integer from 1 to 9; or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diastereomer, a racemate, or a pharmaceutically acceptable mixture thereof.

12. The method of claim 11, wherein each of R3 and R4 is -OH.

13. The method of claim 11, wherein each of R2 and R3 is -OH.

14. The method of claim 11, wherein z is 2 and each of Rs and R9 is -H.

15. The method of claim 11, wherein z is 2; each of R1, R2, R5, Re, Rs and R9 is -H; and each of R3 and R4 is -OH.

16. The method of claim 11, wherein X is O.

17. The method of claim 11, wherein each of R1, R2, R3, Re, Rs and R9 is -H; each of R4 and Rs is -OH; X is O; and Z is 2.

18. The compound of claim 11, wherein the compound of formula II has the following structure: hncQQn / zznz / q / υιλι or a salt, a hydrate, a solvate, a clathrate, an enantiomer, a diastereomer, a racemate or a pharmaceutically acceptable mixture thereof.

19. The method of claim 11, wherein the compound of formula II is a prodrug of the following structure: frncacn / zznz / q / υιλι wherein R1 comprises esters, including ethyl esters, morpholinoethanol esters, acetate, dialkylamine acetates, formates, phosphates, sulfates and benzoate derivatives; carbamates including N,N-dimethylaminocarbonyl functional hydroxy groups, and N-acyl derivatives.

20. The method of claim 11, further comprising the administration of one or more additional therapeutic agents comprising anticancer or chemotherapeutic agents.