Abstract: A method of decreasing the food intake of a subject, comprising the administration of a compound which increases FAO, where the compound does not act in the central nervous system to decrease appetite, where the compound is not a fatty acid, or an NPY-inhibitor, or an FAS inhibitor.

Abstract: A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula IV wherein R21=H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —CH2OR25, —C(O)R25, —CO(O)R25, —C(O)NR25R26, —CH2C(O)R25, or —CH2C(O)NHR25, where R25 and R26 are each independently H, C1-C10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R22=—OH, —OR27, —OCH2C(O)R27, —OCH2C(O)NHR27, —OC(O)R27, —OC(O)OR27, —OC(O)NHNH—R5, or —OC(O)NR27R28, where R27 and R28 are each independently H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R27 and R28 can each optionally contain halogen atoms; R23 and R24, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1.

Abstract: A pharmaceutical diluent and a compound of formula VI: wherein: R10=H, or C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing halogen atoms; R11=H3 or C]-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing halogen atoms; R12=H, or C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing halogen atoms, —C(O)R13, where R13 is H, Ci-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing halogen atoms, or —OH, —OR14 or —NR14, where R14 is H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing halogen atoms.

Abstract: A pharmaceutical composition containing a pharmaceutical diluent and a compound of formula II: wherein: R8?H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —C(O)R4, where R4 is H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing halogen atoms, or —OH, —OR7 or —NR7, where R7 is H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing halogen atoms; R9=—OR5, —NR5, —NH—NH—R5 where R5 is H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, allyl, or alkylaryl, optionally containing halogen atoms; R10?H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, or —CH2C(O)R6, where R6 is OR7 and NR7, where R7?H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, allyl, or alkylaryl and can optionally contain halogen atoms. Also included in the invention are methods of using the pharmaceutical compositions and the chemical compounds used in the compositions.

Abstract: This invention provides a method for inducing weight loss in an animal by administering to the animal a compound which reduces the expression and/or secretion of neuropeptide Y (NPY). The effect may be accomplished directly, indirectly, or humorally. Preferably, administration of this compound has the effect of increasing malonyl CoA levels in the animal. Compounds administered according to this invention may be inhibitors of fatty acid synthase (FAS), including substituted ?-methylene-?-carboxyl-?-butyrolactones, or inhibitors of malonyl Coenzyme A decarboxylase (MCD). Preferably, the compound is administered in an amount sufficient to reduce the amount and/or duration of expression and/or secretion of NPY to levels at or below those observed for lean animals. In another preferred embodiment, the administration will reduce expression and/or secretion to levels observed for fed or satiated animals; more preferably, administration will reduce the level of NPY below that of fed animals.

Abstract: A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula IV wherein R21=H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —CH2OR25, —C(O)R25, —CO(O)R25, —C(O)NR25R26, —CH2C(O)R25, or —CH2C(O)NHR25, where R25 and R26 are each independently H, C1-C10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R22=—OH, —OR27, —OCH2C(O)R27, —OCH2C(O)NHR27, —OC(O)R27, —OC(O)OR27, —OC(O)NHNH—R5, or —OC(O)NR27R28, where R27 and R28 are each independently H, C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R27 and R28 can each optionally contain halogen atoms; R23 and R24, the same or different from each other, are C1-C20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1.

Abstract: Methods and compositions for detecting elevated fatty acid synthase (FAS) expression in the liver of a subject are disclosed. The detection may be of expression in liver cells per se or in a bodily fluid of a subject. Also disclosed are methods for identifying the presence or absence of liver disease or pathology in relation to elevated FAS. The disclosed methods may be practiced with various compositions comprising reagents for detecting FAS expression as described herein.

Abstract: This invention provides methods and compositions for inducing weight loss and maintaining optimum weight comprising administering an agent that stimulates carnitine palmitoyl transferase-1 (CPT-1) activity to the patient in need, including human patients. These methods do not require inhibition of fatty acid synthesis. In particular, this invention provides methods for development of therapeutics that selectively enhance fatty acid oxidation, increase energy production, and reduce adiposity while preserving lean mass, through the pharmacological stimulation of CPT-1 activity. In a preferred mode, the agent is administered in an amount sufficient to increase fatty acid oxidation. In another preferred mode, the agent is administered in an amount sufficient to antagonize malonyl CoA inhibition of CPT-1. In yet another preferred mode, the agent is administered in an amount sufficient to increase malonyl CoA level.

Abstract: This invention provides methods and compositions for inducing weight loss and maintaining optimum weight comprising administering an agent that stimulates carnitine palmitoyl transferase-1 (CPT-1) activity to the patient in need, including human patients. These methods do not require inhibition of fatty acid synthesis. In particular, this invention provides methods for development of therapeutics that selectively enhance fatty acid oxidation, increase energy production, and reduce adiposity while preserving lean mass, through the pharmacological stimulation of CPT-1 activity. In a preferred mode, the agent is administered in an amount sufficient to increase fatty acid oxidation. In another preferred mode, the agent is administered in an amount sufficient to antagonize malonyl CoA inhibition of CPT-1. In yet another preferred mode, the agent is administered in an amount sufficient to increase malonyl CoA level.

Abstract: This invention provides compounds and methods for treating, with said compound, a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R—SOn-Z-CO—Y, where R is an alkyl groups having 6-20 carbon atoms, unsaturated hydrocarbon groups having 6-20 carbon atoms, or alkyl groups having 6-20 carbon atoms interrupted by at least one aromatic ring; Z is —CH2—, —CH2CH2—, —NH—NH—, —O—, ——NH—, —O—NH—, —CH2—NH—, —CH2—O—, —NH—O—, —NH—CH2—, —O—CH2—, and —CH?CH—; Y is —NH2, —O—CH2—C6H5, —CO—CO—O—CH3, and —O—CH3; and n is 1 or 2. It has been discovered that these compounds treat microbially-based infections caused by corynebacteria, nocardiae, rhodococcus, and mycobacteria. These compounds may be used to treat mycobacterial cells, such as Mycobacteria tuberculosis, drug resistant M. tuberculosis, M. avium intracellulare, M. leprae, M. paratuberculosis, and pathogenic Mycobacteria sp.

Abstract: This invention provides methods for treating a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R—SOn-Z-CO—Y, where R is an alkyl group having 6-20 carbons; Z is a radical selected from —CH2—, —O—, and —NH—, two of these radicals coupled together, or —CH2═CH2—; Y is —NH2, O—CH2—C6H5, —CO—CO—O—CH3, or O—CH3; and n is 1 or 2. It has been discovered that these compounds inhibit growth of microbial cells which synthesize &agr;-substitued. &bgr;-hydroxy fatty acids, particularly corynemycolic acid, nocardic acid, and mycolic acid. These compounds may be used to inhibit growth of mycobacterial cells, such as Mycobacterium tuberculosis, drug-resistant M. tuberculosis, M. avium intracellulare, and M. leprae.

Abstract: This invention provides a method for inducing weight loss in an animal by administering to the animal a compound which reduces the expression and/or secretion of neuropeptide Y (NPY). The effect may be accomplished directly, indirectly or humorally. Preferably, administration of this compound has the effect of increasing malonyl CoA levels in the animal. Compounds administered according to this invention may be inhibitors of fatty acid synthase (FAS), including substituted &agr;-methylene-&bgr;-carboxyl-&ggr;-butyrolactones, or inhibitors of malonyl Coenzyme A decarboxylase (MCD). Preferably, the compound is administered in an amount sufficient to reduce the amount and/or duration of expression and/or secretion of NPY to levels at or below those observed for lean animals. In another preferred embodiment, the administration will reduce expression and/or secretion to levels observed for fed or satiated animals; more preferably, administration will reduce the level of NPY below that of fed animals.

Abstract: This invention provides methods for treating a mycobacterial infection by administering to an animal a pharmaceutical composition containing a compound having the formula R—SOn—Z—CO—Y, where R is an alkyl group having 6-20 carbons; Z is a radical selected from —CH2—, —O—, and —NH—, two of these radicals coupled together, or —CH2═CH2—; Y is —NH2, O—CH2—C6H5, —CO—CO—O—CH3, or O—CH3; and n is 1 or 2. It has been discovered that these compounds inhibit growth of microbial cells which synthesize &agr;-substitued, &bgr;-hydroxy fatty acids, particularly corynemycolic acid, nocardic acid, and mycolic acid. These compounds may be used to inhibit growth of mycobacterial cells, such as Mycobacterium tuberculosis, drug-resistant M. tuberculosis, M. avium intracellulare, and M. leprae.

Abstract: This invention describes a method to kill cancer cells by acute elevation of cellular malonyl Coenzyme A (Malonyl CoA) which leads to apoptosis. Elevation of malonyl CoA may be induced by inhibition of fatty acid synthase (FAS), or by other manipulation of fatty acid metabolism tht does not involve inhibition of FAS. Alternatively, growth of tumor cells may be induced by a combination of effects including FAS inhibition in conjunction with other interventions which affect fatty acid metabolism, including inhibition of carnitine palmitoyltransferase-1 (CPT-1). Any combination of drugs which produces an analogous physiologic effect(s) may be expected to lead to the same effect on susceptible tumor cells. For example, combination therapy with drug(s) that inhibit the fatty acid synthesis by inhibiting acetyl CoA carboxylase (the first enzyme in the fatty acid synthesis pathway) and drug(s) that inhibit CPT-1 may be expected to induce apoptosis in tumor cells.

Abstract: Weight loss was noted in nude mice treated with cerulenin, a non-competitive inhibitor of FAS. Sustained reduction of adipocyte mass in humans without toxicity would significantly impact disease prevention worldwide. Aside from psychological and self-esteem improvement, weight loss via reduction of adipocyte mass may: (1) ameliorate hyperglycemia associated with non-insulin-dependent diabetes mellitus thereby reducing diabetic complications such as arterial disease, blindness, cataracts, etc., (2) reduce hypertension, (3) reduce risk of coronary artery vascular disease and stroke, and (4) reduce the risk of other complications of massive obesity such as osteoarthritis, surgical complications, etc. There is also potential use in livestock and poultry to reduce the saturated fat content of meat products. Therefore FAS inhibitors are disclosed herein as novel agents for weight reduction. A family of compounds (.gamma.-substituted-.alpha.-methylene-.beta.-carboxy-.gamma.

Abstract: A method of determining the prognosis of a solid tumor is provided, in which a sample from a patient bearing a tumor is assayed for the presence of a protein which is immunologically cross-reactive with the hpr gene product, but not with haptoglobin 1 or haptoglobin 2. Also provided is a method for preparing antibodies specific for this diagnostic marker which correlates with early relapse and metastasis of breast and other cancers. The marker can be detected using immunological methods employing antibodies specific for Hpr protein and not cross-reactive with haptoglobins 1 or 2.

Abstract: A method of determining the prognosis of a solid tumor is provided, in which a sample from a patient bearing a tumor is assayed for the presence of a protein which is immunologically cross-reactive with the hpr gene product, but not with haptoglobin 1 or haptoglobin 2. Also provided is a method for preparing antibodies specific for this diagnostic marker which correlates with early relapse and metastasis of breast and other cancers. The marker can be detected using immunological methods employing antibodies specific for Hpr protein and not cross-reactive with haptoglobins 1 or 2.

Abstract: Fatty acid synthase (FAS) is overexpressed in carcinomas with poor prognosis, but little FAS expression is identified in normal tissues Inhibition of fatty acid synthesis is selectively toxic to carcinoma cells, while normal cells with low FAS activity are resistant. This invention provides a method of treating cancer patients where fatty acid synthesis by cells of the patient's tumor is inhibited with resultant interruption of the disease process.

Abstract: A method of determining the prognosis of a solid tumor is provided, in which a sample from a patient bearing a tumor is assayed for the presence of a protein which is immunologically cross-reactive with the hr gene product, but not with haptoglobin 1 or haptoglobin 2. Also provided is a method for preparing antibodies specific for this diagnostic marker which correlates with early relapse and metastasis of breast and other cancers. The marker can be detected using immunological methods employing antibodies specific for Hpr protein and not cross-reactive with haptoglobins 1 or 2.

Abstract: A method of determining the prognosis of a solid tumor is provided, in which a sample from a patient bearing a tumor is assayed for the presence of a protein which is immunologically cross-reactive with the hpr gene product, but not with haptoglobin 1 or haptoglobin 2. Also provided is a method for preparing antibodies specific for this diagnostic marker which correlates with early relapse and metastasis of breast and other cancers. The marker can be detected using immunological methods employing antibodies specific for Hpr protein and not cross-reactive with haptoglobins 1 or 2.