Abstract: Compounds and methods useful for the synthesis of (+)-discodermolide, a naturally occurring microtubule stabilizing agent useful as an anti-cancer agent.

Abstract: Various macrolide compounds such as those having the following formulas are provided where the variables have the values provided herein.

Abstract: Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) are used to express recombinant PKS genes in host cells for the production of epothilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.

Abstract: Domains of fostriecin polyketide synthase and modification enzymes and polynucleotides encoding them are provided. Methods to prepare fostriecin in pharmaceutically useful quantities are described, as are methods to prepare fostriecin analogs and other polyketides using the polynucleotides encoding fostriecin polyketide synthase domains or modifying enzymes.

Abstract: During the production of a product compound by fermentation, the concentration of a precursor compound is maintained within a pre-selected concentration range by having an adsorbent resin in contact with the culture medium. The adsorbent resin reversibly adsorbs precursor compound and, as un-adsorbed precursor compound is converted to product compound, adsorbed precursor compound is released from the resin, thus maintaining the concentration of precursor compound within the pre-selected range.

Abstract: Recombinant DNA compounds that encode all or a portion of the narbonolide polyketide synthase are used to express recombinant polyketide synthase genes in host cells for the production of narbonolide, narbonolide derivatives, and polyketides that are useful as antibiotics and as intermediates in the synthesis of compounds with pharmaceutical value.

Abstract: Polypeptides and domains of leptomycin polyketide synthase and the nucleic acids encoding them are provided. Methods to prepare leptomycin, leptomycin analogs, and leptomycin derivatives are described, as are methods to prepare other polyketides using the nucleic acids encoding leptomycin polyketide synthase domains or modifying enzymes.

Abstract: This invention relates to compounds of formula (I) and to pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, R5, W, X, Y, and Ar are as defined herein. Compounds of formula (I) are useful in the treatment of diseases or conditions characterized by cellular hyperproliferation. This invention also relates to means for the preparation of compounds of formula (I); formulations containing compounds of formula (I); and methods for the use of said compounds and formulations in the treatment of a disease or condition characterized by cellular hyperproliferation, including cancer.

Abstract: Compounds having a structure according to formula I wherein the groups R1 and R4 are as defined in the specification, are useful as anti-proliferative agents.

Abstract: Compounds having a structure according to formula I wherein the groups R1 and R4 are as defined in the specification, are useful as anti-proliferative agents.

Abstract: Compounds having a structure according to formula I wherein the groups R1 and R4 are as defined in the specification, are useful as anti-proliferative agents.

Abstract: The present invention relates to in vitro methods for evaluating compounds that better correlate with therapeutic efficiency than evaluating compounds based on potency alone. In general, the inventive method comprises: (i) determining a potency value for a compound against its target receptor; (ii) determining a desensitization value for the compound against its target receptor; and (iii) comparing the potency value with the desensitization value. If the desired action of a compound is as a receptor agonist, then the compound's desensitization value should be larger than the compound's potency value. This ensures that the concentration of a compound required for potency will not also cause the receptor to desensitize at the same time, thus in an essence nullifying the desired effect. The inventive methods are used to evaluate novel motilide compounds as well as ABT-229 and EM-574, two motilide compounds for which clinical trials have been initiated.

Abstract: The invention relates to benzoquinone ansamycin analogs useful for the treatment of cancer and other diseases or conditions characterized by undesired cellular proliferation or hyperproliferation. Therapies involving the administration of such benzoquinone ansamycin analogs, optionally in combination with an inhibitor of an HSP90 client protein, are useful to treat cancer and non-cancerous disease conditions.

Abstract: Compounds having a structure according to formula I wherein the groups R1 and R4 are as defined in the specification, are useful as anti-proliferative agents.

Abstract: The present invention provides a method for treating cancer. The method involves the administration of an HSP90 inhibitor and an antibiotic, where the combined administration provides a synergistic effect. In one aspect of the invention, a method of treating cancer is provided where a subject is treated with a dose of an HSP90 inhibitor in one step and a dose of an antibiotic in another step. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an HSP90 inhibitor and subsequently treated with a dose of an antibiotic. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an antibiotic and subsequently treated with a dose of an HSP90 inhibitor.

Abstract: The present invention provides a method for treating cancer. The method involves the administration of an HSP90 inhibitor and a nuclear export inhibitor, where the combined administration provides a synergistic effect. In one aspect of the invention, a method of treating cancer is provided where a subject is treated with a dose of an HSP90 inhibitor in one step and a dose of a nuclear export inhibitor in another step. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an HSP90 inhibitor and subsequently treated with a dose of a nuclear export inhibitor. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of a nuclear export inhibitor and subsequently treated with a dose of an HSP90 inhibitor.

Abstract: Recombinant nucleic acids that encode all or a portion of the epothilone polyketide synthase (PKS) are used to express recombinant PKS genes in host cells for the production of epothilones, epothilone derivatives, and polyketides that are useful as cancer chemotherapeutics, fungicides, and immunosuppressants.

Abstract: Compounds having a structure according to formula I wherein the groups R1 and R4 are as defined in the specification, are useful as anti-proliferative agents.

Abstract: Domains of disorazole polyketide synthase and polynucleotides encoding them are provided. Methods to prepare disorazoles in pharmaceutically useful quantities are described, as are methods to prepare disorazole analogs and other polyketides using the polynucleotides encoding disorazole polyketide synthase domains or modifying enzymes.

Abstract: The present invention provides a method for treating cancer. The method involves the administration of an HSP90 inhibitor and an immunosuppressant, where the combined administration provides a synergistic effect. In one aspect of the invention, a method of treating cancer is provided where a subject is treated with a dose of an HSP90 inhibitor in one step and a dose of an immunosuppressant in another step. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an HSP90 inhibitor and subsequently treated with a dose of an immunosuppressant. In another aspect of the invention, a method of treating cancer is provided where a subject is first treated with a dose of an immunosuppressant and subsequently treated with a dose of an HSP90 inhibitor.