Abstract: The present invention provides immune stimulating macrolide of formula (I). The macrolide has utility in treating viral diseases and cancer.

Abstract: The present invention relates to a succinate prodrug for use in the treatment or prevention of lactic acidosis.

Abstract: In various embodiments novel rapamycin analogs are provides that show improved mTORC1 specificity.

Abstract: The present invention provides novel cell-permeable succinates and cell permeable precursors of succinateaimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.

Abstract: The present invention provides novel cell-permeable succinates and cell permeable precursors of succinate aimed at increasing ATP-production in mitochondria. The main part of ATP produced and utilized in the eukaryotic cell originates from mitochondrial oxidative phosphorylation, a process to which high-energy electrons are provided by the Kreb's cycle. Not all Kreb's cycle intermediates are readily permeable to the cellular membrane, one of them being succinate. The provision of the novel cell permeable succinates is envisaged to allow passage over the cellular membrane and thus the cell permeable succinates can be used to enhance mitochondrial ATP-output.

Abstract: The present invention relates to a succinate prodrug for use in the treatment or prevention of lactic acidosis.

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogs and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogs and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogs, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).

Abstract: An apparatus for immobilising a component during a machining operation is provided. The component has a securing region and an elongate body to be machined extending therefrom. The apparatus has a clamp which is configured to immobilise the component at the securing region. The clamp, in use, exerts clamping forces on the securing region. The apparatus further has a support fixture which is movable relative to the clamp to confine the elongate body at a support region thereof distal from the securing region. The support fixture is configured such that, without exertion of clamping forces on the support region by the support fixture, the confined support region is unable to move during the machining operation.

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogues and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogues and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogues, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).

Abstract: The present invention relates to macbecin analogues that are useful, e.g. in the treatment of cancer, B-cell malignancies, malaria, fungal infection, diseases of the central nervous system and neurodegenerative diseases, diseases dependent on angiogenesis, autoimmune diseases and/or as a prophylactic pre-treatment for cancer. The present invention also provides methods for the production of these compounds involving incorporation of non-natural starter units and their use in medicine, in particular in the treatment and/or prophylaxis of cancer or B-cell malignancies.

Abstract: The present invention relates to methods of screening for agents that bind to FBP21. In particular the present invention provides a method of identifying anti-angiogenic agents by screening for agents which are able to bind to FBP21. Compounds identified using the methods and screens of the present invention are useful in the prevention and treatment of conditions associated with angiogenesis.

Abstract: According to the invention there are provided derivatives of a C21-deoxy ansamycin or salt thereof which contain a 1-hydroxyphenyl moiety bearing at position 3 an aminocarboxy substituent, in which position 5 and the aminocarboxy substituent at position 3 are connected by an aliphatic chain of varying length characterised in that the 1-hydroxy position of the phenyl ring is derivatised by an aminoalkyleneaminocarbonyl group, which alkylene group (which may optionally be substituted by alkyl groups) has a chain length of 2 or 3 carbon atoms, a phosphoric acid, or a phosphoric acid ester (such as an alkyl ester) group, or a salt thereof, and which derivatising group increases the water solubility and/or the bioavailability of the parent molecule. Such compounds are useful in therapy eg in the treatment of cancer and B-cell malignancies.

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogues and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogues and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogues, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).

Abstract: The present invention relates to derivatives of borrelidin that are useful in medicine, e.g. in the treatment of cancer or B-cell malignancies, or other diseases in which angiogenesis contributes to the pathology including ophthalmic disorders such as diabetic retinopathy as well as age related macular degeneration (AMD), corneal neovascularisation and retinopathy or prematurity. The present invention also provides methods for the production of these compounds and their use in medicine, in particular in the treatment and/or prophylaxis of cancer or B-cell malignancies and other diseases in which angiogenesis is implicated in the pathogenic process.

Abstract: The present invention relates to the biosynthesis of polyketides and derives from the cloning of nucleic acids encoding a polyketide synthase and other associated proteins involved in the synthesis of the polyketide borrelidin. Materials and Methods including enzyme systems, nucleic acids, vectors and cells are provided for the preparation of polyketides including borrelidin and analogues and derivatives thereof. Novel polyketide molecules are also provided.

Abstract: The present invention relates to 18,21-didesoxymacbecin analogues that are useful, e.g. in the treatment of cancer, B-cell malignancies, malaria, fungal infection, diseases of the central nervous system and neurodegenerative diseases, diseases dependent on angiogenesis, autoimmune diseases and/or as a prophylactic pre-treatment for cancer. The present invention also provides methods for the production of these compounds and their use in medicine, in particular in the treatment and/or prophylaxis of cancer or B-cell malignancies.

Abstract: The present invention relates to the biosynthesis of polyketides and derives from the cloning of nucleic acids encoding a polyketide synthase and other associated proteins involved in the synthesis of the polyketide borrelidin. Materials and methods including enzyme systems, nucleic acids, vectors and cells are provided for the preparation of polyketides including borrelidin and analogues and derivatives thereof. Novel polyketide molecules are also provided.

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogues and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogues and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogues, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogues and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogues and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogues, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).

Abstract: The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. One important area is the isolation and potential use of novel FKBP-ligand analogues and host cells that produce these compounds. The invention is particularly concerned with methods for the efficient transformation of strains that produce FKBP analogues and recombinant cells in which cloned genes or gene cassettes are expressed to generate novel compounds such as polyketide (especially rapamycin) FKBP-ligand analogues, and to processes for their preparation, and to means employed therein (e.g. nucleic acids, vectors, gene cassettes and genetically modified strains).