Abstract: Compounds of formula (I) have muscarinic M3 receptor modulating activity; Formula (I) wherein A is an oxygen atom or group —N(R12)—; (i) R1 is C1-C6-alkyl or a hydrogen atom; and R2 is a hydrogen atom or a group —R5, —Z—Y—R5—Z—NR9R10; —Z—CO—NR9R10; —Z—NR9—CO—R5; or —Z—CO2H; and R3 is a lone pair, or C1-C6-alkyl in which case the nitrogen atom to which it is attached is a quaternary nitrogen and carries a positive charge; or (ii) R1 and R3 together with the nitrogen to which they are attached form a heterocycloalkyl ring, and R2 is a hydrogen atom; or a group —R5, —Z—Y—R5, —Z—NR9R10, —Z—CO—NR9R10, —Z—NR9—CO—R5, or —Z—CO2H, in which cases the nitrogen atom to which it is attached is a quaternary nitrogen and carries a positive charge; or (iii) R1 and R2 together with the nitrogen to which they are attached form a heterocycloalkyl ring, said ring being substituted by a group —Y—R5, —Z—Y—R5, —Z—NR9R10; —Z—CO—NR9R10; —Z—NR9—CO—R5; or —Z—CO2H and R3 is a lone pair, or C1-C6-alkyl in which case the nitrogen atom to

Abstract: The present invention relates to the production of secondary metabolites from microorganisms. In particular, there are provided methods for inducing the rapid production of such compounds from a variety of microorganisms.

Abstract: Compounds of formula (I) are useful in the treatment of diseases where enhanced M3 receptor activation is implicated, such as respiratory tract diseases: wherein (i) R1 is C1-C6-alkyl or hydrogen; and R2 is hydrogen or a group —R7, —Z—Y—R7, —Z—NR9R10; —Z—CO—NR9R10, —Z—NR9—[AE11]C(O)O—R7, or —Z—C(O)—R7; and R3 is a lone pair, or C1C6-alkyl; or (ii) R1 and R3 together with the nitrogen to which they are attached form a heterocycloalkyl ring and R2 is a lone pair or a group —R7, —Z—Y—R7, —Z—NR9R10, —Z—CO—NR9R10, —Z—NR9—[AE12]C(O)O—R7; or; —Z—C(O)—R7; or (iii) R1 and R2 together with the nitrogen to which they are attached form a heterocycloalkyl ring, said ring being substituted by a group —Y—R7, —Z—Y—R7, —Z—NR9R10; —Z—CO—NR9R10; —Z—NR9—[AE13]C(O)O—R7; or; —Z—C(O)—R7; and R3 is a lone pair, or C1-C6-alkyl; R4 and R5 are independently selected from the group consisting of aryl, ary-tfused-heterocycloalkyl, heteroaryl, C1-C6-alkyl, cycloalkyl; R6 is —OH, C1-C6-alkyl, C1-C6-alkoxy, hydroxy-C1-C6-alkyl, nitrile, a g

Abstract: This invention relates to M3 antagonists of formula (I) wherein R2, R4, R5, R6, W, V, A, D, X, t, u and v are as defined herein; pharmaceutical compositions containing them; methods for their preparation; and their use in the treatment of diseases where enhanced M3 receptor activation is implicated.

Abstract: The inventions relate generally to vesiculin peptides and vesiculin peptide chains, and fragments, variants and derivatives thereof, related compositions and formulations and their preparation and use, nucleic acids encoding such vesiculin peptides and vesiculin peptide chains, and fragments, variants and derivatives thereof and related vectors and host cells, hybridomas and antibodies, and methods for the prevention and treatment of conditions, diseases and disorders that would be improved, eased, or lessened by the administration of a composition of the invention, including but not limited to glucose metabolism diseases.

Abstract: A novel class or family of TGF-? binding proteins is disclosed. Also disclosed are assays for selecting molecules for increasing bone mineralization and methods for utilizing such molecules.

Abstract: A composition for interacting with a ligand, which composition comprises a non-covalent association of a plurality of distinct conjugates, each conjugate comprising a head group and a tail group, wherein the tail groups of the conjugates form a hydrophobic aggregation and the conjugates are movable within the association so that, in the presence of a ligand, at least two of the head groups are appropriately positioned to form an epitope capable of interacting with the ligand more strongly than each of head groups individually.

Abstract: A novel class or family of TGF-? binding proteins is disclosed. Also disclosed are assays for selecting molecules for increasing bone mineralization and methods for utilizing such molecules.

Abstract: A method for producing and using in treatment a composition for interacting with a ligand, which composition comprises a non-covalent association of a plurality of distinct conjugates, each conjugate comprising a head group and a tail group, wherein the tail groups of the conjugates form a hydrophobic aggregation and the conjugates are movable within the association so that, in the presence of a ligand, at least two of the head groups are appropriately positioned to form an epitope capable of interacting with the ligand more strongly than each of the head groups individually.

Abstract: The invention provides a novel development of the conventional patch clamp technique for measurement of whole cell electrical activity. The invention provides for one or more cell or cells to be suspended in a liquid medium at a liquid/air interface (by virtue of the effect of surface tension at the interface) whereby the cell or cells are accessible at the interface to a microstructure electrode (such as a pipette tip) to which a cell can attach to form an electrical seal, for the purpose of whole cell voltage clamp recording. According to the invention the electrode can be caused to form a high resistance electrical seal with a cell suspended in the liquid at the liquid/air interface without the need to press the cell against a solid support surface. The invention also provides apparatus for carrying out the interface patch clamp technique and control logic for operating a computer to carry out the interface patch clamp technique.

Abstract: A method of comparing two conformers in which any score is obtained by determining the field value for molecule A at the coordinates of molecule B's field point. Molecule B's field point does not have to be very close to molecule A's field point to get a good overlay score: it just needs to be in a region where molecule A's field is large. This overcomes a limitation of conventional pseudo-Coulombic scoring in which a low score is achieved when extrema of large extent overlap but have their minimum points widely separated. The method can be applied to molecular mechanics modelling using atom centred charges (ACCs) and extended electron distributions (XEDs) as well as to quantum mechanics models.

Abstract: The present invention relates to a structure comprising a biological membrane and a porous or perforated substrate, a biological membrane, a substrate, a high throughput screen, methods for production of the structure membrane and substrate, and a method for screening a large number of test compounds in a short period. More particularly it relates to a structure comprising a biological membrane adhered to a porous or perforated substrate, a biological membrane capable of adhering with high resistance seals to a substrate such as perforated glass and the ability to form sheets having predominantly an ion channel or transporter of interest, a high throughput screen for determining the effect of test compounds on ion channel or transporter activity, methods for manufacture of the structure, membrane and substrate, and a method for monitoring ion channel or transporter activity in a membrane.

Abstract: Disclosed are nicotinanilide-N-oxide compounds, methods for their production, pharmaceutical compositions which include these compounds, and methods for their use in various therapies.

Abstract: The invention encompasses novel compounds which are inhibitors of matrix metalloproteinase, ADAM or ADAM-TS enzymes, and which are useful for the treatment of diseases mediated by those enzymes, including degenerative diseases and certain cancers.

Abstract: Isolated nucleic acid molecules are provided which encode Fkhsf, as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors. Assays that are based upon the nucleic acid sequences disclosed herein (as well as mutant forms thereof), may be used for identifying numerous molecules that modulate the immune system. Molecules that specifically bind to an Fkhsf polypeptide are also provided as useful, such as, for modulating the biological activities of Fkhsf. In particular, antibodies that are specific for Fkhsf polypeptide are provided for uses such as for detecting the expression of an Fkhsf polypeptide in cells, isolating an Fkhsf polypeptide, and modulating the activity of an Fkhsf polypeptide.

Abstract: Isolated nucleic acid molecules are provided which encode Fkhsf, as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors. Utilizing assays based upon the nucleic acid sequences disclosed herein (as well as mutant forms thereof), numerous molecules may be identified which modulate the immune system.

Abstract: Methods are disclosed whereby inhibition of proteolytic activity causes an increase in delivery of a transferable label from a viral display package to a target cell. Assaying for the transferable label in the target cell in the presence of a test substance can identify the test substance as a protease inhibitor. Protease inhibitors so identified are used therapeutically, to treat conditions such as cancer, inflammation, rheumatoid arthritis and other autoimmune diseases, and infections, including AIDS, herpes, and hepatitis.

Abstract: Methods are disclosed whereby protease activity is directly linked to replication of viral display packages containing protease-encoding polynucleotides in target cells. The methods can be used, inter alia, to identify proteases, including previously undiscovered proteases or variants of known proteases which may have altered substrate specificity.

Abstract: The subject invention concerns methods and compounds that have utility in the treatment of a condition associated with matrix metalloproteinase, ADAM or ADAM-TS enzymes, a condition that is mediated by TNF &agr; or a condition involving a membrane-shedding event that is mediated by a metalloproteinase. Compounds of the invention are of formula I (B)2N—X—(CH2)m—W—(CR1R2)n—COY  (I) wherein n=0 or 1; m=0 or 1; X is S(O)1-2; Y is OH or NHOH; W is aryl or heteroaryl; and the other groups are as defined herein.

Abstract: Compounds having therapeutic utility are of formula (I) wherein B1, B2, R1 and R2 are each various sub-stituents, or R1 and R2 together form a ring.