Abstract: The present invention relates to protein drug conjugates, methods of manufacturing the same and their use in therapy. In particular, the present invention relates to protein drug conjugates comprising a globular protein, an improved linker and a drug for use in targeted drug delivery applications.

Abstract: The present invention relates to protein drug conjugates, methods of manufacturing the same and their use in therapy. In particular, the present invention relates to protein drug conjugates comprising a globular protein, an improved linker and a drug for use in targeted drug delivery applications.

Abstract: The present invention relates to protein drug conjugates, methods of manufacturing the same and their use in therapy. In particular, the present invention relates to protein drug conjugates comprising a globular protein, an improved linker and a drug for use in targeted drug delivery applications.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for inducing activation of a hedgehog pathway in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as a small molecule, in a sufficient amount to achieve a therapeutic result. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: A compound represented in general formula (X) and (XI):

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: An oligonucleotide analogue having 10 to 200 natural and/or synthetic nucleoside units, linked by internucleoside linkages, at least one of the internucleoside linkages being of formula where the indicated methylene group is attached to a 3′ carbon atom of a nucleoside, the indicated oxygen atom is attached to a 5′-carbon atom of an adjacent nucleside, R1 is hydrogen, hydroxy, O—, thiol, S—, —NH2 or a group of formula R1a, —OR1a, —SR1a, —NHR1b, or —NR1bR1c wherein R1a is an unsubstituted or substituted C1 to C10 alkyl, C2 to C10 alkenyl, C3 to C8 cycloalkyl, C6 to C10 aryl or C7 to C13 aralkyl group; and R1b and R1c are each independently an unsubstituted or substituted C1 to C10 alkyl, C2 to C10 alkenyl, C3 to C8 cycloalkyl, C6 to C10 aryl or C7 to C13 aralkyl group or R1b and R1c together with the nitrogen atom to which they are attached denote a five- or six-membered heterocyclic ring, and X is oxygen or sulfur.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity.

Abstract: A microinjection pump for unrestrained and freely behaving animals is provided. The microinjection pump employs a screw drive mechanism that is actuated by an attached small stepper motor. The pump moves fluid by direct mechanical displacement from two microsyringes arranged in parallel (see FIGS. 1 and 2). The pump pivots and turns freely above an animal cage by an electrical swivel and connects to the animal head only by two small flexible capillary tubes that store and deliver fluids to both sides of its brain. Through associated electronic connections, the pump allows the animal to lever press for self-administration of fluids.

Abstract: The invention provides a process for the preparation of a compound of general formula (I): wherein Im represents an imidazolyl group of the formula: and R1 represents a hydrogen atom or a group as herein defined including —CO2R5, —COR5, —CONR5R6 or —SO2R5 wherein R5 and R6, which may be the same or different, are as herein defined with the proviso that R5 does not represent a hydrogen atom when R1 represents a group —CO2R5 or —SO2R5; one of the groups represented by R2, R3 and R4 is a hydrogen atom or a C1-6alkyl, C3-7cycloaklyl, C3-6alkenyl, phenyl or phenyl C1-3alkyl group, and each of the other two groups, which may be the same or different, represents a hydrogen atom or a C1-6alkyl group; and n represents 2 or 3; which comprises reacting a compound of formula (II) or a protected derivative thereof, with a compound of formula (III): HOCH2-Im  (III) or a salt thereof in the presence of an acid at an elevat