The present invention relates to a dosage form comprising an aqueous solution of a vinca alkaloid drug or its pharmaceutically acceptable salt in a flexible infusion container, and a light protective secondary packaging containing the flexible infusion container, wherein the dosage form is ready-to-infuse and wherein the aqueous solution is stable at room temperature.

The present invention relates to a dosage form comprising an aqueous solution of a vinca alkaloid drug or its pharmaceutically acceptable salt in a flexible infusion container, and a light protective secondary packaging containing the flexible infusion container, wherein the dosage form is ready-to-infuse and wherein the aqueous solution is stable at room temperature.

The complex chemistry underlying the extensive transformations involved in terpene indole alkaloid synthesis makes identification of the biosynthetic genes challenging. The present invention relates to methods for producing a terpene indole alkaloid derivative, comprising the steps of: (1) providing a terpene indole alkaloid; and (2) providing a first enzyme termed “Precondylocarpine Acetate Synthase” (PAS) or a functional variant or homologue thereof; and/or a second enzyme termed “Dehydroprecondylocarpine Acetate Synthase” (DPAS) or a functional variant or homologue thereof, and optionally providing further identified enzymes involved in this pathway. The invention also encompasses related kits, enzymes, expression vectors, host cells and plants.

The invention provides novel LRP5-binding polypeptides, and more specifically novel LRP5-binding immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

The invention provides novel LRP5-binding polypeptides, and more specifically novel LRP5-binding immunoglobulin single variable domain constructs which can inhibit Wnt signaling pathways. The invention also relates to specific sequences of such polypeptides, methods of their production, and methods of using them, including methods of treatment of diseases such as cancer.

Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5] decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier. ##STR00001##

Disclosed herein, inter alia, are prodrug compositions and methods of using the same for treatment and detection of disease. Specifically, disclosed herein is a compound of formula (I) having spiro-fused 1,2,4-trioxolane and piperidine rings, namely, 1,2,4-trioxa-8-azaspiro[4.5] decane. Also disclosed is a pharmaceutical composition containing the compound and a pharmaceutically acceptable carrier. ##STR00001##

The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

The invention provides novel methods for preparing indolinobenzodiazepine dimer compounds and their synthetic precursors.

Synthetically-derived and previously inaccessible modifications of 20′-hydroxy-vinca derivative compounds such as vinblastine, vincristine or vindesine are disclosed that are a stunning 100-fold more active than the natural product (IC.sub.50's 50-75 pM vs 7 nM, HCT116), and are now accessible as a result of advances in the total synthesis of the natural product. Illustrative new ultra-potent vinblastines bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail α/β dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid and extended C20′-urea along the adjacent protein-protein interface. Added molecular complexity was used to markedly enhance target binding and functional biological activity, and represents a general approach to improving the properties of other natural products targeting a protein-protein interaction. A pharmaceutical composition containing an ultra-potent 20′-hydroxy-vinca derivative compound and a method of treating cancerous cells with such a compound are also disclosed.