Abstract: The present disclosure relates to new compounds or pharmaceutically acceptable salts or stereoisomers thereof of formula I as inhibitors of receptor tyrosine kinases (RTK), in particular extracellular mutants of ErbB-receptors. The present disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the treatment of cancer in mammals (e.g. humans).

Abstract: The present disclosure relates to new compounds of formula I and pharmaceutically acceptable salts and stereoisomers thereof, as inhibitors of receptor tyrosine kinases (RTK), in particular extracellular mutants of ErbB-receptors. The disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the treatment of abnormal cell growth in mammals, (e.g., humans).

Abstract: The present disclosure relates to new compounds or pharmaceutically acceptable salts or stereoisomers thereof of formula I as inhibitors of receptor tyrosine kinases (RTK), in particular extracellular mutants of ErbB-receptors. The present disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the treatment of cancer in mammals (e.g. humans).

Abstract: The present disclosure relates to new compounds or pharmaceutically acceptable salts or stereoisomers thereof of formula I as inhibitors of receptor tyrosine kinases (RTK), in particular extracellular mutants of ErbB-receptors. The present disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the treatment of cancer in mammals (e.g. humans).

Abstract: Methods and compositions for treating cancer comprising administering to a patient inhibitors of mT0RC1/C2, IGF-1 R, and IR. In some aspects, a combination of an mT0RC1/C2 inhibitor and an IGF-1 R/IR inhibitor is employed. Other aspects are described herein.

Abstract: Compounds of Formula I, as shown below and defined herein: enriched in deuterium, and pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancers mediated at least in part by IGF-1R and/or IR.

Abstract: The present invention provides diagnostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor that inhibits both IGF-1R and IR kinases. Methods are provided for identifying patients with cancer who are likely to benefit from treatment with an IGF-1R kinase inhibitor that inhibits both IGF-1R and IR kinases. Methods are also provided for identifying patients with cancer who are likely to benefit from treatment with an IGF-1R kinase inhibitor that inhibits both IGF-1R and IR kinases, but who would likely not respond to therapy with an anti-IGF-1R antibody. Methods are also provided for identifying patients with cancer who are more likely to benefit from treatment with anti-IGF-1R antibody. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate these methods are also provided.

Abstract: The present invention provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor of Formula (I) (e.g. OSI-906). Examples of such anti-cancer agents or treatments include doxorubicin, cisplatin, and ionizing radiation. The present invention also provides a pharmaceutical composition comprising an anti-cancer agent that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor of Formula (I), in a pharmaceutically acceptable carrier. The present invention also provides a method of identifying tumor cells that will respond most favorably to treatment with a combination of an anti-cancer agent or treatment that elevates pAkt levels in tumor cells and an IGF-1R kinase inhibitor.

Abstract: The activity of sequence-specific DNA binder proteins, such as DNA methylases, provides a method of obtaining a covalent linkage between a nucleic acid segment and a polypeptide determinant encoded by the nucleic acid segment. The polypeptide determinant is expressed as a fusion protein together with the DNA methylase, which binds in vivo to a cytidine suicide analog when present in a nucleotide sequence. A plasmid suitable for use in this linkage reaction can comprise: (1) a gene fusion construct including a gene encoding a DNA methylase and a gene encoding a polypeptide determinant; (2) a promoter for transcription of the gene fusion construct as messenger RNA; and (3) a methylase conjugation element linked to the gene fusion sequence, the methylase conjugation element including a methylase binding site having at least one copy of a nucleotide sequence including a cytidine suicide analog capable of irreversibly binding the DNA methylase. The plasmid can form a plasmid-polypeptide determinant conjugate.

Abstract: A sailboat with a device for retrieving from the water a person who has fallen overboard. The device consists of a crane mounted on strong, cylindrically-shaped metal tubing fitted over the shroud of the mainmast of the sailboat. The metal tubing consists of an upper tube and a lower tube, the upper tube having a smaller diameter than the lower tube and fitting inside, and has bushings at the top and bottom and also at the point where the upper tube is inserted into the lower tube. The crane consists of a crane arm that can be moved angularly outward and is controlled by a line secured to the metal tubing. A block and tackle with a T-bar rescue device extends from the crane arm. The T-bar rescue device is lowered or raised by the use of the block and tackle device and a hoisting rope, which rope can be drawn manually or by the use of a winch attached to the main mast.

Abstract: This invention concerns novel and useful human antiperspirant compounds which are glucuronides of phenolic anticholinergics or the phenolic derivatives of anticholinergic compounds. These antiperspirant compounds, advantageously, do not have mydriatic properties possessed by the parent anticholinergic compounds.

Abstract: The subject invention concerns a novel process for preparing novel N-oxide compounds of O-.beta.-D-glucuronides of an anticholinergic compound containing a tertiary nitrogen. Examples of suitable glucuronide starting materials are O-.beta.-D-glucuronides of tropicamide, scopolamine, atropine, hyoscyamine, and the like. The novel process gives high yields of the desired N-oxides which are useful as UV filters.