Abstract: The present invention is directed to Niemann-Pick disease, type C1 (NPC1) binding polypeptides and NPC1 binding peptide conjugates comprising these binding polypeptides. The present invention is further directed to pharmaceutical compositions comprising these NPC1 binding polypeptide and binding peptide conjugates and the use of these compositions to treat a variety of conditions, including cancer, infectious diseases, neurodegenerative diseases, inflammatory conditions, and bone conditions. The NPC1 binding conjugates are also useful for enhancing endosomal release of pharmaceutically active moieties.

Abstract: The present disclosure is directed to pharmaceutical and diagnostic compositions comprising macropinocytosis selective non-binding protein-drug conjugates. These non-binding protein-drug conjugates comprise a non-binding fibronectin type III (FN3) domain coupled to a pharmaceutically active moiety or a diagnostic moiety. The disclosure is also directed to methods of treatment and diagnosis that involve administering the pharmaceutical compositions described herein to a subject in need.

Abstract: The present invention is directed to methods of inducing a phenotypic change in a population of monocytes and; or macrophages. The method includes administering to the population of monocytes and/or macrophages, a macrophage stimulating agent coupled to a carrier molecule, wherein the carrier molecule facilitates macropinocytic uptake of the agent by monocytes and macrophages in the population and is defective in neonatal Fc receptor binding, wherein the administering induces a phenotypic change in the monocytes and macrophages in the population.

Abstract: The present invention is directed to methods of inhibiting both proliferation and survival of cancer cells and for treating a subject having cancer. The present invention is further directed to methods of diagnosing cancer in a subject and identifying cancer therapeutics.

Abstract: The present invention is directed to methods of inducing a phenotypic change in a population of monocytes and/or macrophages. The method includes administering to the population of monocytes and/or macrophages, a macrophage stimulating agent coupled to a carrier molecule, wherein the carrier molecule facilitates macropinocytic uptake of the agent by monocytes and macrophages in the population and is defective in neonatal Fc receptor binding, wherein the administering induces a phenotypic change in the monocytes and macrophages in the population.

Abstract: The present invention is directed to methods of inducing a phenotypic change in a population of monocytes and/or macrophages. The method includes administering to the population of monocytes and/or macrophages, a macrophage stimulating agent coupled to a carrier molecule, wherein the carrier molecule facilitates macropinocytic uptake of the agent by monocytes and macrophages in the population and is defective in neonatal Fc receptor binding, wherein the administering induces a phenotypic change in the monocytes and macrophages in the population.

Abstract: The present invention relates to peptides having one or more stable, internally-constrained HBS ?-helices, where the peptide is capable of interacting with Ras and related proteins.

Abstract: The present invention is directed to methods of inhibiting both proliferation and survival of cancer cells and for treating a subject having cancer. The present invention is further directed to methods of diagnosing cancer in a subject and identifying cancer therapeutics.

Abstract: The present invention is directed to methods of inhibiting both proliferation and survival of cancer cells and for treating a subject having cancer. The present invention is further directed to methods of diagnosing cancer in a subject and identifying cancer therapeutics.

Abstract: The present invention is directed to methods of inhibiting tumor growth in a subject. The present invention is further directed to methods of diagnosing cancer in a subject and identifying a suitable course of treatment for the subject based on the diagnosis. The present invention is also directed to an orthotopic animal model of pancreatic cancer.

Abstract: The present invention relates to peptides having a stable, internally-constrained HBS ?-helix, where the peptide mimics at least a portion of the ?-H helix of the Sos protein and contains a mixture of alpha and beta amino acid residues in the pattern ?3/?1. Methods using the peptides of the present invention for inhibiting Ras signaling in a cell, promoting cell death, and treating, preventing, and/or diagnosing a cellular proliferative disorder, differentiative disorder, and/or neoplastic condition in a subject in need thereof are also disclosed.

Abstract: The present invention relates to peptides having one or more stable, internally-constrained HBS ?-helices, where the peptide is capable of interacting with Ras and related proteins.

Abstract: The present invention relates to peptides having one or more stable, internally-constrained HBS ?-helices, where the peptide is capable of interacting with Ras and related proteins.

Abstract: The present invention is directed to methods of inhibiting tumor growth in a subject. The present invention is further directed to methods of diagnosing cancer in a subject and identifying a suitable course of treatment for the subject based on the diagnosis. The present invention is also directed to an orthotopic animal model of pancreatic cancer.

Abstract: The present invention is directed to methods of inhibiting both proliferation and survival of cancer cells and for treating a subject having cancer. The present invention is further directed to methods of diagnosing cancer in a subject and identifying cancer therapeutics.

Abstract: The present invention relates to peptides having one or more stable, internally-constrained HBS ?-helices, where the peptide is capable of interacting with Ras and related proteins.

Abstract: The present invention relates to methods of modulating binding of Son of sevenless to phosphatidic acid and identifying compounds that modulate such binding. In particular, the present invention relates to a method of controlling pleckstrin homology domain-dependent membrane recruitment of Son of sevenless or histone folds domain-dependent membrane recruitment of Son of sevenless. Also disclosed are methods of controlling Ras and treating a subject for a condition mediated by Ras. The present invention also relates to a method of identifying compounds potentially effective in treating a condition mediated by Ras.

Abstract: The present invention relates to methods of modulating binding of Son of sevenless to phosphatidic acid and identifying compounds that modulate such binding. In particular, the present invention relates to a method of controlling pleckstrin homology domain-dependent membrane recruitment of Son of sevenless or histone folds domain-dependent membrane recruitment of Son of sevenless. Also disclosed are methods of controlling Ras and treating a subject for a condition mediated by Ras. The present invention also relates to a method of identifying compounds potentially effective in treating a condition mediated by Ras.

Abstract: The present invention relates to transgenic animal models of chronic pancreatitis. The present invention also provides methods for generating animal models by introducing mutated trypsinogen genes into the germline of animals and screening methods for identifying biologically active compound.

Abstract: A detailed three-dimensional structure for the complex formed between Ras and the Son of sevenless (Sos) protein is provided. Crystals of this complex are also included in the invention. The present invention farther provides procedures for identifying agents that can inhibit tumor proliferation through the use of rational drug design predicated on the crystals and crystallographic data disclosed.