Abstract: Certain embodiments disclosed herein are directed to a method of producing endoderm cells, such as definitive endoderm cells by exposing stem cells such as embryonic stem cells or induced pluripotent stem (iPS) cells to an effective amount of at least one compound described herein to differentiate the stem cells into the endoderm cells such as definitive endoderm cells. Differentiated endoderm cells produced by the methods disclosed herein can be differentiated into pancreatic epithelium, and other endoderm derivatives such as thymus, liver, stomach, intestine and lung. Another aspect of the present invention relates to a method of producing pancreatic progenitor cells, such as Pdx1-positive pancreatic progenitor cells by exposing endoderm cells, such as definitive endoderm cells to an effective amount of at least one compound described herein to differentiate the definitive endoderm cells into Pdx1-positive pancreatic progenitor cells.

Abstract: The invention relates to methods of treating protein degradation disorders, such cellular proliferative disorders (e.g., cancer) and protein deposition disorders (e.g., neurodegenerative disorders). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating multiple myeloma. New HDAC/TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.

Abstract: Certain embodiments disclosed herein are directed to a method of producing endoderm cells, such as definitive endoderm cells by exposing stem cells such as embryonic stem cells or induced pluripotent stem (iPS) cells to an effective amount of at least one compound described herein to differentiate the stem cells into the endoderm cells such as definitive endoderm cells. Differentiated endoderm cells produced by the methods disclosed herein can be differentiated into pancreatic epithelium, and other endoderm derivatives such as thymus, liver, stomach, intestine and lung. Another aspect of the present invention relates to a method of producing pancreatic progenitor cells, such as Pdx1-positive pancreatic progenitor cells by exposing endoderm cells, such as definitive endoderm cells to an effective amount of at least one compound described herein to differentiate the definitive endoderm cells into Pdx1-positive pancreatic progenitor cells.

Abstract: The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

Abstract: Certain embodiments disclosed herein are directed to a method of producing pancreatic cells or pancreatic cell precursors by exposing human embryonic stem cells to an effective amount of at least one compound listed in Table I to differentiate the human embryonic stem cells into the pancreatic cells or the pancreatic cell precursors. Kits and pancreatic cell lines produced using the methods are also described.

Abstract: In recognition of the need to develop novel therapeutic agents and efficient methods for the synthesis thereof, the present invention provides novel bifunctional, trifunctional, or multifunctional compounds for inhibiting histone deacetylases, and pharmaceutically acceptable salts and derivatives thereof. The present invention further provides methods for treating disorders regulated by histone deacetylase activity (e.g., proliferative diseases, cancer, inflammatory diseases, protozoal infections, hair loss, etc.) comprising administering a therapeutically effective amount of an inventive compound to a subject in need thereof. The present invention also provides methods for preparing compounds of the invention.

Abstract: Certain embodiments disclosed herein are directed to a method of producing pancreatic cells or pancreatic cell precursors by exposing human embryonic stem cells to an effective amount of at least one compound listed in Table I to differentiate the human embryonic stem cells into the pancreatic cells or the pancreatic cell precursors. Kits and pancreatic cell lines produced using the methods are also described.

Abstract: Certain embodiments disclosed herein are directed to a method of producing endoderm cells, such as definitive endoderm cells by exposing stem cells such as embryonic stem cells or induced pluripotent stem (iPS) cells to an effective amount of at least one compound described herein to differentiate the stem cells into the endoderm cells such as definitive endoderm cells. Differentiated endoderm cells produced by the methods disclosed herein can be differentiated into pancreatic epithelium, and other endoderm derivatives such as thymus, liver, stomach, intestine and lung. Another aspect of the present invention relates to a method of producing pancreatic progenitor cells, such as Pdx1-positive pancreatic progenitor cells by exposing endoderm cells, such as definitive endoderm cells to an effective amount of at least one compound described herein to differentiate the definitive endoderm cells into Pdx1-positive pancreatic progenitor cells.

Abstract: The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

Abstract: This invention relates to high-throughput, semi-automated methods for identifying compounds that are effective in targeting leukemia stem cells, as well as compounds identified by those methods and uses thereof for treating leukemia.

Abstract: The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.

Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support using isocyanate or isothiocyanate chemistry, wherein the density of the array of compounds is at least 1000 spots per cm2.

Abstract: The present invention relates to macrocyclic small molecule inhibitors of the Sonic Hedgehog signaling pathway, syntheses thereof, and intermediates thereto. Such small molecule modulators of the Sonic Hedgehog signaling pathway are useful in the treatment of proliferative diseases (e.g., basal cell carcinoma, Gorlin syndrome, medulloblastoma, or pancreatic cancer), pulmonary diseases (e.g., interstitial pnuemonitis or interstitial pulmonary fibrosis), and developmental disorders (e.g., phocomelia or cyclopia). Novel non-natural macrocycles are provided that inhibit Sonic Hedgehog induced-protein transcription.

Abstract: Certain embodiments disclosed herein are directed to a method of producing endoderm cells, such as definitive endoderm cells by exposing stem cells such as embryonic stem cells or induced pluripotent stem (iPS) cells to an effective amount of at least one compound described herein to differentiate the stem cells into the endoderm cells such as definitive endoderm cells. Differentated endoderm cells produced by the methods disclosed herein can be differentiated into pancreatic epithelium, and other endoderm derivatives such as thymus, liver, stomach, intestine and lung. Another aspect of the present invention relates to a method of producing pancreatic progenitor cells, such as Pdx1-positive pancreatic progenitor cells by exposing endoderm cells, such as definitive endoderm cells to an effective amount of at least one compound described herein to differentiate the definitive endoderm cells into Pdx1-positive pancreatic progenitor cells.

Abstract: The present invention provides novel compounds of formula (I) and pharmaceutical compositions thereof. The inventive compounds are useful as deacetylase inhibitors (e.g., histone deacetylase inhibitors) and may be useful in the treatment of proliferative diseases such as cancer. In particular, the inventive compounds are HDAC6 inhibitors. The invention also provide synthetic methods for preparing the inventive compounds.

Abstract: The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.

Abstract: The present invention concerns the discovery that proteins encoded by a family of genes, termed here HDx-related genes, which are involved in the control of chromatin structure and, thus in transcription and translation. The present invention makes available compositions and methods that can be utilized, for example to control cell proliferation and differentiation in vitro and in vivo.