The UAB Research Foundation (The University of Alabama at Birmingham)

Southern Research Institute

Other

Joanne Murphy-Ullrich

Mark J Suto

Vandana Gupta

Bini Mathew

David D Roberts

Henry C Krutzsch

Stacey L Schultz-Cherry

Andrew Wayne Cain

Andrew Douglas Penman

Timothy M Wick

Andra Rixse Frost

Wei Zhang

Solange M F Ribeiro

Christian Hugo

Joel L Berry

Vandana V Gupta

The present disclosure is concerned with piperazine-2,5-diones that are capable of inhibiting TGF-&#x3b2; and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Piperazine-2,5-diones as TGF-beta inhibitors

The present disclosure is concerned with dipeptide analogs that are capable of inhibiting TGF-&#x3b2; and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, methods for immunotherapy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Dipeptide analogs as TGF-beta inhibitors

The present disclosure is concerned with oxadiazole and thiadiazole analogs that are capable of inhibiting TGF-&#x3b2; and methods of treating cancers such as, for example, multiple myeloma and a hematologic malignancy, and methods of treating fibrotic conditions using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Oxadiazoles and thiadiazoles as TGF-&#x3b2; inhibitors

The present disclosure relates to compounds, compositions and methods for the treatment of diseases through inhibiting the activity of the transforming growth factor beta (TGF-&#x3b2;). More specifically, the disclosed compounds, compositions and methods are useful in the treatment of certain cancers (e.g. multiple myeloma, hematologic malignancies), diseases associated with excessive TGF-&#x3b2; activity including fibrosis, dermal scarring, immune dysfunction, and bone loss by inhibiting the conversion of latent TGF-&#x3b2; to active TGF-&#x3b2;. A method of preventing the activation of TGF-&#x3b2; in pathology is also provided, comprising administering an amount of the compounds sufficient to inhibit conversion of latent TGF-&#x3b2; to active TGF-&#x3b2; by thrombospondin1 (TSP1), resulting in reduced TGF-&#x3b2; activity and reduced adverse effects such as fibrosis, bone loss, and immune dysfunction.

Compounds, compositions and methods for the treatment of diseases through inhibiting TGF-&#x3b2; activity

Three-dimensional (3D), prevascularized, engineered tissue constructs, 3D prevascularized engineered tissue models of cancer, and bioreactors and bioreactor arrays including the tissue constructs are disclosed. Methods of making the tissue constructs, methods of using the tissue constructs, methods of drug discovery using the tissue constructs and/or cancer models, and the like are also disclosed.

Three-dimensional, prevascularized, engineered tissue constructs, methods of making and methods of using the tissue constructs

The present invention provides a method of treating kidney or renal diseases/conditions in a subject by administering to the subject a pharmaceutically effective amount of a purified LAP peptide, a TSP-1 type 1 repeat peptide, or a fragment thereof to interfere with the activation process of TGF-&bgr; by thrombospondin-1 to reduce and/or prevent renal damage. The present invention further provides a method of improving renal function in a subject having impaired renal function by administering to the subject a pharmaceutically effective amount of a purified LAP peptide, a TSP-1 type 1 repeat peptide, or a fragment thereof.

Use of peptides inhibitory for thrombospondin dependent TGF-&bgr; activation in the treatment of kidney disease

The invention provides a method of stimulating TGF-&bgr; activity, comprising contacting latent TGF-&bgr; with an amount of an activating peptide from TSP effective to convert latent TGF-&bgr; to active TGF-&bgr;. Also provided is a method of inhibiting the stimulation of TGF-&bgr; activity, comprising contacting latent TGF-&bgr; with an amount of an inhibiting peptide from TSP effective to inhibit conversion of latent of TGF-&bgr; to active TGF-&bgr;. The invention also provides a method of enhancing wound healing, comprising the step of administering to the wound site an amount of an activating peptide from TSP effective to convert latent TGF-&bgr; to active TGF-&bgr;, the activation of TGF-&bgr; resulting in enhanced wound healing. A method of preventing excessive fibrosis stimulated by TGF-&bgr; in pathology is also provided, comprising administering to a site of potential fibrosis an amount of inhibiting peptide from TSP effective to inhibit conversion of latent TGF-&bgr; to active TGF-&bgr;, resulting in reduced fibrosis. The invention also provides a method of blocking TGF-&bgr;-mediated inhibition of endothelial cell proliferation comprising contacting the endothelial cells with an inhibiting peptide effective to inhibit conversion of latent TGF-&bgr; to active TGF-&bgr;, resulting in proliferation of endothelial cells.

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Birmingham, AL, United States of America

Joanne Murphy-Ullrich