Other

Colorado State University Research Foundation

Dana-farber-cancer Institute Inc.

University of Notre Dame Du Lac

University of Michigan

University of Pennsylvania

Allegheny-singer Research Institute

Williams Patent Crusher and Pulverizer Company

Faller & Williams Technology, LLC

Ajinomoto Co., Ltd.

G.d. Searle & Company

Research Corporation Technologies, Inc.

The Wistar Institute

Research Corporation Tech., Inc.

Cetya Therapeutics, Inc.

Robert M Williams

Olaf G Wiest

Tenaya L Newkirk

Albert A Bowers

James Bradner

David H Sherman

Douglas V Faller

David B Weiner

Mark I Greene

James Elliott Bradner

William Valentine Williams

Dane James Clausen

Garth David Ehrlich

Thomas Kieber-Emmons

Jeffrey A Cohen

Chenguang Yuan

Christopher M Rath

Benjamin Janto

Tomoyuki Onishi

Joseph B Monahan

Alex A Cordi

Robert M Williams, Sr

Paul H Becherer

Jennifer Marie Guerra

Nobuyoshi Yasuda

Le Zhao

Christine Elizabeth Dunne

Shengying Li

Krithika Anand Srinivasan

Sivanagireddy Koti

Anil M Shelke

Ryan E Cerbone

Subhadip De

Disclosed are various synthetic methods to prepare structural analogs of largazole and derivatives thereof. One structural analog is an amide isostere of largazole. Another structural analog replaces the thiazole ring of largazole with a pyridine moiety or an oxazole moiety. Also disclosed are various intermediate compounds obtained when preparing structural analogs of largazole and derivatives thereof, including macrocycle analogs having an alcohol functionality.

Synthesis of structural analogs of largazole and associated compounds

Analogs of largazole are described herein. Methods of treating cancer and blood disorders using largazole and largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.

Method for preparing largazole analogs and uses thereof

Analogs of largazole are described herein. Methods of treating cancer, blood disorders, autoimmune disease, and Alzheimer's Disease using largazole analogs and pharmaceutical compositions comprising the same are additionally described herein. Methods for preparing largazole analogs are likewise described.

Synthesis and utility of new capgroup largazole analogs

The invention is directed to compounds that are specific inhibitors of PKC delta, and methods and compositions for the treatment and prevention of cancers and other disorders. Compositions comprising compounds of the invention are used to treat cancers such as, for example, carcinoid and neuroendocrine tumors, malignant melanomas, pancreatic, gastrointestinal and lung cancers. Neuroendocrine tumor cell lines of pulmonary and gastrointestinal origin are surprisingly sensitive to PKC delta inhibition by the compounds of the invention. The invention is further directed to methods, compositions and kits containing compounds of the formulas (Ia), (IIa), (IIIa), (IVa), and (V) as disclosed and described in FIGS.and

PKC delta inhibitors for use as therapeutics

The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Their intriguing mode of assembly has long been proposed to feature a non-ribosomal peptide synthetase, a presumed intramolecular Diels-Alderase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of their cyclodipeptide-based structural core. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report a comparative analysis of four natural product metabolic systems of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)/(&#x2212;)-notoamide, paraherquamide and malbrancheamide, in which we propose an enzyme for each step in the biosynthetic pathway based on deep annotation and on-going biochemical studies.

Biosynthetic systems producing fungal indole alkaloids

The present invention is directed to the biosynthetic pathway for a nonribosomal peptide synthetase (NRPS) derived drug and analogs thereof. The invention also discloses polynucleotide sequences useful for heterologous expression in a convenient microbial host for the synthesis of the NRPS derived drug.

Biosynthetic pathway for heterologous expression of a nonribosomal peptide synthetase drug and analogs

Lactones represented by the formula 2or 2: are provided, where each Ph is, independently, an unsubstituted or substituted phenyl group. These lactones are suitable for the synthesis of various &#x3b1;-hydroxy acids and 1,2-diols.

Chiral lactones

A deck panel includes a generally planar body portion having an upper surface and first and second side surfaces on opposed sides of the upper surface. An elongated tongue extends outwardly from and along the first side surface. An elongated groove is defined in and extends along the second side surface, the groove being adapted to receive a second tongue. The deck panel is formed of a polymeric material.

Polymeric deck panels, deck assemblies, decks and methods for forming the same

A rail system for mounting on a vertical support includes a rail assembly having an end portion and including a reinforcement rail and a polymeric sleeve at least partly surrounding the reinforcement rail. A metal bracket defining a rail cavity adapted to receive the attachment end and adapted to secure the rail assembly to the vertical support.

Rail mounting systems and methods

Growing community of inventors

Fort Collins, CO, United States of America

Robert M Williams