Rqx Pharmaceuticals, Inc.

Genentech, Inc.

The Scripps Research Institute

Tucker Curran Roberts

Peter Andrew Smith

Robert Higuchi

Prasuna Paraselli

David Alan Campbell

Jacob Bradley Schwarz

James John Crawford

Huiyong Hu

Floyd E Romesberg

Emily J Hanan

Cuong Q Ly

Michael F T Koehler

Sergio G Duron

Toby Jonathan Blench

Philippe Bergeron

Yongsheng Chen

Zhiyong Yu

Robert I Higuchi

Calum McCleod

Paul Colin Michael Winship

David Campbell

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Macrocyclic broad spectrum antibiotics

Provided herein are analogs of the natural product arylomycin for the treatment of microbial infections. In some embodiments, the compounds described herein have broad spectrum bioactivity. The compounds provided herein can in other embodiments overcome the resistance conferred by single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases) and in other embodiments provide for a broader spectrum of antibiotic bioactivity compared to the natural product. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Broad spectrum antibiotics

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. The compounds provided herein can in other embodiments overcome the resistance conferred by single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases) and in other embodiments provide for a broad spectrum of antibiotic bioactivity. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

Linear peptide antibiotics

Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectrum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.

Broad spectrum antibiotic arylomycin analogs

Growing community of inventors

San Diego, CA, United States of America

Tucker Curran Roberts