Genentech, Inc.

Curis, Inc.

Rqx Pharmaceuticals, Inc.

Michael F T Koehler

Daniel P Sutherlin

Georgette M Castanedo

Shumei Wang

Mark E Reynolds

Mark S Stanley

Scott J Savage

Cuong Q Ly

Peter Andrew Smith

Kimberly Malesky

Liang Bao

Michael S Dina

Rebecca L Lalonde

John A Flygare

Lewis J Gazzard

Jacob Bradley Schwarz

Frederick Cohen

James John Crawford

Prasuna Paraselli

Robert Higuchi

Janet L Gunzner-Toste

Philippe Bergeron

Tucker Curran Roberts

Huiyong Hu

Joseph P Lyssikatos

Anthony A Estrada

Daniel Fred Ortwine

Chudi Obioma Ndubaku

Zhonghua Pei

Jonathan Bayldon Baell

Vickie Hsiao-Wei Tsui

Claudio F Sturino

Wayne J Fairbrother

Richard A Goldsmith

Emily J Hanan

Lan Wang

Brad E Sleebs

Janet Gunzner

Toby Jonathan Blench

Guillaume Laurent Lessene

Kurt Deshayes

Yongsheng Chen

Jonathan Boudreault

Xianrui Zhao

Zhiyong Yu

Kevin Hon Luen Lau

Guillaume Pelletier

Boubacar Sow

Dana Winter

Robert I Higuchi

Calum McCleod

Paul Colin Michael Winship

Mark Stanley

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 peptidases SpsB and/or LepB, 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 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.

The invention provides novel inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A, X, Y R, R, R, R, m and n are as described herein.

Pyridyl inhibitors of hedgehog signalling

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds having the general formula U1-M-U2 wherein M is a linking group covalently joining R2, R3, R4 or R5 of U1 to an R2, R3, R4 or R5 group of U2; U1 and U2 have the general formula (I) and G, X1, X2, R2, R3, R3', R4, R4&#x2032; and R5, are as described herein. 

Inhibitors of IAP

The invention provides novel inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A is a carbocycle or heterocycle; X is alkylene, NRC(O), NRC(S), NRC(NH), NRSO, NRSO, NRC(O)NH, NRC(S)NH, C(O)NR, C(S)NR, C(NH)NR, NRPO or NRPO(OH) wherein Ris H or alkyl; Ris selected from the group consisting of alkyl, cycloalkyl, aryl or a heterocycle each of which is optionally substituted with hydroxy, halogen, amino, nitro, alkyl, acyl, alkylsulfonyl or alkoxy; Ris halogen, hydroxy, alkyl, acyl or alkoxy each optionally substituted with hydroxy, halogen, amino, nitro, alkyl, acyl, alkylsulfonyl or alkoxy; Ris halogen, hydroxy, alkyl, acyl or alkoxy each optionally substituted with hydroxy, halogen, amino, nitro, alkyl, acyl, alkylsulfonyl or alkoxy; m is 0-3; n is 0-3; and salts and solvates thereof. The invention also provides methods of using these compounds for therapy and/or prophylaxis in a mammal of hyperproliferative diseases and angiogenesis mediated diseases due to their activity for inhibiting the hedgehog signaling pathway.

Quinoxaline inhibitors of the hedgehog signalling

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula (I): wherein Q, X, X, Y, Z, Z, Z, Z, R, R, R, R, R4, R, R, R, Rand n are as described herein. 

IAP inhibitors

The invention relates generally to small molecules that mimic the biological activity of certain peptides and proteins, to compositions containing them and to their use. In particular, the invention relates to compounds of the general formula (I) that mimic the biological activity of BH3-only proteins and are capable of binding to and neutralizing pro-survival Bcl-2 proteins: wherein A, A, B, B, B, X, Z, R, R, Rand t are as described herein. The invention also relates to processes of preparing the benzenesulfonamide compounds that mimic portions of peptides and proteins, and to the use of such compounds in the regulation of cell death and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death.

Arylsulfonamide compounds

Disclosed are compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR). 

Pyrimidine compounds, compositions and methods of use

The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula I: wherein Q, X, X, Y, Z R, R, R, R', R, R&#x2032;, R, R, R&#x2032; and n are as described herein. 

Imidazopyridine inhibitors of IAP

Growing community of inventors

Palo Alto, CA, United States of America

Michael F T Koehler