The Johns Hopkins University

Leland Stanford Junior University

The Rockefeller University

James K Chen

Philip Arden Beachy

Anssi Jussi Nikolai Taipale

Anssi J Taipale

Xiaohu Ouyang

Tarun M Kapoor

Joel M Hyman

Joshua S Weinger

Alison Evelynn Ondrus

Cory A Ocasio

Surajit Sinha

Ilya Shestopalov

Ronald K Mann

Tomoyo Sakata Kato

Ari J Firestone

Compounds of formula I: are disclosed. The compounds are inhibitors of Hedgehog pathway activation and are useful in treating solid tumors. An example of such a compound is: 

Imidazo bicyclic iminium compounds as antitumor agents

The present invention makes available, inter alia, methods and reagents for modulating smoothened-dependent pathway activation. In certain embodiments, the subject methods can be used to counteract the phenotypic effects of unwanted activation of a hedgehog pathway, such as resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function mutations.

Regulators of the hedgehog pathway, compositions and uses related thereto

Compounds of formula (I) in which Ris chosen from hydrogen, cyano, nitro, acetyl and C(&#x2550;O)NH, and Ar is optionally substituted monocyclic or bicyclic aryl or heteroaryl, are useful as antitumor agents. 

Quinazolinone inhibitors of dynein

The present disclosure provides for compounds, pharmaceutical preparations, kits and methods for the inhibition of the Hh pathway and the alleviation of cancer and developmental disorders associated with the Hh pathway.

Hedgehog pathway antagonists methods of use

Aromatic compounds for treating various diseases and pathologies are disclosed. The methods use of such compounds are also provided. Accordingly, the present invention makes available methods and compositions for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function.

Hedgehog pathway antagonists

Bifunctional linkers are provided that comprise a photocleavable moiety flanked by two different amine reactive moieties. In some embodiments the photocleavable moiety is a dimethoxynitrobenzyl moiety. In other embodiments the photocleavable moiety is 8-bromo-7-hydroxyquinoline. In other embodiments the photocleavable moiety is nitrodibenzofuran. In other embodiments the photocleavable moiety is 6-bromo-7-hydroxycoumarin-4-ylmethyl. The linkers find use in synthetic methods, including the generation of photocleavable oligonucleotides, e.g. caged morpholinos.

Photocleavable linker methods and compositions

The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity. Such methods and reagents may also inhibit the hedgehog pathway in normal cells, e.g., where normal levels of hedgehog signalling are unwanted.

Modulators of hedgehog signaling pathways, compositions and uses related thereto

Aromatic compounds for treating various diseases and pathologies are disclosed. The methods use of such compounds are also provided. Accordingly, the present invention makes available methods and compositions for inhibiting aberrant growth states in cells having Wnt receptors.

Growing community of inventors

Palo Alto, CA, United States of America

James K Chen