Memorial Sloan Kettering Cancer Center

Sloan-kettering Institute for Cancer Research

Cornell University

Tony Taldone

Gabriela Chiosis

Stefan O Ochiana

Pallav Patel

Yanlong Kang

Weilin Sun

Anna Rodina

Hardik J Patel

NagaVarakishore Pillarsetty

Liza Shrestha

Maulik Patel

Chenghua Yang

Mary L Alpaugh

Erica M Gomes-Dagama

Pengrong Yan

Nagavarakishore Pillarsetty

Jason S Lewis

Steven M Larson

Naga Vara Kishore Pillarsetty

Monica L Guzman

John Koren

Hongliang Zong

This invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor.

Uses of labeled HSP90 inhibitors

The disclosure relates to novel selective Grp94 inhibitors, compositions comprising an effective amount of such compounds, and methods to treat or prevent a condition, such as cancer, comprising administering to an animal in need thereof an effective amount of such compounds.

Selective Grp94 inhibitors and uses thereof

The present invention provides methods for radiolabeling compounds useful as Hsp90 inhibitors. The present invention also provides intermediates useful in such methods, and compositions of radiolabeled compounds. The present invention provides, among other things novel methods for the synthesis of radiolabeled compounds. In certain embodiments, the present invention provides compounds of formula I.

Methods and reagents for radiolabeling

The present subject matter relates to a compound represented by the general formula (I) or (I') or a pharmacologically acceptable salt thereof; pharmaceutical compositions containing at least one of these compounds; methods of making at least one of these compounds; methods of using at least one of these compounds for treating and/or preventing various cancers and/or proliferation disorders; methods of using at least one of these compounds for monitoring the effectiveness of an anticancer therapy against various cancers. In one embodiment, the subject matter relates to compounds that bind with a level of specificity to heat shock protein 70 (Hsp70). In another embodiment, the subject matter relates to compounds that bind with a level of specificity to inhibit both heat shock protein 70 (Hsp70) and heat shock cognate protein 70 (Hsc70).

Heat shock protein binding compounds, compositions, and methods for making and using same

The present invention, among other things, provides compounds and compositions thereof for use in the modulation of Hsp70. In some embodiments, the present invention provides a method for inhibiting Hsp70 activity. In some embodiments, the present invention provides a method of treating a subject suffering from or susceptible to a disease, disorder, or condition responsive to Hsp70 inhibition comprising administering to the subject a therapeutically effective amount of a provided compound. In some embodiments, the present invention provides a method for treating or preventing cancer in a subject suffering therefrom, comprising administering to a patient in need thereof a therapeutically effective amount of a provided compound.

Hsp70 modulators and methods for making and using the same

The present application provides substituted purine derivatives and related compounds of the formulas shown. These compounds are useful as inhibitors of HSP90, and hence in the treatment of related diseases. (Formulae) Z-Z, X-X, X, X, Y and R are as defined in the specification. 

Purine derivatives useful as HSP90 inhibitors

The disclosure relates to Compounds of Formula (1): and pharmaceutically acceptable salts thereof wherein Z, Z, Z, Xa, Xb, Xc, Y, X, and Xare as defined herein, compositions comprising an effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof, and methods to treat or prevent a condition, such as cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof.

Hsp90 inhibitors

The present invention provides methods for radiolabeling compounds useful as Hsp90 inhibitors. The present invention also provides intermediates useful in such methods, and compositions of radiolabeled compounds. The present invention provides, among other things, novel methods for the synthesis of radiolabeled compounds. In certain embodiments, the present invention provides compounds of formula I.

The disclosure relates to Compounds of Formulae (IA) and (IB), and pharmaceutically acceptable salts thereof wherein Z, Z, Z, Xa, Xb, Xc, Xd, Y, X, and Xare as defined herein, compositions comprising an effective amount of a Compound of Formula (IA) and/or (IB), and methods to treat or prevent a condition, such cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (IA) or (IB). The disclosure further relates to compounds of Formulae (IA) and (IB) in which Xis a leaving for introducing a radiolabeled atom, such asI orI and to methods of using such compounds in the preparation of radiolabeled compounds, particularly for use in imaging. 

The present invention provides compounds I and II and compositions thereof for use in the modulation of Hsp70. In some embodiments, the present invention provides a method for inhibiting Hsp70 activity. In some embodiments, the present invention provides a method of treating a subject suffering from or susceptible to a disease, disorder, or condition responsive to Hsp70 inhibition comprising administering to the subject a therapeutically effective amount of a provided compound. In some embodiments, the present invention provides a method for treating or preventing cancer in a subject suffering therefrom, comprising administering to a patient in need thereof a therapeutically effective amount of a provided compound. 

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Forest Hills, NY, United States of America

Tony Taldone