Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Signal Pharmaceuticals, Inc.

Biotheryx, Inc.

Yinon Ben-Neriah

Avraham Yaron

Frank Mercurio

Anthony M Manning

Aaron J Ciechanover

Matti Davis

Ada Hatzubai

Irit Alkalay

Joseph P Vacca

Irit Snir-Alkalay

Dansu Li

Sharo Amit

Avanthika Venkatachalam

Sharon Amit

Guy Brachya

Ido Burstain

Waleed Minzel

Ela Elyada

Irit Alkalay-Snir

Ariel Pribluda

Etti Ben Shushan

Provided herein are heteroaryl compounds, for example, a compound of Formula I or IA, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, ameliorating, or preventing one or more symptoms of a disorder, disease, or condition mediated by a casein kinase 1 (CK1), an interleukin-1 receptor associated kinase (IRAK1), or a cyclin-dependent kinase 9 (CDK9).

Heteroaryl compounds, pharmaceutical compositions thereof, and their therapeutic use

The present invention provides pyrazole derivatives, e.g., a compound of Formula (I), and their uses in methods of treating malignant disease and disorders and methods for treating inflammatory diseases and disorders.

Pyrazole compounds and uses thereof

The present invention provides pyrazole pyrimidine derivatives which inhibit Casein kinase I (CKI) and/or Interleukin-1 receptor-associated kinase 1 (IRAKI) and methods of their manufacture, compositions comprising them and uses thereof in methods of treating malignant disease and disorders and methods for treating inflammatory diseases and disorders.

Pyrazole pyrimidine derivative and uses thereof

The present invention provides pyrazole derivatives of Formula (I), and in particular N1-(4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl) pyridin-2-yl)cyclohexane-1,4-diamine derivatives and related compounds as casein kinase 1 (CK1) and/or interleukin 1 receptor associated kinase 1 (IRAKI) inhibitors for treating cancer, inflammatory and immune related disorders. 

A method of killing a cell having a mutation in an Adenomatous polyposis coli (APC) gene is disclosed. The method comprises contacting the cell with an inhibitor of Casein kinase I (CKI), the CKI being selected from the group consisting of CKI-alpha and CKI-delta and CKI-epsilon, thereby killing the cell. The method may be used for treating cancers. Pharmaceutical compositions for treatment of cancers are also disclosed.

Methods of killing cells and use of same in prevention and treatment of cancer

Compositions and methods for modulating the activation of nuclear factor &#x3ba;B (NF-&#x3ba;B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I&#x3ba;B&#x3b1; and/or I&#x3ba;B&#x3b2;. Such compositions may be used for treating diseases associated with NF-&#x3ba;B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Compounds and methods for modulating activation of NF-&#x3ba;B

Compounds that inhibit ubiquitin-mediated proteolysis of phosphorylated I&#x3ba;B by interfering, directly or indirectly, with the ability of &#x3b2;-TrCP/E3RS to engage in protein-protein association involving hnRNP-U, are useful as drugs for treating conditions associated with NF-&#x3ba;B activation. Cellular and non-cellular screening methods for identifying such compounds are based on monitoring the association/dissociation of &#x3b2;-TrCP/E3RS.

Methods for identifying compounds that inhibit ubiquitin-mediated proteolysis of i&#x3ba;b

Compositions and methods for modulating the activation of nuclear factor &kgr;B (NF-&kgr;B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I&kgr;B&agr; and/or I&kgr;B&bgr;. Such compositions may be used for treating diseases associated with NF-&kgr;B activation. Modulating agents include human E3 ubiquitin ligases, antibodies thereto and variants thereof, as well as related proteins.

Compounds and methods for modulating activation of NF-&kgr;B

Compositions and methods for modulating the activation of nuclear factor .kappa.B (NF-.kappa.B) are provided. The compositions comprise one or more agents that modulate ubiquitination of phosphorylated I.kappa.B.alpha. and/or I.kappa.B.beta.. Such compositions may be used for treating diseases associated with NF-.kappa.B activation. Modulating agents include peptides that comprise a recognition domain for E3 ubiquitin ligase.

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Mevasseret Zion, Israel

Yinon Ben-Neriah