Dana-farber-cancer Institute Inc.

The General Hospital Corporation

The Broad Institute, Inc.

University Court of the University of Dundee

Hwan Geun Choi

Nathanael Schiander Gray

Guang Yang

Yanke Liang

Henry M Kronenberg

Sara Jean Buhrlage

David E Fisher

Ramnik Xavier

Steven P Treon

Alykhan Shamji

Thomas Sundberg

Nisma Mujahid

Nathanael S Gray

Ryo Murakami

Yuan Xiong

Marc Wein

The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind protein kinases (e.g., SIK) and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase (e.g., SIK, (e.g., SIK1, SIK2, or SIK3)) in a subject or cell. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, musculoskeletal disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

Bicyclic urea kinase inhibitors and uses thereof

The present disclosure provides imidazolyl compounds of Formula (I) and methods of preparing the compounds. The provided compounds are able to bind protein kinases and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase in a subject or cell and/or in treating or preventing a disease (e.g., proliferative disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.

Imidazolyl kinase inhibitors and uses thereof

The present disclosure provides methods of treating and/or preventing osteoporosis using salt-inducible kinase (SIK) inhibitors. Also provided are methods of using SIK inhibitors for increasing the function of osteocytes, increasing the number of osteoblasts, increasing the activity of osteoblasts, inhibiting the resorption of a bone, decreasing the number of osteoclasts, inhibiting the activity of osteoclasts, increasing the mass of a bone, down-regulating the expression of the gene SOST, and/or inhibiting the activity of sclerostin. The SIK inhibitors may be combined with Src inhibitors or CSF1R inhibitors. Exemplary SIK inhibitors include the compounds of the formula:

Uses of salt-inducible kinase (SIK) inhibitors for treating osteoporosis

The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.

Uses of pyrimidopyrimidinones as SIK inhibitors

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Chestnut Hill, MA, United States of America

Hwan Geun Choi