Abstract: 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.

Abstract: 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.

Abstract: 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 CSF I R inhibitors. Exemplary SIK inhibitors include the compounds of the formula: (I), (II), (III), (IV), (V) or (VI).

Abstract: Disclosed herein are compounds for the treatment of inflammatory bowel disease. Additionally, provided herein are compositions and methods for using these compounds and compositions in the treatment of inflammatory bowel disease in a subject.

Abstract: A method for treating inflammation and/or autoimmune diseases comprises administering to a subject in need thereof, a composition comprising a CDK8 inhibitor. In another aspect, a method for increasing IL-10 production comprises administering to a subject in need thereof a CDK8 inhibitor. In another aspect, a method for enhancing Treg cell differentiation, comprising administering a composition comprising a CDK8 inhibitor. In certain example embodiments, the subject suffers from an inflammatory bowel disease. In certain other example embodiments, the subject requires immunosuppression to prevent rejection following a transplantation procedure.

Abstract: 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 CSF I R inhibitors. Exemplary SIK inhibitors include the compounds of the formula: (I), (II), (III), (IV), (V) or (VI).

Abstract: The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind C 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.

Abstract: 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.

Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate STK inhibitors of Formula (III)).

Abstract: 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.

Abstract: Disclosed herein are compounds for the treatment of inflammatory bowel disease. Additionally, provided herein are compositions and methods for using these compounds and compositions in the treatment of inflammatory bowel disease in a subject.

Abstract: 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 CSF I R inhibitors. Exemplary SIK inhibitors include the compounds of the formula: (I), (II), (III), (IV), (V) or (VI).

Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate STK inhibitors of Formula (III)).

Abstract: 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.

Abstract: A method for treating inflammation and/or autoimmune diseases comprises administering to a subject in need thereof, a composition comprising a CDK8 inhibitor. In another aspect, a method for increasing IL-10 production comprises administering to a subject in need thereof a CDK8 inhibitor. In another aspect, a method for enhancing Treg cell differentiation, comprising administering a composition comprising a CDK8 inhibitor. In certain example embodiments, the subject suffers from an inflammatory bowel disease. In certain other example embodiments, the subject requires immunosuppression to prevent rejection following a transplantation procedure.

Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate SIK inhibitors of Formula (III)).

Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate SIK inhibitors of Formula (III)).

Abstract: The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof:

Abstract: The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate SIK inhibitors of Formula (III)).

Abstract: The invention relates to compounds of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof: