cc-930 and Idiopathic-Pulmonary-Fibrosis

cc-930 has been researched along with Idiopathic-Pulmonary-Fibrosis* in 2 studies

Other Studies

2 other study(ies) available for cc-930 and Idiopathic-Pulmonary-Fibrosis

Article	Year
Discovery of the c-Jun N-Terminal Kinase Inhibitor Journal of medicinal chemistry, 2021, 12-23, Volume: 64, Issue:24 As a result of emerging biological data suggesting that within the c-Jun N-terminal kinase (JNK) family, JNK1 and not JNK2 or JNK3 may be primarily responsible for fibrosis pathology, we sought to identify JNK inhibitors with an increased JNK1 bias relative to our previous clinical compound tanzisertib (CC-930). This manuscript reports the synthesis and structure-activity relationship (SAR) studies for a novel series of JNK inhibitors demonstrating an increased JNK1 bias. SAR optimization on a series of 2,4-dialkylamino-pyrimidine-5-carboxamides resulted in the identification of compounds possessing low nanomolar JNK inhibitory potency, overall kinome selectivity, and the ability to inhibit cellular phosphorylation of the direct JNK substrate c-Jun. Optimization of physicochemical properties in this series resulted in compounds that demonstrated excellent systemic exposure following oral dosing, enabling in vivo efficacy studies and the selection of a candidate for clinical development, Topics: Animals; Cyclohexylamines; Drug Discovery; Humans; Idiopathic Pulmonary Fibrosis; JNK Mitogen-Activated Protein Kinases; Phosphorylation; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship; Substrate Specificity	2021
Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor. Bioorganic & medicinal chemistry letters, 2012, Feb-01, Volume: 22, Issue:3 In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF. Topics: Administration, Oral; Animals; Catalytic Domain; Cyclohexanols; Dogs; Enzyme Activation; Enzyme Inhibitors; Haplorhini; Idiopathic Pulmonary Fibrosis; Inhibitory Concentration 50; MAP Kinase Kinase 4; Models, Molecular; Molecular Structure; Purines; Rats; Structure-Activity Relationship	2012

Article

Year

Discovery of the c-Jun N-Terminal Kinase Inhibitor

Journal of medicinal chemistry, 2021, 12-23, Volume: 64, Issue:24

As a result of emerging biological data suggesting that within the c-Jun N-terminal kinase (JNK) family, JNK1 and not JNK2 or JNK3 may be primarily responsible for fibrosis pathology, we sought to identify JNK inhibitors with an increased JNK1 bias relative to our previous clinical compound tanzisertib (CC-930). This manuscript reports the synthesis and structure-activity relationship (SAR) studies for a novel series of JNK inhibitors demonstrating an increased JNK1 bias. SAR optimization on a series of 2,4-dialkylamino-pyrimidine-5-carboxamides resulted in the identification of compounds possessing low nanomolar JNK inhibitory potency, overall kinome selectivity, and the ability to inhibit cellular phosphorylation of the direct JNK substrate c-Jun. Optimization of physicochemical properties in this series resulted in compounds that demonstrated excellent systemic exposure following oral dosing, enabling in vivo efficacy studies and the selection of a candidate for clinical development,

Topics: Animals; Cyclohexylamines; Drug Discovery; Humans; Idiopathic Pulmonary Fibrosis; JNK Mitogen-Activated Protein Kinases; Phosphorylation; Protein Kinase Inhibitors; Pyrimidines; Structure-Activity Relationship; Substrate Specificity

2021

Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor.

Bioorganic & medicinal chemistry letters, 2012, Feb-01, Volume: 22, Issue:3

In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.

Topics: Administration, Oral; Animals; Catalytic Domain; Cyclohexanols; Dogs; Enzyme Activation; Enzyme Inhibitors; Haplorhini; Idiopathic Pulmonary Fibrosis; Inhibitory Concentration 50; MAP Kinase Kinase 4; Models, Molecular; Molecular Structure; Purines; Rats; Structure-Activity Relationship

2012