Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor
VP Krenitsky, L Nadolny, M Delgado, L Ayala… - Bioorganic & medicinal …, 2012 - Elsevier
VP Krenitsky, L Nadolny, M Delgado, L Ayala, SS Clareen, R Hilgraf, R Albers, S Hegde…
Bioorganic & medicinal chemistry letters, 2012•ElsevierIn 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.
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.
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.
Elsevier
