BAY 1003803 is a potent topical agonist of the glucocorticoid receptor (GR) transrepression pathway, with less activity on the GR transactivation pathway mediated by GR dimers, which may lead to undesirable side effects. The fluoroaminoquinoline was the only heterocycle among analogs tested that was Ames-negative. The compound appears to have [...]

The Boehringer RORγ antagonist, BI 730357, is an oral once-daily clinical candidate from a new compound class in development for plaque psoriasis. We highlighted two other RORγ modulators last year in February and March. While most clinical RORγ modulators have discontinued development after reaching Ph. II, BI 730357’s Ph. II trial appears [...]

Context. Sebetralstat (KalVista Pharmaceuticals) is an oral, on-demand plasma kallikrein (PKa) inhibitor intended for hereditary angioedema (HAE). As an on-demand medication, it can be administered to treat acute attacks rather than chronically to prevent attacks. Its structure was first disclosed at the ACS Spring Meeting earlier this year [...]

JTE-052 (delgocitinib) is a pan-JAK kinase inhibitor approved as a topical ointment for treatment of atopic dermatitis in Japan. The compound has an interesting azetidine-containing diazaspirocycle core and a relatively high sp3-fraction for a kinase inhibitor.

Remibrutinib (Novartis oral BTK-selective covalent kinase inhibitor clinical candidate)