The Eternity Bioscience/Shanghai Hengrui RORγ antagonist, SHR168442, is a skin-restricted, topical compound intended to treat psoriasis. As a master regulator of Th17 immune cells which are significantly involved in allergic diseases, both positive and negative oral modulators of RORγt had been hotly pursued, though many have ceased clinical [...]

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.

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 [...]

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 [...]

The Biocryst oral plasma kallikrein inhibitor, berotralstat (BCX7353) , was recently approved as the first non-steroidal treatment for prevention of hereditary angioedema attacks. The molecule is given orally (150 mg QD) despite having two basic amines. Interestingly for a chronically administered drug, the molecule is noted to have QT [...]