Compound 8 is a dual 5-HT2A and 5-HT2C receptor inverse agonist developed to address the limitations of pimavanserin.

Cerevance’s CVN293 is an oral, CNS-penetrant, selective inhibitor of potassium efflux-mediated NLRP3-inflammasome activation in microglia for the treatment of neurodegenerative disorders. Cerevance’s NETSseq platform was used to discover a microglia-specific potassium efflux channel, KCNK13, which allows modulation of the NLRP3-inflammasome in the CNS without affecting peripheral innate immunity. Read the full article to discover highlights on the CNS-penetration of highly polar compounds and how particle size can be key to oral bioavailability

JAK kinases are now well-established targets in immunology, but the class has always had safety concerns hanging over it. The safety issues were exacerbated by a recent FDA decision to expand the black box warnings for the class for major cardiovascular events. Inhaled, lung-restricted JAK inhibitors have been of interest because they could [...]

The Takeda GPR139 agonist, TAK-041 , is a CNS-penetrant GPCR agonist being explored for schizophrenia symptoms and is an interesting example of a triazinone-containing clinical candidate. GPR139 is an orphan GPCR that’s highly expressed in the human habenula, which plays a major role in avoidance behavior. Lesions in the habenula cause [...]

Bexotegrast is a dual-selective αvβ6-αvβ1 integrin inhibitor with surprising efficacy and safety data from a Ph. II trial in idiopathic pulmonary fibrosis (IPF). The αv integrins have been studied for decades in indications such as cancer and IPF. Both small molecule and antibody-based integrin inhibitors have demonstrated preclinical toxicities in non-human primates. This article highlights the unmet need for effective therapies for IPF and related conditions, a comparison of bexotegrast with other integrin binders, and possible reasons why bexotegrast is different in terms of safety.