Lorecivivint (SM04690, formerly adavivint) is a Wnt pathway inhibitor being developed by Samumed for immunomodulatory potential. It acts downstream of β-catenin, and its molecular targets are the intranuclear kinases CLK2 and DYRK1A through which it inhibits phosphorylation of serine/arginine-rich splicing factors, and SIRT1 and FOXO1 respectively [3
]. Wnt signalling is upregulated in tissues from osteoarthritic joints, and drives disease pathologies including inflammation [5
]. Wnt pathway inhibition by lorecivivint is being investigated as a disease-modifying treatment for osteoarthritis.
SM04690 is example 10 as claimed in patent US20160297812 [4
]. The chemical structure shown here was produced using the IUPAC name submitted to the WHO for the INN adavivint (via
SMILES generated using Chemicalize) which was later renamed as lorecivivint. This SMILES string resolves to PubChem CID 123710737, although some of the double bonds in the molecule are not fully resolved, when compared to the images in US20160297812. CID 89837869
is an alternative representation.