KVS0001 is a specific and bioavailable small molecule inhibitor of SMG1 kinase, disrupts nonsense mediated decay (NMD).
KVS0001 is highly selective against the other 246 protein or lipid kinases up to 1 uM.
KVS0001 substantially decreases the amount of phosphorylated UPF1, the downstream target of SMG1 kinase activity in NCI-H358 and LS180 cells.
KVS0001 causes MHC class I display of hidden neoantigens, increases the expression of TP53 in cancer cell lines, NCI-H716 and NCI-H2228.
KVS0001 (30 mg/kg) impacts tumor growth in syngeneic models.
KVS0001 elevates the expression of transcripts and proteins resulting from truncating mutations in vivo and in vitro.
