We next asked whether we could use the CMap to discover a compound with a particular activity – in this case, Casein Kinase 1A1 (CSNK1A1). CSNK1A1 is a serine-threonine kinase that was reported as an essential gene in certain subtypes of myelodysplastic syndrome and acute myeloid leukemia, and also has been shown to be targeted for degradation by the drug lenalidomide, which is particularly effective in MDS patients with chromosome 5q deletion (the locus of the CSNK1A1 gene) (Järås et al., 2014; Krönke et al., 2015; Schneider et al., 2014). Furthermore, CSNK1A1 has been reported as a mediator of drug resistance to EGFR inhibitors in lung cancer (Lantermann et al., 2015). Unfortunately, potent and selective CSNK1A1 small molecule inhibitors have yet to be reported.
