Definition

An orally bioavailable inhibitor of the serine/arginine-rich splicing factor protein kinase 1 (SRPK1) and the ATP-binding cassette sub-family G member 2 (ABCG2), with potential chemosensitizing and antineoplastic activities. Upon oral administration, SRPK1/ABCG2 inhibitor SCO-101 targets, binds to and inhibits the activity of SRPK1 and ABCG2. Inhibition of the cellular efflux pump ABCG2 by SCO-101 prevents the efflux of co-administered chemotherapeutic agents from cancer cells. This may abrogate cancer cell drug resistance and may re-sensitize cancer cells to the chemotherapeutic agents. Inhibition of SRPK1 kinase by SCO-101 inhibits the SRPK1-mediated phosphorylation of splicing factors rich in serine/arginine domains, thereby inhibiting the activation of proteins that are involved in the regulation of alternative splicing. This may inhibit cancer cell proliferation. SRPK1 is upregulated in various cancer cell types. Its upregulation is correlated with higher tumor staging, grading, and shorter survival.