SPHINX31 is a potent (IC50 = 5.9 nM) and selective inhibitor of serine/arginine-rich protein kinase 1 (SRPK1), a splice factor kinase involved in VEGF-A isoform formation and other alternative splicing events.1 It displayed antiangiogenic effects in a mouse model of choroidal neovascularization1 a rat model of diabetic retinopathy2. SPHINX31 exhibited antitumor and synergistic (with cisplatin) effects in extranodal lymphoma cells.3 It was able to change splicing of programmed cell death receptor 1 (PD-1) to produce a more soluble form that prevented T cell exhaustion in a cancer model.4 It corrected BIN1, MCL-1, and BCL2 splicing errors in cholangiocarcinoma cells resulting in apoptosis of cancer cells.5
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