SPHINX31 | SRPK1 inhibitor

SPHINX31 (1818389-84-2) 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

References/Citations:

1. Batson et al. (2017), Development of Potent, Selective SRPK1 Inhibitors as Potential Topical Therapeutics for Neovascular Eye Disease; ACS Chem. Biol. 12 825
2. Malhi et al. (2022), Serine-arginine-rich protein kinase-1 inhibition for the treatment of diabetic retinopathy; Am. J. Physiol. Heart Circ. Physiol. 322 H1014
3. He et al. (2022), Inhibition of SRPK1, a key splicing regulator, exhibits antitumor and chemotherapeutic-sensitizing effects on extranodal NK/T-cell lymphoma cells; BMC Cancer 22 1100
4. Wahid et al. (2023), Targeting alternative splicing as a new cancer immunotherapy-phosphorylation of serine arginine-rich splicing factor (SRSF1) by SR protein kinase 1 (SRPK1) regulates alternative splicing of PD1 to generate a soluble antagonistic isoform that prevents T cell exhaustion; Cancer Immunol. Immunother. 72 4001
5. Changphasuk et al. (2024), SRPK Inhibitor Reduce the Phosphorylation and Translocation of SR Protein Splicing Factors, thereby Correcting BIN1, MCL-1 and BCL2 Splicing Errors and Enabling Apoptosis of Cholangiocarcinoma Cells; Front. Biosci. (Schol. Ed.) 16 17