P1, N=170, Recruiting, BlossomHill Therapeutics | N=74 --> 170

P1, N=74, Recruiting, BlossomHill Therapeutics

Finally, we show that SGC-CLK-1 not only reduces serine arginine-rich (SR) protein phosphorylation but also alters SR protein and CLK2 subcellular localization in a reversible way. Therefore, we anticipate that this compound will be a valuable tool for increasing our understanding of CLKs and their targets, SR proteins, at the level of phosphorylation and subcellular localization.

The results proved that the expression levels of the 9 biomarkers could be used to predict the prognosis of CRC patients.

In addition, we critically discuss the available selectivity data and describe the inhibitor's efficacy in cellular models, if reported. Thus, we provide a comprehensive overview on the current state of Clk1 drug discovery and highlight the most promising chemotypes.

P1b, N=30, Active, not recruiting, Biosplice Therapeutics, Inc. | Recruiting --> Active, not recruiting | N=150 --> 30 | Trial primary completion date: Jul 2026 --> Jul 2024

Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.

In PD-1+ human colon cancer cells, NIVO activates tumor survival pathways and could protect tumor cells from conventional therapies.

In vivo, tumor growth inhibition studies testing cirtuvivint at exposures ~2X below the MTD resulted in significant disease control (≥50% TGI) in 38/46 PDX and 38/43 CDX models. These observations indicate broad cancer relevance, at least in the preclinical setting, and expose vulnerabilities to CLK-DYRK-regulated splicing that can potentially be therapeutically addressed with pan CLK/DYRK inhibitors.

In contrast, the cellular SAR highlights correlations between inhibition of specific kinase targets and some but not all cellular effects. Leucettines deserve further development as potential therapeutics against various diseases on the basis of their molecular targets and cellular effects.