clk 1

CLK1 2-IN-3 (Cpd-3) is a potent and selective CLK1 and CLK2 inhibitor with antiproliferative activity and inhibits the activities of CLK1, CLK2, SRPK1, SRPK2, and SRPK3.CLK1 2-IN-3 induces nuclear speckle enlargement, which induces S6K pre-mRNA-selective splicing and subsequent inhibition of cell growth of multiple cancer cell types. cancer cell types cell growth.

Clk1-in-3 is a + selective and highly potent sexual Clk1 inhibitor with an IC50 of 5 nM and 300 pairs higher affinity than Dyrk1A. CLK1-IN-3 also showed highly effective inhibition of Clk2 and Clk4, with IC50 values of 42 and 108 nM, respectively. CLK1-IN-3 is effective in inducing autophagy in vitro and can be used for prevention and human treatment of acute liver injury (ALI).

CLK1-IN-2, a metabolically stable Clk1 inhibitor, exhibits selective activity for Clk1 with an IC50 value of 1.7 nM. It is applicable in researching tumor, Duchenne's muscular dystrophy, and viral infections including HIV-1 and influenza.

CLK1 4-IN-1 (compound 31) is a highly potent and selective inhibitor of Clk1 and Clk4, with IC50 values of 9.7 nM and 6.6 nM, respectively. It effectively inhibits the growth of T24 cancer cells, with a GI50 value of 1.1 μM. CLK1 4-IN-1 has shown promising potential as an anticancer research tool [1].

WAY-322243 has antibacterial and anti-inflammatory activity and has an inhibitory effect on CLK-1, which can be used to study Alzheimer's disease.

Ipivivint, a first-in-class, orally active and potent CDC-like kinase (CLK) inhibitor, inhibits CLK1 (IC50=1.4 μM), CLK2 (IC50=0.002 μM) and CLK3 (IC50=0.022 μM). Ipivivint reduces Wnt pathway signaling gene expression through inhibiting CLK activity and serine and arginine rich splicing factor (SRSF) phosphorylation and disrupting spliceosome activity. Ipivivint can be used for the research of cancer[1]. Ipivivint (SW480 cells; 0.01~10 μM; 1 hour) potently inhibits SRSF5/6 phosphorylation[1].Ipivivint (SW480 cells; 0.03 μM~3 μM; 48 hour) induced apoptosis[1]..Ipivivint (HEK-293T cells; 0.03 μM~3 μM; 1 hour) inhibits Wnt/β-catenin signaling induced by Wnt3a[1].Ipivivint (SW480 cells; 0.3~10 μM; 6 hour) increases nuclear speckle enlargement[1].Ipivivint (SW480 cells; 0.3~3μM; 24hours) significantly decreases expression of Wnt target genes (AXIN2, LEF1, MYC, and TCF7) and TCF7L2. SM08502 (SW480 cells; 0.03~3μM; 24hours) inhibits cytoplasmic or nuclear fractions protein expression. Ipivivint (NCI-N87 cells) inhibits proliferation[1].Ipivivint strongly inhibits Wnt pathway signaling activity (EC50 = 0.046 μM) in SW480 colon cancer cells[1]. Ipivivint (25 mg/kg; p.o.) potently inhibits tumor SRSF6 phosphorylation[1]. [1]. Tam BY, et al. The CLK inhibitor SM08502 induces anti-tumor activity and reduces Wnt pathway gene expression in gastrointestinal cancer models. Cancer Lett. 2020;473:186-197.

Potent and selective CLK inhibitor (IC50 values are 28, 88 and 510 nM for CLK4, 1 and 2, respectively). Exhibits no significant activity at CLK3, DYRK, CDK or GSK3 at a concentration of 10 μM. Inhibits growth of a range of cancer cell lines in vitro at subnanomolar concentrations. Walter et al (2018) Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype. PLoS One 13 e0196761 PMID:29723265

CLK1/2-IN-1 is a CLK1 and CLK2 inhibitor and it also inhibits SRPK1 and SRPK2.

Leucettinib-92 (compound 92) is a kinase inhibitor selective for the DYRK CLK families, with IC50 values of 147 nM for CLK1, 39 nM for CLK2, 5.2 nM for CLK4, 0.8 μM for CLK3, 124 nM for DYRK1A, 204 nM for DYRK1B, 0.16 μM for DYRK2, 1.0 μM for DYRK3, 0.52 μM for DYRK4, and 2.78 μM for GSK3 [1].

CLK1-IN-1 is a potent and selective inhibitor of Cdc2-like kinase 1 (CLK1) with an IC50 of 2 nM.