cdc-like

CLK-IN-T3 is an inhibitor of CLK1, CLK2, and CLK3 with IC50s of 0.67, 15, and 110 nM. CLK-IN-T3 exhibits anti-cancer activity.

Cirtuvivint (SM08502) is a potent, orally active CDC-like kinase (CLK) inhibitor useful for the study of arthritis.

MU1210 (compound 12f) acts as an inhibitor of CDC-like kinases Clk1, Clk2, and Clk4 with IC50 values of 8, 20, and 12 nM, respectively, and exhibits IC50 values of 187 and 1309 nM for HIPK1 and DYRK2. Additionally, MU1210 demonstrates favorable pharmacokinetic properties in mice (10 mg kg, intraperitoneal injection: Cmax=1.24 μM, T1 2=58 minutes; no acute toxicity observed).

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.

CLK-IN-T3N, the negative control of CLK-IN-T3 , is a chemical probe for CDC-like kinase (CLK) .

SRI-29329 is a potent, specific inhibitor of CDC-like kinase (with IC50 of 78 nM, 16 nM and 86 nM for CLK1, CLK2 and CLK4, respectively).