CLK Inhibitor

TG003 is a potent inhibitor of Clk1/Sty; inhibits Clk1 and Clk4 with IC₅₀ values of 20 and 15 nM, respectively.

SLK/STK10-IN-1 is a potent and selective inhibitor of SLK and STK10 with antitumor activity.

CLK-IN-T3 is a high potent, selective, and stable CDC-like kinase (CLK) inhibitor with IC₅₀s of 0.67 nM, 15 nM, and 110 nM for CLK1, CLK2, and CLK3 protein kinases, respectively. CLK-IN-T3 has anti-cancer activity.

Rogocekib is an orally effective CLK 2 inhibitor, with an IC₅₀ of 1.4 nM, showing anti-tumor activity.

T025 is an orally active and highly potent inhibitor of Cdc2-like kinase (CLKs), with K_d values of 4.8, 0.096, 6.5, 0.61, 0.074, 1.5 and 32 nM for CLK1, CLK2, CLK3, CLK4, DYRK1A, DYRK1B and DYRK2, respectively. T025 induces caspase-3/7-mediated cell apoptosis. T025 reduces CLK-dependent phosphorylation. T025 exerts anti-proliferative activities in both hematological and solid cancer cell lines (IC₅₀ values: 30-300 nM). T025 has an anti-tumor efficiency, mainly for MYC-driven disease research.

DYRK2-IN-2 (Compound C17) is a selective inhibitor of DYRK2, with its IC₅₀ value being 40.3 nM. The inhibitory activity of DYRK2-IN-2 on DYRK1A (IC₅₀ = 1842 nM), DYRK1B (IC₅₀ = 1335 nM), DYRK4 (IC₅₀ = 1931 nM), DYRK3 (IC₅₀ = 112 nM), and CLKs (IC₅₀ = 540-6496 NM) is relatively low. DYRK2-IN-2 inhibits the phosphorylation of Tau protein at Thr212 and shows moderate cytotoxicity in HT22 cells. DYRK2-IN-2 can be used in cancer research.

AP4-43 is an orally active CLK1, CLK4, PI3K, DDR1, EGFR and NEK4 inhibitor. AP4-43 reduces growth of mammalian colorectal cancer organoids. AP4-43 improves survival in a transgenic Drosophila model of KRAS-mutant colorectal cancer. AP4-43 can be used for the research of KRAS-mutant colorectal cancer.

ML167 is a highly selective Cdc2-like kinase 4 (Clk4) inhibitor with IC₅₀ of 136 nM, >10-fold selectivity for closely related kinases Clk1, Clk2, Clk3 and Dyrk1A/1B.

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

Leucettine L41 is a potent inhibitor of dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) and CDC-like kinases (CLKs). Leucettine L41 can also inhibit GSK-3 singnaling. Leucettine L41 can inhibit cell apoptosis and ROS production. Leucettine L41 can promote β-cell cell cycle progression, cell proliferation and increase insulin secretion. Leucettine L41 can be used for the researches of neurological disease and metabolic disease, such as Alzheimer’s disease (AD) and diabetes.

KH-CB19 is a potent CLK (cdc2-like kinase) inhibitor (CLK1 IC₅₀=19.7 nM; CLK3 IC₅₀=530 nM). KH-CB19 shows antiviral activity and inhibits influenza virus replication (IC₅₀=13.6?μM).

CC-671 is a dual TTK protein kinase/CDC2-like kinase (CLK2) inhibitor with IC₅₀s of 0.005 and 0.006 μM for TTK and CLK2, respectively.

K00546 is a potent CDK1 and CDK2 inhibitor with IC₅₀s of 0.6 nM and 0.5 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. K00546 is also a potent CDC2-like kinase 1 (CLK1) and CLK3 inhibitor with IC₅₀s of 8.9 nM and 29.2 nM, respectively.

MU1210 (compound 12f), a chemical probe, is an inhibitor of CDC-like kinases Clk1, Clk2, and Clk4 (with IC₅₀ values of 8, 20, and 12 nM respectively), with IC₅₀ for HIPK1 and DYRK2 are 187 and 1309 nM. MU1210 also has favorable pharmacokinetic characteristics (in mice, 10 mg/kg, intraperitoneal injection: C_max=1.24 μM, T_1/2=58 minutes; no acute toxicity observed).

CDD-2807 is an inhibitor for serine/threonine kinase 33 (STK33) with IC₅₀ of 9.2 nM. CDD-2807 exhibits no significant toxicity in mice and can cross the blood-testis barrier without accumulating in the brain. CDD-2807 induces a reversible contraceptive effect and has potential for the development of the male contraceptive.

EHT 5372 is a highly potent and selective inhibitor of DYRK's family kinases with IC₅₀s of 0.22, 0.28, 10.8, 93.2, 22.8, 88.8, 59.0, 7.44, and 221 nM for DYRK1A, DYRK1B, DYRK2, DYRK3, CLK1, CLK2, CLK4, GSK-3α, and GSK-3β, respectively.

S6K1-IN-1 is a selective S6K1 inhibitor with an IC₅₀ value of 52 nM. S6K1-IN-1 can be used in the research of obesity and insulin resistance-related diseases.

CLK1-IN-3 (compound 10ad) is a potent and selective Clk1 inhibitor, with an IC₅₀ of 5 nM and over 300-fold selectivity for Dyrk1A. CLK1-IN-3 also shows a relatively potent inhibition against Clk2 and Clk4, with IC₅₀ values of 42 and 108 nM, respectively. CLK1-IN-3 potently induces autophagy in vitro. CLK1-IN-3 can be used for acute liver injury (ALI) research.

HS-243 is a potent and selective IRAK-4 and IRAK-1 inhibitor, with IC₅₀ values of 20 and 24 nM. HS-243 shows minimal TAK1 (transforming growth factor β-activated kinase 1) inhibition activity, with a IC₅₀ of 0.5 μM. HS-243 shows anti-inflammatory and anticancer activity.

KH-CB20, an E/Z mixture, is a potent and selective inhibitor of CLK1 and the closely related isoform CLK4, with an IC₅₀ of 16.5 nM for CLK1. KH-CB20 can also inhibit DYRK1A (IC₅₀=57.8 nM) and CLK3 (IC₅₀=488 nM).