DYRK2 Inhibitor

GSK-626616 is a potent, orally bioavailable inhibitor of DYRK3 (IC₅₀=0.7 nM). GSK-626616 inhibits other members of the DYRK family (e.g., DYRK1A and DYRK2) with similar potency, which is a potential therapy for the treatment of anemia.

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.

Protein kinase inhibitor 1 hydrochloride is a potent HIPK2 inhibitor, with IC₅₀s of 136 and 74 nM for HIPK1 and HIPK2, and a K_d of 9.5 nM for HIPK2.

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.

Dyrk1A-IN-5 (Compound 5j) is a potent and selective DYRK1A inhibitor, with an IC₅₀ of 6 nM. yrk1A-IN-5 exhibits significant selectivity for DYRK1B (IC₅₀ = 600 nM) and CLK1 (IC₅₀ = 500 nM), but shows almost no inhibition of DYRK2 (IC₅₀ > 10 μM). Dyrk1A-IN-5 can be used for Down syndrome 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.

DYRK2-IN-2 hydrochloride is a selective DYRK2 inhibitor with an IC₅₀ of 40.3 nM. DYRK2-IN-2 hydrochloride shows weaker inhibitory activity against DYRK1A (IC₅₀ = 1842 nM), DYRK1B (IC₅₀ = 1335 nM), DYRK4 (IC₅₀ = 1931 nM), DYRK3 (IC₅₀ = 112 nM) and CLK (IC₅₀ = 540-6496 nM). DYRK2-IN-2 hydrochloride inhibits the phosphorylation of Thr212 in Tau protein. DYRK2-IN-2 hydrochloride is applicable for neuronal research.

YK-2-69 is a highly selective DYRK2 inhibitor with an IC₅₀ value of 9 nM. YK-2-69 specifically interacts with Lys-231 and Lys-234 of DYRK2 and can be utilized in researches related to prostate cancer.

Dyrk1A-IN-4 is a potent and orally active Dyrk1A inhibitor. Dyrk1A-IN-4 exhibits IC₅₀s against DYRK1A and DYRK2 of 2 nM and 6 nM. Dyrk1A-IN-4 exhibits the inhibition of the DYRK1A pSer520 autophosphorylation in U2OS cells with an IC₅₀ of 28 nM. Dyrk1A-IN-4 can be used for the studies of ovarian adenocarcinoma, neuroblastoma and cervical squamous cell carcinoma.

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).

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.

ON 108600 (108600) is a CK2 (CK2α1: IC₅₀ = 50 nM; CK2α2 = 5 nM), TNIK (IC₅₀ = 5 nM) and DYRK (DYRK1A: IC₅₀ = 16 nM; DYRK1B = 7 nM; DYRK2: = 28 nM). ON 108600 suppresses the growth of CD44high/CD24low breast cancer stem cell (BCSC) populations, induces G2/M arrest and apoptosis in triple negative breast cancer (TNBC) cells, and inhibits tubulin polymerization. ON 108600 can be used for the study of chemotherapy-resistant and metastatic TNBC.

LDN-192960 is an inhibitor of Haspin and Dual-specificity Tyrosine-regulated Kinase 2 (DYRK2) with IC₅₀s of 10 nM and 48 nM, respectively.

LDN-192960 hydrochloride is an inhibitor of Haspin and Dual-specificity Tyrosine-regulated Kinase 2 (DYRK2) with IC₅₀s of 10 nM and 48 nM, respectively.

LDN-209929 dihydrochloride is a potent and selective haspin kinase inhibitor (IC₅₀=55 nM) with180-fold selectivity verses DYRK2 (IC₅₀=9.9 μM). LDN-209929 is a optimized analogue of LDN-192960 (HY-13455).

ZJCK-6-46 (32) is a potential and orally activeDYRK1A inhibitor (IC₅₀ = 0.68 nM) with high BBB permeability (CNS+). ZJCK-6-46 (32) reduces tau phosphorylation. ZJCK-6-46 (32) ameliorates cognitive dysfunction by obviously reducing the expression of phosphorylated tau and neuronal loss _{in vivo}.

GSK3-IN-10 (Compound 4) is a multi-target inhibitor, that mainly targets GSK3α and GSK3β with IC₅₀ of 1.0 nM and 2.0 nM. GSK3-IN-10 inhibits the activation of β-catenin, promotes the neuronal survival, and exhibits a protective effect against endoplasmic reticulum stress.

MU1787 is a highly selective homeodomain-interacting protein kinase (HIPK) inhibitor with a furopyridine core, and shows improved selectivity against CLKs, with inactivity against DYRK1B, DYRK2, and MLK2/3 in in vitro cellular assays. MU1787 can be used for the research of malignancies.

RD0448 is a potent inhibitor of DYRK1A, DYRK1B, and DYRK2. RD0448 selectively targets the non-native (folded intermediate) state of DYRK1A and DYRK1B. The binding site of RD0448 is hidden in the native state of DYRK1A and DYRK1B, and as a stabilizing binder, it binds tightly to both DYRK1A and DYRK1B, forming a stable complex with slow dissociation kinetics. In contrast, RD0448 targets the native state of DYRK2 without selectivity between its native and non-native states, acting as a weak binder with weaker binding affinity to DYRK2 and forming a rapidly dissociating complex.