DYRK1 Inhibitor

Harmine is a natural dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) inhibitor with anticancer and anti-inflammatory activities. Harmine has a high affinity of 5-HT_2A serotonin receptor, with an K_i of 397 nM.

GNF2133 is a potent, selective and orally active DYRK1A inhibitor with IC₅₀s of 0.0062, >50 µM for DYRK1A and GSK3β, respectively. GNF2133 shows good proliferation potency and efficacy on rat and human primary β-cell. GNF2133 significantly improves glucose disposal capacity and increases insulin secretion. GNF2133 has the potential for the research of type 1 diabetes.

AZ191 is a potent inhibitor that selectively inhibits DYRK1B with IC₅₀ of 17 nM.

Harmine Hydrochloride (Telepathine Hydrochloride) is a natural DYRK inhibitor with anticancer and anti-inflammatory activities. Harmine has a high affinity of 5-HT_2A serotonin receptor, with an K_i of 397 nM.

GNF4877 is a potent DYRK1A and GSK3β inhibitor with IC₅₀s of 6 nM and 16 nM, respectively, which leads to blockade of nuclear factor of activated T-cells (NFATc) nuclear export and increased β-cell proliferation (EC₅₀ of 0.66 μM for mouse β (R7T1) cells).

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.

Atalaphyllidine is a natural product. Atalaphyllidine can be isolated from the stem bark of Glycosmis chlorosperma. Atalaphyllidine inhibits DYRK1A kinase activity with an IC₅₀ of 2.2 μM. Atalaphyllidine can be used in the research of neurodegenerative diseases.

VS-II-173 is a pan-Pim kinase inhibitor with IC₅₀ values ​​of 0.07 μM and 0.02 μM for Pim1 and Pim3, respectively, and a residual activity of 46% for Pim2 at 1 μM. VS-II-173 also inhibits kinases such as HIPK2, PRK2, RSK1, DYRK1a and AMPK_α1, selectively inhibiting acute myeloid leukemia (AML) cells with significantly lower toxicity to non-malignant cells (EC₅₀ > 30 μM). VS-II-173 weakens the phosphorylation of substrates such as Stat5 (Y694), MDM2 (S166), Bad (S112), and 4E-BP1 (T37/46) by inhibiting Pim kinase-mediated signaling pathways, blocking pro-survival signals in AML cells and inducing apoptosis. VS-II-173 synergistically enhances anti-AML activity when combined with Daunorubicin (HY-13062A). VS-II-173 can be used in AML research, especially for AML with FLT3-ITD mutations and NPM1 mutations .

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.

INDY is a potent and ATP-competitive Dyrk1A and Dyrk1B inhibitor with IC₅₀s of 0.24 μM and 0.23 μM, respectively. INDY binds in the ATP pocket of the enzyme and has a K_i value of 0.18 μM for Dyrk1A. INDY sharply reduces the self-renewal capacity of normal and tumorigenic cells in primary Glioblastoma (GBM) cell lines and neural progenitor cells.

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.

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.

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.

DYRK1-IN-1 is a highly selective and ligand-efficient DYRK1A inhibitor. DYRK1-IN-1 inhibits DYRK1A phosphorylation activity with an IC₅₀ value of 220 nM. DYRK1-IN-1 can be used for the research of central nervous system penetrant DYRK1A chemical probe.

RO5454948 (Compound 9) is the inhibitor for Dyrk1B and Dyrk1A with IC₅₀ of 68 nM and 22 nM. RO5454948 exhibits cytotoxicity in cancer cell SW620 with EC₅₀ of 1.9 μM.

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.

AZ-Dyrk1B-33 is a potent and selective Dyrk1B kinase inhibitor, with an IC₅₀ of 7 nM.

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.

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.