Casein Kinase Inhibitor

Casein kinase 1δ-IN-28 (Compound 4) is the inhibitor for CK1ε with an IC₅₀ of 0.0146 μM. Casein kinase 1δ-IN-28 exhibits a metabolite rate in human liver microsomes of 52%.

LRRK2/JNK3-IN-1 is a brain-penetrant multi-target inhibitor of LRRK2 (including G2019S mutant and wild-type) and JNK3, with enzymatic IC₅₀ values of 3.90 nM against LRRK2^G2019S, 3.24 nM against wild-type LRRK2, and 22.1 nM against JNK3. LRRK2/JNK3-IN-1 displays favorable selectivity in a 97-kinase profiling screen, and also shows inhibitory activity against JNK1, JNK2, and MKNK2. LRRK2/JNK3-IN-1 can be used for the research of Parkinson's disease.

(E/Z)-Chk2-IN-1 ((E/Z)-Hymenialdisine analogue-1) (Compound 1) is a potent and selective cell cycle kinase Chk2 inhibitor with an IC₅₀ of 8 nM. (E/Z)-Chk2-IN-1 exhibits low inhibitory activity against other kinases (such as CK1δ, MEK1, and PKCα/βⅡ) with IC₅₀ values both >89 nM. (E/Z)-Chk2-IN-1 can be used for the research of cancer.

CK1α-IN-1 (Compound 7a) is a selective CK1α inhibitor with an IC₅₀ of 10.96 nM. CK1α-IN-1 dose-dependently stabilizes p53 protein. CK1α-IN-1 has anticancer activity against acute monocytic leukemia.

EGFR-IN-57 (Compound 25a) is a potent, orally active EGFR-TK inhibitor with an IC₅₀ of 0.054 µM. EGFR-IN-57 also inhibits VEGFR-2, CK2α, topoisomerase IIβ and tubulin polymerization with IC₅₀ values of 0.087, 0.171, 0.13 and 3.61 µM, respectively. EGFR-IN-57 induces cell cycle arrest at G2/M and pre-G1 phases. EGFR-IN-57 induces cancer cell apoptosis.

Casein kinase 1δ-IN-15 is an inhibitor for casein kinase 1 (CK1δ), with an IC₅₀ of 0.045 μM.

SR-2890 is a highly selective, ATP-competitive inhibitor of casein kinase CK1δ and CK1ε, with IC₅₀ values ​​of 4 nM and 44 nM, respectively, and a K_i of 14 nM for CK1δ. SR-2890 exhibits antiproliferative effects. SR-2890 blocks the serine/threonine kinase activity of CK1δ and weakly inhibits a few off-target kinases such as FLT3, CDK4. SR-2890 has an oral bioavailability of 10% and a blood-brain barrier penetration rate of <1%. SR-2890 demonstrates stable in vitro metabolism and favorable in vivo pharmacokinetic properties, effectively inhibiting the growth of human A375 melanoma cells. SR-2890 can be used in melanoma research and is also a useful compound for studying CK1δ/ε-related diseases such as Alzheimer's disease.

CSNK2A-IN-2 (compound 6c) is a selective CSNK2A inhibitor with antiviral activity. CSNK2A-IN-2 exhibits an inhibitory effect on viral replication and is selective for PIM3.

Levobunolol (l-Bunolol) is a non-selective β-adrenergic antagonist and vasodilator. By blocking calcium ion influx and reducing the sensitivity of vascular smooth muscle to calcium, Levobunolol effectively dilates the ciliary arteries and increases ocular blood flow, so it is widely used in research on glaucoma and ocular hypertension. Levobunolol inhibits the β-receptor signaling pathway and the expression of related proliferation markers (such as CK3, CK14, CK19, Ki67) in corneal cells. In rabbit models, Levobunolol not only does not inhibit corneal epithelial regeneration, but also accelerates the healing of mechanical injury without adverse effects. Levobunolol also inhibits histamine-induced vasoconstriction and intracellular calcium elevation, exhibiting unique vascular regulatory activity. Levobunolol protects ocular blood flow and promotes corneal repair.

CHX-3107 is a casein kinase 2 inhibitor .

Casein kinase 1δ-IN-19 (compound 492) is a potent casein kinase 1δ inhibitor. Casein kinase 1δ-IN-19 can be used in the study of neurodegenerative diseases such as Alzheimer's disease.

WAY-606344 (Compound 97) is a Casein kinase 1δ inhibitor. WAY-606344 is promising for research of Alzheimer's disease.

Multi-kinase-IN-6 (compound 10e) is a multikinase inhibitor that shows good enzyme inhibitory activity against TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2. Multi-kinase-IN-6 reveals antiproliferative activity against MCF7, HCT116 and EKVX with IC₅₀ values of 3.36 μM, 1.40 μM and 3.49 μM, respectively. Multi-kinase-IN-6 shows cell cycle arrest at the G1/S phase and G1 phase in MCF7 and HCT116 cells with good apoptotic effect.

Casein kinase 1δ-IN-5 is a potent and selective protein kinase CK-1δ inhibitor with an IC₅₀ of 47 nM. Casein kinase 1δ-IN-5 shows neuroprotective and anti-inflammatory properties both in vitro. Casein kinase 1δ-IN-5 has the potential for neurodegenerative diseases research.

HS-276 formic is an orally active, potent and highly selective TAK1 inhibitor, with a K_i of 2.5 nM. HS-276 formic shows significant inhibition of TAK1, CLK2, GCK, ULK2, MAP4K5, IRAK1, NUAK, CSNK1G2, CAMKKβ-1, and MLK1, with IC₅₀ values of 8.25, 29, 33, 63, 125, 264, 270, 810, 1280, and 5585 nM, respectively. HS-276 formic reduces the expression of TNF, IL-6, and IL-1β. HS-276 formic can be used for rheumatoid arthritis (RA) research.

Casein kinase 1δ-IN-17 (compound 753) is a casein kinase 1δ (CK1δ) inhibitor. Casein kinase 1δ-IN-17 can be utilized in neurodegenerative disorders research.

CK2-IN-7 (compound 2) is an inhibitor of casein kinase 2 (CK2). CK2-IN-7 shows synergistic effect with structurally distinct CK2 chemical probe: SGC-CK2-1, against cancer.

Casein kinase 1δ-IN-22 (compound 484) is a potent casein kinase 1δ inhibitor. Casein kinase 1δ-IN-22 can be used in the study of neurodegenerative diseases such as Alzheimer's disease.

Casein kinase 1δ-IN-18 (compound 660) is a casein kinase 1δ (CK1δ) inhibitor. Casein kinase 1δ-IN-18 can be utilized in neurodegenerative disorders research.

HDAC/CK2-IN-1 (compound 38) is a HDAC1 (IC₅₀ = 1.46 μM), HDAC6 (IC₅₀ = 0.66 μM), and CK2 (IC₅₀ = 3.67 μM) inhibitor. HDAC/CK2-IN-1 exhibits promising antproliferative activity against Jurkat, MCF-7, HCT-116, and HL-60 cell lines.