Casein Kinase Inhibitor

SR-3029 is a potent and ATP competitive CK1δ and CK1ε inhibitor, with IC₅₀s of 44 nM and 260 nM, respectively, and K_is of 97 nM for both kinases.

VRK1/CK1-IN-1 (compound 36) is a dual VRK1 and CK1 family inhibitor, with a K_i of 37.9 nM against human VRK1, 8.3 nM against human CK1δ, and 7.8 nM against human CK1ε. VRK1/CK1-IN-1 exhibits extremely low activity against VRK2. VRK1/CK1-IN-1 can be used in studies related to p53-deficient tumors.

IC261 is a selective, ATP-competitive CK1 inhibitor, with IC₅₀s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively.

TMX-4116 is a casein kinase 1α (CK1α) degrader. TMX-4116 shows the degradation preference for CK1α with DC₅₀s less than 200 nM in MOLT4, Jurkat, and MM.1S cells. TMX-4116 can be used for the research of multiple myeloma.

Kirenol is a diterpenoid compound, an orally active apoptosis inducer and signaling pathway regulator, with a K_d value of 5.47 μM against the target CK2. Kirenol promotes the cleavage of Bid into tBid, regulates the protein levels/phosphorylation of Bax, Bcl-2, p53 and p21, and induces caspase-independent apoptosis, S-phase cell cycle arrest, ROS accumulation and cytotoxicity in cancer cells. Kirenol activates the CK2/AKT and AMPK-mTOR-ULK1 pathways, inhibits the signaling of NF-κB, TGF-β/Smads and NLRP3 inflammasome, and regulates the GSK3β, BMP and Wnt/β-catenin pathways. Kirenol induces autophagy, mitophagy and osteoblast differentiation, promotes mitochondrial fusion, and exerts antioxidant, anti-inflammatory, antifibrotic, renoprotective, cardioprotective, neuroprotective and analgesic effects. Kirenol is applicable to research related to chronic myeloid leukemia, ischemic stroke, diabetic nephropathy, heart failure, acute lung injury and osteoporosis.

PF-5006739 is a potent and selective inhibitor of CK1δ/ε with IC₅₀s of 3.9 nM and 17.0 nM, respectively. PF-5006739 is a potential therapeutic agent for a range of psychiatric disorders with low nanomolar in vitro potency for CK1δ/ε and high kinome selectivity. PF-5006739 attenuats opioid agent-seeking behavior in a rodent operant reinstatement model in animals in a dose-dependent manner. PF-5006739 improves glucose tolerance in both diet-induced obesity (DIO) and genetic (ob/ob) mice models of obesity.

BioE-1115 is a highly selective and potent PAS kinase (PASK) inhibitor with an IC₅₀ of ~4 nM. BioE-1115 is also a potent casein kinase 2α inhibitor with an IC₅₀ of ~10 μM.

Hematein is a oxidation product of hematoxylin acted as a dye. Hematein is an allosteric casein kinase II inhibitor with an IC₅₀ of 0.74 μM. Hematein inhibits Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increases apoptosis in lung cancer cells.

BAY-888 is a selective CK1α/CSNK1A1 (casein kinase 1α) ATP-competitive inhibitor (IC₅₀: 4 nM@10 μM ATP; 63 nM@1 mM ATP). BAY-888 blocks the negative regulation of p53 and other signaling pathways by CK1α, induces apoptosis and inhibits proliferation of tumor cells. BAY-888 has shown inhibitory efficacy against cancers such as acute myeloid leukemia (AML) in PRISM barcoded cell line screening and can mimic the effects of shRNA-mediated CK1α knockdown. BAY-888 is primarily used for the development of anticancer drugs for p53 wild-type tumors and for the study of the mechanisms of CK1α-related signaling pathways.

(E/Z)-GO289 is a potent and selective casein kinase 2 (CK2) inhibitor (IC₅₀=7 nM). (E/Z)-GO289 strongly lengthens circadian period. (E/Z)-GO289 exhibits cell type–dependent inhibition of cancer cell growth that correlated with cellular clock function.

BAY-204 (BRD3727) is a potent, ATP-competitive, and selective CSNK1α inhibitor (IC₅₀ = 2 nM at 10 μM ATP; 12 nM at 1 mM ATP). BAY-204 can be used for the study of acute myeloid leukemia (AML).

CK1-IN-2 (compound Nr.4) is a potent CK1 inhibitor with an IC₅₀ values of 123, 19.8, 26.8, 74.3 nM for CK1a, CK1d, CK1e, p38a, respectively.

CKI-7 free base is a potent and ATP-competitive casein kinase 1 (CK1) inhibitor with an IC₅₀ of 6 μM and a K_i of 8.5 μM. CKI-7 free base is a selective Cdc7 kinase inhibitor. CKI-7 free base also inhibits SGK, ribosomal S6 kinase-1 (S6K1) and mitogen- and stress-activated protein kinase-1 (MSK1). CKI-7 free base has a much weaker effect on casein kinase II and other protein kinases.

AMG-548, an orally active and selective p38α inhibitor (K_i=0.5 nM), shows slightly selective over p38β (K_i=36 nM) and >1000 fold selective against p38γ and p38δ. AMG 548 is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC₅₀=3 nM). AMG-548 inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε.

Longdaysin is a inhibitor of the Wnt/β-catenin signaling pathway, which exerts antitumor effect through blocking CK1δ/ε-dependent Wnt signaling. Longdaysin inhibits CK1α, CK1δ, CDK7, and ERK2 with IC₅₀s of  5.6 µM, 8.8 µM, 29 µM, and 52 µM, respectively.

CSNK1-IN-2 is a CSNK1A1 inhibitor. CSNK1-IN-1 has inhibitory activity for CSNK1A1 kinase with IC₅₀ values of 44 nM. CSNK1-IN-2 can be used for the research of proliferative disorders.

CK2/ERK8-IN-1 is a dual casein kinase 2 (CK2) (K_i of 0.25 µM) and ERK8 (MAPK15, ERK7) inhibitor with IC₅₀s of 0.50 μM. CK2/ERK8-IN-1 also binds to PIM1, HIPK2 (homeodomain-interacting protein kinase 2), and DYRK1A with K_is of 8.65 µM, 15.25 µM, and 11.9 µM, respectively. CK2/ERK8-IN-1 has pro-apoptotic efficacy.

Orobol is one of the major soy isoflavones and has various pharmacological activities, including anti-skin-aging and anti-obesity effects. Orobol inhibits CK1ε, VEGFR2, MAP4K5, MNK1, MUSK, TOPK, and TNIK (IC₅₀=1.24-4.45 μM). Orobol also inhibits PI3K isoforms (IC₅₀=3.46-5.27 μM for PI3K α/β/γ/K/δ).

Levobunolol (l-Bunolol) hydrochloride 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 hydrochloride effectively dilates the ciliary arteries and increases ocular blood flow, so it is widely used in research on glaucoma and ocular hypertension. Levobunolol hydrochloride 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 hydrochloride not only does not inhibit corneal epithelial regeneration, but also accelerates the healing of mechanical injury without adverse effects. Levobunolol hydrochloride also inhibits histamine-induced vasoconstriction and intracellular calcium elevation, exhibiting unique vascular regulatory activity. Levobunolol hydrochloride protects ocular blood flow and promotes corneal repair.

CK2 inhibitor 2 is a potent, selective and orally active inhibitor of CK2, with an IC₅₀ of 0.66 nM. CK2 inhibitor 2 shows high selectivity for Clk2 (IC₅₀=32.69 nM)/CK2. CK2 inhibitor 2 exhibits favorable antiproliferative and antitumor activity.