CK1 Inhibitor

IWP-2 is an inhibitor of Wnt processing and secretion with an IC₅₀ of 27 nM. IWP-2 targets the membrane-bound O-acyltransferase porcupine (Porcn) and thus preventing a crucial Wnt ligand palmitoylation. IWP-2 is also an ATP-competitive CK1δ inhibitor with an IC₅₀ of 40 nM for the gatekeeper mutant ^M82FCK1δ.

D4476 is a potent, selective and cell-permeable inhibitor of casein kinase 1(CK1) with an IC₅₀ value of 0.3 μM in vitro.

PF-670462 dihydrochloride is a potent and selective inhibitor of casein kinase (CK1ε and CK1δ), with IC₅₀s of 7.7 nM and 14 nM, respectively.

FPFT-2216, a “molecular glue” compound, degrades phosphodiesterase 6D (PDE6D), zinc finger transcription factors Ikaros (IKZF1), Aiolos (IKZF3), and casein kinase 1α (CK1α). FPFT-2216 can be used for the research of cancer and inflammatory disease.

BTX-A51 (Casein Kinase inhibitor A51) is a potent and orally active casein kinase 1α (CK1α) inhibitor. BTX-A51 induces leukemia cell apoptosis, and has potent anti-leukemic activities.

IWP-4 (GMP) is the GMP-grade form of IWP-4 (HY-12879). IWP-4 is a Wnt inhibitor with an IC₅₀ of 25 nM. IWP-4 specifically inhibits casein kinase 1δ/ε (CK1δ/ε), with an IC₅₀ of 1.06 μM against wild-type CK1δ, 1.02 μM against the CK1δ kinase domain, and 7.07 μM against CK1ε; it shows enhanced inhibitory activity against the M82F CK1δ mutant (IC₅₀ = 0.14 μM). IWP-4 is applicable to research related to cancer, Alzheimer's disease (AD), and heart failure.

FP1-24 is a non-selective CK1 kinase inhibitor, with IC₅₀ values of 40 nM, 10 nM, 10 nM, and 40 nM against human CK1γ1, CK1γ2, CK1γ3 and CK1δ, respectively. FP1-24 exerts its activity by reducing the phosphorylation level of LRP5/6 at the T1479 site during WNT signaling pathway activation. The non-specific binding of FP1-24 to multiple kinases can be used for biological studies of specific CK1γ.

TAK-715 is an orally active and potent p38 MAPK inhibitor with IC₅₀s of 7.1 nM, 200 nM for p38α and p38β, respectively. TAK-715 inhibits casein kinase I (CK1δ/ε) to regulate activation of Wnt/β-catenin signaling. TAK-715 shows good significant efficacy in a rat arthritis model.

PF-4800567 is a potent and selective inhibitor of casein kinase 1? (CK1?), with an IC₅₀ of 32 nM, which is greater than 20-fold selectivity over CK1δ (IC₅₀, 711 nM).

AMG-548 dihydrochloride, 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 dihydrochloride is also extremely potent in the inhibition of whole blood LPS stimulated TNFα (IC₅₀=3 nM). AMG-548 dihydrochloride inhibits Wnt signaling by directly inhibiting Casein kinase 1 isoforms δ and ε.

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.

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.

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.

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.

CK1-IN-1 (Compound 1c) is a casein kinase 1 (CK1) inhibitor with IC₅₀ values of 15 nM and 16 nM for CK1δ and CK1ε, respectively. CK1-IN-1 inhibits p38α MAPK with an IC₅₀ of 73 nM. CK1-IN-1 can be used to study cardiomyogenesis.