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.

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.

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.

BTX161, a Thalidomide (HY-14658) analog, is a molecular glue degrader targeting CK1α. BTX161 recruits CK1α and the CK1α-FAM83 complex to the Cul4ACRBN E3 ligase complex, thereby driving ubiquitination and proteasomal degradation. BTX161 reduces FAM83G abundance through CK1α-FAM83G co-stability, slightly decreases FAM83H levels, but has no effect on the expression of FAM83B. BTX161 activates DNA damage response (DDR) and upregulates Wnt target genes including MYC. BTX161 can be used in research related to colorectal cancer, type b myelomonocytic leukemia and acute myeloid leukemia.

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.

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.

TA-01 is a potent CK1 and p38 MAPK inhibitor, with IC₅₀s of 6.4 nM, 6.8 nM, 6.7 nM for CK1ε, CK1δ and p38 MAPK, respectively. TA-01 acts as a cardiogenic inhibitor.

IWP-3 is a Wnt production inhibitor with an IC₅₀ of 40 nM. IWP-3 also acts as a CK1δ inhibitor, with an IC₅₀ of 1.89 μM against rat full-length CK1δ. IWP-3 inhibits the function of Porcupine (Porcn), thereby blocking the palmitoylation of Wnt proteins, suppressing the canonical Wnt signaling pathway, reducing the proliferative capacity of cancer cells, promoting the differentiation of mesoderm into cardiomyocytes and increasing cardiomyocyte yield. IWP-3 reduces embryonic cell division, alters the cell movement along the anterior-posterior axis of embryos, and causes embryonic shortening. IWP-3 can be used in studies related to cancers such as pancreatic cancer.