sik

HG-9-91-01 (SIK inhibitor 1) is a potent and highly selective salt-inducible kinase (SIKs) inhibitor with IC50s of 0.92 nM, 6.6 nM and 9.6 nM for SIK1, SIK2 and SIK3respectively.

YKL-05-099 is an inhibitor of the salt-inducible kinase(SIK1 and SIK3 ; IC50s: 10 and 30 nM, respectively). It has a slightly less potent SIK2-inhibitory (IC50:40 nM).

GLPG3970 GLPG3970 is a novel orally available selective dual SIK2/SIK3 inhibitor.GLPG3970 has potential anti-inflammatory activity for the study of autoimmune diseases.

YKL-06-062 is a second-generation salt-inducible kinase (SIK) inhibitor that targets SIK1, SIK2, and SIK3, with IC50 values of 2.12 nM, 1.40 nM, and 2.86 nM, respectively.

MRT 67307 dihydrochloride is a dual inhibitor of the IKKε and TBK-1 with IC50s of 160 and 19 nM, respectively. MRT67307 dihydrochloride also inhibits ULK1 and ULK2 with IC50s of 45 and 38 nM, respectively. MRT67307 dihydrochloride also blocks autophagy in cells.

ARN-3236 is an orally active and selective inhibitor of salt-inducible kinase 2 (SIK2), with IC50 values of <1 nM for SIK2, 21.63 nM for SIK1, and 6.63 nM for SIK3. ARN-3236 exhibits anti-cancer activity.

WH-4-025 is a Salt-inducible kinase (SIK) inhibitor that targets the SIK family of proteins.

YKL-06-061 is a selective salt-inducible kinase (SIK) inhibitor with IC50 values of 6.56 nM/1.77 nM/20.5 nM for SIK1/2/3, respectively.

Pterosin B is a salt-inducible kinase 3 (Sik3) signaling inhibitor widely found in leaves and shoots of green plants.Pterosin B promotes the expression of G6pc, protects against Ang II-induced cardiomyocyte hypertrophy, and acts through the regulation of the expression level of NAD(P)H oxidase 2 4.

SIK-IN-1 (Compound 53) acts as a potent inhibitor of salt-inducible kinase (SIK), specifically targeting SIK1, SIK2, and SIK3 with IC50 values of 0.1, 0.4, and 1.5 nM, respectively. Additionally, it effectively suppresses TNFa release with an IC50 of 0.5 nM and enhances LPS-induced IL-10 release in human macrophages with an EC50 of 4 nM [1].

SIK-IN-2 (Compound 45) is a potent inhibitor of salt-inducible kinase (SIK), effectively targeting SIK1, SIK2, and SIK3 with IC50 values of 0.1, 0.2, and 0.4 nM, respectively. Additionally, it suppresses TNFa release with an IC50 of 0.5 nM and promotes LPS-induced IL-10 release with an EC50 of 2 nM in human macrophages [1].

SIK2-IN-1 (compound 8g) is a potent and selective inhibitor of SIK2 over other AMPK-family kinases, exhibiting favorable ADMET profiles in vitro and robust cellular activities [1].

SIK1 activator 1 can enhances the SIK1 phosphorylation and ameliorated the hyperglyceamia of type 2 diabetic mice. SIK1 activator 1 exhibited remarkable inhibitory activity on hepatic gluconeogenesis.

Prexasertib (LY2606368) is an inhibitor of checkpoint kinase 1 (chk1) with potential antineoplastic activity.

AMARA peptide acetate is a substrate for SIK and AMPK.AMARA peptide is a minimal substrate of several members of the protein kinases family. It consists of the phosphorylation site for AMP-activated Protein Kinase (AMPK).

MRT199665 is an effective and ATP-competitive, selective MARK/SIK/AMPK inhibitor (IC50s of 2/2/3/2 nM, 10/10 nM, and 110/12/43 nM for MARK1/MARK2/MARK3/MARK14, AMPKα1/AMPKα2, and SIK1/SIK2/SIK3, respectively). MRT199665 suppresses the phosphorylation of S

SIKs-IN-1 (compound 8h), a pyrimidine-5-carboxamide derivative, functions as an inhibitor of Salt-inducible kinases (SIKs), which play a role in M1 M2 macrophage polarization linked to inflammation. By inhibiting SIK activity, this compound increases anti-inflammatory cytokine IL-10 and decreases pro-inflammatory cytokine IL-12, demonstrating significant anti-inflammatory efficacy in a DSS-induced colitis model [1].

Campsiketalin is a natural product for research related to life sciences. The catalog number is TN5830 and the CAS number is 93675-96-8.

Sikokianin E, a biflavonone derivative, is isolable from Coreopsis tinctoria [1].

Sikokianin C is a biflavonoid isolated from Wikstroemia sikokiana.Sikokianin C is a selective cystathionine β-synthase inhibitor with antitumour activity for the treatment of human colon cancer.

Sikokianin A shows in vitro antiviral activity against HBsAg secretion.

GLPG3312 (Compound 28), characterized as a selective pan-SIK inhibitor, exhibits IC50 values of 2.0 nM for SIK1, 0.7 nM for SIK2, and 0.6 nM for SIK3. Demonstrating both anti-inflammatory and immunomodulatory activities, this compound effectively targets human primary myeloid cells in vitro and mouse models in vivo. With favorable oral bioavailability, GLPG3312 serves as a promising agent for the study of inflammatory and immune diseases [1].

Prexasertib dihydrochloride (LY2606368) is an ATP-competitive CHK1 inhibitor (Ki: 0.9 nmol/L). in the cell-free assay, its IC50 values are 8 nM and 9 nM for CHK2 and RSK, respectively.

MRIA9, an ATP-competitive inhibitor targeting pan Salt-Inducible Kinases (SIK) and PAK2 3, demonstrates IC50 values of 516 nM, 180 nM, and 127 nM for SIK1, SIK2, and SIK3, respectively [1].

MRT67307 is an inhibitor for TBK1, IKKε , MARK1-4 and NUAK1 with IC50 value of 19, 160, 27-52 and 230nM , respectively [1]. It is an inhibitor for ULK1and ULK2 with IC50 value of 45 and 38nM, respectively [2]. Also, it is a salt inducible kinase (SIK) inhibitor with IC50 value of 250, 67 and 430nM for SIK1, SIK2 and SIK3, respectively.
SIKs prevent the formation of regulatory macrophages and their inhibition induces increasing in some markers of regulatory macrophages, such as IL-10 and other anti-inflammatory molecules. IKKε and TBK-1 mediate the phosphorylation of interferon regulatory factor 3 (IRF3). MARK1 is a Serine/threonine-protein kinase.
In macrophages, MRT67307 prevented the production of IFNβ and the phosphorylation of IRF3 without suppressing the activation of NF-κB, which showed that MRT67307 blocked the induction of Pellino 1 through inhibiting TBK1/IKKε kinase activity [1] [3]. Also, MRT67307 completely blocked the TBK1- or IKKε-induced decrease in the mobility of Pellino 1 [3]. Exposed macrophages to MRT67307 increased the levels of the anti-inflammatory cytokines IL-1ra and IL-10 and decreased the levels of proinflammatory cytokines (such as IL-6, IL-12, and TNF) in response to bacterial lipopolysaccharide (LPS) [4].