sik1

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

YKL-05-099 is a salt-inducible kinase (SIK) inhibitor. It can inhibit the activity of SIK1 (IC50: 10 nM) and SIK3 (IC50: 30 nM), and has a slightly weaker inhibitory effect on SIK2 (IC50: 40 nM). [1]

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-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.

JRD-SIK1/2i-4 is a SIK1/2 inhibitor that induces nuclear translocation of CRTC3 at low micromolar concentrations. It is expected to saturate SIK1 and SIK2, but not SIK3.

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.

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.

Phanginin A, a natural product discovered in Caesalpinia sappan Linn, activates SIK1 and inhibits gluconeogenesis in mouse primary hepatocytes. Phanginin A increases PDE4 activity and suppresses the hepatic cAMP/PKA/CREB pathway, improving metabolic disorders in ob/ob mice. It may be used in studies of type 2 diabetes.

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

Through its effects on ULK1 and ULK2, MRT67307 blocks autophagy. MRT67307 prevents the phosphorylation of IRF3 and the production of IFN-β and increases toll-like receptor-induced IL-10 and IL-1ra secretion in macrophages. MRT67307 is a kinase inhibitor that has been shown to inhibit TBK1, MARK1-4, IKKε, and NUAK1 (IC50 values are 19, 27-52, 160, and 230 nM, respectively), the salt-inducible kinases (SIKs; IC50s =250, 67, and 430 nM for SIK1, SIK2, and SIK3, respectively) and ULK1 and ULK2 (IC50s = 45 and 38 nM, respectively).

PF-07899895 is an inhibitor of SIK. The IC50 values for SIK1, SIK2 and SIK3 are 1.2 nM, 0.9 nM and 1.8 nM respectively.

SIK2-IN-3 is an orally active selective inhibitor of SIK1/2 with IC50 values of 0.128/0.084 μM. It hinders the phosphorylation of CRTC3 and suppresses the production of pro-inflammatory factors in myeloid cells. Additionally, SIK2-IN-3 alleviates systemic and tissue inflammatory responses in a mouse anti-CD40 colitis model.

SIK-IN-3 (Compound 6B) is an inhibitor of salt-induced kinases (SIK), demonstrating inhibitory effects on SIK1, SIK2, and SIK3 with IC50 values of 0.1, 0.3, and 0.8 nM respectively. SIK-IN-1 inhibits TNFa release in human macrophages with an IC50 of 0.6 nM and stimulates LPS-induced IL-10 release with an EC50 of 3 nM.

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].

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.

GLPG3312 is a selective and potent pan-SIK inhibitor with the advantage of oral activity, with IC50=0.6-2.0 nM for SIK1, SIK2 and SIK3, and exhibits anti-inflammatory and immunomodulatory activity in both human primary myeloid cells and mouse models.

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].