Salt-inducible Kinase (SIK) Inhibitor

HG-9-91-01 is a potent and highly selective salt-inducible kinase (SIK) inhibitor with IC₅₀s of 0.92 nM, 6.6 nM and 9.6 nM for SIK1, SIK2 and SIK3 respectively.

YKL-05-099 is a salt-inducible kinase (SIK) inhibitor. YKL-05-099 binds to SIK1 and SIK3 with IC₅₀s of ~10 and ~30 nM, respectively. YKL-05-099 has slightly less potent SIK2-inhibitory (IC₅₀=40 nM).

GLPG3970 (compound 88) is a first-in-class SIK2/SIK3 inhibitor. GLPG3970 can be used for the research of inflammation and autoimmune disease.

GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC₅₀ values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.

MRT199665 is a potent and ATP-competitive, selective MARK/SIK/AMPK inhibitor with 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 causes apoptosis in MEF2C-activated human acute myeloid leukemias (AML) cells. MRT199665 inhibits the phosphorylation of SIK substrate CRTC3 at S370.

SIK-IN-6 is a selective SIK3 inhibitor with an IC₅₀ of 15 nM. SIK-IN-6 exerts anticancer activity in acute myeloid leukemia with high MEF2C expression, but does not exhibit significant anticancer activity in acute myeloid leukemia with low MEF2C expression or in ovarian cancer. SIK-IN-6 can be used for the research of acute myeloid leukemia.

SIK2/3-IN-3 (Example 15) is a potent, selective SIK2/3 inhibitor that exhibits preferential inhibitory activity against SIK2 (IC₅₀ = 10.3 nM) and SIK3 (IC₅₀ = 0.8 nM) over SIK1 (IC₅₀ = 801 nM). SIK2/3-IN-3 can be used for the study of inflammatory diseases.

ARN-3236 is an oral active and selective inhibitor of salt-inducible kinase 2 (SIK2), with IC₅₀s of <1 nM, 21.63 nM and 6.63 nM for SIK2, SIK1 and SIK3, respectively. Has anti-cancer activity.

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

YKL-06-061 is a potent, selective, second-generation 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 an orally active indanone. Pterosin B can be obtained from Pteridium aquilinum. Pterosin B is a Sik3 signaling inhibitor. Pterosin B inhibits Klf5 expression and reduces β-amyloid deposition. Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice. Pterosin B inhibits cardiomyocyte hypertrophy, improves cognitive impairment, and lowers blood glucose. Pterosin B can be used in research on arthritis, Alzheimer's disease, pathological cardiac hypertrophy and diabetes.

WH-4-025 is a Salt-inducible kinase (SIK) inhibitor (WO2016023014 A2).

MRIA9, a chemical probe, is an ATP-competitive, pan Salt-Inducible kinase (SIK) and PAK2/3 inhibitor, with IC₅₀ values of 516 nM, 180 nM and 127 nM for SIK1, SIK2 and SIK3, respectively.

GLPG4970 is a potent, selective and orally active salt-inducible kinase 2/3 (SIK2/SIK3) dual inhibitor with IC₅₀ values of 0.3 nM and 0.7 nM. GLPG4970 has weak inhibition of hERG channel with an IC₅₀ of 29 μM. GLPG4970 can decrease TNFα release and increase IL-10 release GLPG4970 can be used for the researches of inflammation and immunology, such as colitis.

SIC-19 is a SIK2 inhibitor and promotes SIK2 protein degradation via the ubiquitination pathway. SIC-19 inhibits cancer cell growth and sensitizes cells to PARP inhibitors (Such as Olaparib (HY-10162)), as well as in ovarian cancer organoids and xenograft models.

PF-07899895 (Compound 34) is a SIK inhibitor, with IC₅₀ values of 1.2 nM, 0.9 nM, and 1.8 nM against SIK1, SIK2, and SIK3, respectively. PF-07899895 modulates the anti-inflammatory cytokine IL-10 in immune cells. PF-07899895 is applicable to research related to inflammatory diseases.

(R)-MRT199665 is an isomer of MRT199665 (HY-120877). MRT199665 is a potent and ATP-competitive, selective MARK/SIK/AMPK inhibitor with 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 causes apoptosis in MEF2C-activated human acute myeloid leukemias (AML) cells. MRT199665 inhibits the phosphorylation of SIK substrate CRTC3 at S370.

SIK3 Human Pre-designed siRNA Set A contains three designed siRNAs for SIK3 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.

MR22 is a potent pan-SIK (salt-inducible kinase) inhibitor. MR22 no longer exhibits activity on STE group kinases and displays excellent selectivity in a representative kinase panel. MR22-dependent SIK inhibition led to centrosome dissociation and subsequent cell-cycle arrest in ovarian cancer cells.

SK-124 is an orally active salt-inducible kinase (SIK) inhibitor with an IC₅₀ of 230 nM against SIK1, 4.1 nM against SIK2, and 21 nM against SIK3, exhibiting excellent kinome selectivity. SK-124 blocks SIK-mediated CRTC2 phosphorylation, promotes CRTC2 nuclear translocation, and regulates vitamin D metabolism by upregulating renal Cyp27b1 and downregulating Cyp24a1. SK-124 upregulates the expression of bone-related genes, increases serum Ca²⁺, 1,25-vitamin D and intact FGF23 levels, and suppresses endogenous PTH levels. SK-124 can be used in studies related to osteoporosis, male osteoporosis, and chronic kidney disease-mineral and bone disorder.