sik3

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

GLPG3970 (compound 88) is a small molecule inhibitor, a dual SIK2/SIK3 inhibitor (SIK2 IC50=7.8 nM, SIK3 IC50=3.8 nM) with selectivity over SIK1, oral activity, and cellular permeability. This compound possesses anti-inflammatory activity and can be used for research on autoimmune and inflammatory diseases.

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.

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.

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.

PF-07899895 (compound 34) is a potent SIK (salt-induced kinase) inhibitor with IC50 values of 1.2/0.9/1.8 nM for SIK1/SIK2/SIK3.

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.

ODM-203, a Selective Inhibitor of FGFR and VEGFR, Shows Strong Antitumor Activity, and Induces Antitumor Immunity

ODM-203 sodium is an orally available, selective, and efficient FGFR and VEGFR inhibitor, with antitumor activity, inhibiting FGFR3/1/2 and VEGFR3/2/1/4, inducing antitumor immunity, useful in solid tumor research.

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).

Pterosin B, a type of indanone found in Pteridium aquilinum, is an inhibitor of salt-induced kinase 3 (Sik3) signal transduction. Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.

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.

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.

GLPG4970 is a potent, selective, orally active dual inhibitor of salt-inducible kinases 2 and 3 (SIK2/SIK3), with IC50 values of 0.3 nM and 0.7 nM, respectively. It exhibits weak inhibition of the hERG channel, with an IC50 value of 29 μM. GLPG4970 reduces the release of tumor necrosis factor α (TNFα) and increases the release of interleukin 10 (IL-10). This compound is applicable for research in inflammation and immunology, such as studies on colitis.

SIK1-IN-1 (Compound 27) is a selective inhibitor of salt-inducible kinase 1 (SIK1) with an IC50 of 0.7 nM, demonstrating greater potency for SIK1 compared to SIK2 and SIK3. It shows no cytotoxicity in HEK293 cells and PBMC at concentrations up to 30 μM. Additionally, SIK1-IN-1 effectively inhibits 392 kinases, particularly tyrosine kinases such as FGR, HCK, and LYN.

SIK2/3-IN-2 (compound 12, compound I-200) is a potent SIK2/3 inhibitor, with IC50 values of 65 nM for SIK2 and 14 nM for SIK3. It also acts as an inhibitor of p21-activated kinase (PAK)1, with a Ki of 20.7 nM. SIK2/3-IN-2 is applicable in research on proliferative diseases and cancer, such as paclitaxel-resistant ovarian cancer.

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].

DB1113 (Example 24) is a bifunctional compound designed for the targeted degradation of various kinases, including ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2, and ULK1. This capability positions DB1113 as a valuable tool for research into diseases or disorders associated with aberrant kinase activity [1].

DB0614 (Example 21) is a bifunctional compound designed for the targeted degradation of kinases, effectively breaking down AAK1, AURKA, BMP2K, CAMKK1, CDK16, CML, CDK6, EIF2AK2, FER, GAK, LCK, LIMK2, MAP3KH, MAPK8, MAPK9, NEK9, PLK4, PTK2B, SIK2, STK17A, STK17B, ULK1, ULK3, and WEE1. This compound has potential applications in research on diseases or disorders caused by aberrant kinase activity [1].

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].