Salt-inducible Kinase (SIK)

MRT67307 is a potent and dual IKKε and TBK1 inhibitor with IC50 of 160 and 19 nM, respectively.

ARN-3236 is potent, orally active and selective SIK2 inhibitor. ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μmol/L.

YKL-06-061 is a potent and selective SIK (salt-inducible kinase) inhibitor.

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).

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.

DB0614 is a PROTAC molecule utilizing a cereblon ligand, designed as a selective and potent degrader of NEK9 and other kinases. It induces the degradation of multiple kinases, including ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1–3, MAP4K5, MAPK14, MAPK7–9, MAPKAPK2/3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1/3, SIK2/3, STK35, TNK2, and ULK1. DB0614 is suitable for research involving diseases or disorders driven by aberrant kinase activity.

DB1113 is a bifunctional compound designed for targeted protein degradation of various kinases. It effectively induces degradation of ABL1, ABL2, BLK, CDK4, CDK11B, EPHA3, MAPK7, RIPK1, and others, facilitating the investigation of kinase-related signaling pathways. DB1113 is suitable for research focusing on diseases or disorders associated with dysregulated kinase activity, providing a valuable tool for exploring therapeutic interventions in cancer and other conditions.

GLPG3312 is a potent SIK inhibitor, demonstrating IC50 values of 2.0 nM, 0.7 nM, and 0.6 nM for SIK1, SIK2, and SIK3, respectively. It exhibits significant anti-inflammatory and immunomodulatory activities both in vitro on human primary myeloid cells and in vivo in mouse models. Due to its favorable oral bioavailability, GLPG3312 is an important reagent for research into various inflammatory and immune-related diseases.

SIK2-IN-4 is a highly selective inhibitor of SIK1 and SIK2, exhibiting IC50 values of 0.143 μM and 0.076 μM, respectively. By targeting SIK1/2, SIK2-IN-4 reduces the phosphorylation of transcription coactivator 3 (CRTC3), thereby modulating cAMP response element binding protein (CREB)-dependent transcriptional activity. This compound demonstrates inhibitory effects on pro-inflammatory cytokines such as TNF, IL-12/23 p40, and IL-23, while promoting the expression of the anti-inflammatory cytokine IL-10. SIK2-IN-4 is a valuable tool for investigating intestinal inflammation and other chronic inflammatory conditions.

YKL-05-093 is a selective SIK (Salt-Induced Kinase) inhibitor, demonstrating a binding affinity (Kd) of 7.1 nM for SIK2. This compound effectively reduces the phosphorylation levels of HDAC4, HDAC5, and CRTC2, while inhibiting SOST expression and stimulating RANKL expression both in vitro and in vivo. YKL-05-093 is suitable for research applications focusing on bone diseases and related signaling pathways.

MRT199665 is a potent, ATP-competitive inhibitor targeting MARK, SIK, and AMPK pathways, exhibiting IC50 values of 2 nM for MARK1, 10 nM for AMPKα1, and 110 nM for SIK1. This compound induces apoptosis in MEF2C-activated human acute myeloid leukemia (AML) cells by effectively inhibiting the phosphorylation of the SIK substrate CRTC3 at S370. MRT199665 serves as a valuable tool for investigating the roles of MARK, SIK, and AMPK in cellular signaling and cancer biology.

MRIA9 is an ATP-competitive inhibitor targeting pan Salt-Inducible kinases (SIK) as well as PAK2 and PAK3. It exhibits potent biological activity with IC50 values of 516 nM for SIK1, 180 nM for SIK2, and 127 nM for SIK3. MRIA9 is suitable for applications in signaling pathway research and the study of various cellular processes influenced by SIK and PAK kinases.

PF-07899895 is a selective SIK inhibitor, demonstrating potent activity with IC50 values of 1.2 nM, 0.9 nM, and 1.8 nM against SIK1, SIK2, and SIK3, respectively. This compound effectively modulates the production of the anti-inflammatory cytokine IL-10 in immune cells. PF-07899895 is highly relevant for research into inflammatory diseases and understanding immunological responses.

SIK-IN-1 is a potent inhibitor of salt-inducible kinases (SIK1, SIK2, and SIK3), exhibiting IC50 values of 0.1 nM, 0.4 nM, and 1.5 nM, respectively. This compound effectively inhibits the release of TNF-alpha with an IC50 of 0.5 nM and promotes LPS-induced IL-10 release, demonstrating an EC50 of 4 nM in human macrophages. SIK-IN-1 is a valuable tool for research investigating inflammatory responses and macrophage polarization.

SIK-IN-2 is a potent inhibitor of salt-inducible kinases (SIK), selectively targeting SIK1, SIK2, and SIK3 with IC50 values of 0.1, 0.2, and 0.4 nM, respectively. This compound has demonstrated significant biological activity by inhibiting the release of TNF-alpha with an IC50 of 0.5 nM and enhancing LPS-induced IL-10 release in human macrophages with an EC50 of 2 nM. SIK-IN-2 is valuable for research applications focused on inflammatory responses and immune modulation.

SIK2/3-IN-2 is a potent inhibitor of salt-inducible kinases 2 and 3 (SIK2 and SIK3), with IC50 values of 65 nM and 14 nM, respectively. Additionally, it acts as a p21-activated protein kinase (PAK) 1 inhibitor with a Ki of 20.7 nM. This compound is valuable for investigating hyperproliferative diseases and cancer, particularly in studies related to Paclitaxel-resistant ovarian cancer.

GLPG3970 is a selective inhibitor of SIK2 and SIK3, targeting these kinases to modulate their activity. This compound demonstrates significant potential in studying inflammatory responses and autoimmune diseases, contributing to the understanding of their underlying mechanisms and potential therapeutic approaches. Its role as a first-in-class inhibitor positions GLPG3970 as a valuable tool in biomedical research focused on these critical areas.

SK-124 is an orally active inhibitor of salt-inducible kinases 2 and 3 (SIK2/SIK3). It selectively inhibits SIK2 and SIK3, leading to enhanced levels of pro-peptide of type I collagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). This modulation results in increased bone formation and bone mass, making SK-124 a valuable tool for research on bone metabolism and associated disorders.

YKL-06-062 is a selectively potent inhibitor of salt-inducible kinases (SIKs), demonstrating IC50 values of 2.12 nM, 1.40 nM, and 2.86 nM for SIK1, SIK2, and SIK3, respectively. This compound is pivotal for research involving cellular stress responses, inflammatory processes, and metabolic regulation. Its specificity and efficacy make it a valuable tool for exploring SIK-related signaling pathways in various biological contexts.

Pterosin B is an orally active indanone and a selective inhibitor of the SIK3 signaling pathway. It has demonstrated key biological activities, including the inhibition of Klf5 expression and a reduction in β-amyloid deposition, making it relevant in Alzheimer's disease research. Additionally, Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mouse models, while also inhibiting cardiomyocyte hypertrophy and improving cognitive impairment and glycemic control. This compound is valuable for studies related to arthritis, neurodegenerative disorders, pathological cardiac hypertrophy, and diabetes.

WH-4-025 is an inhibitor of salt-inducible kinases (SIKs), which play a critical role in regulating various cellular processes, including metabolism, inflammation, and transcription. This compound has demonstrated significant biological activity by modulating SIK signaling pathways, making it a valuable tool for investigating the roles of SIKs in cellular response to environmental stressors. WH-4-025 is suitable for research applications aimed at understanding diseases linked to SIK dysregulation, such as metabolic disorders and cancer.

SIC-19 is a selective inhibitor of SIK2, promoting its degradation through the ubiquitination pathway. This compound exhibits significant antiproliferative activity against cancer cells and enhances the sensitivity of these cells to PARP inhibitors, including Olaparib. Additionally, SIC-19 demonstrates efficacy in ovarian cancer organoids and xenograft models, making it a valuable tool for cancer research and therapeutic development.

MR22 is a potent inhibitor of salt-inducible kinases (SIKs), demonstrating excellent selectivity in a representative kinase panel, while lacking activity against STE group kinases. This compound effectively induces centrosome dissociation and contributes to cell-cycle arrest in ovarian cancer cells. MR22 holds potential for research in cancer biology and the therapeutic targeting of SIK-related pathways.

SIKs-IN-1 is a pyrimidine-5-carboxamide derivative that functions as an inhibitor of Salt-inducible kinases (SIKs). It modulates the balance between M1 and M2 macrophages, playing a crucial role in the inflammatory response. SIKs-IN-1 effectively inhibits SIK activity, leading to the upregulation of the anti-inflammatory cytokine IL-10 and the downregulation of the pro-inflammatory cytokine IL-12. This compound demonstrates significant anti-inflammatory effects in models of DSS-induced colitis, making it valuable for research into inflammatory diseases.

SIK2-IN-3 is a selective inhibitor of SIK1 and SIK2, with IC50 values of 0.128 μM and 0.084 μM, respectively. This compound effectively inhibits the phosphorylation of CRTC3 and reduces pro-inflammatory cytokine production in myeloid cells. SIK2-IN-3 demonstrates potential in mitigating systemic and tissue inflammatory responses, as evidenced by its efficacy in a mouse anti-CD40 colitis model, making it a valuable tool for research in inflammation and immune response mechanisms.

SIK2/3-IN-1 is a selective inhibitor of Salt-Inducible Kinases 2 and 3 (SIK2/3). It has demonstrated significant efficacy in inhibiting tumor growth in the MV4-11 acute myeloid leukemia (AML) mouse xenograft model, while maintaining animal body weight. This compound is valuable for investigating MEF2C-dependent pathways in acute myeloid leukemia research.