SIK2
SIK2 is an AMPK-related serine/threonine kinase that is highly expressed in adipocytes and regulated by cAMP-dependent PKA phosphorylation at Ser358[1]. Mechanistically, SIK2 localizes at centrosomes, phosphorylates C-Nap1, and supports centrosome splitting, bipolar mitotic spindle formation, and mitotic progression[2]. In ovarian cancer models, SIK2 is overexpressed in adipocyte-rich metastatic deposits, promotes abdominal metastasis, and couples adipocyte-induced metabolic signaling with cancer-cell survival through ACC phosphorylation and PI3K/AKT activation[3]. Compared with related SIK isoforms, SIK2 is distinguished by stronger evidence in ovarian cancer centrosome biology and adipocyte-rich metastatic niches[2][3]. For experimental applications, ARN-3236 inhibits SIK2, suppresses ovarian cancer cell growth, blocks centrosome splitting, reduces AKT/survivin signaling, and sensitizes ovarian cancer cell lines and xenografts to paclitaxel[4].
References:
- [1]. Henriksson E, et al. The AMPK-related kinase SIK2 is regulated by cAMP via phosphorylation at Ser358 in adipocytes. Biochem J. 2012 Jun 15;444(3):503-14. [Content Brief]
- [2]. Ahmed AA, et al. SIK2 is a centrosome kinase required for bipolar mitotic spindle formation that provides a potential target for therapy in ovarian cancer. Cancer Cell. 2010 Aug 9;18(2):109-21. [Content Brief]
- [3]. Miranda F, et al. Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche. Cancer Cell. 2016 Aug 8;30(2):273-289. [Content Brief]
- [4]. Zhou J, et al. A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel. Clin Cancer Res. 2017 Apr 15;23(8):1945-1954. [Content Brief]
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SIK2 관련 제품 (18)
관련 제품 (18)
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HG-9-91-01
0 ImagesSynonyms: SIK inhibitor 1HG-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.
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GLPG3312
0 ImagesGLPG3312 (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.
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MRT199665
0 ImagesMRT199665 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.
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DB1113
0 ImagesDB1113 (Example 24) is a bifunctional compound targeted protein degradation of kinases. DB1113 degrades 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. DB1113 can be used for research of disease or disorder mediated by aberrant kinase activity.
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SIK2/3-IN-2
0 ImagesCat. No.: HY-164534CAS No.: 1648864-21-4SIK2/3-IN-2 (compound 12, compound I-200) is a potent SIK2/3 inhibitor (SIK2 IC50 = 65 nM, SIK3 IC50 = 14 nM). SIK2/3-IN-2 is also a p21-activated protein kinase (PAK) 1 inhibitor with a Ki of 20.7 nM. SIK2/3-IN-2 can be used for hyperproliferative diseases and cancer research, such as Paclitaxel (HY-B0015)-resistant ovarian cancer.
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SIK-IN-6
0 ImagesCat. No.: HY-184954SIK-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.
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SIK2/3-IN-3
0 ImagesCat. No.: HY-182804CAS No.: 3069526-08-2
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RSS0680
0 ImagesRSS0680 is a small noncoding RNA (sRNA) targeting the mRNA ribosome binding site (RBS) and a PROTAC. RSS0680 competitively binds to RBS through the conserved CCUCCUCCC anti-Shine-Dalgarno (aSD) sequence and inhibits the translation initiation of target genes. RSS0680 can interact with the DUF1127 protein CcaF1, regulate its own stability and participate in bacterial oxidative stress defense, enhancing the host's resistance to heat shock and oxidative damage by affecting pathways such as C1 metabolism and pyruvate dehydrogenase complex. RSS0680 degrades AAK1, CDK1, CDK16, CDK2, CDK4, CDK6, EIF2AK4, GAK, LATSl, LIMK2, MAPK6, MAPKAPK5, MARK2, MARK4, MKNK2, NEK9, RPS6KB1, SIK2, SNRK, STK17A, STK17B, STK35, and WEEl. RSS0680 can be used to study diseases or disorders mediated by aberrant kinase activity and regulatory mechanisms of noncoding RNAs in α-proteobacteria[1][2].
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MRIA9
0 ImagesMRIA9, 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.
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GLPG4970
0 ImagesGLPG4970 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.
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DB0614
0 ImagesDB0614 is a PROTAC based on Cereblon ligand, which is a selective and potent targeted protein degrader of NEK9 inhibitor. DB0614 can degrade 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. DB0614 can be used for research of disease or disorder mediated by aberrant kinase activity.(Blue: Thalidomide-4-OH (HY-103596), Black: linker, Pink: FLT3-IN-17 (HY-148070))
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SK-124
0 ImagesCat. No.: HY-173191CAS No.: 2760404-50-8SK-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.
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SIK2-IN-4
0 ImagesSIK2-IN-4 (Compound 4) is a highly selective SIK1/2 inhibitor (IC50s 0.143 and 0.076 μM, respectively). SIK2-IN-4 reduces the phosphorylation of transcription coactivator 3 (CRTC3) by targeting SIK1/2, thereby regulating cAMP response element binding protein (CREB)-dependent transcriptional activity. SIK2-IN-4 inhibits the production of pro-inflammatory cytokines such as TNF (IC50: 0.11 µM), IL-12/23 p40 (IC50: 0.25 µM), and IL-23 (IC50: 0.47 µM), while inducing the expression of the anti-inflammatory cytokine IL-10. SIK2-IN-4 can be used to study intestinal inflammation and other chronic inflammatory diseases.
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SIK2-IN-3
0 ImagesCat. No.: HY-171590CAS No.: 2810809-10-8SIK2-IN-3 is an orally active SIK1/2 selective inhibitor (IC50: 0.128/0.084 μM). SIK2-IN-3 inhibits CRTC3 phosphorylation and myeloid cell pro-inflammatory cytokine production. SIK2-IN-3 ameliorates systemic and tissue inflammatory responses in a mouse anti-CD40 colitis model.
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SIK2/3-IN-1
0 ImagesCat. No.: HY-170237CAS No.: 3038863-24-7SIK2/3-IN-1 (Compound 7S) is a selectively inhibitory agent of SIK2/3 with oral activity. SIK2/3-IN-1 can significantly inhibit tumor growth (without any body weight loss) in the MV4-11 AML mice CDX model. SIK2/3-IN-1 can be used in the research of MEF2C-dependent acute myeloid leukemia.
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SIK1-IN-1
0 ImagesCat. No.: HY-178014SIK1-IN-1 (Compound 27) is a selective Salt-inducible kinase 1 (SIK1) inhibitor with an IC50 of 0.7 nM for SIK1 over SIK2 and SIK3. SIK1-IN-1 has no cytotoxicity against HEK293 cells and PBMCs (maximum concentration of 30 μM). SIK1-IN-1 also has potent inhibitory activities for 392 kinases, in particular tyrosine kinases, such as FGR, HCK and LYN).
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