NUAK2
NUAK family kinase 2 (NUAK2), also known as SNARK, is a serine/threonine kinase within the AMPK-related kinase family that functions downstream of the tumor suppressor kinase LKB1 and participates in cellular stress adaptation, cytoskeletal regulation, and signal transduction pathways linked to tissue homeostasis and disease progression[1][2]. Mechanistically, NUAK2 is integrated into transforming growth factor-β (TGF-β) signaling, where TGF-β induces NUAK2 expression and NUAK2 subsequently reinforces TGF-β pathway output, establishing a positive feedforward regulatory circuit that influences cellular differentiation, motility, and mesenchymal responses[2]. This regulatory role distinguishes NUAK2 from the closely related isoform NUAK1, which acts predominantly as a negative regulator of TGF-β signaling, indicating that the two kinases exert opposing effects on pathway activity despite belonging to the same AMPK-related kinase subfamily[2]. In disease models, elevated NUAK2 expression has been associated with melanoma progression, and experimental depletion of NUAK2 suppresses tumor growth and cell migration, supporting a functional role in oncogenic phenotypes[3]. Recent studies further demonstrated that NUAK2 promotes pancreatic cancer cell proliferation, migration, and invasion through regulation of SMAD2/3 signaling and enhances resistance to apoptosis, highlighting its utility as a mechanistic target in cancer research models[4]. For experimental applications, the growing development of small-molecule NUAK inhibitors has provided pharmacological tools to interrogate NUAK-dependent signaling networks and evaluate therapeutic vulnerabilities associated with aberrant NUAK2 activity[5].
References:
- [1]. Skalka GL, et al. NUAK: never underestimate a kinase. Essays Biochem. 2024 Nov 18;68(3):295-307.
- [2]. van de Vis RAJ, et al. NUAK1 and NUAK2 Fine-Tune TGF-β Signaling. Cancers (Basel). 2021 Jul 5;13(13):3377. [Content Brief]
- [3]. Namiki T, et al. AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma. Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6597-602. [Content Brief]
- [4]. Wang R, et al. The NF-κB/NUAK2 signaling axis regulates pancreatic cancer progression by targeting SMAD2/3. iScience. 2024 Mar 4;27(4):109406. [Content Brief]
- [5]. Faisal M, et al. Development and Therapeutic Potential of NUAKs Inhibitors. J Med Chem. 2021 Jan 14;64(1):2-25. [Content Brief]
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NUAK2 Related Products (5)
Related Products (5)
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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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HTH-02-006
0 ImagesCat. No.: HY-156397Purity: 99.42%HTH-02-006 is a NUAK2 inhibitor, with an IC50 value of 126 nM. HTH-02-006 inhibits NUAK2-mediated signaling by reducing phosphorylation of its substrate MYPT1 at S445 and downstream MLC. HTH-02-006 shows growth inhibitory efficacy in YAP-high cancer cells (HuCCT-1, SNU475). HTH-02-006 significantly suppresses YAP-induced hepatomegaly (reduced liver/body weight ratio) in TetO-YAP S127A transgenic mice and demonstrates significant anti-tumor efficacy in mice bearing HMVP2 prostate cancer allografts. HTH-02-006 can be used for the study of liver cancer and prostate cancer.
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NUAK1-IN-3
0 ImagesCat. No.: HY-182361CAS No.: 3097515-05-1NUAK1-IN-3 is a potent and selective NUAK1 inhibitor with an IC50 of 0.49 nM. NUAK1-IN-3 also inhibits NUAK2 and JAK3 with IC50 values of 265 and 225 nM. NUAK1-IN-3 engages Glu139 of NUAK1, forms a salt bridge between its bicyclic ring nitrogen and Asp142, and uses a fluorine atom to enhance hydrophobic binding interactions. NUAK1-IN-3 attenuates MYPT1 phosphorylation, suppresses the NUAK1-MYPT1 signaling axis, and inhibits proliferation, migration, and invasion of triple-negative breast cancer cells. NUAK1-IN-3 reverses TGF-β1-induced epithelial-mesenchymal transition (EMT) marker alterations, downregulates Snail and N-cadherin, and upregulates E-cadherin in tumor tissues. NUAK1-IN-3 suppresses tumor growth in triple-negative breast cancer xenograft models. NUAK1-IN-3 can be used for the research of triple-negative breast cancer.
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OICR19451
0 ImagesCat. No.: HY-182743CAS No.: 2803349-61-1OICR19451 is an orally active dual NUAK1/NUAK2 and MARK2/MARK3 kinase inhibitor, with IC50 values of 12 nM and 10 nM against NUAK1 and NUAK2, and 101 nM and 124 nM against MARK2 and MARK3, respectively. OICR19451 modulates the Hippo signaling pathway, increases the phosphorylation level of YAP, enhances the cytoplasmic localization of YAP/TAZ, and inhibits the expression of oncogenes. OICR19451 inhibits cancer cell growth, reduces metastasis, promotes tumor capsule formation, and improves mouse survival in an orthotopic breast cancer model. OICR19451 can be used for research related to triple-negative breast cancer.
