NEK1

NIMA-related kinase 1 (NEK1) is a serine/threonine kinase that regulates cell cycle progression, ciliogenesis, and DNA repair^[1]^[2]. Mechanistically, NEK1 phosphorylates α-tubulin and importin-β1 to maintain microtubule homeostasis and nuclear import in motor neurons^[1]. NEK1 also modulates the localization and phosphorylation of α-adducin (ADD1) and Myosin X (MYO10) during meiosis, ensuring proper spindle assembly and chromosome congression^[3]. In DNA damage response, NEK1 acts upstream of ATR and Chk1, facilitating checkpoint control independently of ATM and ATR activity^[4]^[5]. NEK1 interacts with C21ORF2 through its C-terminal interaction domain, a complex essential for ciliogenesis and homologous recombination, and pathogenic mutations disrupt this association^[6]. Compared with related NEK isoforms, NEK1 uniquely integrates microtubule regulation, ciliary function, and DNA repair, which underscores its pleiotropic cellular roles^[7]^[8]. Experimental inhibition of NEK1 with kinase inhibitors or genetic knockdown impairs DNA repair, ciliary function, and microtubule stability, while stabilization of microtubules or HDAC6 inhibition can rescue these defects in ALS and iPSC-derived models^[1]^[9]. Structural characterization of the NEK1 kinase domain provides a framework for designing selective inhibitors for cancer and neurodegenerative disease research^[2]. These studies establish NEK1 as a critical target for functional interrogation of cell cycle regulation, neurodegeneration, and DNA damage repair pathways^[10].

References:

[1]. Mann JR, et al. Loss of function of the ALS-associated NEK1 kinase disrupts microtubule homeostasis and nuclear import. Sci Adv. 2023 Aug 18;9(33):eadi5548. [Content Brief]

[2]. Melo-Hanchuk TD, et al. NEK1 kinase domain structure and its dynamic protein interactome after exposure to Cisplatin. Sci Rep. 2017 Jul 14;7(1):5445. [Content Brief]

[3]. Chen Y, et al. Nek1 kinase functions in DNA damage response and checkpoint control through a pathway independent of ATM and ATR. Cell Cycle. 2011 Feb 15;10(4):655-63. [Content Brief]

[4]. Gregorczyk M, et al. Functional characterization of C21ORF2 association with the NEK1 kinase mutated in human in diseases. Life Sci Alliance. 2023 May 15;6(7):e202201740. [Content Brief]

[5]. Noh MY, et al. Mutations in NEK1 cause ciliary dysfunction as a novel pathogenic mechanism in amyotrophic lateral sclerosis. Mol Neurodegener. 2025 May 20;20(1):59. [Content Brief]

[6]. Brieño-Enríquez MA, et al. NIMA-related kinase 1 (NEK1) regulates the localization and phosphorylation of α-Adducin (ADD1) and Myosin X (MYO10) during meiosis. bioRxiv. 2017:110098.

[7]. Baker BM, et al. NEK Family Kinases: Structure, Function, and Role in Disease. Biomolecules. 2025 Oct 2;15(10):1406. [Content Brief]

[8]. Roy SM, et al. Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models. ACS Chem Neurosci. 2015 Apr 15;6(4):666-80. [Content Brief]

[9]. Folahan JT, et al. NEK kinases in cell cycle regulation, DNA damage response, and cancer progression. Tissue Cell. 2025 Jun;94:102811. [Content Brief]

[10]. Singh V, et al. Identification of the proteome complement of humanTLK1 reveals it binds and phosphorylates NEK1 regulating its activity. Cell Cycle. 2017 May 19;16(10):915-926. [Content Brief]

NEK1 Inhibitor (1)

NEK1 Related Products (2):

By Type:	Selective (1)

Cat. No.	Product Name	Effect	Purity

HY-144425

BSc5367		98.21%
BSc5367 is a potent Nek1 inhibitor with an IC₅₀ of 11.5 nM. NIMA-related protein kinase Nek1 is crucially involved in cell cycle regulation, DNA repair and microtubule regulation and dysfunctions of Nek1 play key roles in amyotrophic lateral sclerosis (ALS), polycystic kidney disease (PKD) and several types of radiotherapy resistant cancer.

HY-103646

CK7	Inhibitor	99.72%
CK7, a Cdk2/9 inhibitor, can be used for the synthesis of Nek1 inhibitor BSc5231 and BSc5367.

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