NEK7

NEK6 is a NIMA-related serine/threonine kinase required for mitotic progression, and loss of NEK6 function arrests cells in M phase and triggers apoptosis^[1]. Mechanistically, NEK9/Nercc1 activates NEK6 during mitosis through Ser206 phosphorylation, placing NEK6 in a mitotic kinase cascade important for cell-cycle progression^[2]. NEK6 and NEK7 both support spindle formation and cytokinesis, but they are not redundant because NEK6 localizes to spindle microtubules and the midbody more clearly than NEK7^[3]. NEK6 also acts on EML4 with NEK7 to reduce microtubule affinity and promote chromosome congression^[4]. In cancer models, NEK6 overexpression induces anchorage-independent transformation in JB6 Cl41 cells, whereas NEK6 inhibition promotes premature senescence and cell death in cancer cells^[5]^[6]. For experimental applications, ATP-site NEK6 inhibitors identified by virtual screening provide kinase-focused tools for testing NEK6-dependent tumor-cell phenotypes^[7].

References:

[1]. Yin MJ, et al. The serine/threonine kinase Nek6 is required for cell cycle progression through mitosis. J Biol Chem. 2003 Dec 26;278(52):52454-60. [Content Brief]

[2]. Belham C, et al. A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases. J Biol Chem. 2003 Sep 12;278(37):34897-909. [Content Brief]

[3]. O'Regan L, et al. The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis. Mol Cell Biol. 2009 Jul;29(14):3975-90. [Content Brief]

[4]. Adib R, et al. Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity of EML4 to promote chromosome congression. Sci Signal. 2019 Aug 13;12(594):eaaw2939. [Content Brief]

[5]. Jeon YJ, et al. Role of NEK6 in tumor promoter-induced transformation in JB6 C141 mouse skin epidermal cells. J Biol Chem. 2010 Sep 3;285(36):28126-33.

[6]. Jee HJ, et al. The inhibition of Nek6 function sensitizes human cancer cells to premature senescence upon serum reduction or anticancer drug treatment. Cancer Lett. 2013 Jul 10;335(1):175-82.

[7]. De Donato M, et al. Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. Sci Rep. 2018 Oct 30;8(1):16047. [Content Brief]

NEK7 Verwandte Produkte (12):

By Type:	Pan (1) Selective (3)
By Effects:	Inhibitors (4) Degraders (7)

Art. -Nr.	Produktname	Wirkung	Reinheit

HY-172162

LC-04-045	Degrader	99.56%
LC-04-045 is a selective NIMA-related kinase 7 (NEK7) molecular glue degrader. LC-04-045 induces NEK7 degradation via the CRBN-based ubiquitin-proteasome system, dependent on the glycine 57-containing degron motif. LC-04-045 inhibits secretion of downstream cytokines IL-1β and IL-18. LC-04-045 can be used for the research of lymphoblastic leukemia.

HY-159520

Ofirnoflastum	Inhibitor	99.93%
Ofirnoflastum (Ofirnoflast) is an orally active first-in-class allosteric NEK7 inhibitor with an IC₅₀ of 46 nM. Ofirnoflastum binds an allosteric site adjacent to NEK7’s ATP-binding pocket, induces conformational shifts, disrupts NEK7-NLRP3 binding, blocks NLRP3 inflammasome assembly, spares NEK7’s physiological functions, and suppresses caspase-1, caspase-8, NF-κB, and TNF activity. Ofirnoflastum reduces pro-inflammatory cytokine production, suppresses ASC specks, IL-1β release, pyroptotic cell death, and leukemic burden, induces apoptosis and erythroid differentiation, restores hematopoiesis, and improves outcomes in colitis models. Ofirnoflastum can be used for the research of myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

HY-173154B

NK7-902 diTFA	Degrader	99.88%
NK7-902 diTFA is a selective and orally active CRBN-dependent NEK7 molecular glue degrader with K_d values of 1.5 and 2.6 μM for hNEK7 and mNEK7. NK7-902 diTFA fully degrades NEK7 in human primary monocytes and whole blood but only partially inhibits NLRP3-dependent IL-1β production. NK7-902 diTFA shows activity in murine systems and induces a profound and long-lasting NEK7 degradation but only transiently blocks NLRP3 inflammasome activation. NK7-902 diTFA can be used for the research of inflammation, such as cryopyrin-associated periodic syndromes.

HY-175452

MRT-3486	Degrader	99.62%
MRT-3486 is a molecular glue degrader.MRT-3486 induces ternary complex formation between CRBN and predicted β-hairpin G-loop proteins.MRT-3486 is selected from an internal compound library for proximity-ligation experiments.

HY-163358

SLC3037	Inhibitor	99.85%
SLC3037 is a NLRP3 inhibitor which blocks NLRP3 from binding to NEK7 or oligomerization, inhibiting inflammasome caused by MSU and other inflammasome activators. SLC3037 can be used for research of gout, cardiovascular diseases, metabolic syndrome or neurodegenerative diseases.

HY-185311

NEK7 degrader-3	Degrader
NEK7 degrader-3 is an orally active and brain-penetrant NEK7 molecular glue degrader with a DC₅₀ of 33.1 nM. NEK7 degrader-3 mediates interaction between NEK7 and E3 ligase cereblon, promoting proteasomal degradation of NEK7 and attenuating NLRP3 inflammasome-mediated inflammatory responses. NEK7 degrader-3 inhibits caspase-1 activity, cytokine release of IL-1β, IL-1α, and IL-18, and pyroptosis-related plasma membrane permeabilization. NEK7 degrader-3 shows antiinflammatory activity in an LPS (HY-D1056)-induced neuroinflammation mouse model. NEK7 degrader-3 can be used for the research of neuroinflammation.

HY-180890

PPARγ agonist-21	Inhibitor
PPARγ agonist-21 (Compound 9a) is a PPARγ agonist with an EC₅₀ of 3.12 μM. PPARγ agonist-21 activates PPAR-γ to inhibit NF-κB and attenuate NLRP3 inflammasome assembly. PPARγ agonist-21 blocks NLRP3-ASC and NLRP3-NEK7 interaction. PPARγ agonist-21 attenuates the severity of gouty arthritis.

HY-176860

NEK7 degrader-1	Degrader	99.94%
NEK7 degrader-1 is a NEK7 molecular glue degrader with a DC₅₀ of 9  nM. NEK7 degrader-1 dose-dependently inhibits caspase-1 activity and IL-Ιβ release in macrophages in response to NLRP3 inflammasome activation. NEK7 degrader-1 can be used for autoinflammatory and autoimmune disorders like multiple sclerosis, neurodegeneraive diseases like Alzheimer's disease and cardiovascular and melabolic disorders like pericarditis and Type 2 diabetes research.

HY-174270

NLRP3-IN-79	Inhibitor	99.10%
NLRP3-IN-79 is an orally active NLRP3 inhibitor. NLRP3-IN-79 inhibits NLRP3 inflammasome with an IC₅₀ of 10.69 nM. NLRP3-IN-79 blocks NLRP3 inflammasome assembly by directly binding to NLRP3 and disrupting the NEK7-NLRP3 interaction. NLRP3-IN-79 can be used for the study of NLRP3-driven diseases model, including systemic inflammation, peritonitis, and colitis.

HY-W998347

ABS-752 hydrochloride		98.81%
ABS-752 is an orally active prodrug of CRBN-modulating molecular glue targeting. ABS-752 can effectively degrade GSPT1. ABS-752 can degrade NEK7. ABS-752 does not form ternary complexes with CRBN and the neosubstrates. ABS-752 is a prodrug activated by the monoamine oxidase, VAP-1, to an aldehyde intermediate and subsequently to the active molecule, ABT-002. ABS-752 can be used for the study of hepatocellular carcinoma (HCC).

HY-177433

NEK7 degrader-4	Degrader
NEK7 degrader-4 is a NEK7 molecular glue degrader with a DC₅₀ of 9  nM. NEK7 degrader-4 can be used for autoinflammatory and autoimmune disorders like multiple sclerosis, neurodegeneraive diseases like Alzheimer's disease and cardiovascular and melabolic disorders like pericarditis and Type 2 diabetes research.

HY-177559

NEK7 degrader-2	Degrader
NEK7 degrader-2 (Compound 25) is a NEK7 degrader. NEK7 degrader-2 shows dose-dependent NEK7 degradation ability in human PBMC-derived macrophages. NEK7 degrader-2 reduce the release level of pro-inflammatory cytokines IL-1β induced by NLRP3 inflammasome activation. NEK7 degrader-2 can be used for the study of inflammatory diseases.

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