Table 1.

Drugs and inhibitors of NEK family members.

Drug Name	Chemical Formula	NEK Targets	Action/Effects	Stage of Development	Selectivity	References
Fostamatinib	C23H26FN6O9P	NEK1 NEK3 NEK4 NEK5 NEK9 NEK11	Inhibits signal transduction by Fcγ receptors involved in the antibody-mediated destruction of platelets. NEKs 1,2,3,4 5,9,11 are included in the list of targets	Approved for the treatment of chronic immune thrombocytopenia (ITP). Under investigation for other diseases	The active metabolite of fostamatinib, named R406, presents a lack of selectivity among several kinases	[203]
5-[(Z)-(5-Chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene) methyl]-N,2,4-trimethyl-1H-pyrrole-3-carboxamide	C17H16ClN3O2	NEK2	Interacts with NEK2	Experimental	No off-targets have been described	[204]
NCI code 51,525 and 58991	-	NEK2	Inhibits NEK2	Experimental	No off-targets have been described	[205]
MBM-17 and MBM-55	C28H29N6 and C28H28N6O2F respectively	NEK2	Inhibits NEK2 and has antiproliferative/antitumor properties	Experimental	It has low nanomolar activity and a great selectivity for NEK2	[206]
di-demethylchlorpromazine and 2-[5-fluoro-1H-indol-3-yl] propan-1-amine	C15-H15-Cl-N2-S.Cl-H and C11H14ClFN2 respectively	NEK2	Inhibits NEK2	Pre-experimental (in silico)	No off-targets have been described	[207]
(5Z)-2-hydroxy-4-methyl-6-oxo-5-[(5-phenylfuran-2-yl)methylidene]-5,6-dihydropyridine-3-carbonitrile) or compound 8	C22H24F3N8O2	NEK6 NEK1	Inhibits NEK6. Displays anti-proliferative effects on several cancer cell lines with low IC50 values. Induces cell cycle arrest in the G2/M phases and has a synergistic effect with cisplatin and paclitaxel in ovarian cancer. It can inhibit NEK1.	Experimental	Inhibits NEK6 and NEK1. No off-targets have been described	[208]
Metformin	C4H11N5	NEK7	Metformin inhibits NEK7 expression in an experimental diabetic periodontitis model	Approved for type II diabetes	Activates AMPK, inhibits electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH), and glycerol-3-phosphate dehydrogenase [NAD(+)] (GPD1)	[175,209,210,211]
Ethyl 1-(2-hydroxypentyl) 5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate or GeGe3	-	NEK10	Screening for GeGe3-targeted kinases revealed NEK10 as candidate targets, such as Aurora B. Inhibits physiological and tumor angiogenesis.	Experimental	Strongly inhibits aurora B, aurora C, NEK 10, polo like kinases 2 and 3 (PLK2/PLK3), dystrophia myotonica protein kinase 1 (DMPK), and calcium/calmodulin-dependent protein kinase type 1 (CaMK1)	[212]
Dabrafenib	C23H20F3N5O2S2	NEK11	Reduces the proliferation and regression of tumors in xenograft models.	Approved for the treatment of metastatic melanoma with BRAF V600E mutations	Inhibits serine/threonine-protein kinase B-raf (BRAF1), proto-oncogene c-RAF (RAF), serine/threonine-protein kinase SIK1 (SIK-1), NEK11, and LIM domain kinase 1 (LIMK-1)	[213,214]