NH125 is a selective inhibitor of eEF-2 with IC50 value of 60 nM [1].
Eukaryotic elongation factor-2 kinase (eEF-2 kinase or eEF-2K), also known as calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase (CaMKIII) is a highly conserved protein kinase in the calmodulin-mediated signaling pathway and plays an important role in regulating protein [1, 2].
NH125 is a potent eEF-2 inhibitor and has 1000- to >100000-fold more potent against eEF-2 compared with PKC, PKA and CamK-II. When tested with a panel of 10 cancer cell lines (C6, T98-G, U-138 MG, and so forth), NH125 treatment inhibited cell viability with IC50 value ranges from 0.7 to 4.8 μM. And NH125 decreased the cellular content of p-eEF-2 without affecting total content eEF-2 and arrested cell in G0-G1 phase in C6 glioma cells [1]. In HUVECs, NH125 treatment inhibited TNF-α-induced inflammatory responses at the dose of 1μM/L [3]. When tested with a panel of human cancer cell lines (glioblastoma, breast cancer, and so on), NH125 sensitized cells at the dose of 0.25 μM which thus reinforced the efficacy of ER stress-inducing drug by inhibiting eEF-2 [2].
In spontaneously hypertensive-SHR (10 wk old) rat model, administration of NH125 (500 μg·kg?1·day?1) for 6 weeks resulted in significant reduction SBP, reduced the increased expression of VCAM-1 and E-selectin and inhibited the increased ROS production and wall thickness in SHR [3].
It is also reported that NH125 inhibited protein kinase C (PKC), protein kinase A (PKA), and calmodulin-dependent kinase II (CamK-II) with IC50 value of 7.5 μM, 80 μM and > 100 μM, respectively [1].
References:
[1]. Arora, S., et al., Identification and characterization of an inhibitor of eukaryotic elongation factor 2 kinase against human cancer cell lines. Cancer Res, 2003. 63(20): p. 6894-9.
[2]. Cheng, Y., et al., Integrated regulation of autophagy and apoptosis by EEF2K controls cellular fate and modulates the efficacy of curcumin and velcade against tumor cells. Autophagy, 2013. 9(2): p. 208-19.
[3]. Usui, T., et al., Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation. Am J Physiol Heart Circ Physiol, 2013. 305(5): p. H756-68.
