NCT-504 is a selective allosteric inhibitor of PIP4Kγ, with an IC50 of 15.8 μM. NCT-504 is potential for the research of Huntington's disease[1].
NCT-504 dose not impair the intrinsic ATP-hydrolytic activity of PIP4Kγ in the absence of PI5P substrate[1].NCT-504 does not inhibit PIP4Kbeta and weakly inhibits PIP4Kalpha phosphorylation of PI5P [1].NCT-504 dose not inhibit PIP4Kbeta or PIP4Kalpha (IC50 between 50 μM and 100 μM) at 50 μM concentration[1].NCT-504 elevates the levels of PI(3,5)P2, PI3P and PI5P in MEFs[1].NCT-504 (10 μM; 12 hours) does not affect cell viability in MEFs[1].NCT-504 (5 μM, 10 μM; 2 hours, 6 hours) elevates both the induction of autophagy as well as the rate of turnover of autophagic cargo[1].NCT-504 treatment causes a robust increase in the formation of autolysosomes with only a modest elevation in autophagosomes[1].NCT-504 increases autophagy flux and decreases huntingtin protein in 293A cells[1].NCT-504 reduces mHtt protein levels in immortalized striatal cells from knock-in HD mice[1].
[1]. Ismael Al-Ramahi, et al. Inhibition of PIP4Kγ Ameliorates the Pathological Effects of Mutant Huntingtin Protein. Elife. 2017 Dec 26;6:e29123.