ZM 39923 HCl is an JAK1/3 inhibitor with pIC50 of 4.4/7.1 and almost no activity to JAK2 and modestly potent to EGFR. ZM39923 breaks down to form the JAK3 inhibitor ZM449829 which exhibit similar IC50 values. ZM39923 decomposes in neutral buffer to afford potent inhibition of the Janus kinase 3, and could be used as a standard Jak3 inhibitor in assays where breakdown could occur. ZM39923 is reduced by 300-fold in the presence of DTT (10 mM) in inhibiting TGM2. ZM39923 is reversible inhibitors when TGM2 is incubated with inhibitors in the absence of Ca2+. ZM39923 shows significant inhibition of crosslinking activity with IC50 of 25 nM in the absence of DTT and IC50 of 10 μM in the presence of DTT. ZM39923 prevents early death in a Drosophila Melanogaster model of a polyQ repeat disorder called Machado-Joseph Disease. M39923 inhibits the generation of AICD-FLAG and both Aβ40 and Aβ42 by purified γ-secretase in a concentration-dependent fashion with an approximate IC50 of 20 μM. ZM39923 decreases photoaffinity-labeled PS1-CTF in the presense of γ-secretase.