Spermine oxidase (SMOX) is a highly inducible enzyme. Specifically, its imbalance can change polyamine homeostasis. SMOX, spermine spermidine acetyltransferase (SSAT), and acetyl polyamine oxidase (APAO) are the main enzymes regulating the reverse transformation of polyamines. Besides, SMOX and SSAT are highly inducible, but APAO is constitutively expressed. SMOX is a FAD-dependent enzyme that is part of the polyamine interconversion cycle. It is located in the cytoplasm and nucleus of mammalian cells. Moreover, it is a key enzyme in polyamine catabolism and plays an important role in maintaining polyamine homeostasis. Furthermore, SMOX selectively oxidizes spermine to produce spermidine and reactive oxygen species hydrogen peroxide (H2O2) and aldehyde 3-aminopropionaldehyde (3-AP). These may lead to cell damage and pathological changes. Meanwhile, 3-AP produced by SMOX is spontaneously transformed into a highly active unsaturated aldehyde, called acrolein. Acrolein is highly toxic and an effective medium for oxidative damage.
Nonetheless, SMOX is relevant to neurodegenerative diseases. SMO is relevant to the etiology of drug response, cell apoptosis, response to stress stimulation, and several pathological conditions, including cancer. Particularly, SMO substrate Spm is a tetramine, which plays an important role in a variety of cell functions. For example, DNA synthesis, cell proliferation, regulation of ion channel function, cell signal transduction, nitric oxide synthesis, and inhibition of immune response. Here, we will introduce an inhibitor of SMOX, JNJ-9350.
JNJ-9350 is an inhibitor of Spermine Oxidase (SMOX).
First of all, JNJ-9350 is an inhibitor of SMOX with an IC50 value of 0.01 μM. Importantly, JNJ-9350 also inhibits polyamine oxidase (PAO) with an IC50 value of 0.79 μM. Obviously, JNJ-9350 has the potential for the research of cancer.
In the second place, JNJ-9350 (0-100 μM) shows an inhibitory effect on SMOX, PAO, and LSD1 with IC50 values of 10 nM, 790 nM and ＞60 μM, respectively. In particular, JNJ-9350 (1.1-70 µM) binds with SMOX with a Ki value of 9.9 nM.
All in all, JNJ-9350 is an inhibitor of SMOX.