(IC50=1.9 nM). However, 4-MA was never marketed as it showed hepatotoxicity. There is no detailed data about the cause of hepatotoxicity in 4-MA regarding SAR, but a conclusion may be drawn that the R2 group is the cause as there are other 4-azasteroid compounds containing the same R1 group as 4-MA, or CH3, without showing hepatotoxicity. Nonsteroidal The common factor in nonsteroidal 5-ARI discovery is that the first compounds were all selective inhibitors to 5α-reductase type 1 only, but were then developed in order to get dual inhibition on both type 1 and 2, since inhibition of the type 2 isozyme is a more important factor in treating the disease of BPH. Benzo(c)quinolizinones are tricyclic derivatives of 10-azasteroids. The D-ring has been removed and the C-ring substituted for an aromatic one. The first compounds developed were selective 5-alpha reductase type 1 inhibitors, but the most potent one inhibits both type 1 and 2. The fluorine atom is an important part of the structure. Benzo(f)quinolonone are also tricyclic compounds, but derivatives of the 4-azasteroid structure. The compounds that have been designed can be divided into two categories, hexahydro derivatives and octahydro derivatives. The octahydro derivatives have been proven to be more potent. Compound LY 191704, later named bexlosteride, is the most potent octahydro derivative designed. It is a selective inhibitor to the type 1 isozyme, especially because of the chlorine atom and the amino-methyl group. Piperidones are also 4-azasteroid derivatives but both B- and D-ring have been removed. The original compounds designed were type 1 selective, especially the ones containing a chlorine atom connected to the aromatic ring. By inserting a styryl group to the piperidones type 2 inhibitory activity increased. Nonsteroidal carboxylic acids are tricyclic compounds designed to resemble steroidal carboxylic acids such as episteride. As with the other nonsteroidal inhibitors, they have been designed by removing steroid ring systems. As with the piperidones, addition of a styryl group provides good dual inhibition on isozyme 1 and 2, but the nonsteroidal carboxylic acids are mostly type 1 selective. Natural products Saw palmetto extract The European Medicines Agency (EMA) has concluded that the extract of the natural product Saw palmetto can be used to treat symptoms of benign prostatic hyperplasia (BPH) as research has shown its 5-ARI effects. An extract of Serenoa repens, also known as saw palmetto extract, is a 5-ARI that is sold as an over-the-counter dietary supplement. It