Background: Many bacteria synthesize spermidine but lack orthologues of polyamine biosynthetic enzymes S-adenosylmethionine decarboxylase and spermidine synthase. Results: An alternative spermidine biosynthetic pathway is essential in Campylobacter jejuni. Conclusion:The alternative route via carboxyspermidine is the dominant pathway in the human gut microbiota and deep sea hydrothermal vents. Significance: A multiplicity of polyamine biosynthetic pathways exist, providing novel targets for development of antimicrobial drugs.

Indication Target/marker/ pathway Summary Licensing status Publication and contact information Neurology Parkinson's disease (PD) Dopamine D3 receptor An SAR study characterized a series of heterocyclic analogs of 7-{[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol as dopamine D3 receptor agonists that could help treat PD. The most potent compound had a K i value of 0.92 nM and exhibited higher selectivity for the D3 receptor than for the D2 receptor. In a rat model of PD, the compound inhibited parkinsonian-like movements for up to 10 hours. Ongoing in vitro and in vivo studies are investigating the neuroprotective activity of the most potent compound. Boehringer Ingelheim GmbH and Pfizer Inc. comarket Mirapex pramipexole, a dopamine D2 and D3 receptor agonist, to treat PD. GlaxoSmithKline plc markets Requip ropinirole, also a dopamine D2 and D3 receptor agonist, for PD. Patented by Wayne State University; available for licensing Biswas, S. et al.

A bicyclam-based biodegradable polycation with CXCR4 antagonistic activity was developed with potential for combined drug/gene cancer therapies. The dual-function polycation prevents cancer cell invasion by inhibiting CXCL12 stimulated CXCR4 activation, while at the same time efficiently and safely delivers plasmid DNA into cancer cells.