Conference Reports
236th American Chemical Society Conference
Philadelphia,
17-22 Aug 2008
Located in the heart of Philadelphia, the Pennsylvania Convention Center was the setting for the 236th American Chemical Society National Meeting and Exposition. Just a stone's throw from the world-famous Comcast Center, 13,805 attendees from the worlds of chemistry, pharmaceuticals and academia gathered to hear the latest trends and developments from their respective fields.
The highlight of the meeting, the National Exposition held from 18-20th August, introduced attendees to a record 355 exhibiting companies from various fields. Aside from this, numerous oral presentations allowed attendees to hear about key developments as companies outlined their product portfolios and technologies. Evening poster sessions featured developments from numerous sources ranging from big Pharma to academic institutions, offering something for every interest. In the medicinal chemistry division, subject areas were covered ranging from the treatment of neurological disorders including schizophrenia to treatments for pain, Type II diabetes, osteoporosis and obesity.
The oral presentations were a dominant feature of the conference, with pharmaceutical companies presenting pipeline updates and licensing opportunities. In one of many informative presentations, Wyeth introduced data on two of its compounds, PSI-421 and PSI-697. PSI-697 is a compound from a first-generation series of P-selectin inhibitors, under development for the treatment of ocular scleritis, and is currently in Phase I trials. PSI-421 is the lead in Wyeth’s second generation P-selectin inhibitors for the treatment of inflammatory vascular disorders, including atherosclerosis and deep vein thrombosis (DVT), and is currently in preclinical development. In a balloon occlusion model of DVT, PSI-421 given 3 days pre- and 6 days post-occlusion significantly increased lumen patency compared to the low molecular weight heparin, enoxoparin.
Pfizer also provided an update on compounds in its pipeline, including PF-4217903 and PF-4254644. PF-4217903 is a selective ATP-competitive c-Met kinase inhibitor, under development for the treatment of cancer. It has shown antitumour activity in preclinical models, with inhibition of c-Met phosphorylation and c-Met-dependent cell proliferation. In a GTL- 16 model, it showed both in vitro and in vivo selectivity, good predicted pharmacokinetic properties, and a good safety margin. Another c-Met inhibitor, PF-4254644 was also discussed. Also under development for the treatment of cancer, PF- 4254644 has previously shown nanomolar potency against c- Met in both in vitro and in vivo studies, also demonstrating good oral pharmacokinetics.
In addition to the many presentations of clinical and preclinical results, AstraZeneca gave details of AZ-11657312, a purinoreceptor P2X7 antagonist for the treatment of arthritis. Although in preclinical trials it did not have any activity in reducing swelling, pain sensations were reduced, cartilage was preserved and radiological outcomes were improved. A series of glutamate racemase inhibitors for the treatment of Helicobacter pylori infections and a series of myriocin derivatives for the potential treatment of cardiometabolic syndromes, including atherosclerosis and Type II diabetes were also featured.
Bristol-Myers Squibb featured highly, once again, presenting a plethora of preclinical and clinical results for many of its presented products. Notably, BMS-606056 was presented as a highly potent and effective growth hormone secretagogue for use in the treatment of osteoporosis, cancer cachexia and HIV wasting disease. BMS-694153, a CYP3A4 inhibitor was also reported as a potential treatment for migraine.
GlaxoSmithKline detailed its lead in a series of glycine transporter 1 inhibitors: GSK-931145 for schizophrenia and GSK- 982, an opioid antagonist for the treatment of obesity. Both products were in animal studies and early signs suggested potency. Lexicon reproduced a large amount of data on its deoxycytidine kinase inhibitor, LP-661438, which has potential for use in cancer, immunological disorders and viral infections.
A prominent feature of this year’s meeting was the evening poster sessions, providing an intriguing mix of posters from pharmaceutical companies and academic institutions. Two giants from the world of big Pharma, Merck & Co and Boehringer Ingelheim, presented interesting insights into their early-stage products. Merck introduced its dual orexin antagonist programme for the treatment of insomnia. Compounds in the series have been shown to be potent and brain penetrant. In EEG-implanted rats, the lead compound reduced active wake by 2.5 hours, and produced an increase in REM sleep at 2.5 hours post-dose. Boehringer Ingelheim outlined data from its novel series of Pim-2 kinase inhibitors, for the treatment of inflammatory diseases. Pim kinases play an important role in cell survival, and elevated Pim-2 is associated with inflammatory conditions such as inflammatory bowel disease (IBD). The compounds are currently at the hit-to-lead stage.
In closing, the 2008 Fall ACS once again encompassed a broad spectrum of promising therapies in a multitude of disease areas. A great deal of presentations also declared the importance of ensuring the ongoing education of research scientists and the important role for chemical drugs, alongside the popular biotechnologies which are currently receiving the majority of media attention.
Jonathan Stephens & Rebecca Bridge
Pharmaprojects Analysts
