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Posts Tagged → Elan

Drug Candidate Structures Revealed At #ACSAnaheim

1PM Pacific: There’s one hour left before chemists will pack a ballroom in Anaheim to see potential new drugs’ structures unveiled for the first time. Watch this space for updates.

2:39PM Pacific: CEP-26401
This drug candidate now has a name: irdabisant
company: Cephalon
meant to treat: deficits in cognition and/or attention in diseases such as Alzheimer’s and schizophrenia
mode of action: inverse agonist of histamine H3 receptor, which regulates several neurotransmitter pathways involved in cognition, attention, memory
medicinal chemistry tidbits: Cephalon’s goal was to bring a high quality compound to the clinic to define the utility, if any, of H3 antagonists for these indications. The team studied compounds in this area that failed. Among the things they learned was that several adverse events could be tied to drug candidates’ lipophilicity. So the team prioritized lipophilicity and other such characteristics in its discovery workflow. status in the pipeline: completing Phase I in the beginning of April 2011, advancing to Phase II
structure coming soon!
UPDATED 3/29 with structure:


3:16PM Pacific: BMS-663068
company: Bristol-Myers Squibb
meant to treat: HIV
mode of action: inhibits HIV attachment to host cells by binding to the viral envelope gp120 protein and interfering with its attachment to host CD4 receptors
medicinal chemistry tidbits: potency and getting the drug candidates to reach the bloodstream efficiently were key. Replacing a methoxy group on with heterocycles, such as triazoles, gave a big boost in potency.
status in the pipeline: Completed Phase IIa clinical trials. Phase IIb studies are planned for later this year.


4:24PM Pacific:LX1031
company: Lexicon
meant to treat: irritable bowel syndrome
mode of action: blocks a subtype of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, in the gut.
medicinal chemistry tidbits: Lexicon started their medchem program with an open mind. They could have made a molecule that was exquisitely selective for the subtype of tryptophan hydroxylase in the gut, they could avoid hitting the other subtype by making their molecule stay out of the brain, or both. They ultimately ended up using the latter strategy, making molecules slightly on the heavy side (above 500 or 550 molecular weight) and adding groups like a carboxylic acid, that tend to keep things out of the brain.
status in the pipeline: Completed Phase IIa clinical trials.

5:30PM Pacific: MK-0893
company: Merck
meant to treat: type 2 diabetes
mode of action: blocks the receptor for the hormone glucagon. Glucagon is released by the pancreas in response to falling glucose levels.
medicinal chemistry tidbits: Merck kept several chemical scaffolds in play during this research program. But the team’s big breakthrough was adding a methyl group to the benzylic position of a promising compound, which greatly improved potency. This methyl group strategy hadn’t worked for previous compound series, but the team revisited it anyway.
status in the pipeline: Completed some Phase II trials, according to clinicaltrials.gov

company: Elan
meant to treat: Alzheimer’s disease
mode of action: blocks gamma-secretase, a key enzyme in the production of amyloid-beta, the peptide behind the plaques that mar Alzheimer’s patients’ brains.
medicinal chemistry tidbits: Adding a cyclopropyl group and a trifluoromethyl group enhanced molecules’ metabolic stability.
status in the pipeline: discontinued because of adverse liver side effects unrelated to its mode of action.

5:31PM Pacific: That’s all for now, folks. I hope to update with more structure information later. Watch for my full story on this symposium in a mid-April issue of C&EN.

First Time Drug Disclosures at #ACSAnaheim

Medicinal chemists, it’s that time of year once again. Time for the ACS National Meeting, and the accompanying symposium where drug companies reveal the structures of drug candidates in clinical trials for the first time. I’ll be on the ground in Anaheim and will be posting from that session (which lasts from 2PM-5PM Pacific Sunday the 27th) and others. Here is the Anaheim Division of Medicinal Chemistry program (pdf).
And here is the list of disclosures:

  • Discovery and characterization of CEP-26401: A potent, selective histamine H3 receptor inverse agonist: R. Hudkins, Cephalon
  • Discovery of BMS-663068, an HIV attachment inhibitor for the treatment of HIV-1: J. Kadow, Bristol-Myers Squibb
  • Discovery and development of LX1031, a novel serotonin synthesis inhibitor for the treatment of irritable bowel syndrome: A. Main, Lexicon
  • Discovery of MK-0893: A glucagon receptor antagonist for the treatment of type II diabetes: E. Parmee, Merck
  • Discovery of ELND006: A selective γ-secretase inhibitor: G. Probst, Elan

Another Week in Pharma Job Cuts

This week brought a stream of bad news on the pharma job front, with at least four companies announcing substantial cutbacks. Worse, scientists were the main target for layoffs at three of those companies—Sanofi-Aventis, Arena, and Elan. As everyone’s favorite employment watchdog Chemjobber commented on an In the Pipeline post about cuts at Abbott: When, when, when will it stop? Here’s a look back at the news from this week:

–Sanofi is shedding 90 research jobs at its Bridgewater, N.J., site as part of “the evolution of the R&D portfolio towards more biologic-based therapies,” the company told C&EN. The French pharma firm is ceasing chemical library and chemical development activities, including pharmaceutical development and analytical science. Meanwhile, discovery-stage laboratory activities within several groups, including Lead Identification Technologies, Structure, Design & Informatics, and Analytical Sciences, will be reduced.

Some people will be shifted over to the company’s Molecular Innovative Therapeutics group, which will be transformed into “a cluster of small multidisciplinary biotechs with specialized expertise in key diverse therapeutic approaches.” This new approach sounds an awful lot like what GlaxoSmithKline has been doing over the last two years—creating smaller, more independent units in the hopes of mimicking the culture and innovative spirit of small biotechs.

–Arena Pharmaceuticals is cutting 25% of its staff, or 66 employees, by the end of March. The move isn’t unexpected. Last fall, FDA gave the San Diego-based biotech a thumbs down for its obesity drug lorcaserin based on concerns that it had caused tumors in rats. Now, FDA is asking for a slew of new data, meaning Arena will be unlikely to refile its application for approval until 2012, analysts say. See here and here for more on its lorcaserin trials and tribulations.

–Abbott is slashing 1,900 jobs in the U.S., mirroring layoffs it made last year in Europe following its acquisition of Solvay Pharmaceuticals. The cuts will come from its commercial and manufacturing operations, with over half the job losses concentrated in Northern Illinois. In a conference call, Abbott CEO Miles D. White blamed the restructuring on several factors: the slow recovery of the global economy, costs associated with healthcare reform, European pricing pressures, and a harsher regulatory environment that has made it tough for drugs to get approved.

–And last but not least, Elan has laid off 10% of its staff, or about 130 workers, with its R&D site in South San Francisco most heavily impacted. Researchers accounted for about half of the job losses.

If we’ve missed any layoffs that chemists should be aware of, drop us a note or leave a comment.