Vorfreude ist die schönste Freude
Microcide Pharmaceuticals Announces Presentation of 24 Papers at the 40th
Annual ICAAC Conference in Toronto
Presentations by Microcide Scientists and Collaborators Highlight Scientific Progress Across
Microcide`s Targeted Antimicrobial and Targeted Genomics Programs
MOUNTAIN VIEW, Calif., Sept. 19 /PRNewswire/ -- Microcide Pharmaceuticals, Inc. (Nasdaq: MCDE - news) today announced that Microcide scientists and
collaborators will present 24 research papers at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held in Toronto, Ontario,
Canada from September 17th to 20th, 2000.
``We are extremely pleased that Microcide is again able to present on a broad range of our antimicrobial discovery and product development work in this session of
ICAAC,`` said James E. Rurka, president and chief executive officer, Microcide Pharmaceuticals. ``Our strong scientific presence at this 40th ICAAC is testimony
to the progress and productivity of our research, and underscores the deep commitment of Microcide`s scientists to the discovery and development of important new
classes of antimicrobials.``
Targeted Antibiotics -- Cephalosporins
Microcide Pharmaceuticals continues a broad research effort aimed at the discovery of new antibacterial agents effective against drug-resistant pathogenic bacteria.
The collaboration with the R.W. Johnson Pharmaceutical Research Institute (RWJPRI) earlier produced the novel cephalosporin antibiotic RWJ-54428
(MC-02,479); first described at the 1997 ICAAC, now in Phase I clinical development for use in treating problematic Gram-positive infections. RWJPRI and its
collaborators are presenting three papers on this compound in Toronto. Microcide and RWJPRI now describe, in eight papers, the discovery of a new
cephalosporin, RWJ-333441 (MC-04,546).
RWJ-333441 is a new cephalosporin antibiotic having bactericidal activity against MRS and other Gram-positive pathogens, and displaying enhanced
pharmacokinetic properties. This agent was selected from a group of structurally-related compounds after extensive evaluation of pharmacological properties,
including antimicrobial spectrum and potency, stability to beta-lactamases, pharmacokinetics in multiple animal species, and efficacy in animal models of infection. In
addition to the presentations detailing these microbiological and pharmacological studies, papers describing preparation and evaluation of prodrug derivatives of
RWJ-333441 will be presented. One of these prodrugs, RWJ-333442, was selected for advanced evaluation, and the pharmacological profiling of this agent is also
described.
Cephalosporin antibiotics are extremely well-accepted by clinicians, with over 30 years of clinical use demonstrating their safety and efficacy. However, their use for
treating Gram-positive infections has been severely compromised by the dissemination of methicillin-resistant strains of staphylococci (MRS). While the incidence of
MRS in hospitals in the U.S. has been increasing over the last three decades, more recent studies show that methicillin-resistance is increasing in isolates recovered
from patients in the community setting, particularly children. The resistance of MRS to all clinically-used cephalosporins and other beta-lactam antibiotics is due to
the microbial protein PBP2a, which unlike other PBPs involved in the synthesis of the bacterial cell wall, has very low affinity to currently-used beta-lactam
antibacterials. Microcide`s program has been directed toward discovery of cephalosporins with enhanced affinity to PBP2a. Alternative treatment choices for
physicians are limited, and reduced susceptibility of MRS to the standard drug vancomycin has been reported in the U.S.
The company`s chief scientist and senior vice president, George H. Miller, Ph.D., will co-chair the New Antimicrobial Agents -- Poster Session on Sunday,
September 17, 2000. Dr. Scott Hecker of Microcide was invited to this session to summarize the work on RWJ-333441 (MC-04-546) presented at the meeting by
our scientists.
Targeted Antibiotics -- Bacterial and Fungal Efflux Pump Inhibitors
In addition to its presentations on developments in the cephalosporin program, Microcide researchers will present seven papers on its Bacterial Efflux Pump
technology. This program focuses on Gram-negative bacteria that have developed antibiotic resistance by means of a pump-like mechanism that expels antibiotics
from the cell before lethal quantities can accumulate. Microcide is developing potentiators that inhibit this pump action, thereby enabling various antibiotics to more
effectively kill both resistant and susceptible strains of bacteria.
Scientists from Microcide and Daiichi Pharmaceutical Co., Ltd. are continuing to make progress in their efforts to enhance the activity of fluoroquinolones against
Pseudomonas. Four presentations summarize some of our work in biology, chemistry, microbiology and pharmacology with dipeptide amide efflux pump inhibitors.
In addition, three other presentations by Microcide`s scientists summarize our research efforts to identify other opportunities in this exciting field, such as potentiation
of macrolides and aminoglycosides.
The scientific knowledge and expertise gained in Microcide`s bacterial efflux pump program has led to the development of a program to inhibit efflux pumps which
are important causes of both intrinsic and acquired resistance in pathogenic fungi, including Aspergillus and Candida. Three presentations summarize experiments in
the basic biology of fungal efflux pump inhibitors, their potential in vivo efficacy and the impact of efflux pump inhibitors on the susceptibility of clinical isolates to
azoles and allylamines.
Targeted Genomics
In addition to Microcide`s Targeted Antimicrobial Programs, a second research platform for the discovery of novel agents is encompassed in the Targeted Genomics
efforts of the company. Targeted Genomics uses the principles of functional genomics to define new antibacterial and antifungal targets. Microcide has developed
proprietary genetic tools and screening methodologies that allow rapid ``gene-to-screen`` progression, defining pharmaceutically-relevant targets within the vast
collection of genes identified by microbial genome sequencing.
There are two presentations by scientists from our Targeted Genomics Programs. One of these describes studies in our Bacterial In Vivo Survival Genes (IVSG)
Program on the regulation of gene expression during the infectious process, and the other describes the use of DNA Microarrays in our Fungal Genomics Program.
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SOURCE: Microcide Pharmaceuticals, Inc.