Detecting future drugs (antibiotics)

MolScores-Antibiotics is able to detect future antibiotics. The expert system has been validated with novel antibacterial substances, which are now in clinical development.

 An expert system to identify suitable antibacterial candidates.
 

New Chemical Entities (NCE)
are recognised by MolScore- Antibiotics.
 

An expert system for finding
suitable
drug candidates.
 

 An expert system to identify suitable antiviral candidates.
 

Antibiotic or not?

More than 95% have been assigned correctly. Analysis based on
5000 compounds (independent validation data).
 

Please be aware that drug status changes and the information provided here may be outdated.
For actual and comprehensive information about current drug status or clinical trials please check on the company’s home page.
 

Pradofloxacin:

Iclaprim:

Iclaprim from Arpida Ltd. is a novel selective dihydrofolate inhibitor, which was developed by rational drug design. Injectable iclaprim has completed a Phase II clinical trial. In March 2005, Arpida received clearance from FDA to conduct Phase III clinical trials for injectable iclaprim in the USA. An oral formulation of iclaprim is in Phase I clinical trials. Arpida has completed first-in-man studies comparing oral and injectable iclaprim in healthy volunteers to determine absorption, distribution, metabolism and excretion. Iclaprim demonstrated high absorption and extensive distribution in this study. In March 2006 Arpida Ltd. announced that it has received the recommendation from an independent Data and Safety Monitoring Board to continue the Phase III clinical trials for intravenous iclaprim for the indication complicated Skin and Skin Structure Infection.

Kohlhoff SA, Roblin PM, Reznik T, Hawser S, Islam K, Hammerschlag MR. In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C. pneumoniae. Antimicrob Agents Chemother. 2004 May; 48(5):1885-6.

Schneider P, Hawser S, Islam K., Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett. 2003 Dec 1;13(23):4217-21.
 

Pradofloxacin (Bayer AG) was developed for use in animals, see Susanne Heinzl, Chemother. J. 2003; 12 : 21-20.

Der Wirkstoff Pradofloxacin, welcher sich zurzeit in der klinischen Entwicklung befindet, wurde bei den EU-Regulationsbehörden zur Zulassung eingereicht.

A-72310:

A-692345:

BAL 5788:

BAL 9141:

BAL5788 (Ceftobiprole, Basilea Pharmaceutica Ltd) is the first of a new generation of anti-MRSA cephalosporins with good activity against methicillin-resistant Staphylococcus aureus (MRSA). Ceftobiprole entered into phase III clinical trials in November 2004. BAL9141 is the active principle of prodrug BAL5788, which is water-soluble. In March 2006 Basilea Pharmaceutica Ltd. announced positive results for its first comparative phase III trial with ceftobiprole.
 
Schmitt-Hoffmann A, Nyman L, Roos B, Schleimer M, Sauer J, Nashed N, Brown T, Man A, Weidekamm E. Multiple-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin (BAL5788) in healthy volunteers. Antimicrob Agents Chemother. 2004 Jul;48(7):2576-80.
 

Peter J. Dandliker et al. from Abbott Laboratories, reported the discovery and characterisation of a novel ribosome inhibitor (NRI) class that exhibits selective and broad-spectrum antibacterial activity. The chemical structure of the NRI class is related to antibacterial quinolones, but the differences in structure are sufficient to completely alter the biochemical and intracellular mechanisms of action. Some compounds in the NRI series appear to inhibit bacterial ribosomes by a new mechanism, because NRI-resistant strains are not cross-resistant to other ribosome inhibitors, such as macrolides, chloramphenicol, tetracycline, aminoglycosides, or oxazolidinones. The NRIs are a promising new antibacterial class with activity against all major drug-resistant respiratory pathogens.

Peter J. Dandliker,  Steve D. Pratt, Angela M. Nilius, Candace Black-Schaefer, Xiaoan Ruan, Danli L. Towne, Richard F. Clark, Erika E. Englund, Rolf Wagner, Moshe Weitzberg, Linda E. Chovan, Robert K. Hickman, Melissa M. Daly, Stephan Kakavas, Ping Zhong, Zhensheng Cao, Caroline A. David, Xiaoling Xuei, Claude G. Lerner, Niru B. Soni, Mai Bui, Linus L. Shen, Yingna Cai, Philip J. Merta, Anne Y. C. Saiki, and Bruce A. Beutel Novel Antibacterial Class, Antimicrob. Agents Chemother. 2003, 47, 12, 3831.

In July 2005 Paratek Pharmaceuticals announced phase I trial of PTK0796, a new broad-spectrum antibiotic. PTK 0796 inhibits bacterial protein synthesis.

In December 2005 Theravance, Inc. announced that results with the investigational antibiotic telavancin (TD-6424), from a phase 2 clinical study in patients with complicated gram-positive skin and skin structure infections and from a phase I study in healthy volunteers, were presented at the 45th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in Washington D.C.

PTK0796 (BAY 73-6944):

Telavancin:

 

 An expert system for finding molecules with antibiotic activity.
 

Our
expert systems
are based on novel models and innovative methods in the field of drug design.
 

We use proprietary molecular descriptors and a huge amount of data and knowledge from literature to find relationships between molecular structures and biological activity.
 

The knowledge of our expert systems is used by our clients to filter large compound libraries.
 

Please be aware that drug status changes and the information provided here may be outdated.
For actual and comprehensive information about current drug status or clinical trials please check on the company’s home page.
 

Below are some examples of substances which are currently in development by various companies. New chemical entities are recognised by MolScore-Antibiotics, regardless of substance-classes, mechanism of action or molecular weight.

96% of clinical candidates have been correctly classified as antibacterial substances, which are suitable for further development into drugs.

As much as 70% of these molecules had a  prediction result between 0,9 and 1,0. This validation demonstrates the excellent prediction capability of MolScore-Antibiotics to detect antibacterial clinical candidates.

BC-1175 and BC-2901:

AC98-6446 represents of a novel class of glycopeptide antibiotics. It exhibits excellent in vitro activity against resistant gram-positive pathogens, which was also demonstrated in vivo in three different animal models of infection. It was selected for further study.

AC98-6446:

BC-1175 is a novel broad spectrum cephem-3-azomethine. It exhibited an excellent antimicrobial profile including various Enterobacteriaceae, E. faecalis, S. aureus and MRSA and was selected for further investigations.

BC-2901 is a broad-spectrum cephalosporin exhibited an excellent antimicrobial profile including various Enterobacteriaceae, Enterococcus faecalis, P. aeruginosa and S. aureus. It was selected for further development.

The glycosylated polyketide defines a new antibacterial structural class.

ECO-0501:

NXL101:

NXL101 is a novel antibacterial currently in preclinical development. The inhibitor of bacterial topoisomerase is highly active against gram positive pathogens.

NXL104 (AVE-1330A):

NXL-104  is a representative of a novel class of bridged bicyclico[3.2.1] diazabicyclo-octanones.
The compound a potent inhibitor of a wide range of beta-lactamases.
It has demonstrated, in partnership with beta-lactam antibiotics, the potential to treat drug resistant gram-negative bacteria.