Enoyl reductase: One target, Two major Global Threats

Tuberculosis and Malaria are two major global threats; both account for 5 million deaths annually (mostly in developing countries). Despite the worldwide ravages of Tuberculosis and Malaria, chemotherapeutic regimens against these two diseases have remained largely unchanged. There is an urgent need to develop novel, effective, and affordable drugs to treat both diseases because the resistance has developed or is developing to existing therapy. Scientists around the world are seeking new ways to combat the two opportunistic pathogens.

Mycobacterium tuberculosis and Plasmodium Falciparum are causative agents of tuberculosis and malaria, respectively. Both organisms share enzymatic components of the type II fatty acid biosynthetic pathway (FAS-II). Enoyl acyl carrier protein reductase (ENR) is one of the key type II enzymes, has been repeatedly validated as an effective antimicrobial target (e.g., INH, diazoborines, triclosan, and thiolactomycin).

Triclosan, the ENR inhibitor, showed excellent activity against both organisms. Targeting ENR  with a new class of compounds may yield new drugs against these devastating pathogens.

The Future of Drug Discovery

 The new technologies promise to fill drug development pipelines with small-molecule candidates unfulfilled, so the pharmaceutical industry is currently undergoing rapid changes. They are moving aggressively into large molecule (biologics) drug development.

"Drug space” that is not part of the current drug development includes non-Lipinski NCEs, nanomedicines, nucleic acid-based drugs, etc. will include in the future. One of the major challenges for a medicinal chemist is to find small molecule inhibitors for protein-protein interactions.

Toxicophores Simplified

Toxicophore is a portion of a chemical structure (molecular functionalities) responsible for the toxic properties of a pharmacologically activity compound. Medicinal chemists study toxicophores to predict and replace the potential reactive moieties in the early drug development process to avoid the drug candidate's later-stage failure. A simplified version of the toxicophores is attached here.

Bottom of the pyramid

Indian patients no longer have to wait for the drug to become generic. Recently BMS and Astra Zeneca launched their new oral pill Saxagliptin (DDP 4 inhibitors ) to treat type 2 diabetes in India, less than one year after its US approval. India is the first Asian country where the drug is available at an affordable price which is 1/5 of its US cost.

Pharma Companies now realize that there is tremendous opportunity in emerging markets, not only because they entail low operating costs but also because of the fast-growing middle-class population; they are emerging as a huge market for global products. As the economy grows lifestyle associated diseases grow along with it. Therefore companies try to launch drugs for these lifestyle-related diseases such as diabetes. Forecasts suggest 50% of business will be in those markets by 2020. Acquisition of Daichi to Ranbaxy and Abbot by Piramals makes it clear that big pharma companies want to make a strong market presence in India.

“Rather than trying to find a use for approved medicines that were developed for a non-Asian phenotype, the move is to discover and develop medicines specifically to treat Asian diseases,” explains Paul Bolno, VP of Oncology R&D, Business Development at GSK. Here is a Nature article

However, it will take a long time for the local doctors here in India to stop giving the pills without any label and any expiry dates on them. (pic; a local hospital gave me these medicines for a mild fever, you have to remember the tablets by its color).

PhD fellowships

Faculty of Pharmaceutical Sciences, University of Copenhagen, announces that eight Ph.D. fellowships will be available from 1 October 2010. You can read more about it here.