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.

Kinase Inhibitors: beyond Oncology

We recently published a paper in Bioorganic and Medicinal Chemistry, targeting Interleukin-2 inducible T-cell kinase (ITK) for treating Asthma. 

Protein kinases are prime targets for anticancer therapies, but achieving specificity for a particular kinase is challenging because of their close structural similarities. This leads to unwanted side effects, and the toxic outcome may also be due to the result of tissue distribution of kinase inhibitors. Imatinib has been highly successful in treating both chronic myelogenous leukemia, gastrointestinal stromal tumors, and other cancers but is associated with severe cardiotoxicity. Toxicity may be of less concern with oncologic kinases; what about non-cancer indications? Emerging clinical evidence (Nature Drug Discovery) of oral kinase inhibitors other than cancer shows that kinases could effectively inhibit the number of inflammatory pathways.

Almost all the p38MAPK inhibitors having hepatotoxicity issue. For example, SCIO 469 and Arry 797 initially developed for RA but went into the clinic for post operative dental pain; here, the potential toxicity problems will not show up because the drugs are used only for a very short time. Are BMS-582949 and VX 702 still in development? Different companies have spent hundreds of millions on P38 with nothing to show at the end.

Tasocitinib may be the first kinase inhibitor (JAK3) for non-oncology indication and the first oral DMARD for RA in a decade if it successfully completes Phase III clinical trials.