Imatinib for the treatment of Scleroderma ?

We know that Imatinib (its mesylate salt, Novartis) is a drug used to treat certain types of cancer. It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other cancers. It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.

More over the discovery of this compound itself is interesting & its one drug obtained via, High Throughput Screening (HTS). Chemists used a HTS of chemical libraries to identify the molecule 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib. More interesting part of this drug is a recent discovery, i.e., GLEEVEC^® (imatinib mesylate) can be used to treat Scleroderma. As per the claim by the researchers, until now no drug has been shown to be effective in treating scleroderma in a clinical trial. Several years ago, a small study provided some evidence that a chemotherapy drug called cyclophosphamide may help scleroderma patients, but the benefit was minimal and this drug causes side effects including infertility and secondary cancers.

The investigators reported an interim analysis of their results, although the study is ongoing. At one year, the investigators saw a 23 percent improvement in skin scores. The researchers also saw an improvement in forced vital capacity scores by 9.6 percent and diffusion capacity scores by 11 percent in the 18 patients who had completed one year of treatment. The lung function data was really exciting,” Dr. Spiera said. “In patients with scleroderma, you usually see lung function tests getting worse over time, and if doctors try a therapy for a year and a patient doesn’t get any worse, we get pretty excited. What is amazing to me in this study is that we actually saw improvements in both lung function tests. Congrats for this remarkable achievement.....

Ref : http://www.hss.edu/newsroom_drug-provide-treatment-scleroderma.asp

Novel Mass Spectrometry Application for drug discovery?

In one of my earlier blog, Dec., 28th 2008, ( FBDD- A New Approach Of Drug Discovery) I did mention about the use of a number of biophysical techniques as screening tools including high-throughput x-ray crystallography (the advantage of giving the best picture of how the fragment sits in the target) and when paired with NMR allows you to create a structure-based lead.

With different companies approaching this new route in different ways like :

1. high-throughput x-ray crystallography
2. NMR-fragment screening
3. fluorescence polarization assay and many other interesting ways like Protien-Protein interactions etc., this field I think have important role to play.

The drug discovery field got a momentum and has lead to a new direction.....

While reading Science Daily (Online issue, Sept 21, 2009), I found this interesting (article ) and really innovative finding , which I want to share...

Preliminary studies by the researchers (Dr. Ken & Dr.Rakesh )have shown that the new mass spectrometry tool—known as MALDI-QqQMS (matrix-assisted laser desorption ionization-triple quadruple mass spectrometer)—provides a superior means of measuring the enzyme reactions critical to drug discovery at speeds comparable to currently available high-throughput screening systems at significantly lower costs. As per the claim by the researchers, Dr. Ken Greis, "If introduced broadly, the new generation mass spectrometry-based method the researchers are proposing could significantly reduce the cost of running drug compound screening assays while also saving drug development teams substantial time by improving the accuracy of data collected. As per the claim by these researchers the above mentioned methods are costly.

Dr. Ken Greis and Dr. Rakesh Rathore have developed a custom high-throughput screening method using a generalized platform. Unlike the commercially available systems that analyze byproducts and coupled reactions, their system directly measures and quantifies the substrate and the end product of the reaction. They say using mass spectrometry to measure the mass and quantity of the product gives researchers a direct measure of the assay and more reliable compounds to explore, eliminating the chances for molecular interference common with chemiluminescence and fluorescence-based systems. Its a remarkable achievement and hope in the near future we will have an automated system for commercial use with least expense. Best of luck. For More....