Tuesday, March 11, 2008

The Return of Drug Discovery

The more observant amongst you will notice that this is the first offering from Advances in Drug Discovery for a while.....in fact one year. This is not to say that there has been a lack of advances over the past 12 months. Quite the opposite and our silence has been due to the efforts that we have been placing on redesigning our main site, LeadDiscovery to better cover drug discovery.

Just a few words on what we have been up to before we continue from where we stopped this time last year.

DailyUpdates, our alert service now highlights key research and breaking news across 12 different therapeutics channels. The service is now a key intelligence tool across the pharmasphere. DailyUpdates is now supported by a monthly service, UpdatesPlus which takes a deep dive into R&D activity providing detailed analysis on selected indications or drug classes. Our portfolio of PharmaReports, in depth pharmaceutical market research and pipeline analysis reports, has expanded with over 1,000 reports now on offer. All in all we now offer insight into drug discovery at increasing levels of detail....so if you need to track a particular area of drug discovery let us help you, we can!

Anyway enough of us and onto the blog.

Todays edition of DailyUpdates covers nearly 50 key journal articles published over the past couple of weeks, a selection of trials and all the most important news. One of the journal articles that we would like to highlight here looks at the therapeutic potential of AT-101 which is featured in a paper highlighted on DailyUpdates-Oncology.

Cottoning onto apoptosis...

Ascenta Therapeutics' AT-101 is an enantiomer of gossypol, a natural product of cotton. The molecule is an orally active inhibitor of the Bcl-2 family of anti-apoptotic proteins and is in Phase 2 cancer trials in a number of oncology indications.

Apoptosis, or programmed cell death represents a pathway targeted by multiple oncology therapeutic candidates. The Bcl-2 proteins (Bcl-2 stands for B-cell lymphoma) comprise the best known anti-apoptotic group. Proteins from this family are frequently over-expressed in cancer making the cells resistant to death signaled by natural or therapeutic stimuli. There are at least five well characterized members of the Bcl-2 family: those most implicated in cancer progression and resistance to conventional therapies are Bcl-2, Bcl-XL and Mcl-1. Over-expression of anti-apoptotic members of the Bcl-2 family are observed in the majority of Non-Hodgkin's lymphomas (NHLs) , contributing to intrinsic and acquired drug resistance. Since AT-101, inhibits each of these proteins there is strong proof of concept to support the development of AT-101 as a treatment of NHL.

NHL is the most common hematological malignancy and is comprised of around 30 different disease subtypes. Each of these present with a distinct set histological, genetic and clinical characteristics. Treatment options in NHL include chemotherapy, targeted therapies, stem cell transplantation and radiotherapy (see our recent feature Non-Hodgkin's Lymphoma - Is there room to emulate Rituxan's success?)

Rituxan-based regimens constitute the mainstay of first-line treatment options in several NHL subtypes. There is however a lack of consensus over the treatment of relapsed and refractory disease in most NHL subtypes. Refractory patients are poorly served by currently available treatment options. Consequantly the NHL late-phase pipeline is relatively active, with 10 Phase IIII drugs and 46 Phase II drugs.

In their upcoming paper in the journal Blood, Paolluzi et al characterize AT-101, one of these phase II candidates in B cell lymphoma. The IC50 for AT-101 was reported to be between 1 and 10 microM for a diverse panel of B-cell lymphomas. In a mouse model of drug resistant B-cell lymphoma, 35 mg/kg/day of AT-101 was safe and efficacious. The addition of AT-101 to cyclophosphamide and rituximab in a schedule-dependent manner enhanced the efficacy of the conventional therapy.

These data support the open-label, phase II trial of 52 NHL patients comparing rituximab with AT-101 and rituximab which commenced in the US in 2006.

LeadDiscovery currently featured 24 market research reports analyzing various aspects of NHL (click here for listing) and nearly 300 journal article selected for their importance to drug discovery (click here for listing). Interested readers can view our entire oncology portfolio here


Post a Comment

<< Home