Open access chemical probes for epigenetic targets

نویسندگان

  • Peter J Brown
  • Susanne Müller
چکیده

BACKGROUND High attrition rates in drug discovery call for new approaches to improve target validation. Academia is filling gaps, but often lacks the experience and resources of the pharmaceutical industry resulting in poorly characterized tool compounds. DISCUSSION The SGC has established an open access chemical probe consortium, currently encompassing ten pharmaceutical companies. One of its mandates is to create well-characterized inhibitors (chemical probes) for epigenetic targets to enable new biology and target validation for drug development. CONCLUSION Epigenetic probe compounds have proven to be very valuable and have not only spurred a plethora of novel biological findings, but also provided starting points for clinical trials. These probes have proven to be critical complementation to traditional genetic targeting strategies and provided sometimes surprising results.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Chemical probes targeting epigenetic proteins: Applications beyond oncology

Epigenetic chemical probes are potent, cell-active, small molecule inhibitors or antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, ...

متن کامل

Epigenetic chemical probes.

Epigenetic control of gene expression occurs at two distinctlevels: DNA methylation and histone modification. Over thepast 10 years, the discovery of epigenetic targets has acceleratedto the point where more than 400 domains have beenidentified that are involved in either DNA methylation, themodification of histones (and some nonhistones), or translationof these modifications into changes in ge...

متن کامل

Epigenetic targets and drug discovery: part 1: histone methylation.

Dynamic chromatin structure is modulated by post-translational modifications on histones, such as acetylation, phosphorylation and methylation. Research on histone methylation has become the most flourishing area of epigenetics in the past fourteen years, and a large amount of data has been accumulated regarding its biology and disease implications. Correspondingly, a lot of efforts have been m...

متن کامل

Chemical genetics approaches for selective intervention in epigenetics

Chemical genetics is the use of biologically active small molecules (chemical probes) to investigate the functions of gene products, through the modulation of protein activity. Recent years have seen significant progress in the application of chemical genetics to study epigenetics, following the development of new chemical probes, a growing appreciation of the role of epigenetics in disease and...

متن کامل

Targeting Low-Druggability Bromodomains: Fragment Based Screening and Inhibitor Design against the BAZ2B Bromodomain

Bromodomains are epigenetic reader domains that have recently become popular targets. In contrast to BET bromodomains, which have proven druggable, bromodomains from other regions of the phylogenetic tree have shallower pockets. We describe successful targeting of the challenging BAZ2B bromodomain using biophysical fragment screening and structure-based optimization of high ligand-efficiency fr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2015