Submit Chemical Probes Targeting BCL2 or Bromodomain Proteins Today!

The Chemical Probes Portal is excited to announce a growth campaign focusing on the Bromodomain and BCL2 family proteins. These classes of proteins are known to contain important drug targets, particularly for cancer, and have seen a lot of chemical probe activity.

Bromodomains are epigenetic proteins that ‘read’ information conveyed through chromatin modifications by binding to acetylated histones. Through the recruitment of protein partners, these proteins impact gene expression.

BCL2 proteins regulate apoptosis, and inhibitors typically mimic the BH3 domain. There have been many compounds reported in the literature that bind the BH3 domain in vitro but that do not behave as a BH3 mimetic in cells or that act through an alternate mechanism in cells (e.g., activation of NOXA). We are looking for bona fide cellular BH3 mimetics.

BH3 mimics should mimic the BH3 domain of a pro-apoptotic BCL2 family member, bind with high affinity to the pro-survival BCL2 proteins, induce BAX/BAK-dependent apoptosis, induce cytotoxicity that is correlated with cellular BCL2 protein levels, and should trigger specific biomarkers in animal or ex vivo models (see below) (Soderquist & Eastman, 2016; Lessene et al., 2008).

  • BCL2 inhibitors induces rapid (<6 hours) apoptosis in CLL cells ex vivo.
  • BCLXL inhibitors induces rapid apoptosis in platelets.
  • MCL1 inhibitors decrease its degradation, thereby leading to its rapid accumulation.

We are currently working to identify the best available chemical probes that target proteins in these two important classes. We are also looking to identify any compounds that are not suitably selective or active in cells but that are commonly misused as probes (Historic compounds).

If you’ve generated a chemical probe for a Bromodomain or BCL2 protein, please submit it.

If you know of an excellent probe, please nominate it.

If you know of a historic compound, please let us know about it.

All submissions and nominations can be submitted to the Portal here.

Submit your probes and nominations as soon as possible so we can share helpful information about this important target class with our users in the coming weeks.

 

This week we also published new probes:

GSK481 (RIPK1)

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