The Bcl-2 antibody database covers a family of at least 25 proteins, which may be either pro or anti-apoptotic. Proteins from the two groups interact to regulate apoptosis, inhibition of which can lead to cancer. We have a large catalog of Bcl-2 antibodies, which are widely used in cancer research.
The interplay between the different Bcl-2 proteins, and the way in which they influence mitochondrial porosity, is of great interest to clinical researchers, both in developing novel cancer therapies, and combating resistance to drugs. Antibody studies have confirmed that over-expression of anti-apoptotic Bcl-2 proteins is one way in which tumours acquire chemotherapy resistance. Many research groups are therefore working to develop Bcl-2 inhibitors, using an anti-sense approach.
Antibody research has shown that the pro and anti-apoptotic Bcl-2 proteins antagonise each other in a heterodimeric manner. It has also been proposed that homodimerisation occurs within the two subfamilies. This has been used as a base to develop small-molecule Bcl-2 antagonists, which act as monomeric modulators at Bcl-2 domains to combat anti-apoptotic activity.
In 2007, Wang et al used Bcl-2 antibodies to develop a series of BH3I-1based dimeric inhibitors. These showed enhanced binding activity
against anti-apoptotic Bcl-2 proteins, and also enhanced mitochondrial cytochrome c release, when compared to their monomeric counterparts. This suggested dimerisation of monomeric modulators as a possible way to enhance Bcl-2 antagonistic activity.
A number of Bcl-2 inhibitors are now being developed for clinical use. These include Oblimersen (trade name Genasense), an anti-sense oligonucleotide which is at the final stage of clinical trials. As well as being a cancer therapy in its own right, it could also increase cellular sensitivity, improving the outcome of existing chemotherapy treatments.
Although no Bcl-2 inhibitors have received FDA approval to date, antibody suppliers are confident that a breakthrough is on the horizon. We at Novus Biologicals have an extensive antibody catalog covering apoptosis and cancer research.