This web page was produced as an assignment for Genetics 677, an undergraduate course at UW‐Madison.
The PubChem
The PubChem enables users to find small molecules or drugs that are related to a certain gene product. Entering "BLM" in the PubChem BioAssay search engine, there were 50 results returned; however, there was a few that I think are highly related to BLM protein: qHTS Validation Assay for Inhibitors of Bloom's syndrome helicase (BLM), qHTS Assay for Inhibitors of Bloom's syndrome helicase (BLM), and qHTS Confirmation Assay for Inhibitors of Bloom's syndrome helicase (BLM). In fact, for each of the Bio-assay, there are at least 30 bio-active compounds that have been tested to target Bloom Syndrome protein (BLM). Instead of listing all, I decided to show the structure of one bio-active compounds from each assay. See below for the small molecules' structure. Also, I showed the conserved domains of BLM helicase targeted by the small molecules.
qHTS Validation Assay for Inhibitors of Bloom's syndrome helicase (BLM)
There are 30 compounds found in this assay. Shown below is Tyrphostin AG 528
qHTS Assay for Inhibitors of Bloom's syndrome helicase (BLM)
There are 673 compounds found to be active in this assay. Shown below is 1 of the 673 compounds- MLS001139223
qHTS Confirmation Assay for Inhibitors of Bloom's syndrome helicase (BLM)
There are 83 compounds are found in this assay. Shown below is CGC00164568-01
Target Protein- BLM Helicase
Figure 4. The red triangles indicate where the small molecules bind to in the BLM protein. The small molecules are designed to bind mostly to the helicase core of the BLM protein, which comprised of DEAD box helicase domain and helicase C-terminus domain. Until now, it seemed like there is no small molecule that is developed to target to the BDHCT, RQC, and HRDC domains.
Analysis
The fact that as many as 673 bio-active compounds inhibiting BLM helicase were found through one of the assays indicates that BLM protein has been extensively studied. Instead of working as drugs to cure Bloom's Syndrome, these compounds are used to inactivate BLM helicase. Since the development of Bloom's Syndrome is due to non-functional BLM protein, small molecules that inactivate BLM are not effective as drugs. Instead, these molecules are mainly used to manipulate the BLM protein in experiments trying to better understand Bloom's Syndrome.
References:
1) The PubChem