MOBIO Member Highlight
4340 Duncan Avenue
BioGenerator Labs, Suite 222 Louis, MO 63110
support@arraybridge.com
Array Bridge is a US-based privately owned preclinical stage biotech company. For the first several years, Array Bridge was focused on the development of products for the biotech industry, more than 100 products were developed and supplied to many of the leading pharmaceutical companies. Array Bridge also set up an effective distributor network and license arrangements for the products and services. Today Array Bridge has a solid and steady revenue-generating business with a diverse customer base.
For the past 6 years, Array Bridge is developing a new class of drugs based on target protein conformational disruption. Array Bridge used a propriety technology called Protein Conformational Array to screen for compounds that are capable of target protein disruption. There are several advantages for the PCA technology: first, the selection of compounds is not limited to one pre-defined site like the other allosteric regulators that just target one defined pocket. In the PCA screening, any molecule that can disrupt SHP2 conformation from any sites will be selected, thus this technology expands the diversity of the molecules. Second, the molecules selected could have three different modes of action instead of just inhibiting phosphatase activity. It can just disrupt the SHP2 conformation to the point that the SHP2 and its partner protein interaction is disrupted, thus blocking the signal transduction process such as the inactivation of P-ERK. Third, the molecules can disrupt SHP2 conformation to the point that the disrupted (possibly partially unfolded) conformation was recognized by the cellular proteosome system to induce SHP2 degradation, this is what we have observed in the cell line testing of several compounds, Fig. 1 is a diagram of the Array Bridge PCA drug discovery platform.
Fig. 1. Diagram of the Array Bridge PCA platform for drug discovery.
Preclinical Development
The drug discovery platform has identified 15 compounds from both the FDA-approved drug collection and the NCI Diversity Compound Library that can effectively disrupt SHP2 conformation. Further testing with 6 different cancer cell lines demonstrated that many of the identified drugs or novel compounds inactivate P-ERK, the intended target pathway. Even more interesting, some of the compounds identified was capable of inducing SHP2 degradation in multiple cancer cell lines, Fig. 2 is an example of the SHP2 degradation analyzed by Western Blot.
Fig. 2. SHP2 degradation was observed by identified FDA-approved drugs and NCI compounds in multiple cancer cell line testing.
Array Bridge is currently seeking collaborations in three areas: 1. Preclinical and clinical development of the FDA-approved drugs as repurposing drug in cancer treatment. 2. Preclinical and clinical development of the novel compounds with activity against multiple cancer cell lines and SHP2 degradation. 3. Expand the PCA Assays from SHP2 to other promising anti-tumor targets, currently 85% of the anti-tumor targets are considered undruggable because there is no defined site for traditional small molecule screen, PCA technology is based on protein conformational disruption, thus break this limitation in drug discovery. For both the FDA-approved drug repurposing and novel drug as cancer treatment, Array Bridge has secured the IP position with patent filings.
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