Drug Mechanisms of Action
The breadth and depth of our molecular profiling capabilities, and attendant data analysis and bioinformatics, provides our partners with the ability to assess comprehensively the effects of pharmacological intervention on in vivo systems. We can rapidly analyze both preclinical and clinical samples, providing a critical link between discovery and development. Whether it includes established marketed products or a series of novel leads, such comparison provides an informed basis for critical decisions.
Mechanism of Action studies with BG Medicine serve to:
- Elucidate on- and off-target effects
- Discover novel indications
- Increase out-licensing value or decrease in-licensing risk
- Empower go/no go decisions
This in depth analysis also allows for identification of novel structure-activity relationships. We call this ‘reverse pharmacology’ - using molecular profiles of existing products to design new entries in established drug classes. There are many opportunities to which this applies across all therapeutic categories.
The ability to cost-effectively conduct comparative pharmacology studies can revive interest in drug classes that produced blockbusters, but where discovery interest waned because traditional pharmacology was unable to identify superior follow-on compounds. We can help partners identify new compounds that meet rigorous target product profiles. These may include elimination of side effects for which mechanisms are poorly understood or addition of complementary activities to a single molecular entity.
On- and Off-Target Molecular Effects
- Example of Correlation Network™ analysis of in vivo drug-induced effects. Top panel (A) is a network comprising approximately 100 analytes (integrating proteins as well as lipids; each analyte denoted as a node in the network representation) and the empirically measured correlations among them (represented as red or green connections; p<0.01), in a healthy phenotype. The correlations reflect the underlying metabolism and biochemical pathways which are active and which regulate analyte behavior. (B) Analogous network upon administration of a development compound in a disease phenotype. It is seen that the drug maintains many correlations, however also effects multiple biochemical pathways which are reflected in changes in the network structure. Note the dramatic off-target effect in the lower left-hand portion of panel (B).
