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Understanding Drug Failures and the Role of Chemical Probes
Numerous studies indicate that most drug failures in Phase 2 clinical trials originate from an incomplete understanding of the underlying biological pathways (1). When conclusions are drawn from experimental biology using a poorly characterized probe molecule (2), this can result in unsuccessful drug discovery campaigns targeting biological entities that offer minimal or questionable therapeutic benefits (3, 4). As a result, chemical probes are considered one of the most essential classes of molecules for investigating new biological questions (5). In summary, a chemical probe is a small-molecule modulator of a biological target, enabling researchers to explore mechanistic and phenotypic (6) questions in biochemical, cell-based, or animal studies.
Our Approach to Chemical Probe Development
At ALVO LAB, our goal is to design chemical probes that adhere to a Target Probe Profile, following established guidelines from the literature (7). These criteria include:
Biochemical potency below 100 nM;
Target-Engagement in cells with potency below 1 µM;
Greater than 30-fold selectivity to targets from the same family;
An inactive version of the probe, at least 100-fold less active;
No compound toxicity in cells (with a window greater than 10-fold compared to cellular potency, unless toxicity is target-mediated).
Collaborative Opportunities
Collaborative Opportunities
If you are interested in developing a collaborative project focused on new chemical probes, please contact us.
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