Condensate-Based Drug Discovery Strategies

Biomolecular condensates play an important role in normal and abnormal cellular functions. CD BioSciences offers comprehensive biomolecular condensate physiological functional analysis services and biomolecular condensate pathological functional analysis services to explore their functions in human health and disease and develop condensate-based drug discovery approaches. Traditional drug development typically involves drugs that bind to and inhibit disease-causing targets. For example, protein degraders can target non-enzymatic proteins in the presence of ligandable pockets. However, most proteomes and transcriptomes lack well-defined pockets and remain difficult to drug. In the track of biomolecular condensates, there are currently two technical approaches, one to restore a sclerotic condensate to normal (liquid state) and one to harden a pathological condensate in the liquid state. Which pathway is better is largely influenced by the disease itself and the role of condensates in the disease both have their own characteristics, which are relevant to the disease of choice.

Fig. 1. Phase modulators for novel therapeutic opportunities. (Afeyan L K, 2022)

Our Solutions

CD BioSciences is committed to developing multiple condensate-based drug discovery strategies to provide solutions for many untargetable drug targets. Our competitive advantage mainly lies in the adjustment scheme of the pathological aggregate state. By promoting the protein to form biomolecular condensate and activating the function of proteins, we can target the phase separation mediated by these disordered regions and regulate the current "untargetable" to target function.

Depending on the indication, our condensate-based drug discovery strategies are based on the following technical paths:

• Repaiir Condensatopathy
  We can prevent the formation of abnormal condensates when they are clearly associated with causing disease. If abnormal condensate has formed, we can eliminate or remove them by lysing pathological biomolecular condensates. Our expert team evaluates the condensate behavior in the model system in an initial screening and further validates the hits in a disease-related secondary assay. The advantages of this strategy are that:
  • Does not require a specific target or pathway.
  • Does not require any hypothetical molecular mechanism to achieve an effect on condensates.
• Disrupts the Normal Function of Disease-Associated Condensates
  If the normal function of the condensate is related to the core biological process of the disease, we can induce a liquid-solid phase transition in the condensate, causing hardening of the condensate, loss of mobility, and resulting in the inability of all condensate components to function. This strategy will only interfere in cells associated with the disease. Our expert team evaluates condensate behavior in the model system in an initial screen and further validates hits in a disease-related secondary assay.
• Prevent Target from Functioning
  We can prevent target from functioning by disabling the target in its natural condensate or by separating the target from its natural condensate. The focus of this strategy is to track the behavior of that particular target.

CD BioSciences offers a variety of strategies to implement condensate-based drug development along these lines. These strategies can be used individually or in combination, and the preferred strategy in any case will depend on your desired pharmacological outcome and on the composition, structure, and function of the given condensate.

• Modulation of The Condensate Scaffold for Drug Discovery
• Modulation of Condensate Composition for Drug Discovery
• Modulation of The Condensate Conformation and Interaction for Drug Discovery
• Degradation of Condensate for Drug Discovery
• Modulation of Condensate Regulatory Processes for Drug Discovery
• Optimization Partitioning of Drugs into Condensates

CD BioSciences has cutting-edge interdisciplinary experimental techniques, computational technologies, and artificial intelligence to advance condensate-based drug discovery in a rapid manner, from target selection and lead compound optimization to clinical development. If you are interested in our solutions, please contact us now to seize new drug development opportunities.