Diverse Modalities

Cyprotex has a wide range of services available for a broad range of drug modalities including, but not limited to, small molecules, targeted protein degraders, peptides and oligonucleotides. Our comprehensive range of in vitro DMPK/ADME and safety (toxicology) services are flexible and customizable allowing assessment of diverse modalities whose physicochemical properties may sit outside the typical rule of 5 (Ro5) chemical space. Such physicochemical properties may create some unique challenges in performing in vitro experiments or analysing samples by mass spectroscopy.

Cyprotex capabilities in diverse modalities are underpinned by state-of-the-art analytical capabilities and expertise combined with extensive experience in the design and execution of ADME and toxicology experiments for a range of diverse modalities.

Whether your project requires early stage ADME screening, measurement of key physicochemical parameters, determining potential drug-drug interaction risk, or looking to assess the safety profile of your compound, Cyprotex have the experience and expertise to partner with you to provide appropriate solutions.

Targeted Protein Degraders

Targeted protein degraders (TPDs) are a relatively new therapeutic modality designed to selectively degrade disease-related proteins and potentially capable of acting on targets that have previously been difficult to target with traditional small molecules. The mechanism of action of TPDs utilizes the ubiquitin-proteasome system, the body’s internal protein degradation system, to eliminate specific target proteins.

The diverse physicochemical properties of some TPDs can result in practical experimental challenges related to their lipophilicity, such as non-specific binding and poor aqueous solubility. Therefore, experimental modifications may be required or alternative in vitro approaches may be necessary. 

Peptides

There are a large number of commercial peptide drugs on the market, treating a broad range of diseases. They are an attractive chemical space for drug discovery due to the potential for high potency and target selectivity. They are associated with a lower drug-drug interaction risk and off-target safety risk. However, there are challenges with low membrane permeability and poor in vivo stability.

Peptides can be large, hydrophobic molecules that may be multiply charged and prone to non-specific binding, and so modified analytical workflows and specific compound handling practices may be required. Additionally, peptides often demonstrate high protein binding, limited aqueous solubility and are subject to chemical and enzymatic instability which can create experimental challenges.

Oligonucleotides

Oligonucleotides, including antisense oligonucleotides (ASOs) and small interfering ribonucleic acids (siRNAs), represent a significant growth area for drug discovery and precision medicine in recent years. They work by modulating gene and protein expression through targeting of specific RNA sequences.

Oligonucleotides are typically large molecules and can be challenging to analyse due to being highly negatively charged, polar molecules. There can be difficulties in extracting oligonucleotides from biological matrices and they are prone to adsorption to polar surfaces, making post-assay processing critical in achieving analytical sensitivity. Due to their inherent ADME properties, many ‘routine’ ADME assays are not appropriate for oligonucleotide chemistry. For example, drug-drug interaction (DDI) risk assessment focuses on oligonucleotides as potential perpetrators as they are unlikely to be a victim of enzyme- or transporter-mediated DDI.