Modalities Beyond Small Molecules

Novel therapeutic approaches are now possible by incorporating small molecules into PROTACs, through antibody–drug conjugates, or by deriving drugs from peptide-based structures. Our medicinal chemists are versed in a broad range of therapeutic modalities and we leverage their extensive hands-on experience in these exciting new fields to chemically enable your drug.

Proteolysis targeting chimeras (PROTACs) have recently emerged as a promising new paradigm in drug discovery, and NUVISAN has established a platform to expedite PROTACs research. Our services include the identification of a protein of interest (POI) and E3-ligase binders, as well as optimization of exit vectors, linker length, and linker composition to achieve oral bioavailability. Our PROTACs toolbox enables accelerated proof of concept regarding in vitro targeted degradation. All activities are supported by our Digital Life Sciences department (e.g., design of binders to POI/E3 ligases, structure-based linker optimization, de novo linker design, ternary complex prediction. Together with NUVISAN’s capabilities in pharmacology and DMPK, we can accelerate program timelines and have already helped our clients deliver preclinical PROTACs compounds!

Antibody–drug conjugates (ADCs) comprise a monoclonal antibody—conjugated via a linker to a small-molecule toxicophore—that interacts with antigens expressed on, for example, cancer cell surfaces, bringing the toxicophore into close proximity. This approach can reduce systemic exposure and limit toxicity. At NUVISAN, we have long-standing expertise with ADC synthesis and linker optimization.

Peptides are another unique class of therapeutic agents. Our expertise in this area includes the design and parallel synthesis of peptides in 48/96-well reactors with up to 20 amino acids and the synthesis of non-natural aminos acids for incorporation into peptides. NUVISAN chemists have also worked on projects involving 18F-labeling, peptide stapling, the design and synthesis of cyclic peptides, and SAR generation and PK optimization for peptide-based small-molecule projects.


Lerchen, HG., et al., A Small Molecule–Drug Conjugate (SMDC) Consisting of a Modified Camptothecin Payload Linked to an αVß3 Binder for the Treatment of Multiple Cancer Types. Cancers (Basel) (2022)

Atilaw, Y., et al., Solution Conformations Shed Light on PROTAC Cell Permeability. ACS Med Chem Lett (2020)