NMR Fragment-Based Immune Checkpoint Targeted Small Molecule Drug Discovery

As a leading company in the drug development markets, experts at Creative Biolabs possess enriched experience in immune checkpoint targeted small molecule development. Our specialized and dedicated team provides the most extended range of services for immune checkpoint targeted small molecule drug design to meet each requirement from our global customers.

The immune system plays a pivotal role in detecting and blocking the development of cancer. Recently, it has been found that immune checkpoint pathways involving programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can be manipulated by tumor cells to escape from immune surveillance. Since ligand-receptor interactions adjust these immune checkpoints, they can be blocked by specific immune checkpoint inhibitors. Drugs targeting these checkpoints can block the transmission of the inhibitory signal and induce anti-tumor effects in T cells. Among the existing clinical drugs, checkpoint inhibitors have occupied a larger market share than the rest.

NMR Fragment-Based Drug Design

NMR can provide structural information at different resolution levels with a trade-off between the amount of information/ambiguity versus throughput. The bottom layer of the NMR pyramid represents a high-throughput, but low information content, screening phase that can be used to establish whether a small molecule binds to the target. If well-characterized tool molecules are available including antibodies, protein binding partners, nucleic acids, natural cofactors, or synthetic molecules, binding site information can be obtained at a similar throughput of typically a few thousand compounds per week using a competition binding assay.

The NMR pyramid for structure elucidation. Fig.1 The NMR pyramid for structure elucidation. (Marta, 2017)

Paramagnetic NMR Approach in Drug Discovery

Paramagnetic NMR in drug discovery is a new and emerging field. The paramagnetic approach could be very beneficial for structure-based drug discovery by NMR, especially when only low-resolution crystal structures can be obtained. In general, the paramagnetic NMR approach has some compelling advantages:

  • Since only the NMR spectrum of the ligand is observed, no isotope labeling is needed. This also removes many constraints on the size and amount of protein required for the study.
  • The laborious procedure of backbone and side-chain assignment might be omitted.
  • The pseudo contact shifts (PCS) effects are long-range, making it more likely that interaction could be detected, extending the applicability of structure-based drug discovery by NMR to weak-binding fragments.

Creative Biolabs has a comprehensive NMR platform that can provide customers with NMR fragment-based immune checkpoint targeted small molecule drug design services. We can provide you with one-stop protein structure determination, and immune checkpoint targeted small molecule drug design services, including protein expression, protein purification, drug design, drug screening, NMR data collection, data molecule, and protein structure analysis.

Please contact us for more detailed information to know how we can help.


  1. Marta, G.C.; et al. NMR in structure-based drug design. Essays in Biochemistry. 2017, 61(5):485-493.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.