Researchers at Charles University faced a hurdle: translating their exciting discoveries on cyclin-dependent kinase (CDK) and glycogen synthase kinase 3 (GSK3) inhibitors – molecules with the potential to combat cancer, schizophrenia, depression, and dementia – into concrete drug candidates. While the initial research held promise, they lacked the expertise to scale up production for crucial biological testing and preclinical trials.

Identifying the issue

Associate Professor Milan Jakubek’s research group (First Faculty of Medicine, Charles University) needed a partner to bridge the gap between their innovative research and large-scale development of drugs against specific diseases (Leukemia 1998, 12 (6), 845-859; Cancer treatment reviews 2017, 60, 130-138; Current drug targets 2019, 20 (7), 716-726.). Specifically, they sought expertise in custom synthesis and efficiently scaling up production to facilitate biological testing and preclinical trials.

Methodology insight

SigutLabs joined forces with the research group, leveraging extensive experience in contract research and custom synthesis. The collaboration began with a comprehensive dive into existing research, conducting a thorough literature review and patent search to identify promising structural motifs. This joint effort led to a breakthrough: the discovery of a novel, patentable scaffold not covered by existing patents (Figure 1).

Following the successful synthesis of the initial molecule, we delved into biological and toxicological testing. Furthermore, SigutLabs optimized the synthetic pathway, enabling the production of over ten different analogs. This systematic approach allowed researchers to explore the critical relationship between a molecule’s structure and its biological activity. It ultimately led to the rapid identification of a lead compound with promising therapeutic potential.

SigutLabs’ strength in scale-up chemistry then allowed for a smooth transition: taking the lead compound from milligram quantities to gram-scale production suitable for preclinical trials.

Positive outcome

This successful collaboration serves as a powerful example of the synergy achieved by combining academic research with the resources of commercial contract research organizations. SigutLabs’ expertise in custom synthesis and scale-up was instrumental in propelling the client’s drug discovery program forward. This collaborative effort not only led to the identification of promising new therapeutic candidates but also secured significant follow-on funding from the Technology Agency of the Czech Republic.