Kinases are a group of over 500 proteins that are involved in a large variety of physiological processes and diseases. These kinases form a network of proteins known as the human kinome that affords potential tractable targets for therapeutic intervention. However, much of our kinome is still unexplored. “We have only scratched the surface of what is possible and the imposing goal of a chemical probe or drug for every kinase remains far from realisation,” says Senior Researcher Christopher Asquith at the University of Eastern Finland.
Kinases represent one of the most successfully targeted protein families in drug development, with over 100 clinically approved drugs currently available. However, research efforts within the kinome are unevenly distributed. A small subset of kinases dominates the research literature, while many others remain largely unexplored. For instance, there are already 90 000 publications on EGFR and 30 000 on SRC, but only 15 on STK35 and nine on HIPK4. This disparity highlights the existence of a substantial “dark kinome”, comprising understudied kinases with potentially important biological and therapeutic roles.
Asquith leads a medicinal chemistry group focused on kinase inhibitor research at the University of Eastern Finland’s School of Pharmacy. Their work has provided insight into emerging trends and targets within the kinase field, including 13 highlight articles published in Nature Reviews Drug Discovery. “These target watches are designed to draw attention to understudied or 'dark' kinases and to outline their potential as therapeutic targets,” Asquith says.
The featured kinases in the article series include RIOK2, ADCK3/COQ8A, PKMYT1, PIP5K1A, STK19, the WNK kinase family, CDC42BPA, BCKDK, eEF2K, PIKfyve, PKN3, TLK2, and most recently PIP4K2C. Collectively, these concise perspectives have served to stimulate interest, guide research priorities and promote the development of chemical probes and experimental tools. The series focuses on how advances in chemical probe development and resource availability have disseminated into the broader scientific community. In addition, they serve to demonstrate how the landscape of kinase research has evolved over the past decade, reflecting a gradual shift toward more systematic exploration of previously neglected targets.
“Kinases offer a wealth of therapeutic opportunities and while current drugs focus on cancer interventions, a more systemic approach has the potential to yield a broader repertoire beyond oncology,” Asquith notes.
Identifying novel kinase mechanisms and kinase vulnerabilities beyond cancer therapeutics is a key foundational element to future kinase inhibitor development from targeting TLK2 in viral latency to PIKfyve in neurodegenerative disorders.
“Indeed, several of these highlighted kinases are now in clinical development which is a testament to the momentum in the research field and the opportunities yet to be discovered by targeting the kinome.”
The article series also contributes to broader initiatives such as the Illuminating the Druggable Genome (IDG) programme supported by the NIH Common Fund.
For further information, please contact:
Senior Researcher Christopher Asquith, https://uefconnect.uef.fi/en/christopher.asquith/
The latest article in the series:
Pozzetti L, Mishra M, Einav S, Asquith CRM. PIP4K2C: an emerging fulcrum for multiple diseases. Nat Rev Drug Discov.2026, 25, (3), 166. doi: 10.1038/d41573-026-00030-8. PMID: 41709023
References:
Pozzetti L, East MP, Laitinen T, Asquith CRM. TLK2: a target for cancer and viral latency. Nat Rev Drug Discov. 2024, 23, (12), 886. doi: 10.1038/d41573-024-00163-8. PMID: 39420118
PKN3: a target in cancer metastasis. Temme L, Laitinen T, Asquith CRM. Nat Rev Drug Discov. 2022, 21, (10), 704. doi: 10.1038/d41573-022-00154-7. PMID: 36104477
