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Myriad digital health interventions, applications, devices and technologies have, and are, being developed to help refine and personalise medicine from the patient, healthcare professional (HCP), healthcare system and industry perspectives. At a gathering of leaders in digital health, discussion included the current landscape of such digital health tools (DHTs), with specific examples from cardiology and respiratory medicine, and both the benefits and sometime downfalls of such tools. While DHTs can help patients and HCPs detect and monitor health conditions, the experts discussed how adoption of DHTs may be hampered by issues such as access to technology; data privacy and security concerns; technology integration into current healthcare systems; cost and reimbursement; and lack of guidelines and regulatory hurdles. The experts suggested solutions to such issues, including wider availability of healthcare 'booths' local to a patient; easy to understand and use phone applications; patient and HCP incentives to use DHTs and clear paths to adoption within a healthcare system. These should help with integration of DHTs into the healthcare system to aid shared decision-making and, ultimately, streamline and personalise healthcare for all., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Background: Cyclin-dependent kinase 2 (CDK2) is an important target for structure-based design of antitumor agents. Monomeric CDK2 is inactive. Activation requires rearrangements to key structural elements of the enzyme's active site, which accompany cyclin binding and phosphorylation. To assess the validity of using monomeric CDK2 as a model for the active kinase in structure-based drug design, we have solved the structure of the inhibitor indirubin-5-sulphonate (E226) complexed with phospho-CDK2-cyclin A and compared it with the structure of E226 bound to inactive, monomeric CDK2., Results: Activation of monomeric CDK2 leads to a rotation of its N-terminal domain relative to the C-terminal lobe. The accompanying change in position of E226 follows that of the N-terminal domain, and its interactions with residues forming part of the adenine binding pocket are conserved. The environment of the ATP-ribose site, not explored by E226, is significantly different in the binary complex compared to the monomeric complex due to movement of the glycine loop. Conformational changes also result in subtle differences in hydrogen bonding and electrostatic interactions between E226's sulphonate and CDK2's phosphate binding site. Affinities calculated by LUDI for the interaction of E226 with active or inactive CDK2 differ by a factor of approximately ten., Conclusions: The accuracy of monomeric CDK2 as an inhibitor design template is restricted to the adenine binding site. The general flexibility observed for the glycine loop and subtle changes to the phosphate binding site suggest a need to study interactions between inhibitors and active CDK2 in structure-based drug design programs.