Dr Biswas co-authored the review article with Dr Anupriya M Geethakumari, a postdoctoral fellow, and Wesam S Ahmed, a doctor of philosophy student in Biological and Biomedical Sciences at the CHLS, both members of the Biswas Lab, an interdisciplinary group engaged in understanding the mechanisms of cellular adhesion and signalling, and developing means to manipulate the same.
Dr Biswas’s laboratory employs a variety of approaches including engineering precision biosensors and biointerfaces.
Reviewing the structure of phosphodiesterase 5 (PDE5), a relatively well-studied multidomain enzyme, and how its function is regulated, the article focused on the clinically-relevant inhibitors that target the protein with the aim of better understanding the structural bases of their affinity and specificity.
The pharmacological inhibition of PDE5 has already been demonstrated to have several therapeutic applications.
While they are designed to inhibit PDE5, the inhibitors show different affinities and specificities against various other PDE subtypes.
Understanding how these inhibitors interact with PDE5 and the structural basis of their selectivity is critically important for the design of novel, highly-selective PDE5 inhibitors as well as precision medicine-based therapy.
The article also notes that while PDE5 inhibitors have several therapeutic applications, only three of these are approved by the US Food and Drug Administration.
With increasing evidence that PDE5 inhibitors could play a role in managing a number of diseases, including cancer and coronavirus (Covid-19) complications, clinical studies are warranted to extend the therapeutic applications of these inhibitors to a wider range of diseases.
Dr Dindial Ramotar, professor and head of the Division of Biological and Biomedical Sciences at the CHLS, said: “PDE5 inhibitors have shown their potential for multiple medical applications, including potential treatment for cancer and heart disease, and as a result there is an understandably heightened keenness for developing novel PDE5 inhibitors.
“Our study at the Biswas Lab aimed to fulfil a fundamental aspect of such work, and that is to collate what we know about this enzyme and its inhibitors in order to fully understand their therapeutic indications.”