RESUMEN
The discipline of structure-based drug design (SBDD) is several decades old and it is tempting to think that the proliferation of experimental structures for many drug targets might make computer-aided drug design (CADD) straightforward. However, this is far from true. In this review, we illustrate some of the challenges that CADD scientists face every day in their work, even now. We use Rho-associated protein kinase (ROCK), and public domain structures and data, as an example to illustrate some of the challenges we have experienced during our project targeting this protein. We hope that this will help to prevent unrealistic expectations of what CADD can accomplish and to educate non-CADD scientists regarding the challenges still facing their CADD colleagues.
RESUMEN
Atopic dermatitis (AD) is a common inflammatory and pruritic allergic skin disease in humans and dogs worldwide. The pathogenesis of AD is multifactorial, immunologically complex, and may involve genetic factors, epidermal barrier dysfunction, microbiome changes, immune dysregulation, and allergic sensitization. Across species, prevalence of AD is on the rise. At present, there is no cure for canine AD (CAD). The treatment for CAD is multifaceted and aimed at controlling the pruritus, associated inflammation, and infections, repairing the skin barrier function, and dietary management. This review presents data on prevalence, impact, and complex immunological interactions in AD with a focus on subsequent management of the disease in the canine population. A multimodal approach for management of CAD to address varying clinical signs and responses to therapies is discussed.