Publications by authors named "Caroline Hellawell"

Off-target pharmacology may contribute to both adverse and beneficial effects of a new drug. In vitro pharmacological profiling is often applied early in drug discovery; there are fewer reports addressing the relevance of broad profiles to clinical adverse effects. Here, we have characterized the pharmacological profile of the active metabolite of fostamatinib, R406, linking an understanding of drug selectivity to the increase in blood pressure observed in clinical studies.

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The traditional drug discovery strategy of pursuing "one compound-one target" has had difficulties delivering novel therapies for complex diseases currently lacking adequate treatments. An alternative and complementary approach is the design of multitargeted modulators simultaneously addressing multiple pathological mechanisms or overcoming pathway robustness. In this study, we propose a methodology to increase the probability of success for developing dual-acting modulators by systematically and rationally evaluating all dual-acting modulator opportunities within a specific disease area.

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Background: Biomarkers of cartilage metabolism have prognostic potential.

Objective: To examine whether serum cartilage biomarkers, cartilage oligomeric matrix protein (COMP), N-propeptide of type IIA procollagen (PIIANP), type II collagen breakdown product (collagen type-II cleavage (C2C)) predict cartilage volume loss and knee joint replacement.

Methods: 117 subjects with knee osteoarthritis (OA) had MRI at baseline and 2 years.

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Article Synopsis
  • The study aimed to find out if specific serum markers related to bone formation and resorption could help identify knee osteoarthritis patients who lose cartilage at different rates over two years.
  • Researchers measured cartilage volume changes in 117 knee OA subjects using MRI and looked at the relationship between these changes and levels of various bone formation (PINP, osteocalcin) and resorption markers (NTX-I, CTX-I).
  • The findings indicated that higher levels of bone formation markers were linked to less cartilage loss when associated with higher resorption markers, suggesting a complex relationship in how bone remodeling affects cartilage health.
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