Claire Patterson, Srividya Balachander, Iain Grant et al. present the Design and optimisation of dendrimer-conjugated Bcl-2/xL inhibitor, AZD0466, with improved therapeutic index for cancer therapy The publication describes the use of preclinical and mathematical models to determine the optimal release rate of the drug from the dendrimer.
The AZD4320-dendrimer conjugate (AZD0466) identified, through mathematical modelling, resulted in an improved therapeutic index and thus enabled progression of this promising dual Bcl-2/Bcl-xL inhibitor into clinical development (NCT04214093).
This work was a collaborative effort between Starpharma (using their DEP® dendrimer platform) and AstraZeneca (where Claire was formerly employed). It exemplifies the potential value add of complex drug delivery systems such as nanomedicines, and in particular, how their design can be guided by pharmacokinetic modelling.
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