Communications Biology (Jan 2021)
Design and optimisation of dendrimer-conjugated Bcl-2/xL inhibitor, AZD0466, with improved therapeutic index for cancer therapy
- Claire M. Patterson,
- Srividya B. Balachander,
- Iain Grant,
- Petar Pop-Damkov,
- Brian Kelly,
- William McCoull,
- Jeremy Parker,
- Michael Giannis,
- Kathryn J. Hill,
- Francis D. Gibbons,
- Edward J. Hennessy,
- Paul Kemmitt,
- Alexander R. Harmer,
- Sonya Gales,
- Stuart Purbrick,
- Sean Redmond,
- Matthew Skinner,
- Lorraine Graham,
- J. Paul Secrist,
- Alwin G. Schuller,
- Shenghua Wen,
- Ammar Adam,
- Corinne Reimer,
- Justin Cidado,
- Martin Wild,
- Eric Gangl,
- Stephen E. Fawell,
- Jamal Saeh,
- Barry R. Davies,
- David J. Owen,
- Marianne B. Ashford
Affiliations
- Claire M. Patterson
- Pharmaceutical Sciences, R&D, AstraZeneca
- Srividya B. Balachander
- Oncology R&D, AstraZeneca
- Iain Grant
- Pharmaceutical Technology and Development, Operations, AstraZeneca
- Petar Pop-Damkov
- Oncology R&D, AstraZeneca
- Brian Kelly
- Starpharma
- William McCoull
- Oncology R&D, AstraZeneca
- Jeremy Parker
- Pharmaceutical Sciences, R&D, AstraZeneca
- Michael Giannis
- Starpharma
- Kathryn J. Hill
- Pharmaceutical Technology and Development, Operations, AstraZeneca
- Francis D. Gibbons
- Oncology R&D, AstraZeneca
- Edward J. Hennessy
- Oncology R&D, AstraZeneca
- Paul Kemmitt
- Oncology R&D, AstraZeneca
- Alexander R. Harmer
- Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca
- Sonya Gales
- Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca
- Stuart Purbrick
- Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca
- Sean Redmond
- Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca
- Matthew Skinner
- Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca
- Lorraine Graham
- Pharmaceutical Sciences, R&D, AstraZeneca
- J. Paul Secrist
- Oncology R&D, AstraZeneca
- Alwin G. Schuller
- Oncology R&D, AstraZeneca
- Shenghua Wen
- Oncology R&D, AstraZeneca
- Ammar Adam
- Oncology R&D, AstraZeneca
- Corinne Reimer
- Oncology R&D, AstraZeneca
- Justin Cidado
- Oncology R&D, AstraZeneca
- Martin Wild
- Oncology R&D, AstraZeneca
- Eric Gangl
- Oncology R&D, AstraZeneca
- Stephen E. Fawell
- Oncology R&D, AstraZeneca
- Jamal Saeh
- Oncology R&D, AstraZeneca
- Barry R. Davies
- Oncology R&D, AstraZeneca
- David J. Owen
- Starpharma
- Marianne B. Ashford
- Pharmaceutical Sciences, R&D, AstraZeneca
- DOI
- https://doi.org/10.1038/s42003-020-01631-8
- Journal volume & issue
-
Vol. 4,
no. 1
pp. 1 – 14
Abstract
Claire Patterson et al. present the design and development of AZD0466, a drug-dendrimer conjugate, and use preclinical and mathematical models to determine the optimal release rate of the drug from the dendrimer carrier for maximal therapeutic index in terms of anti-tumour efficacy and cardiovascular tolerability. This study identifies this promising dual Bcl-2/Bcl-xL inhibitor for progression to clinical development.
