Nature Communications (Dec 2018)
Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia
- Adriana E. Tron,
- Matthew A. Belmonte,
- Ammar Adam,
- Brian M. Aquila,
- Lawrence H. Boise,
- Elisabetta Chiarparin,
- Justin Cidado,
- Kevin J. Embrey,
- Eric Gangl,
- Francis D. Gibbons,
- Gareth P. Gregory,
- David Hargreaves,
- J. Adam Hendricks,
- Jeffrey W. Johannes,
- Ricky W. Johnstone,
- Steven L. Kazmirski,
- Jason G. Kettle,
- Michelle L. Lamb,
- Shannon M. Matulis,
- Ajay K. Nooka,
- Martin J. Packer,
- Bo Peng,
- Philip B. Rawlins,
- Daniel W. Robbins,
- Alwin G. Schuller,
- Nancy Su,
- Wenzhan Yang,
- Qing Ye,
- Xiaolan Zheng,
- J. Paul Secrist,
- Edwin A. Clark,
- David M. Wilson,
- Stephen E. Fawell,
- Alexander W. Hird
Affiliations
- Adriana E. Tron
- Oncology, IMED Biotech Unit, AstraZeneca
- Matthew A. Belmonte
- Oncology, IMED Biotech Unit, AstraZeneca
- Ammar Adam
- Oncology, IMED Biotech Unit, AstraZeneca
- Brian M. Aquila
- Oncology, IMED Biotech Unit, AstraZeneca
- Lawrence H. Boise
- Department of Hematology and Medical Oncology, Emory University School of Medicine
- Elisabetta Chiarparin
- Oncology, IMED Biotech Unit, AstraZeneca
- Justin Cidado
- Oncology, IMED Biotech Unit, AstraZeneca
- Kevin J. Embrey
- Discovery Sciences, IMED Biotech Unit, AstraZeneca
- Eric Gangl
- Oncology, IMED Biotech Unit, AstraZeneca
- Francis D. Gibbons
- Oncology, IMED Biotech Unit, AstraZeneca
- Gareth P. Gregory
- School of Clinical Sciences at Monash Health, Monash University
- David Hargreaves
- Discovery Sciences, IMED Biotech Unit, AstraZeneca
- J. Adam Hendricks
- Discovery Sciences, IMED Biotech Unit, AstraZeneca
- Jeffrey W. Johannes
- Oncology, IMED Biotech Unit, AstraZeneca
- Ricky W. Johnstone
- Peter MacCallum Cancer Centre
- Steven L. Kazmirski
- Discovery Sciences, IMED Biotech Unit, AstraZeneca
- Jason G. Kettle
- Oncology, IMED Biotech Unit, AstraZeneca
- Michelle L. Lamb
- Oncology, IMED Biotech Unit, AstraZeneca
- Shannon M. Matulis
- Department of Hematology and Medical Oncology, Emory University School of Medicine
- Ajay K. Nooka
- Department of Hematology and Medical Oncology, Emory University School of Medicine
- Martin J. Packer
- Oncology, IMED Biotech Unit, AstraZeneca
- Bo Peng
- Oncology, IMED Biotech Unit, AstraZeneca
- Philip B. Rawlins
- Discovery Sciences, IMED Biotech Unit, AstraZeneca
- Daniel W. Robbins
- Oncology, IMED Biotech Unit, AstraZeneca
- Alwin G. Schuller
- Oncology, IMED Biotech Unit, AstraZeneca
- Nancy Su
- Discovery Sciences, IMED Biotech Unit, AstraZeneca
- Wenzhan Yang
- Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca
- Qing Ye
- Oncology, IMED Biotech Unit, AstraZeneca
- Xiaolan Zheng
- Oncology, IMED Biotech Unit, AstraZeneca
- J. Paul Secrist
- Oncology, IMED Biotech Unit, AstraZeneca
- Edwin A. Clark
- Oncology, IMED Biotech Unit, AstraZeneca
- David M. Wilson
- Oncology, IMED Biotech Unit, AstraZeneca
- Stephen E. Fawell
- Oncology, IMED Biotech Unit, AstraZeneca
- Alexander W. Hird
- Oncology, IMED Biotech Unit, AstraZeneca
- DOI
- https://doi.org/10.1038/s41467-018-07551-w
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 14
Abstract
High expression of Mcl-1 promotes tumorigenesis and resistance to anticancer therapies. Here they report a macrocyclic molecule with high selectivity and affinity for Mcl-1 that exhibits potent anti-tumor effects as single agent and in combination with bortezomib or venetoclax in preclinical models of multiple myeloma and acute myeloid leukemia.
