M
Matthew A. Belmonte
Researcher at AstraZeneca
Publications - 13
Citations - 602
Matthew A. Belmonte is an academic researcher from AstraZeneca. The author has contributed to research in topics: Leukemia & Myeloid leukemia. The author has an hindex of 8, co-authored 12 publications receiving 427 citations.
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Journal ArticleDOI
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 Aquila,Brian Aquila,Lawrence H. Boise,Elisabetta Chiarparin,Justin Cidado,Kevin J. Embrey,Eric Gangl,Francis D. Gibbons,Gareth P. Gregory,Gareth P. Gregory,David J. Hargreaves,J. Adam Hendricks,Jeffrey W. Johannes,Ricky W. Johnstone,Ricky W. Johnstone,Steven L. Kazmirski,Jason Grant Kettle,Michelle Lamb,Shannon M. Matulis,Ajay K. Nooka,Martin J. Packer,Bo Peng,Philip B. Rawlins,Daniel W. Robbins,Alwin Schuller,Nancy Su,Wenzhan Yang,Qing Ye,Xiaolan Zheng,J. Paul Secrist,Edwin Clark,David Matthew Wilson,Stephen Fawell,Alexander Hird +36 more
TL;DR: AZD5991 is 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.
Journal ArticleDOI
Inhibition of Mcl-1 through covalent modification of a noncatalytic lysine side chain
Gizem Akçay,Matthew A. Belmonte,Brian Aquila,Claudio Chuaqui,Alexander Hird,Michelle Lamb,Philip B. Rawlins,Nancy Su,Sharon Tentarelli,Neil P. Grimster,Qibin Su +10 more
TL;DR: The first reversible covalent inhibitors for Mcl-1, a protein-protein interaction (PPI) target that has proven difficult to inhibit via traditional medicinal chemistry strategies, are generated using aryl boronic acid carbonyl warheads to covalently target a noncatalytic lysine side chain.
Journal ArticleDOI
Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors.
Jeffrey W. Johannes,Stephanie M. Bates,Carl Beigie,Matthew A. Belmonte,John Breen,Shenggen Cao,Paolo A. Centrella,Matthew A. Clark,John W. Cuozzo,Christoph E. Dumelin,Andrew D. Ferguson,Sevan Habeshian,David J. Hargreaves,Camil Joubran,Steven L. Kazmirski,Anthony D. Keefe,Michelle Lamb,Haiye Lan,Yunxia Li,Hao Ma,Scott Mlynarski,Martin J. Packer,Philip B. Rawlins,Daniel W. Robbins,Haidong Shen,Eric A. Sigel,Holly H. Soutter,Nancy Su,Dawn M. Troast,Haiyun Wang,Kate F. Wickson,Chengyan Wu,Ying Zhang,Qiuying Zhao,Xiaolan Zheng,Alexander Hird +35 more
TL;DR: The use of protein-ligand crystal structures and binding kinetics contributed to the design and understanding of the potency gains, and exploration of a key hydrophobic interaction with Mcl-1 protein and also with the moiety that engages Arg256 led to additional potency improvements.
Proceedings ArticleDOI
Abstract DDT01-02: AZD5991: A potent and selective macrocyclic inhibitor of Mcl-1 for treatment of hematologic cancers
Alexander Hird,J. Paul Secrist,Ammar Adam,Matthew A. Belmonte,Eric Gangl,Frank Gibbons,David J. Hargreaves,Jeffrey W. Johannes,Stephen L. Kazmirski,Jason Grant Kettle,Stephen E. Kurtz,Michelle Lamb,Martin J. Packer,Bo Peng,Stewart Craig Robert,Jeffrey W. Tyner,Wenzhan Yang,Qing Ye,Xiaolan Zheng,Edwin Clark +19 more
TL;DR: Analysis of ex vivo activity in primary samples from leukemia patients indicates that a high percentage of leukemia patients should respond to drug treatment, which supports the plan for a phase I trial of AZD5991 in patients with hematologic cancers.
Journal ArticleDOI
The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells
Shaheen Kabir,Shaheen Kabir,Justin Cidado,Courtney L. Andersen,Cortni Dick,Pei-Chun Lin,Therese Mitros,Hong Ma,Seung Hyun Baik,Matthew A. Belmonte,Lisa Drew,Jacob E. Corn +11 more
TL;DR: Levels of the BH3-only pro-apoptotic proteins Bim and Noxa are proteasomally regulated by the CRL5 complex, which suggests the potential to improve combination treatments.