An exceptionally potent inhibitor of human CD73

Christine E Bowman; Rafael G da Silva; Amber  Pham; Stephen W. Young

doi:10.1021/acs.biochem.9b00448

An exceptionally potent inhibitor of human CD73

Christine E Bowman, Rafael G da Silva, Amber Pham, Stephen W. Young

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Abstract

We recently reported the initiation of a Phase I clinical trial with AB680, a potent human CD73 inhibitor, being developed for the treatment of solid tumors (NCT03677973). We undertook a detailed kinetic analysis of the interaction between human CD73 and AB680 to determine the mode of inhibition. We found AB680 to be a reversible, slow-onset competitive inhibitor of human CD73 with a K_i of 5 pM. Clinical candidates of this potency are uncommon and deserve special consideration during lead optimization.

Original language	English
Pages (from-to)	3331-3334
Number of pages	4
Journal	Biochemistry
Volume	58
Issue number	31
Early online date	23 Jul 2019
DOIs	https://doi.org/10.1021/acs.biochem.9b00448
Publication status	Published - 6 Aug 2019

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10.1021/acs.biochem.9b00448

Bowman_2019_Biochemistry_HumanCD73_AAM
Copyright © 2019 American Chemical Society. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1021/acs.biochem.9b00448
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title = "An exceptionally potent inhibitor of human CD73",

abstract = "We recently reported the initiation of a Phase I clinical trial with AB680, a potent human CD73 inhibitor, being developed for the treatment of solid tumors (NCT03677973). We undertook a detailed kinetic analysis of the interaction between human CD73 and AB680 to determine the mode of inhibition. We found AB680 to be a reversible, slow-onset competitive inhibitor of human CD73 with a Ki of 5 pM. Clinical candidates of this potency are uncommon and deserve special consideration during lead optimization.",

author = "Bowman, \{Christine E\} and \{da Silva\}, \{Rafael G\} and Amber Pham and Young, \{Stephen W.\}",

note = "The research described in this manuscript was fully funded by Arcus Biosciences, Inc. a publicly traded biotechnology company.",

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AU - Young, Stephen W.

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PY - 2019/8/6

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An exceptionally potent inhibitor of human CD73

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Rafael Guimaraes da Silva

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An exceptionally potent inhibitor of human CD73

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Rafael Guimaraes da Silva

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