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A selective inhibitor of the UFM1-activating enzyme, UBA5.

Abstract：

:Protein conjugation with ubiquitin and ubiquitin-like small molecules, such as UFM1, is important for promoting cancer cell survival and proliferation. Herein, the development of the first selective micromolar inhibitor of the UBA5 E1 enzyme that initiates UFM1 protein conjugation is described. This organometallic inhibitor incorporates adenosine and zinc(II)cyclen within its core scaffold and inhibits UBA5 noncompetitively and selectively over other E1 enzymes and a panel of human kinases. Furthermore, this compound selectively impedes the cellular proliferation (above 50μM) of cancer cells containing higher levels of UBA5. This inhibitor may be used to further probe the intracellular role of the UFM1 pathway in disease progression.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

da Silva SR,Paiva SL,Bancerz M,Geletu M,Lewis AM,Chen J,Cai Y,Lukkarila JL,Li H,Gunning PT

doi

10.1016/j.bmcl.2015.10.015

subject

Has Abstract

pub_date

2016-09-15 00:00:00

pages

4542-4547

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)30124-4

journal_volume

26

pub_type

杂志文章

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