Pevonedistat, a NEDD8-activating enzyme inhibitor, is active in mantle cell lymphoma and enhances rituximab activity in vivo

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F16%3A10327537" target="_blank" >RIV/00064165:_____/16:10327537 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/16:10327537

Result on the web

<a href="http://dx.doi.org/10.1182/blood-2015-04-640920" target="_blank" >http://dx.doi.org/10.1182/blood-2015-04-640920</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/blood-2015-04-640920" target="_blank" >10.1182/blood-2015-04-640920</a>

Result language

angličtina

Original language name

Pevonedistat, a NEDD8-activating enzyme inhibitor, is active in mantle cell lymphoma and enhances rituximab activity in vivo

Original language description

Mantle cell lymphoma(MCL) is characterized by an aggressive clinical course and inevitable development of refractory disease, stressing the need to develop alternative therapeutic strategies. To this end, we evaluated pevonedistat (MLN4924), a novel potent and selective NEDD8-activating enzyme inhibitor in a panel of MCL cell lines, primary MCL tumor cells, and 2 distinct murine models of human MCL. Pevonedistat exposure resulted in a dose-, time-, and caspase-dependent cell death in the majority of the MCL cell lines and primary tumor cells tested. Of interest, in the MCL cell lines with lower half-maximal inhibitory concentration (0.1-0.5 mu M), pevonedistat induced G1-phase cell cycle arrest, down-regulation of Bcl-xL levels, decreased nuclear factor (NF)-kappa B activity, and apoptosis. In addition, pevonedistat exhibited additive/synergistic effects when combined with cytarabine, bendamustine, or rituximab. In vivo, as a single agent, pevonedistat prolonged the survival of 2 MCL-bearing mouse models when compared with controls. Pevonedistat in combination with rituximab led to improved survival compared with rituximab or pevonedistat monotherapy. Our data suggest that pevonedistat has significant activity in MCL preclinical models, possibly related to effects on NF-kappa B activity, Bcl-xL downregulation, and G1 cell cycle arrest. Our findings support further investigation of pevonedistat with or without rituximab in the treatment of MCL.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

<a href="/en/project/NT13201" target="_blank" >NT13201: Role of angiogenesis in mantle cell lymphoma (MCL) survival, growth, spread and response to therapy</a><br>

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Blood

ISSN

0006-4971

e-ISSN

—

Volume of the periodical

127

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

1128-1137

UT code for WoS article

000373401700013

EID of the result in the Scopus database

2-s2.0-84960469722