YM155 inhibits neuroblastoma growth through degradation of MYCN: A new role as a USP7 inhibitor.

Autor: Li X; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Yang F; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., He N; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Zhang M; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Lv Y; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Yu Y; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Dong Q; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Hou X; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Hao Y; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., An Z; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Zhang H; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Yang Z; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Zhai H; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Guo D; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Cao Z; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Jiang VC; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA., Chen Y; Cothera Bioscience, Inc., 155 Bovet Road, Suite 660, San Mateo, CA 94402, USA. Electronic address: yychen@zkbymed.com.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2023 Feb 01; Vol. 181, pp. 106343. Date of Electronic Publication: 2022 Nov 24.
DOI: 10.1016/j.ejps.2022.106343
Abstrakt: Amplification of the MYCN gene (MNA) is observed in approximately 25 to 35% of neuroblastoma patients, and is a well-recognized marker of tumor aggressiveness and poor outcome. Targeting MYCN is a novel therapy strategy to induce tumor regression. Here, we discovered that a BIRC5/Survivin inhibitor, YM155, specifically inhibits MNA neuroblastoma cell growth in vitro. We found that YM155 promotes MYCN degradation in MNA cells. Further, we found that YM155 inhibits USP7 deubiquitinase activity in vitro, using Ub-aminomethylcoumarin (Ub-AMC) as substrate. Results from in vivo studies further demonstrated that YM155 significantly inhibited the tumor growth in MNA neuroblastoma xenograft model. Our data support a novel mechanism of action of YM155 in inhibition of growth of cancer cells through inducing MYCN degradation by inibition of activity of deubiquitinase like USP7.
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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