Expanded Safety Analysis of Pevonedistat, a First-in-class NEDD8-activating Enzyme Inhibitor, in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes

Overview

Journal Blood Cancer J

Date 2017 Feb 4

PMID 28157218

Citations 23

Authors

R T Swords

J Watts

H P Erba

J K Altman

M Maris

F Anwer

Z Hua

H STEIN

H Faessel

F Sedarati

B J Dezube

F J Giles

B C Medeiros

D J DeAngelo

Affiliations

Soon will be listed here.

Citing Articles

Functional genomics pipeline identifies CRL4 inhibition for the treatment of ovarian cancer.

Claridge S, Nath S, Baum A, Farias R, Cavallo J, Rizvi N Clin Transl Med. 2025; 15(2):e70078.

PMID: 39856363 PMC: 11761363. DOI: 10.1002/ctm2.70078.

A phase I study of pevonedistat, azacitidine, and venetoclax in patients with relapsed/refractory acute myeloid leukemia.

Guru Murthy G, Saliba A, Szabo A, Harrington A, Abedin S, Carlson K Haematologica. 2024; 109(9):2864-2872.

PMID: 38572562 PMC: 11367232. DOI: 10.3324/haematol.2024.285014.

NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.

Zhou L, Lin X, Zhu J, Zhang L, Chen S, Yang H Cell Death Discov. 2023; 9(1):23.

PMID: 36690633 PMC: 9871045. DOI: 10.1038/s41420-023-01337-w.

New Therapeutic Strategies for Adult Acute Myeloid Leukemia.

Ishii H, Yano S Cancers (Basel). 2022; 14(11).

PMID: 35681786 PMC: 9179253. DOI: 10.3390/cancers14112806.

Pevonedistat in East Asian patients with acute myeloid leukemia or myelodysplastic syndromes: a phase 1/1b study to evaluate safety, pharmacokinetics and activity as a single agent and in combination with azacitidine.

Handa H, Cheong J, Onishi Y, Iida H, Kobayashi Y, Kim H J Hematol Oncol. 2022; 15(1):56.

PMID: 35545778 PMC: 9097234. DOI: 10.1186/s13045-022-01264-w.

References

Swords R, Erba H, DeAngelo D, Bixby D, Altman J, Maris M . Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study. Br J Haematol. 2015; 169(4):534-43. DOI: 10.1111/bjh.13323. View

Soucy T, Smith P, Milhollen M, Berger A, Gavin J, Adhikari S . An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009; 458(7239):732-6. DOI: 10.1038/nature07884. View

Soucy T, Smith P, Rolfe M . Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer. Clin Cancer Res. 2009; 15(12):3912-6. DOI: 10.1158/1078-0432.CCR-09-0343. View

Mathewson N, Toubai T, Kapeles S, Sun Y, Oravecz-Wilson K, Tamaki H . Neddylation plays an important role in the regulation of murine and human dendritic cell function. Blood. 2013; 122(12):2062-73. PMC: 3778550. DOI: 10.1182/blood-2013-02-486373. View

Shah J, Jakubowiak A, OConnor O, Orlowski R, Harvey R, Smith M . Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma. Clin Cancer Res. 2015; 22(1):34-43. PMC: 5694347. DOI: 10.1158/1078-0432.CCR-15-1237. View

McCormack R, Lyapichev K, Olsson M, Podack E, Munson G . Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2. Elife. 2015; 4. PMC: 4626573. DOI: 10.7554/eLife.06505. View

Milhollen M, Narayanan U, Soucy T, Veiby P, Smith P, Amidon B . Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer Res. 2011; 71(8):3042-51. DOI: 10.1158/0008-5472.CAN-10-2122. View

Milhollen M, Thomas M, Narayanan U, Traore T, Riceberg J, Amidon B . Treatment-emergent mutations in NAEβ confer resistance to the NEDD8-activating enzyme inhibitor MLN4924. Cancer Cell. 2012; 21(3):388-401. DOI: 10.1016/j.ccr.2012.02.009. View

Swords R, Kelly K, Smith P, Garnsey J, Mahalingam D, Medina E . Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. Blood. 2010; 115(18):3796-800. DOI: 10.1182/blood-2009-11-254862. View

10.

Wolenski F, Fisher C, Sano T, Wyllie S, Cicia L, Gallacher M . The NAE inhibitor pevonedistat (MLN4924) synergizes with TNF-α to activate apoptosis. Cell Death Discov. 2016; 1:15034. PMC: 4979425. DOI: 10.1038/cddiscovery.2015.34. View

11.

Sarantopoulos J, Shapiro G, Cohen R, Clark J, Kauh J, Weiss G . Phase I Study of the Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (TAK-924/MLN4924) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2015; 22(4):847-57. DOI: 10.1158/1078-0432.CCR-15-1338. View

12.

Chiba T, Tanaka K . Cullin-based ubiquitin ligase and its control by NEDD8-conjugating system. Curr Protein Pept Sci. 2004; 5(3):177-84. DOI: 10.2174/1389203043379783. View

13.

Chen Y, Yang Z, Meng M, Zhao Y, Dong N, Yan H . Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. Mol Cell. 2009; 35(6):841-55. DOI: 10.1016/j.molcel.2009.09.004. View

14.

Zhou L, Chen S, Zhang Y, Kmieciak M, Leng Y, Li L . The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR. Blood. 2016; 127(18):2219-30. PMC: 4859196. DOI: 10.1182/blood-2015-06-653717. View