Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium

Raushan T. Kurmasheva; Abhik Bandyopadhyay; Edward Favours; Vanessa Del Pozo; Samson Ghilu; Doris A. Phelps; Gerard M. McGeehan; Stephen W. Erickson; Malcolm A. Smith; Peter J. Houghton

doi:10.1002/pbc.28284

Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium

Raushan T. Kurmasheva, Abhik Bandyopadhyay, Edward Favours, Vanessa Del Pozo, Samson Ghilu, Doris A. Phelps, Gerard M. McGeehan, Stephen W. Erickson, Malcolm A. Smith, Peter J. Houghton

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Resumen

Background: VTP-50469 is a potent inhibitor of the menin-MLL1 interaction and is implicated in signaling downstream of EWSR1-FLI1. Procedure: VTP-50469 was evaluated against seven Ewing sarcoma (EwS) xenograft models and in vitro against EwS cell lines. Results: VTP-50469 showed limited antitumor activity, statistically significantly slowing tumor progression in four tumor models but with no evidence of tumor regression. In vitro, the IC₅₀ concentration was 10 nM for the mixed lineage leukemia (MLL)-rearranged leukemia cell line MV4;11, but > 3 μM for EwS cell lines. Conclusions: In contrast to its high level of activity against MLL1-rearranged leukemia xenografts, VTP-50469 shows little activity against EwS models.

Idioma original	English (US)
Número de artículo	e28284
Publicación	Pediatric Blood and Cancer
Volumen	67
N.º	7
DOI	https://doi.org/10.1002/pbc.28284
Estado	Published - jul 1 2020

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Hematology
Oncology

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Kurmasheva, R. T., Bandyopadhyay, A., Favours, E., Pozo, V. D., Ghilu, S., Phelps, D. A., McGeehan, G. M., Erickson, S. W., Smith, M. A., & Houghton, P. J. (2020). Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium. Pediatric Blood and Cancer, 67(7), Artículo e28284. https://doi.org/10.1002/pbc.28284

@article{f57fbc70fa12423496acf452208bdfe1,

title = "Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium",

abstract = "Background: VTP-50469 is a potent inhibitor of the menin-MLL1 interaction and is implicated in signaling downstream of EWSR1-FLI1. Procedure: VTP-50469 was evaluated against seven Ewing sarcoma (EwS) xenograft models and in vitro against EwS cell lines. Results: VTP-50469 showed limited antitumor activity, statistically significantly slowing tumor progression in four tumor models but with no evidence of tumor regression. In vitro, the IC50 concentration was 10 nM for the mixed lineage leukemia (MLL)-rearranged leukemia cell line MV4;11, but > 3 μM for EwS cell lines. Conclusions: In contrast to its high level of activity against MLL1-rearranged leukemia xenografts, VTP-50469 shows little activity against EwS models.",

keywords = "Ewing sarcoma, pediatric oncology, xenograft",

author = "Kurmasheva, {Raushan T.} and Abhik Bandyopadhyay and Edward Favours and Pozo, {Vanessa Del} and Samson Ghilu and Phelps, {Doris A.} and McGeehan, {Gerard M.} and Erickson, {Stephen W.} and Smith, {Malcolm A.} and Houghton, {Peter J.}",

note = "Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals, Inc.",

year = "2020",

month = jul,

day = "1",

doi = "10.1002/pbc.28284",

language = "English (US)",

volume = "67",

journal = "Pediatric Blood and Cancer",

issn = "1545-5009",

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number = "7",

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TY - JOUR

T1 - Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium

AU - Kurmasheva, Raushan T.

AU - Bandyopadhyay, Abhik

AU - Favours, Edward

AU - Pozo, Vanessa Del

AU - Ghilu, Samson

AU - Phelps, Doris A.

AU - McGeehan, Gerard M.

AU - Erickson, Stephen W.

AU - Smith, Malcolm A.

AU - Houghton, Peter J.

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Background: VTP-50469 is a potent inhibitor of the menin-MLL1 interaction and is implicated in signaling downstream of EWSR1-FLI1. Procedure: VTP-50469 was evaluated against seven Ewing sarcoma (EwS) xenograft models and in vitro against EwS cell lines. Results: VTP-50469 showed limited antitumor activity, statistically significantly slowing tumor progression in four tumor models but with no evidence of tumor regression. In vitro, the IC50 concentration was 10 nM for the mixed lineage leukemia (MLL)-rearranged leukemia cell line MV4;11, but > 3 μM for EwS cell lines. Conclusions: In contrast to its high level of activity against MLL1-rearranged leukemia xenografts, VTP-50469 shows little activity against EwS models.

AB - Background: VTP-50469 is a potent inhibitor of the menin-MLL1 interaction and is implicated in signaling downstream of EWSR1-FLI1. Procedure: VTP-50469 was evaluated against seven Ewing sarcoma (EwS) xenograft models and in vitro against EwS cell lines. Results: VTP-50469 showed limited antitumor activity, statistically significantly slowing tumor progression in four tumor models but with no evidence of tumor regression. In vitro, the IC50 concentration was 10 nM for the mixed lineage leukemia (MLL)-rearranged leukemia cell line MV4;11, but > 3 μM for EwS cell lines. Conclusions: In contrast to its high level of activity against MLL1-rearranged leukemia xenografts, VTP-50469 shows little activity against EwS models.

KW - Ewing sarcoma

KW - pediatric oncology

KW - xenograft

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U2 - 10.1002/pbc.28284

DO - 10.1002/pbc.28284

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C2 - 32333633

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JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

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Evaluation of VTP-50469, a menin-MLL1 inhibitor, against Ewing sarcoma xenograft models by the pediatric preclinical testing consortium

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