Discovery of a novel class NSD2 inhibitor for multiple myeloma with t(4;14)+ Article Swipe
Sae Matsuoka
,
Naoki Osada
,
Hirokazu Kubota
,
Ko Kikuzato
,
Hiroo Koyama
,
Takeshi Sonoda
,
Akiko Idei
,
Minoru Yoshida
,
Masaki Kikuchi
,
Takashi Umehara
,
Chiduru Watanabe
,
Teruki Honma
,
Hiroshi Yasui
,
Sho Ikeda
,
Naoto Takahashi
,
Hideki Nakasone
,
Jiro Kikuchi
,
Yusuke Furukawa
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.bneo.2025.100091
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.bneo.2025.100091
The prognosis for multiple myeloma (MM) has continued to improve with the development of a series of novel molecular targeted drugs over time. However, the prognosis remains poor for cases with high-risk chromosomal abnormalities. Of such abnormalities, t(4;14) is the second most common, occurring in 15% of patients with MM. MM cells carrying t(4;14) strongly express histone methyltransferase with a SET domain, called NSD2, making them resistant to drugs against MM. Therefore, NSD2 is a promising therapeutic target for MM carrying t(4;14). Subsequently, we performed high-throughput screening and identified RK-0080552 (RK-552) as a novel class NSD2 inhibitor. RK-552 was significantly cytotoxic against t(4;14)+ MM compared with t(4;14)- MM cells in vitro and in vivo via transcriptional suppression of the IRF4 gene, coincided with a decrease in histone H3 lysine 36 dimethylation. Moreover, RK-552 acted additively with pomalidomide in vitro and prolonged the survival of recipient mice without side effects. These results suggest that RK-552 may be a clinically relevant NSD2 inhibitor with specific cytotoxicity to MM cells carrying t(4;14). Our study also provides a molecular basis and rationale for the inclusion in current treatment strategies. Therefore, the clinical use of RK-552 may significantly improve the treatment outcome of MM with t(4;14).
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.bneo.2025.100091
- OA Status
- diamond
- Cited By
- 1
- References
- 45
- Related Works
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- OpenAlex ID
- https://openalex.org/W4408326309
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4408326309Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.bneo.2025.100091Digital Object Identifier
- Title
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Discovery of a novel class NSD2 inhibitor for multiple myeloma with t(4;14)+Work title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-03-11Full publication date if available
- Authors
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Sae Matsuoka, Naoki Osada, Hirokazu Kubota, Ko Kikuzato, Hiroo Koyama, Takeshi Sonoda, Akiko Idei, Minoru Yoshida, Masaki Kikuchi, Takashi Umehara, Chiduru Watanabe, Teruki Honma, Hiroshi Yasui, Sho Ikeda, Naoto Takahashi, Hideki Nakasone, Jiro Kikuchi, Yusuke FurukawaList of authors in order
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https://doi.org/10.1016/j.bneo.2025.100091Publisher landing page
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YesWhether a free full text is available
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diamondOpen access status per OpenAlex
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https://doi.org/10.1016/j.bneo.2025.100091Direct OA link when available
- Concepts
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Multiple myeloma, Class (philosophy), Computational biology, Computer science, Medicine, Biology, Internal medicine, Artificial intelligenceTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.resistant | 66 |
| abstract_inverted_index.screening | 86 |
| abstract_inverted_index.treatment | 183, 195 |
| abstract_inverted_index.RK-0080552 | 89 |
| abstract_inverted_index.Therefore, | 71, 185 |
| abstract_inverted_index.additively | 134 |
| abstract_inverted_index.clinically | 157 |
| abstract_inverted_index.identified | 88 |
| abstract_inverted_index.inhibitor. | 96 |
| abstract_inverted_index.<i>IRF4</i> | 119 |
| abstract_inverted_index.chromosomal | 32 |
| abstract_inverted_index.development | 12 |
| abstract_inverted_index.strategies. | 184 |
| abstract_inverted_index.suppression | 116 |
| abstract_inverted_index.therapeutic | 76 |
| abstract_inverted_index.cytotoxicity | 163 |
| abstract_inverted_index.pomalidomide | 136 |
| abstract_inverted_index.Subsequently, | 82 |
| abstract_inverted_index.significantly | 99, 192 |
| abstract_inverted_index.abnormalities, | 36 |
| abstract_inverted_index.abnormalities. | 33 |
| abstract_inverted_index.dimethylation. | 130 |
| abstract_inverted_index.high-throughput | 85 |
| abstract_inverted_index.transcriptional | 115 |
| abstract_inverted_index.methyltransferase | 57 |
| abstract_inverted_index.t(4;14)<sup>+</sup> | 102 |
| abstract_inverted_index.t(4;14)<sup>-</sup> | 106 |
| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 91 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 18 |
| citation_normalized_percentile.value | 0.85052936 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |