Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates

Ota, Yosuke; Itoh, Yukihiro; Kurohara, Takashi; Singh, Ritesh; Elboray, Elghareeb E.; Hu, Chenliang; Zamani, Farzad; Mukherjee, Anirban; Takada, Yuri; Yamashita, Yasunobu; Morita, Mie; Horinaka, Mano; Sowa, Yoshihiro; Masuda, Mitsuharu; Sakai, Toshiyuki; Suzuki, Takayoshi

doi:https://doi.org/10.1021/acsmedchemlett.2c00126

Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates

Ota, Yosuke; Itoh, Yukihiro; Kurohara, Takashi et al.

ACS Medicinal Chemistry Letters, 2022, 13(10), 1568-1573

Number of Access:1,848（2025-09-29 10:02 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/89872

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Title	Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates
Creator	CreatorName Ota, Yosuke
	NRID 1000030636402 1000030636402 ORCID 0000-0002-3410-2924 0000-0002-3410-2924 researchmap permalink itohy itohy Scopus Author ID 55270583500 55270583500 CreatorName Itoh, Yukihiro
	NRID 1000090865776 1000090865776 CreatorName Kurohara, Takashi
	CreatorName Singh, Ritesh
	CreatorName Elboray, Elghareeb E.
	CreatorName Hu, Chenliang
	CreatorName Zamani, Farzad
	CreatorName Mukherjee, Anirban
	NRID 1000020902357 1000020902357 ORCID 0000-0002-7955-6567 0000-0002-7955-6567 researchmap permalink takada-yuri takada-yuri Scopus Author ID 57226083805 57226083805 CreatorName Takada, Yuri
	NRID 1000010873408 1000010873408 researchmap permalink ysnbyamashita ysnbyamashita Scopus Author ID 55736209900 55736209900 CreatorName Yamashita, Yasunobu
	CreatorName Morita, Mie
	NRID 1000080512037 1000080512037 CreatorName Horinaka, Mano
	NRID 1000070315935 1000070315935 CreatorName Sowa, Yoshihiro
	NRID 1000010305568 1000010305568 CreatorName Masuda, Mitsuharu
	NRID 1000020186993 1000020186993 CreatorName Sakai, Toshiyuki
	NRID 1000090372838 1000090372838 researchmap permalink read0135968 read0135968 Scopus Author ID 55977244300 55977244300 CreatorName Suzuki, Takayoshi
Subject	anticancer drug
	vorinostat
	prodrug
	LSD1
	targeted therapy
Description	Yosuke Ota, Yukihiro Itoh, Takashi Kurohara, Ritesh Singh, Elghareeb E. Elboray, Chenliang Hu, Farzad Zamani, Anirban Mukherjee, Yuri Takada, Yasunobu Yamashita, Mie Morita, Mano Horinaka, Yoshihiro Sowa, Mitsuharu Masuda, Toshiyuki Sakai, and Takayoshi Suzuki. ACS Medicinal Chemistry Letters 2022 13 (10), 1568-1573. DOI: 10.1021/acsmedchemlett.2c00126. Copyright © 2022 American Chemical Society.
Abstract	Anticancer drug delivery by small molecules offers a number of advantages over conventional macromolecular drug delivery systems. We previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) as small-molecule-based drug delivery vehicles for targeting lysine-specific demethylase 1 (LSD1)-overexpressing cancers. In this study, we applied this PDC strategy to the HDAC-inhibitory anticancer agent vorinostat. Among three synthesized PCPA or arylcyclopropylamine (ACPA)-vorinostat conjugates 1, 9, and 32, conjugate 32 with a 4-oxybenzyl linker showed sufficient stability in buffer solutions, potent LSD1 inhibition, efficient LSD1-dependent vorinostat release, and potent and selective antiproliferative activity toward LSD1-expressing human breast cancer and small-cell lung cancer cell lines. These results indicate that the conjugate selectively releases vorinostat in cancer cells. A similar strategy may be applicable to other anticancer drugs.
Publisher	American Chemical Society
Source Title	ACS Medicinal Chemistry Letters
Volume (Issue)	13(10)
Page	1568-1573
Date of Issued	2022-10-13
Language	English
Handle URL	https://hdl.handle.net/11094/89872
eISSN	19485875
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1021/acsmedchemlett.2c00126
Access Rights	open access
CopyRight	This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsmedchemlett.2c00126.
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	ACS Medicinal Chemistry Letters. 2022, 13(10), p. 1568-1573
DC.title	Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates
DC.creator	Ota, Yosuke
	Itoh, Yukihiro
	Kurohara, Takashi
	Singh, Ritesh
	Elboray, Elghareeb E.
	Hu, Chenliang
	Zamani, Farzad
	Mukherjee, Anirban
	Takada, Yuri
	Yamashita, Yasunobu
	Morita, Mie
	Horinaka, Mano
	Sowa, Yoshihiro
	Masuda, Mitsuharu
	Sakai, Toshiyuki
	Suzuki, Takayoshi
DC.publisher	American Chemical Society
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2022-10-13
DC.identifier	https://doi.org/10.1021/acsmedchemlett.2c00126
DC.subject	anticancer drug
	vorinostat
	prodrug
	LSD1
	targeted therapy
DC.description	Yosuke Ota, Yukihiro Itoh, Takashi Kurohara, Ritesh Singh, Elghareeb E. Elboray, Chenliang Hu, Farzad Zamani, Anirban Mukherjee, Yuri Takada, Yasunobu Yamashita, Mie Morita, Mano Horinaka, Yoshihiro Sowa, Mitsuharu Masuda, Toshiyuki Sakai, and Takayoshi Suzuki. ACS Medicinal Chemistry Letters 2022 13 (10), 1568-1573. DOI: 10.1021/acsmedchemlett.2c00126. Copyright © 2022 American Chemical Society.
DCTERMS.abstract	Anticancer drug delivery by small molecules offers a number of advantages over conventional macromolecular drug delivery systems. We previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) as small-molecule-based drug delivery vehicles for targeting lysine-specific demethylase 1 (LSD1)-overexpressing cancers. In this study, we applied this PDC strategy to the HDAC-inhibitory anticancer agent vorinostat. Among three synthesized PCPA or arylcyclopropylamine (ACPA)-vorinostat conjugates 1, 9, and 32, conjugate 32 with a 4-oxybenzyl linker showed sufficient stability in buffer solutions, potent LSD1 inhibition, efficient LSD1-dependent vorinostat release, and potent and selective antiproliferative activity toward LSD1-expressing human breast cancer and small-cell lung cancer cell lines. These results indicate that the conjugate selectively releases vorinostat in cancer cells. A similar strategy may be applicable to other anticancer drugs.
DC.rights	This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsmedchemlett.2c00126.
DC.format	89872
citation_title	Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates
citation_author	Ota, Yosuke
	Itoh, Yukihiro
	Kurohara, Takashi
	Singh, Ritesh
	Elboray, Elghareeb E.
	Hu, Chenliang
	Zamani, Farzad
	Mukherjee, Anirban
	Takada, Yuri
	Yamashita, Yasunobu
	Morita, Mie
	Horinaka, Mano
	Sowa, Yoshihiro
	Masuda, Mitsuharu
	Sakai, Toshiyuki
	Suzuki, Takayoshi
citation_publisher	American Chemical Society
citation_language	English
citation_date	2022-10-13
citation_journal_title	ACS Medicinal Chemistry Letters
citation_volume	13
citation_issue	10
citation_firstpage	1568
citation_lastpage	1573
citation_doi	https://doi.org/10.1021/acsmedchemlett.2c00126
citation_public_url	https://hdl.handle.net/11094/89872

Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates

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