ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity

Binbin Wu; Jack C.H. Chen; Chloe H.Y. Ma; Maxwell Kwok; Valerie T. Chan; Chun C. Sung; Yi Song; Tao Zhang; Hin S. Lam; Fang Meng; Yonghao Liang; Chantelle Tsoi; Ruixia Deng; Stephen K.W. Tsui; Kam T. Leung; Chi C. Wang; Godfrey C.F. Chan; Kenneth R. Boheler; Kenny K.K. Chung; Ellen N. Poon

doi:10.1016/j.jacbts.2025.101459

ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity

Binbin Wu
, Jack C.H. Chen
, Chloe H.Y. Ma
, Maxwell Kwok
, Valerie T. Chan
, Chun C. Sung
, Yi Song
, Tao Zhang
, Hin S. Lam
, Fang Meng
, Yonghao Liang
, Chantelle Tsoi
, Ruixia Deng
, Stephen K.W. Tsui
, Kam T. Leung
, Chi C. Wang
, Godfrey C.F. Chan
, Kenneth R. Boheler
, Kenny K.K. Chung
, Ellen N. Poon

Research output: Contribution to journal › Article › peer-review

Abstract

Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell–derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.

Original language	English (US)
Article number	101459
Journal	JACC: Basic to Translational Science
Volume	11
Issue number	2
DOIs	https://doi.org/10.1016/j.jacbts.2025.101459
State	Published - Feb 2026
Externally published	Yes

Keywords

ICG-001
cardiotoxicity
doxorubicin
human pluripotent stem cell derived cardiomyocytes
mitochondria

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2025.101459

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Wu, B., Chen, J. C. H., Ma, C. H. Y., Kwok, M., Chan, V. T., Sung, C. C., Song, Y., Zhang, T., Lam, H. S., Meng, F., Liang, Y., Tsoi, C., Deng, R., Tsui, S. K. W., Leung, K. T., Wang, C. C., Chan, G. C. F., Boheler, K. R., Chung, K. K. K., & Poon, E. N. (2026). ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity. JACC: Basic to Translational Science, 11(2), Article 101459. https://doi.org/10.1016/j.jacbts.2025.101459

Wu, B, Chen, JCH, Ma, CHY, Kwok, M, Chan, VT, Sung, CC, Song, Y, Zhang, T, Lam, HS, Meng, F, Liang, Y, Tsoi, C, Deng, R, Tsui, SKW, Leung, KT, Wang, CC, Chan, GCF, Boheler, KR, Chung, KKK & Poon, EN 2026, 'ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity', JACC: Basic to Translational Science, vol. 11, no. 2, 101459. https://doi.org/10.1016/j.jacbts.2025.101459

@article{54d25bb4499f4a93967149730fa38e70,

title = "ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity",

abstract = "Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell{\textendash}derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.",

keywords = "ICG-001, cardiotoxicity, doxorubicin, human pluripotent stem cell derived cardiomyocytes, mitochondria",

author = "Binbin Wu and Chen, \{Jack C.H.\} and Ma, \{Chloe H.Y.\} and Maxwell Kwok and Chan, \{Valerie T.\} and Sung, \{Chun C.\} and Yi Song and Tao Zhang and Lam, \{Hin S.\} and Fang Meng and Yonghao Liang and Chantelle Tsoi and Ruixia Deng and Tsui, \{Stephen K.W.\} and Leung, \{Kam T.\} and Wang, \{Chi C.\} and Chan, \{Godfrey C.F.\} and Boheler, \{Kenneth R.\} and Chung, \{Kenny K.K.\} and Poon, \{Ellen N.\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors.",

year = "2026",

month = feb,

doi = "10.1016/j.jacbts.2025.101459",

language = "English (US)",

volume = "11",

journal = "JACC: Basic to Translational Science",

issn = "2452-302X",

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T1 - ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity

AU - Wu, Binbin

AU - Chen, Jack C.H.

AU - Ma, Chloe H.Y.

AU - Kwok, Maxwell

AU - Chan, Valerie T.

AU - Sung, Chun C.

AU - Song, Yi

AU - Zhang, Tao

AU - Lam, Hin S.

AU - Meng, Fang

AU - Liang, Yonghao

AU - Tsoi, Chantelle

AU - Deng, Ruixia

AU - Tsui, Stephen K.W.

AU - Leung, Kam T.

AU - Wang, Chi C.

AU - Chan, Godfrey C.F.

AU - Boheler, Kenneth R.

AU - Chung, Kenny K.K.

AU - Poon, Ellen N.

PY - 2026/2

Y1 - 2026/2

N2 - Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell–derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.

AB - Doxorubicin is effective against cancer but can cause doxorubicin-induced cardiotoxicity (DCT). Drug discovery efforts against DCT are hampered by the need to balance cardioprotection and cancer control. This study demonstrates that ICG-001 suppressed DCT in patient-derived human induced pluripotent stem cell–derived cardiomyocytes in vitro and in mice in vivo, comparable to conventional treatment, dexrazoxane. Unlike dexrazoxane, ICG-001 was cytotoxic to cancer cells. Mechanistically, ICG-001 protected the mitochondria in cardiomyocytes via DPR1 inhibition, but suppressed cancer by repressing Wnt signaling. These dual mechanisms underscore the potential of ICG-001 as an adjunct treatment to doxorubicin to improve its safety and efficacy.

KW - ICG-001

KW - cardiotoxicity

KW - doxorubicin

KW - human pluripotent stem cell derived cardiomyocytes

KW - mitochondria

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ICG-001 Provides Cardioprotection Against Doxorubicin-Induced Cardiotoxicity and Enhances Cancer Cytotoxicity

Abstract

Keywords

ASJC Scopus subject areas

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