Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA

Kun Fang; Guoqiang Dong; Hongyu Wang; Shipeng He; Shanchao Wu; Wei Wang; Chunquan Sheng

doi:10.1002/cmdc.201700666

Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA

Kun Fang
, Guoqiang Dong
, Hongyu Wang
, Shipeng He
, Shanchao Wu
, Wei Wang
, Chunquan Sheng

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

24 Scopus citations

Abstract

Herein we report the first exploration of a dual-targeting drug design strategy to improve the efficacy of small-molecule cancer immunotherapy. New hybrids of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first-in-class examples of such molecules, they were found to exhibit significantly enhanced anticancer activity in vitro and in vivo with low toxicity. This proof-of-concept study has established a critical step toward the development of a novel and effective immunotherapy for the treatment of cancers.

Original language	English (US)
Pages (from-to)	30-36
Number of pages	7
Journal	ChemMedChem
Volume	13
Issue number	1
DOIs	https://doi.org/10.1002/cmdc.201700666
State	Published - Jan 8 2018
Externally published	Yes

Keywords

IDO1
antitumor activity
cancer immunotherapy
multitarget drug design

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
Pharmacology, Toxicology and Pharmaceutics(all)
Organic Chemistry

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10.1002/cmdc.201700666

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title = "Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA",

abstract = "Herein we report the first exploration of a dual-targeting drug design strategy to improve the efficacy of small-molecule cancer immunotherapy. New hybrids of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first-in-class examples of such molecules, they were found to exhibit significantly enhanced anticancer activity in vitro and in vivo with low toxicity. This proof-of-concept study has established a critical step toward the development of a novel and effective immunotherapy for the treatment of cancers.",

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author = "Kun Fang and Guoqiang Dong and Hongyu Wang and Shipeng He and Shanchao Wu and Wei Wang and Chunquan Sheng",

note = "Funding Information: This work was supported by the National Key R\&D Program of China (2017YFA0506000 to C.S.) and the National Natural Science Foundation of China (21738002 to W.W. and C.S., and 81725020 to C.S.). Publisher Copyright: {\textcopyright} 2018 Wiley-VCH Verlag GmbH \& Co. KGaA, Weinheim",

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doi = "10.1002/cmdc.201700666",

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AU - Fang, Kun

AU - Dong, Guoqiang

AU - Wang, Hongyu

AU - He, Shipeng

AU - Wu, Shanchao

AU - Wang, Wei

AU - Sheng, Chunquan

N1 - Funding Information: This work was supported by the National Key R&D Program of China (2017YFA0506000 to C.S.) and the National Natural Science Foundation of China (21738002 to W.W. and C.S., and 81725020 to C.S.). Publisher Copyright: © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2018/1/8

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N2 - Herein we report the first exploration of a dual-targeting drug design strategy to improve the efficacy of small-molecule cancer immunotherapy. New hybrids of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first-in-class examples of such molecules, they were found to exhibit significantly enhanced anticancer activity in vitro and in vivo with low toxicity. This proof-of-concept study has established a critical step toward the development of a novel and effective immunotherapy for the treatment of cancers.

AB - Herein we report the first exploration of a dual-targeting drug design strategy to improve the efficacy of small-molecule cancer immunotherapy. New hybrids of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and DNA alkylating nitrogen mustards that respectively target IDO1 and DNA were rationally designed. As the first-in-class examples of such molecules, they were found to exhibit significantly enhanced anticancer activity in vitro and in vivo with low toxicity. This proof-of-concept study has established a critical step toward the development of a novel and effective immunotherapy for the treatment of cancers.

KW - IDO1

KW - antitumor activity

KW - cancer immunotherapy

KW - multitarget drug design

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Improving the Potency of Cancer Immunotherapy by Dual Targeting of IDO1 and DNA

Abstract

Keywords

ASJC Scopus subject areas

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