Discovery of O-alkylamino-tethered niclosamide derivatives as potent and orally bioavailable anticancer agents

Haijun Chen; Zhengduo Yang; Chunyong Ding; Lili Chu; Yusong Zhang; Kristin Terry; Huiling Liu; Qiang Shen; Jia Zhou

doi:10.1021/ml3003082

Discovery of O-alkylamino-tethered niclosamide derivatives as potent and orally bioavailable anticancer agents

Haijun Chen, Zhengduo Yang, Chunyong Ding, Lili Chu, Yusong Zhang, Kristin Terry, Huiling Liu, Qiang Shen, Jia Zhou

Pharmacology & Toxicology

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

93 Scopus citations

Abstract

Niclosamide has been identified to potently inhibit the activation, nuclear translocation, and transactivation of STAT3. Nevertheless, the poor aqueous solubility and bioavailability of niclosamide have hindered its further clinical development for cancer therapy. To discover new molecules with enhanced druglike properties, a series of novel O-alkylamino-tethered derivatives of niclosamide have been designed, synthesized, and biologically evaluated. Among them, compound 11 (HJC0152) has been demonstrated to significantly suppress MDA-MB-231 xenograft tumor growth in vivo (ip and po), indicating its great potential as efficacious and orally bioavailable therapeutics for human cancer.

Original language	English (US)
Pages (from-to)	180-185
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	4
Issue number	2
DOIs	https://doi.org/10.1021/ml3003082
State	Published - Feb 14 2013

Keywords

STAT3
niclosamide derivatives
orally bioavailable
water solubility

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1021/ml3003082

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title = "Discovery of O-alkylamino-tethered niclosamide derivatives as potent and orally bioavailable anticancer agents",

abstract = "Niclosamide has been identified to potently inhibit the activation, nuclear translocation, and transactivation of STAT3. Nevertheless, the poor aqueous solubility and bioavailability of niclosamide have hindered its further clinical development for cancer therapy. To discover new molecules with enhanced druglike properties, a series of novel O-alkylamino-tethered derivatives of niclosamide have been designed, synthesized, and biologically evaluated. Among them, compound 11 (HJC0152) has been demonstrated to significantly suppress MDA-MB-231 xenograft tumor growth in vivo (ip and po), indicating its great potential as efficacious and orally bioavailable therapeutics for human cancer.",

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T1 - Discovery of O-alkylamino-tethered niclosamide derivatives as potent and orally bioavailable anticancer agents

AU - Chen, Haijun

AU - Yang, Zhengduo

AU - Ding, Chunyong

AU - Chu, Lili

AU - Zhang, Yusong

AU - Terry, Kristin

AU - Liu, Huiling

AU - Shen, Qiang

AU - Zhou, Jia

PY - 2013/2/14

Y1 - 2013/2/14

N2 - Niclosamide has been identified to potently inhibit the activation, nuclear translocation, and transactivation of STAT3. Nevertheless, the poor aqueous solubility and bioavailability of niclosamide have hindered its further clinical development for cancer therapy. To discover new molecules with enhanced druglike properties, a series of novel O-alkylamino-tethered derivatives of niclosamide have been designed, synthesized, and biologically evaluated. Among them, compound 11 (HJC0152) has been demonstrated to significantly suppress MDA-MB-231 xenograft tumor growth in vivo (ip and po), indicating its great potential as efficacious and orally bioavailable therapeutics for human cancer.

AB - Niclosamide has been identified to potently inhibit the activation, nuclear translocation, and transactivation of STAT3. Nevertheless, the poor aqueous solubility and bioavailability of niclosamide have hindered its further clinical development for cancer therapy. To discover new molecules with enhanced druglike properties, a series of novel O-alkylamino-tethered derivatives of niclosamide have been designed, synthesized, and biologically evaluated. Among them, compound 11 (HJC0152) has been demonstrated to significantly suppress MDA-MB-231 xenograft tumor growth in vivo (ip and po), indicating its great potential as efficacious and orally bioavailable therapeutics for human cancer.

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KW - niclosamide derivatives

KW - orally bioavailable

KW - water solubility

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Discovery of O-alkylamino-tethered niclosamide derivatives as potent and orally bioavailable anticancer agents

Abstract

Keywords

ASJC Scopus subject areas

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