Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity <i>in vivo</i>.

Luo, Guoshun; Li, Zhenbang; Lin, Xin; Li, Xinyu; Chen, Yu; Xi, Kun; Xiao, Maoxu; Wei, Hanlin; Zhu, Lizhe; Xiang, Hua

Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity in vivo.

Luo, Guoshun; Li, Zhenbang; Lin, Xin; Li, Xinyu; Chen, Yu; Xi, Kun; Xiao, Maoxu; Wei, Hanlin; Zhu, Lizhe; Xiang, Hua.

Afiliación

Luo G; State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Li Z; State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Lin X; State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Li X; School of Life and Health Sciences and Warshel Institute for Computational Biology, the Chinese University of Hong Kong, Shenzhen 518172, China.
Chen Y; Key Laboratory of Smart Drug Delivery, Ministry of Education School of Pharmacy, Fudan University, Shanghai 201203, China.
Xi K; School of Life and Health Sciences and Warshel Institute for Computational Biology, the Chinese University of Hong Kong, Shenzhen 518172, China.
Xiao M; State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Wei H; State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
Zhu L; School of Life and Health Sciences and Warshel Institute for Computational Biology, the Chinese University of Hong Kong, Shenzhen 518172, China.
Xiang H; State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.

Acta Pharm Sin B ; 11(5): 1300-1314, 2021 May.

Article en En | MEDLINE | ID: mdl-34094835

Palabras clave

CRBN, cereblon; CVD, cardiovascular disease; Cholesterol reduction; DC50, half degradation concentration; ER, endoplasmic reticulum; H&E, hematoxylin/eosin; HDAC, histone deacetylase; HMGCR; HMGCR, 3-hydroxy-3-methylglutaryl coenzyme A reductase; LDL-C, low-density lipoprotein cholesterol; MFD, medium fat diet; ORO, oil-red O; Oral bioavailability; PK, pharmacokinetic; PROTAC, proteolysis-targeting chimera; PROTACs; SAR, structureactivity relationship; TC, total cholesterol; TG, triglyceride; VHL, von Hippel-Lindau

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline Idioma: En Revista: Acta Pharm Sin B Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos

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