2. Academic Validation
  3. Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs

Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs

  • Eur J Med Chem. 2020 Jun 15;196:112271. doi: 10.1016/j.ejmech.2020.112271.
Chao Wang 1,  Dandan Xi 2,  Han Wang 2,  Yan Niu 2,  Lei Liang 2,  Fengrong Xu 2,  Yihong Peng 3,  Ping Xu 4
Affiliations

Affiliations

  • 1 National Pharmaceutical Teaching Laboratory Center, School of Pharmaceutical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
  • 2 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
  • 3 Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
  • 4 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. Electronic address: pingxu@bjmu.edu.cn.
PMID: 32305784 DOI: 10.1016/j.ejmech.2020.112271
Abstract

A series of hybrids of MEK Inhibitor and nitric oxide donor have been designed and synthesized. Compound 18h [4-(3-((3-(2-fluoro-3-((N-methylsulfamoyl)amino)benzyl)-4-methyl-2-oxo-2H-chromen-7-yl)oxy) propoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide] was proven to be more potent than the clinical compound RO5126766 in MDA-MB-231 cells. Compound 18h can significantly reduce the levels of pMEK and PERK, induce cell Apoptosis in MDA-MB-231 cells, and release NO in cells efficiently, suggesting that these hybrids, while displaying the properties of both MEK inhibitors and NO donors have a mechanism of action different from that of MEK inhibitors and NO donors. Thus, we are able to report a series of multitarget hybrids with better antitumor potency than a known MEK Inhibitor and NO donor.

Keywords

Antitumor; Hybrid; MEK; Multitarget; NO donor.

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