2. Academic Validation
  3. Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation

Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation

  • Molecules. 2018 Oct 24;23(11):2750. doi: 10.3390/molecules23112750.
Jitendra Shrestha 1,  Sung Hwan Ki 2,  Sang Mi Shin 3,  Seon Woong Kim 4,  Joo-Youn Lee 5 6,  Hee-Sook Jun 7 8,  Taeho Lee 9,  Sanghee Kim 10,  Dong Jae Baek 11,  Eun-Young Park 12
Affiliations

Affiliations

  • 1 College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea. [email protected].
  • 2 College of Pharmacy, Chosun University, Gwangju, 61452, Korea. [email protected].
  • 3 College of Pharmacy, Chosun University, Gwangju, 61452, Korea. [email protected].
  • 4 College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea. [email protected].
  • 5 College of Pharmacy, Seoul National University, Seoul 08826, Korea. [email protected].
  • 6 Korea Chemical Bank, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea. [email protected].
  • 7 Lee Gil Ya Cancer and Diabetes Institute, Department of Molecular Medicine, Gachon University, Incheon 21999, Korea. [email protected].
  • 8 College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Korea. [email protected].
  • 9 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea. [email protected].
  • 10 College of Pharmacy, Seoul National University, Seoul 08826, Korea. [email protected].
  • 11 College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea. [email protected].
  • 12 College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 58554, Korea. [email protected].
PMID: 30355990 DOI: 10.3390/molecules23112750
Abstract

FTY720 inhibits various cancers through PP2A activation. The structure of FTY720 is also used as a basic structure for the design of sphingosine kinase (SK) inhibitors. We have synthesized derivatives using an amide chain in FTY720 with a phenyl backbone, and then compounds were screened by an MTT cell viability assay. The PP2A activity of compound 7 was examined. The phosphorylation levels of Akt and ERK, downstream targets of PP2A, in the presence of compound 7, were determined. Compound 7 may exhibit Anticancer effects through PP2A activation rather than the mechanism by inhibition of SK1 in Cancer cells. In the docking study of compound 7 and PP2A, the amide chain of compound 7 showed an interaction with Asn61 that was different from FTY720, which is expected to affect the activity of the compound.

Keywords

FTY720; colorectal cancer; derivative; protein phosphatase 2A; sphingosine kinase.

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