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Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation.

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.

SUBMITTER: Shrestha J

PROVIDER: S-EPMC6278267 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Synthesis of Novel FTY720 Analogs with Anticancer Activity through PP2A Activation.

Shrestha Jitendra J Ki Sung Hwan SH Shin Sang Mi SM Kim Seon Woong SW Lee Joo-Youn JY Jun Hee-Sook HS Lee Taeho T Kim Sanghee S Baek Dong Jae DJ Park Eun-Young EY

Molecules (Basel, Switzerland) 20181024 11

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 <b>7</b> was examined. The phosphorylation levels of AKT and ERK, downstream targets of PP2A, in the presence of compound <b>7</b>, were determined. ...[more]

PMID: 30355990

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