Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors.

ABSTRACT:

Purpose

Sphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile.

Methods

Field template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models.

Results

Field template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new S

SUBMITTER: Alshaker H 

PROVIDER: S-EPMC6208908 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature