Crystal structure of sphingosine kinase 1 with PF-543

Wang, Jing and Knapp, Stefan and Pyne, Nigel J. and Pyne, Susan and Elkins, Jonathan M. (2014) Crystal structure of sphingosine kinase 1 with PF-543. Medicinal Chemistry Letters, 5 (12). pp. 1329-1333. ISSN 1948-5875 (https://doi.org/10.1021/ml5004074)

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Abstract

The most potent inhibitor of Sphingosine Kinase 1 (SPHK1) so far identified is PF-543. The crystal structure of SPHK1 in complex with inhibitor PF-543 to 1.8 Å resolution reveals the inhibitor bound in a bent conformation analogous to that expected of a bound sphingosine substrate but with a rotated head group. The structural data presented will aid in the design of SPHK1 and SPHK2 inhibitors with improved properties.

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