Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jan 15;18(2):573-9.
doi: 10.1016/j.bmc.2009.12.012. Epub 2009 Dec 11.

Design and synthesis of selective inhibitors of placental alkaline phosphatase

Marion Lanier  1 , Eduard Sergienko, Ana Maria Simão, Ying Su, Thomas Chung, José Luis Millán, John R Cashman
Affiliations

Design and synthesis of selective inhibitors of placental alkaline phosphatase

Marion Lanier et al. Bioorg Med Chem. .

Abstract

Placental Alkaline Phosphatase (PLAP) is a tissue-restricted isozyme of the Alkaline Phosphatase (AP) superfamily. PLAP is an oncodevelopmental enzyme expressed during pregnancy and in a variety of human cancers, but its biological function remains unknown. We report here a series of catechol compounds with great affinity for the PLAP isozyme and significant selectivity over other members of the AP superfamily. These selective PLAP inhibitors will provide small molecule probes for the study of the pathophysiological role of PLAP.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Examples of AP inhibitors
Figure 2
Figure 2
Depiction of the three regions of screening “hit” 1 explored by chemical synthesis: Left Hand Side (LHS), Right Hand Side (RHS) and Linker region (encircled).
Figure 3
Figure 3
Examples of commercially available analogs 27-33 purchased and their IC50 values in the PLAP assay.
Figure 4
Figure 4
Effect of increasing concentrations of compound 1, 8, 11 and 17 on the inhibition of PLAP (●) and GCAP (○).
Figure 5
Figure 5
Summary of the IC50 values for selective PLAP inhibitors 10, 13 and 20.
Scheme 1
Scheme 1
Synthetic approach to explore the SAR of the LHS and RHS of screening “hit” 1; preparation of analogs 3-20, X is nitrogen or sulfur. (a) 1 equiv. HXR2R3, dioxane.
Scheme 2
Scheme 2
Synthetic approach to explore the linker region of screening “hit” 1: preparation of analogs 22, 25 and 26. (a) 2-amino 4,6-dimethyl pyrimidine, NaBH(OAc)3, DCE; (b) 4,5-dimethyl 2-furoic acid, HBTU, DIEA, DMF
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Millán JL. Mammalian alkaline phosphatases. From Biology to Applications in Medicine and Biotechnology. Wiley-VCH Verlag GmbH & Co; Weinheim, Germany: 2006. pp. 1–322.
    1. McComb RB, Bowers GN, Jr, Posen S. Alkaline Phosphatase. New York: Plenum; 1979.
    1. Galperin MY, Bairoch A, Koonin EV. Protein Sci. 1998;7:1829. - PMC - PubMed
    1. Hessle L, Johnson KA, Anderson HC, Narisawa S, Sali A, Goding JW, Terkeltaub R, Millán JL. Proc Natl Acad Sci U S A. 2002;99:9445. - PMC - PubMed
    1. Harmey D, Hessle L, Narisawa S, Johnson KA, Terkeltaub R, Millán JL. Am J Pathol. 2004;164:1199. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources