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. 2024 Jul 2;14(1):15100.
doi: 10.1038/s41598-024-65668-z.

Design and radiosynthesis of class-IIa HDAC inhibitor with high molar activity via repositioning the 18F-radiolabel

Sulan Xu  1   2 , Chun-Han Huang  1   2   3 , Christopher Eyermann  1   4 , Georgios V Georgakis  1   4 , Nashaat Turkman  5   6   7
Affiliations

Design and radiosynthesis of class-IIa HDAC inhibitor with high molar activity via repositioning the 18F-radiolabel

Sulan Xu et al. Sci Rep. .

Abstract

The design and radiosynthesis of [18F]NT376, a high potency inhibitor of class-IIa histone deacetylases (HDAC) is reported. We utilized a three-step radiochemical approach that led to the radiosynthesis of [18F]NT376 in a good radiochemical yield, (17.0 ± 3%, decay corrected), high radiochemical purity (> 97%) and relatively high molar activity of 185.0 GBq/µmol (> 5.0 Ci/µmol). The repositioning of the 18F-radiolabel into a phenyl ring (18F-Fluoro-aryl) of the class-IIa HDAC inhibitor avoided the shortcomings of the direct radiolabeling of the 5-trifluoromethyl-1,2,4-oxadiazole moiety that was reported by us previously and was associated with low molar activity (0.74-1.51 GBq/µmol, 20-41 mCi/µmol). This radiochemical approach could find a wider application for radiolabeling similar molecules with good radiochemical yield and high molar activity.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Chemical structures of the previously reported radiolabeled inhibitors of class-IIa HDACs, and current work.
Figure 2
Figure 2
Chemical synthesis of NT376.
Figure 3
Figure 3
Selective endogenous class-IIa HDACs inhibition by NT376 in HT-29 cell line.
Figure 4
Figure 4
Synthesis of the key nitro-precursor 7 and intermediate 8.
Figure 5
Figure 5
Radiosynthesis of [18F]NT376.
See this image and copyright information in PMC

References

    1. Linares A, et al. Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers. Mol. Oncol. 2019;13:1534–1547. doi: 10.1002/1878-0261.12505. - DOI - PMC - PubMed
    1. Rastogi B, et al. Overexpression of HDAC9 promotes oral squamous cell carcinoma growth, regulates cell cycle progression, and inhibits apoptosis. Mol. Cell Biochem. 2016;415:183–196. doi: 10.1007/s11010-016-2690-5. - DOI - PubMed
    1. Wanek J, et al. Pharmacological inhibition of class IIA HDACs by LMK-235 in pancreatic neuroendocrine tumor cells. Int. J. Mol. Sci. 2018 doi: 10.3390/ijms19103128. - DOI - PMC - PubMed
    1. Wang Z, et al. A small molecular compound CC1007 induces cross-lineage differentiation by inhibiting HDAC7 expression and HDAC7/MEF2C interaction in BCR-ABL1(-) pre-B-ALL. Cell Death Dis. 2020;11:738. doi: 10.1038/s41419-020-02949-1. - DOI - PMC - PubMed
    1. Yu D, et al. VEGF-PKD1-HDAC7 signaling promotes endothelial progenitor cell migration and tube formation. Microvasc. Res. 2014;91:66–72. doi: 10.1016/j.mvr.2013.10.006. - DOI - PubMed

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