Pracinostat

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Pracinostat
Pracinostat.svg
Names
IUPAC name
(E)-3-(2-Butyl-1-(2-(diethylamino)ethyl)-1H-benzo[d]imidazol-5-yl)-N-hydroxyacrylamide
Other names
Pracinostat
Identifiers
3D model (JSmol)
ChemSpider
Properties
C20H30N4O2
Molar mass 358.486 g·mol−1
Density 1.1±0.1 g/cm3
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Pracinostat (SB939) is an orally bioavailable, small-molecule histone deacetylase (HDAC) inhibitor based on hydroxamic acid with potential anti-tumor activity characterized by favorable physicochemical, pharmaceutical, and pharmacokinetic properties.

Activity[edit]

Pracinostat selectively inhibits HDAC class I,II,IV without class III and HDAC6 in class IV,[1] but has no effect on other Zn-binding enzymes, receptors, and ion channels. It accumulates in tumor cells and exerts a continuous inhibition to histone deacetylase,resulting in acetylated histones accumulation, chromatin remodeling, tumor suppressor genes transcription, and ultimately, apoptosis of tumor cells.[2]

Clinical medication[edit]

Clinical studies suggests that pracinostat has potential best pharmacokinetic properties when compared to other oral HDAC inhibitors.[3] In March 2014, pracinostat has granted Orphan Drug for acute myelocytic leukemia (AML) and for the treatment of T-cell lymphoma by the Food and Drug Administration.

References[edit]

  1. ^ "In vitro enzyme activity of SB939 and SAHA". 22 Aug 2014.
  2. ^ "The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML". Blood Cancer Journal. doi:10.1038/bcj.2012.14. PMC 3366067.
  3. ^ Veronica Novotny-Diermayr; et al. (March 9, 2010). "SB939, a Novel Potent and Orally Active Histone Deacetylase Inhibitor with High Tumor Exposure and Efficacy in Mouse Models of Colorectal Cancer". Mol Cancer Ther. doi:10.1158/1535-7163.MCT-09-0689.