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

Pracinostat selectively inhibits HDAC class I, II, IV without class III and HDAC6 in class IIb,[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

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

  1. ^ "In vitro enzyme activity of SB939 and SAHA". 22 Aug 2014.
  2. ^ Novotny-Diermayr, V.; Hart, S.; Goh, K. C.; Cheong, A.; Ong, L-C; Hentze, H.; Pasha, M. K.; Jayaraman, R.; Ethirajulu, K.; Wood, J. M. (2012). "The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML". Blood Cancer Journal. 2 (5): e69–. doi:10.1038/bcj.2012.14. PMC 3366067. PMID 22829971.
  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. 9 (3): 642–652. doi:10.1158/1535-7163.MCT-09-0689. PMID 20197387.