Pracinostat

Pracinostat
Names
	Preferred IUPAC name (2E)-3-{2-Butyl-1-[2-(diethylamino)ethyl]-1H-1,3-benzimidazol-5-yl}-N-hydroxyprop-2-enamide
	Other names Pracinostat
Identifiers
CAS Number	929016-96-6 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:95071;
ChemSpider	25027185;
PubChem CID	49855250;
UNII	GPO2JN4UON ;
CompTox Dashboard (EPA)	DTXSID00239196 ;
	InChI InChI=1S/C20H30N4O2/c1-4-7-8-19-21-17-15-16(10-12-20(25)22-26)9-11-18(17)24(19)14-13-23(5-2)6-3/h9-12,15,26H,4-8,13-14H2,1-3H3,(H,22,25)/b12-10+ Key: JHDKZFFAIZKUCU-ZRDIBKRKSA-N; InChI=1/C20H30N4O2/c1-4-7-8-19-21-17-15-16(10-12-20(25)22-26)9-11-18(17)24(19)14-13-23(5-2)6-3/h9-12,15,26H,4-8,13-14H2,1-3H3,(H,22,25)/b12-10+ Key: JHDKZFFAIZKUCU-ZRDIBKRKBK;
	SMILES CCCCC1=NC2=C(N1CCN(CC)CC)C=CC(=C2)/C=C/C(=O)NO;
Properties
Chemical formula	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

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

^ "In vitro enzyme activity of SB939 and SAHA". 22 Aug 2014.
^ 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.
^ 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.

[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.

[1]

[2]

[3]