pracinostat   Click here for help

GtoPdb Ligand ID: 8365

Synonyms: SB 939 | SB-939
Compound class: Synthetic organic
Comment: Pracinostat is an orally available, potent pan-HDAC inhibitor [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 70.39
Molecular weight 358.24
XLogP 3.19
No. Lipinski's rules broken 0
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Canonical SMILES CCCCc1nc2c(n1CCN(CC)CC)ccc(c2)C=CC(=O)NO
Isomeric SMILES CCCCc1nc2c(n1CCN(CC)CC)ccc(c2)/C=C/C(=O)NO
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+
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Summary of Clinical Use Click here for help
In March 2014, the US FDA granted pracinostat orphan designation for the treatment of the rare disease acute myelocytic leukemia (AML). In addition, the drug is currently being tested in Phase 2 trials in combination with azacitidine for the treatment of newly diagnosed AML in elderly patients (NCT01912274) and a further Phase 2 trial is assessing pracinostat + the Janus kinase inhibitor ruxolitinib in patients with myelofibrosis (MF) (see NCT02267278).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
HDAC inhibitors have shown clinical efficacy in AML, myelodysplastic syndrome and myeloproliferative neoplasms [2,4]. The HDAC inhibitor vorinostat was the first compound designed to inhibit HDACs to be approved for clinical use. HDAC inhibition increases acetylation of histone H3 and leads to downstream activation of the PI3K/Akt and MAPK/Ras signaling pathways and ultimately results in cell cycle arrest and apoptosis [1]. Mithraprabhu et al (2010) review the use of HDAC inhibitors in myeloproliferative neoplasms, and discuss the benefits of combination therapies with kinase inhibitors [2].