. Author manuscript; available in PMC: 2013 Aug 1.

Published in final edited form as: Nat Med. 2012 Aug;18(8):1194–1204. doi: 10.1038/nm.2828

Table 2.

Chromatin modifying drugs as potential therapies for neurological disease

Drug type and mechanism	Representative compound(s)	CNS effects in preclinical models	FDA approval for non-neurological condition
Sequesters DNMT at DNA replication fork	5-aza-cytidine, zebularine (nucleoside analogues)	Disrupted hippocampal learning and also reward behavior^87–90 in wild-type mice and rats. Conferred stroke protection in mice ^93,94	Yes
DNMT active site inhibitor	RG108	Prevented cell death in a mouse model of motor neuron disease model ⁵¹. Impaired hippocampal learning⁹² in rats.
Class I/II HDAC inhibitor	phenylbutyrate, SAHA, TSA	Had a broad neuroprotective profile in acute and chronic injury and neurodegeneration models, including ischemia, Huntington’s and other polyglutamine andtriplet diseases, and a Parkinson’s disease model (MPTP toxicity)^8–11 Improved hippocampus-dependent learning and cognition and exerted antidepressant-like effects ^62,63	Yes
Class III HDAC inhibitor	nicotinamide AGK2	Reduced amounts of phospho-tau and improved cognition in hippocampal learning tasks in a mouse model of Alzheimer’s disease⁷³ Reduced α-synuclein toxicity and dopaminergic cell death in a Drosophila model of Parkinson’s disease ⁷⁴
Histone methyltransferase Glp/G9a inhibitor	BIX-01294	Enhanced reward behavior in mice after exposure to a stimulant drug (cocaine)⁸⁵
p300 histone acetyl transferase inhibitor	C646	Reduced amounts of tau l and neurotoxicity in cultured rat neurons and cells from people with Alzheimer’s disease⁷¹.
Topoisomerase I inhibitor	Topotecan, irinotecan	Reversed imprinting-mediated silencing of Ube3a(the Angelman’s syndrome gene) in mouse brain ⁹⁶	Yes
Topoisomerase II inhibitor	Etoposide, dexrazoxane	Reversed imprinting-mediated silencing of Ube3a in mouse brain⁹⁶	Yes