Name:	ST101
Other Names:	spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one, ZSET1446
Therapy Types:	Oral, small molecule
Development Status:	investigational in U.S.
FDA Phase:	Inactive
Role in Alzheimer's Disease:	ZSET1446/ST101 is an azaindolizinone derivative compound that has demonstrated cognitive enhancer activity in numerous rodent models of cognitive impairment, improving methamphetamine-induced memory impairment in rats (Ito et al 2007), olfactory bulbectomy-induced cognitive deficits in mice (Han et al 2008). In Alzheimer’s Disease-related preclinical tests, ZSET1446 improves cognitive function impaired by ICV Abeta(1-40) infusion or scopolamine-induced memory deficits, and stimulates acetylcholine release (Yamaguchi et al 2006). Chronic administration of ZSET1446 improved neurogenesis impairment following olfactory bulbectomy in mice (Shioda et al 2010), stimulating ERK and PI3K/Akt pathways in new dentate gyrus neurons.
Companies:	Sonexa Therapeutics, Inc.
Notes:	For clinical trials of ST101 for Alzheimer's disease on clinicaltrials.gov see ST101 trials. This entry was last updated December 12, 2011.

References

Shioda N, Yamamoto Y, Han F, Moriguchi S, Yamaguchi Y, Hino M, Fukunaga K. A novel cognitive enhancer, ZSET1446/ST101, promotes hippocampal neurogenesis and ameliorates depressive behavior in olfactory bulbectomized mice. J Pharmacol Exp Ther. 2010 Apr;333(1):43-50. POW link

Han F, Shioda N, Moriguchi S, Yamamoto Y, Raie AY, Yamaguchi Y, Hino M, Fukunaga K. Spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101) treatment rescues olfactory bulbectomy-induced memory impairment by activating Ca2+/calmodulin kinase II and protein kinase C in mouse hippocampus. J Pharmacol Exp Ther. 2008 Jul;326(1):127-34. POW link

Ito Y, Takuma K, Mizoguchi H, Nagai T, Yamada K. A novel azaindolizinone derivative ZSET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) improves methamphetamine-induced impairment of recognition memory in mice by activating extracellular signal-regulated kinase 1/2. J Pharmacol Exp Ther. 2007 Feb;320(2):819-27. POW link

Yamaguchi Y, Miyashita H, Tsunekawa H, Mouri A, Kim HC, Saito K, Matsuno T, Kawashima S, Nabeshima T. Effects of a novel cognitive enhancer, spiro[imidazo-[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446), on learning impairments induced by amyloid-beta1-40 in the rat. J Pharmacol Exp Ther. 2006 Jun;317(3):1079-87. POW link