Inhibitor of hedgehog (Hh) signaling
Cholesterol synthesis inhibitor; inhibits both 7-dehydrocholesterol 7-reductase and 8,7-sterol isomerase. A sonic hedgehog inhibitor
Inhibitor of hedgehog (Hh) signaling, possibly via several mechanisms. Inhibits Δ 7 -dehydrocholesterol reductase (IC 50 = 13 nM), thus reduces cholesterol biosynthesis, and also inhibits cholesterol esterification. May also directly block the cellular response to Hh proteins. Teratogenic in vivo .
Poison by ingestion.Experimental teratogenic and reproductive effects.Inhibits cholesterol synthesis. When heated todecomposition it emits very toxic fumes of NOx and Cl-.
AY 9944 (7.5 mg/kg; i.h. every 6 days once from postnatal day 2 to postnatal day 20) reduces brain cholesterol until 400 days after stop treatment[3].
| Animal Model: | Long–Evans hooded rats[3]. |
| Dosage: | 7.5 mg/kg |
| Administration: | Subcutaneous injection; 7.5 mg/kg every 6 days once; from postnatal day 2 to postnatal day 20 |
| Result: | Reduced brain cholesterol and increased 7-dehydrocholesterol in all brain regions of rats till the treatment stopped for 400 days and showed a more severe effect on the change of sterols in plasma and liver of female rats. |
room temperature (desiccate)
[1]. moebius, f.f., et al., molecular cloning and expression of the human delta7-sterol reductase. proc natl acad sci u s a, 1998. 95(4): p. 1899-902.
[2]. achour, a., et al., restoration of immune response by a cationic amphiphilic drug (ay 9944) in vitro: a new approach to chemotherapy against human immunodeficiency virus type 1. antimicrob agents chemother, 1998. 42(10): p. 2482-91.
[3]. xu, l., et al., novel oxysterols observed in tissues and fluids of ay9944-treated rats: a model for smith-lemli-opitz syndrome. j lipid res, 2011. 52(10): p. 1810-20.
