AY 9944

AY 9944 prevents cholesterol biosynthesis by inhibiting the 7-dehydro cholesterol Δ⁷-reductase (DHCR7) enzyme (IC₅₀ = 13 nM), which interferes with the conversion of 7-dehydro cholesterol (Item No. 14612) to cholesterol.^1,2 Furthermore, by upregulating the expression of DHCR7, AY 9944 can block Hedgehog signaling at the level of Smoothened or by loss of Suppressor of Fused.³ AY 9944 inhibition of DHCR7 has been used to recapitulate phenotypes of Smith-Lemli-Opitz syndrome, a disorder brought about by mutations in the DHCR7 gene, in animal models.^2,4 However, AY 9944 is highly teratogenic, producing congenital defects in offspring when fed to pregnant animals.⁵

WARNING This product is not for human or veterinary use.

1. Horlick, L. Effect of a new inhibitor of cholesterol biosynthesis (AY 9944) on serum and tissue sterols in the rat. J. Lipid Res. 7(1), 116-121 (1966).

2. Moebius, F.F., Fitzky, B.U., Lee, J.N., et al. Molecular cloning and expression of the human Δ7-sterol reductase. Proc. Natl. Acad. Sci. USA 95(4), 1899-1902 (1998).

3. Lauth, M., Rohnalter, V., Bergström, A., et al. Antipsychotic drugs regulate hedgehog signaling by modulation of 7-dehydrocholesterol reductase levels. Mol. Pharmacol. 78(3), 486-496 (2010).

4. Keller, R.K., Mitchell, D.A., Goulah, C.C., et al. Hepatic isoprenoid metabolism in a rat model of Smith-Lemli-Opitz Syndrome. Lipids 48(3), 219-229 (2013).

5. Xu, G., Salen, G., Shefer, S., et al. Reproducing abnormal cholesterol biosynthesis as seen in the Smith-Lemli-Opitz syndrome by inhibiting the conversion of 7-dehydrocholesterol to cholesterol in rats. J. Clin. Invest. 95(1), 76-81 (1995).