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Chemical Compound Review

AY-9944     N-[(2-chlorophenyl)methyl]-1- [4-[[(2...

Synonyms: Tocris-1639, CHEMBL2062162, SureCN7614548, SureCN7614558, AC1L1TMV, ...
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Disease relevance of AY-9944


Psychiatry related information on AY-9944


High impact information on AY-9944

  • A time course study that examined the effects of the female estrous cycle on the chronic slow spike-and-wave discharges (SSWDs), gamma-aminobutyric B receptor (GABA(B)R) binding, and GABA(B)R protein expression was conducted in Long Evans hooded rats treated during development with a cholesterol synthesis inhibitor AY9944 (AY) [5].
  • The data indicate that there is a significant increase in both the duration of SSWD and GABA(B)R binding in the AY model, during the proestrus stage of the estrous cycle, the stage during which the levels of progesterone are at their highest [5].
  • The effects of different concentrations of the hypocholesterolemic drug AY9944, an inhibitor of delta7-reductase, on organotypic cultures of fetal mouse spinal cord, were studied by light and electron microscopy [6].
  • Both, hypoosmotic ROS generation and p47(phox) serine phosphorylation were sensitive to the acidic sphingomyelinase inhibitors AY9944 and desipramine, the protein kinase C (PKC)zeta-inhibitory pseudosubstrate peptide, the NMDA receptor antagonist MK-801 and the intracellular Ca(2+) chelator BAPTA-AM [7].
  • The method relies on the ability of AY9944, a potent and relatively selective inhibitor of cholesterol synthesis, to cause the time-dependent accumulation of 7-dehydrocholesterol (DHC), a cholesterol precursor detected with sensitivity and specificity by reverse-phase HPLC-coupled spectrophotometry at 282 nm [8].

Chemical compound and disease context of AY-9944

  • Our aim is to verify the validity of a rat model proposed for Smith-Lemli-Opitz (SLO) syndrome, a developmental disorder characterized by a defect in 7-dehydrocholesterol-delta 7 (7DHC)-reductase and by facial dysmorphism close to the holoprosencephaly caused by the teratogen AY9944 [4].

Biological context of AY-9944


Anatomical context of AY-9944


Associations of AY-9944 with other chemical compounds


Gene context of AY-9944

  • At the early-somite stage we observed a reduction of Shh signaling in AY9944 treated embryos, resulting in the definition of a narrower ventral domain [15].
  • Treatment of pregnant rats with inhibitors of 7-DHC reductase, either AY9944 or BM15.766, has provided a valuable model to study the pathogenesis in SLOS [16].
  • Removal of lipoprotein fraction from culture media corrects the reduction of acid sphingomyelinase activity induced by AY9944 [17].

Analytical, diagnostic and therapeutic context of AY-9944

  • Neonatal treatment of Long-Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 has been shown to increase occurrence of spike-waves in EEG recordings and decrease benzodiazepines sensitivity of GABA(A) receptor-mediated responses in neurons from the thalamic reticular nuclei (nRt, Wu et al., 2004) [18].
  • Inhibition of DNA synthesis occurred if AY9944 was added at the early stages of blast transformation but not when the response was well established [14].


  1. Regulation of bile acid synthesis. V. Inhibition of conversion of 7-dehydrocholesterol to cholesterol is associated with down-regulation of cholesterol 7 alpha-hydroxylase activity and inhibition of bile acid synthesis. Pandak, W.M., Vlahcevic, Z.R., Heuman, D.M., Hylemon, P.B. J. Lipid Res. (1990) [Pubmed]
  2. GABAB receptor antagonism abolishes the learning impairments in rats with chronic atypical absence seizures. Chan, K.F., Burnham, W.M., Jia, Z., Cortez, M.A., Snead, O.C. Eur. J. Pharmacol. (2006) [Pubmed]
  3. Abnormal cholesterol biosynthesis as in Smith-Lemli-Opitz syndrome disrupts normal skeletal development in the rat. Kolf-Clauw, M., Chevy, F., Ponsart, C. J. Lab. Clin. Med. (1998) [Pubmed]
  4. Inhibition of 7-dehydrocholesterol reductase by the teratogen AY9944: a rat model for Smith-Lemli-Opitz syndrome. Kolf-Clauw, M., Chevy, F., Wolf, C., Siliart, B., Citadelle, D., Roux, C. Teratology (1996) [Pubmed]
  5. Hormonal regulation of atypical absence seizures. Persad, V., Ting Wong, C.G., Cortez, M.A., Wang, Y.T., Snead, O.C. Ann. Neurol. (2004) [Pubmed]
  6. Effect of hypocholesterolemic drug AY9944 on cultured nervous tissue: morphologic and biochemical studies. Zagoren, J.C., Suzuki, K., Bornstein, M.B., Chen, S.M., Suzuki, K. J. Neuropathol. Exp. Neurol. (1975) [Pubmed]
  7. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Reinehr, R., Görg, B., Becker, S., Qvartskhava, N., Bidmon, H.J., Selbach, O., Haas, H.L., Schliess, F., Häussinger, D. Glia (2007) [Pubmed]
  8. Enzyme blockade: a nonradioactive method to determine the absolute rate of cholesterol synthesis in the brain. Keller, R.K., Small, M., Fliesler, S.J. J. Lipid Res. (2004) [Pubmed]
  9. Light-induced exacerbation of retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome. Vaughan, D.K., Peachey, N.S., Richards, M.J., Buchan, B., Fliesler, S.J. Exp. Eye Res. (2006) [Pubmed]
  10. Combined effects of AY9944 and plasma LDL (or whole plasma) on lymphocyte blastic transformation. Rampini, C., Adriambinintsoa, C., Barbu, V., Maziere, J.C., Maziere, C., Roux, C. Biochem. Pharmacol. (1989) [Pubmed]
  11. Effects of the cholesterol biosynthesis inhibitor ay9944 on organotypic cultures ofmouse spinal cord. Retarded myelinogenesis and induction of cytoplasmic inclusions. Kim, S.U. Lab. Invest. (1975) [Pubmed]
  12. Effect of hypocholesterolemic agents on central nervous system cholesterol biosynthesis III. Zuclomiphene in combination with AY9944 and triparanol. Ramsey, R.B. Biochem. Pharmacol. (1978) [Pubmed]
  13. The effect of the hypocholesteremic drug, AY 9944 on the synthesis of bile salts in rat liver. Botham, K.M., Boyd, G.S. Eur. J. Biochem. (1981) [Pubmed]
  14. Inhibition of sterol and DNA synthesis in peripheral blood lymphocytes by AY9944. Kay, G., Wilce, P.A. Biochem. Biophys. Res. Commun. (1983) [Pubmed]
  15. Expression of Sonic Hedgehog downstream genes is modified in rat embryos exposed in utero to a distal inhibitor of cholesterol biosynthesis. Gofflot, F., Gaoua, W., Bourguignon, L., Roux, C., Picard, J.J. Dev. Dyn. (2001) [Pubmed]
  16. Absence of ventral cell populations in the developing brain in a rat model of the Smith-Lemli-Opitz syndrome. Gofflot, F., Kolf-Clauw, M., Clotman, F., Roux, C., Picard, J.J. Am. J. Med. Genet. (1999) [Pubmed]
  17. Removal of lipoprotein fraction from culture media corrects the reduction of acid sphingomyelinase activity induced by AY9944. Yoshikawa, H., Sakuragawa, N. J. Inherit. Metab. Dis. (1992) [Pubmed]
  18. Selective changes in thalamic and cortical GABAA receptor subunits in a model of acquired absence epilepsy in the rat. Li, H., Kraus, A., Wu, J., Huguenard, J.R., Fisher, R.S. Neuropharmacology (2006) [Pubmed]
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