AY 9944 dihydrochlorideHedgehog Inhibitor CAS# 366-93-8 |
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Quality Control & MSDS
3D structure
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| Cas No. | 366-93-8 | SDF | Download SDF |
| PubChem ID | 9704 | Appearance | Powder |
| Formula | C22H30Cl4N2 | M.Wt | 464.3 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble to 50 mM in water | ||
| Chemical Name | N-[(2-chlorophenyl)methyl]-1-[4-[[(2-chlorophenyl)methylamino]methyl]cyclohexyl]methanamine;dihydrochloride | ||
| SMILES | C1CC(CCC1CNCC2=CC=CC=C2Cl)CNCC3=CC=CC=C3Cl.Cl.Cl | ||
| Standard InChIKey | NRVIEWRSGDDWHP-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C22H28Cl2N2.2ClH/c23-21-7-3-1-5-19(21)15-25-13-17-9-11-18(12-10-17)14-26-16-20-6-2-4-8-22(20)24;;/h1-8,17-18,25-26H,9-16H2;2*1H | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Inhibitor of hedgehog (Hh) signaling, possibly via several mechanisms. Inhibits Δ7-dehydrocholesterol reductase (IC50 = 13 nM), thus reduces cholesterol biosynthesis, and also inhibits cholesterol esterification. May also directly block the cellular response to Hh proteins. Teratogenic in vivo. |
AY 9944 dihydrochloride Dilution Calculator
AY 9944 dihydrochloride Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.1538 mL | 10.7689 mL | 21.5378 mL | 43.0756 mL | 53.8445 mL |
| 5 mM | 0.4308 mL | 2.1538 mL | 4.3076 mL | 8.6151 mL | 10.7689 mL |
| 10 mM | 0.2154 mL | 1.0769 mL | 2.1538 mL | 4.3076 mL | 5.3844 mL |
| 50 mM | 0.0431 mL | 0.2154 mL | 0.4308 mL | 0.8615 mL | 1.0769 mL |
| 100 mM | 0.0215 mL | 0.1077 mL | 0.2154 mL | 0.4308 mL | 0.5384 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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AY 9944 dihydrochloride is a selective inhibitor of Δ7-sterol reductase with IC50 value of 13 nM [1].
Δ7-sterol reductase (Dhcr7) is an enzyme and plays an important role in catalyzing the production of cholesterol from 7-Dehydrocholesterol through using NADPH [2, 3].
AY 9944 dihydrochloride is a potentΔ7-sterol reductase inhibitor and has higher inhibition thanΔ7-sterol reductase inhibitor BM15766 and triparanol. When tested with Saccharomyces cerevisiae expressed cDNA without an N-terminal 9E10 c-myc epitope (mycD7-ORF) and 5’ noncoding region (D7-ORF), AY 9944 dihydrochloride exhibited highly inhibition on D7-ORF (recombinant humanΔ7-sterol reductase ) with IC50 value of 13 nM [1]. In PBMCs isolated from AIDS patients, AY 9944 treatment exhibited ability to restore the normal mitogenic responses and cytokine profiles [2].
In Sprague-Dawley rats model of Smith-Lemli-Opitz syndrome, administration of AY9944 elevated 7-DHC expression and reduced cholesterol in all biological tissues by inhibitingΔ7-sterol reductase [3].
References:
[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.
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Cholesterol in signal transduction.[Pubmed:10712926]
Curr Opin Cell Biol. 2000 Apr;12(2):193-203.
Membrane cholesterol impinges on signal transduction in several ways, which is highlighted in particular by the Hedgehog signaling pathway. In Hedgehog signaling, cholesterol is important for ligand biogenesis, as well as for signal transduction in receiving cells. Hedgehog ligands are post-translationally modified by cholesterol, and the Hedgehog receptor, Patched, is structurally similar to the Niemann-Pick C1 protein, which functions in intracellular lipid transport. Although the exact role of cholesterol in Hedgehog signal transduction remains elusive and is probably multifaceted, studies over the past year have implicated raft membrane subdomains, cholesterol transport and a link between protein and lipid trafficking in endocytic compartments.
Teratogen-mediated inhibition of target tissue response to Shh signaling.[Pubmed:9616123]
Science. 1998 Jun 5;280(5369):1603-7.
Veratrum alkaloids and distal inhibitors of cholesterol biosynthesis have been studied for more than 30 years as potent teratogens capable of inducing cyclopia and other birth defects. Here, it is shown that these compounds specifically block the Sonic hedgehog (Shh) signaling pathway. These teratogens did not prevent the sterol modification of Shh during autoprocessing but rather inhibited the response of target tissues to Shh, possibly acting through the sterol sensing domain within the Patched protein regulator of Shh response.
Molecular cloning and expression of the human delta7-sterol reductase.[Pubmed:9465114]
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1899-902.
Inhibitors of the last steps of cholesterol biosynthesis such as AY9944 and BM15766 severely impair brain development. Their molecular target is the Delta7-sterol reductase (EC 1.3.1.21), suspected to be defective in the Smith-Lemli-Opitz syndrome, a frequent inborn disorder of sterol metabolism. Molecular cloning of the cDNA revealed that the human enzyme is a membrane-bound protein with a predicted molecular mass of 55 kDa and six to nine putative transmembrane segments. The protein is structurally related to plant and yeast sterol reductases. In adults the ubiquitously transcribed mRNA is most abundant in adrenal gland, liver, testis, and brain. The Delta7-sterol reductase is the ultimate enzyme of cholesterol biosynthesis in vertebrates and is absent from yeast. Microsomes from Saccharomyces cerevisiae strains heterologously expressing the human cDNA remove the C7-8 double bond in 7-dehydrocholesterol. The conversion to cholesterol depends on NADPH and is potently inhibited by AY9944 (IC50 0.013 microM), BM15766 (IC50 1.2 microM), and triparanol (IC50 14 microM). Our work paves the way to clarify whether a defect in the delta7-sterol reductase gene underlies the Smith-Lemli-Opitz syndrome.
