Azalanstat dihydrochloride | CAS#143484-79-1 | lanosterol Inhibitor

MedKoo Cat#: 465846 | Name: Azalanstat HCl

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Azalanstat is an anti-obesity drug acting as a lanosterol 14α-demethylase inhibitor. Azalanstat has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg/kg/day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg/kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1.

Chemical Structure

Azalanstat HCl

CAS#143484-82-6 (HCl)

Theoretical Analysis

MedKoo Cat#: 465846

Name: Azalanstat HCl

CAS#: 143484-82-6 (HCl)

Chemical Formula: C22H26Cl3N3O2S

Exact Mass: 0.0000

Molecular Weight: 502.88

Elemental Analysis: C, 52.55; H, 5.21; Cl, 21.15; N, 8.36; O, 6.36; S, 6.38

Price and Availability

Size	Price	Availability
1mg	USD 150.00	Ready to Ship
5mg	USD 450.00	Ready to Ship
10mg	USD 750.00	Ready to Ship
25mg	USD 1,350.00	Ready to Ship
50mg	USD 2,450.00	Ready to Ship
100mg	USD 3,650.00	Ready to Ship

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Related CAS #

143484-82-6 (HCl) 143393-27-5 (free base) 143484-77-9 (sulfate) 143484-80-4 (mesylate) 143484-81-5 (phosphate) 143484-78-0 (maleate) 143484-79-1 (2 maleate)

Synonym

Azalanstat dihydrochloride; Azalanstat HCl; RS-21607-197; RS 21607-197; RS21607-197; RS-21607197; RS 21607197; RS21607197;

IUPAC/Chemical Name

Benzenamine, 4-(((2-(2-(4-chlorophenyl)ethyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methyl)thio)-, dihydrochloride, (2S-cis)-

InChi Key

UTHWWPSFKXCLMU-HWELVIDPSA-N

InChi Code

1S/C22H24ClN3O2S.2ClH/c23-18-3-1-17(2-4-18)9-10-22(15-26-12-11-25-16-26)27-13-20(28-22)14-29-21-7-5-19(24)6-8-21;;/h1-8,11-12,16,20H,9-10,13-15,24H2;2*1H/t20-,22-;;/m0../s1

SMILES Code

NC1=CC=C(SC[C@H]2O[C@](CN3C=CN=C3)(CCC4=CC=C(Cl)C=C4)OC2)C=C1.[H]Cl.[H]Cl

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#Y22X12M06

QC Data

View QC data: current batch, Lot#Y22X12M06

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Azalanstat is an anti-obesity drug acting as a lanosterol 14α-demethylase inhibitor.

In vitro activity:

The deduced aa sequence shows a high degree of identity to the yeast LDM (lanosterol 14 alpha-demythylase) sequences, as well as sequences which match typical P-450 sequence motifs. When produced in a baculovirus/insect cell culture system, LDM activity was detected and inhibited by the specific inhibitor azalanstat with an IC50 value of less than 2 nM. The isolation of this full-length coding sequence should facilitate research into understanding the direct and indirect effects of LDM in the regulation of cholesterol biosynthesis and the search for cholesterol-lowering drugs. Reference: Gene. 1995 Aug 19;161(2):243-8. https://pubmed.ncbi.nlm.nih.gov/7665087/

In vivo activity:

Therefore, this study investigated the efficacy of azalanstat (AZA), an imidazole-dioxolane, towards inhibiting HO activity in 7-day-old mice. This study found that a single dose of AZA at 500 micromol.kg(-1) body mass (BM) administered i.p. significantly inhibited HO activity and reduced in vivo bilirubin production. Reference: Can J Physiol Pharmacol. 2008 Oct;86(10):651-9. https://pubmed.ncbi.nlm.nih.gov/18841169/

Preparing Stock Solutions

The following data is based on the product molecular weight 502.88 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Sloane DL, So OY, Leung R, Scarafia LE, Saldou N, Jarnagin K, Swinney DC. Cloning and functional expression of the cDNA encoding rat lanosterol 14-alpha demethylase. Gene. 1995 Aug 19;161(2):243-8. doi: 10.1016/0378-1119(95)00211-n. PMID: 7665087. 2. Burton PM, Swinney DC, Heller R, Dunlap B, Chiou M, Malonzo E, Haller J, Walker KA, Salari A, Murakami S, et al. Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with cholesterol-lowering activity. Biochem Pharmacol. 1995 Aug 8;50(4):529-44. doi: 10.1016/0006-2952(95)00152-p. PMID: 7646560. 3. Morisawa T, Wong RJ, Bhutani VK, Vreman HJ, Stevenson DK. Inhibition of heme oxygenase activity in newborn mice by azalanstat. Can J Physiol Pharmacol. 2008 Oct;86(10):651-9. doi: 10.1139/y08-069. PMID: 18841169. 4. Swinney DC, So OY, Watson DM, Berry PW, Webb AS, Kertesz DJ, Shelton EJ, Burton PM, Walker KA. Selective inhibition of mammalian lanosterol 14 alpha-demethylase by RS-21607 in vitro and in vivo. Biochemistry. 1994 Apr 19;33(15):4702-13. doi: 10.1021/bi00181a030. PMID: 8161528.

In vitro protocol:

In vivo protocol:

1. Morisawa T, Wong RJ, Bhutani VK, Vreman HJ, Stevenson DK. Inhibition of heme oxygenase activity in newborn mice by azalanstat. Can J Physiol Pharmacol. 2008 Oct;86(10):651-9. doi: 10.1139/y08-069. PMID: 18841169. 2. Swinney DC, So OY, Watson DM, Berry PW, Webb AS, Kertesz DJ, Shelton EJ, Burton PM, Walker KA. Selective inhibition of mammalian lanosterol 14 alpha-demethylase by RS-21607 in vitro and in vivo. Biochemistry. 1994 Apr 19;33(15):4702-13. doi: 10.1021/bi00181a030. PMID: 8161528.

1: Burton PM, Swinney DC, Heller R, Dunlap B, Chiou M, Malonzo E, Haller J, Walker KA, Salari A, Murakami S, et al. Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with cholesterol-lowering activity. Biochem Pharmacol. 1995 Aug 8;50(4):529-44. doi: 10.1016/0006-2952(95)00152-p. PMID: 7646560. 2: Vlahakis JZ, Kinobe RT, Bowers RJ, Brien JF, Nakatsu K, Szarek WA. Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors. Bioorg Med Chem Lett. 2005 Mar 1;15(5):1457-61. doi: 10.1016/j.bmcl.2004.12.075. PMID: 15713406. 3: Morisawa T, Wong RJ, Bhutani VK, Vreman HJ, Stevenson DK. Inhibition of heme oxygenase activity in newborn mice by azalanstat. Can J Physiol Pharmacol. 2008 Oct;86(10):651-9. doi: 10.1139/y08-069. PMID: 18841169. 4: Salerno L, Floresta G, Ciaffaglione V, Gentile D, Margani F, Turnaturi R, Rescifina A, Pittalà V. Progress in the development of selective heme oxygenase-1 inhibitors and their potential therapeutic application. Eur J Med Chem. 2019 Apr 1;167:439-453. doi: 10.1016/j.ejmech.2019.02.027. Epub 2019 Feb 12. PMID: 30784878. 5: Vlahakis JZ, Kinobe RT, Bowers RJ, Brien JF, Nakatsu K, Szarek WA. Imidazole- dioxolane compounds as isozyme-selective heme oxygenase inhibitors. J Med Chem. 2006 Jul 13;49(14):4437-41. doi: 10.1021/jm0511435. PMID: 16821802. 6: Rahman MN, Vukomanovic D, Vlahakis JZ, Szarek WA, Nakatsu K, Jia Z. Structural Insights into Azole-based Inhibitors of Heme Oxygenase-1: Development of Selective Compounds for Therapeutic Applications. Curr Med Chem. 2018;25(42):5803-5821. doi: 10.2174/0929867325666180606082512. PMID: 30674243. 7: Rahman MN, Vlahakis JZ, Roman G, Vukomanovic D, Szarek WA, Nakatsu K, Jia Z. Structural characterization of human heme oxygenase-1 in complex with azole- based inhibitors. J Inorg Biochem. 2010 Mar;104(3):324-30. doi: 10.1016/j.jinorgbio.2009.10.011. Epub 2009 Oct 24. PMID: 19917515. 8: Intagliata S, Salerno L, Ciaffaglione V, Leonardi C, Fallica AN, Carota G, Amata E, Marrazzo A, Pittalà V, Romeo G. Heme Oxygenase-2 (HO-2) as a therapeutic target: Activators and inhibitors. Eur J Med Chem. 2019 Dec 1;183:111703. doi: 10.1016/j.ejmech.2019.111703. Epub 2019 Sep 17. PMID: 31550661. 9: Pittalà V, Salerno L, Romeo G, Modica MN, Siracusa MA. A focus on heme oxygenase-1 (HO-1) inhibitors. Curr Med Chem. 2013;20(30):3711-32. doi: 10.2174/0929867311320300003. PMID: 23746277. 10: Vaknin KM, Lazar S, Popliker M, Tsafriri A. Role of meiosis-activating sterols in rat oocyte maturation: effects of specific inhibitors and changes in the expression of lanosterol 14alpha-demethylase during the preovulatory period. Biol Reprod. 2001 Jan;64(1):299-309. doi: 10.1095/biolreprod64.1.299. PMID: 11133687. 11: Rahman MN, Vukomanovic D, Vlahakis JZ, Szarek WA, Nakatsu K, Jia Z. Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds. J R Soc Interface. 2013 Jan 6;10(78):20120697. doi: 10.1098/rsif.2012.0697. Epub 2012 Nov 8. PMID: 23097500; PMCID: PMC3565801. 12: Ahmed H, McLaughlin BE, Soong J, Marks GS, Brien JF, Nakatsu K. The source of endogenous carbon monoxide formation in human placental chorionic villi. Cell Mol Biol (Noisy-le-grand). 2005 Oct 3;51(5):447-51. PMID: 16309566. 13: Vlahakis JZ, Hum M, Rahman MN, Jia Z, Nakatsu K, Szarek WA. Synthesis and evaluation of imidazole-dioxolane compounds as selective heme oxygenase inhibitors: effect of substituents at the 4-position of the dioxolane ring. Bioorg Med Chem. 2009 Mar 15;17(6):2461-75. doi: 10.1016/j.bmc.2009.01.078. Epub 2009 Feb 12. PMID: 19268600. 14: Sloane DL, So OY, Leung R, Scarafia LE, Saldou N, Jarnagin K, Swinney DC. Cloning and functional expression of the cDNA encoding rat lanosterol 14-alpha demethylase. Gene. 1995 Aug 19;161(2):243-8. doi: 10.1016/0378-1119(95)00211-n. PMID: 7665087. 15: Floresta G, Fallica AN, Romeo G, Sorrenti V, Salerno L, Rescifina A, Pittalà V. Identification of a potent heme oxygenase-2 (HO-2) inhibitor by targeting the secondary hydrophobic pocket of the HO-2 western region. Bioorg Chem. 2020 Nov;104:104310. doi: 10.1016/j.bioorg.2020.104310. Epub 2020 Sep 24. PMID: 33010625. 16: Wang C, Xie H, Song X, Ning G, Yan J, Chen X, Xu B, Ouyang H, Xia G. Lanosterol 14alpha-demethylase expression in the mouse ovary and its participation in cumulus-enclosed oocyte spontaneous meiotic maturation in vitro. Theriogenology. 2006 Sep 15;66(5):1156-64. doi: 10.1016/j.theriogenology.2006.01.065. Epub 2006 May 2. PMID: 16650467. 17: Xie H, Xia G, Byskov AG, Andersen CY, Bo S, Tao Y. Roles of gonadotropins and meiosis-activating sterols in meiotic resumption of cultured follicle- enclosed mouse oocytes. Mol Cell Endocrinol. 2004 Apr 15;218(1-2):155-63. doi: 10.1016/j.mce.2003.11.030. PMID: 15130520. 18: Jin S, Zhang M, Lei L, Wang C, Fu M, Ning G, Xia G. Meiosis activating sterol (MAS) regulate FSH-induced meiotic resumption of cumulus cell-enclosed porcine oocytes via PKC pathway. Mol Cell Endocrinol. 2006 Apr 25;249(1-2):64-70. doi: 10.1016/j.mce.2006.01.008. Epub 2006 Feb 24. PMID: 16500744. 19: Swinney DC, So OY, Watson DM, Berry PW, Webb AS, Kertesz DJ, Shelton EJ, Burton PM, Walker KA. Selective inhibition of mammalian lanosterol 14 alpha- demethylase by RS-21607 in vitro and in vivo. Biochemistry. 1994 Apr 19;33(15):4702-13. doi: 10.1021/bi00181a030. PMID: 8161528. 20: Hrboticky N, Becker A, Kruse HJ, Weber PC. Increased cellular triglyceride levels in human monocytic and rat smooth muscle cells after lovastatin. Biochim Biophys Acta. 1997 Nov 30;1349(3):211-21. doi: 10.1016/s0005-2760(97)00136-7. PMID: 9434135.

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Description:

Chemical Structure

Theoretical Analysis

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