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Wnt&Beta catenin

AZD3839 (1227163-84-9)

AZD3839 (free base) is a potent and selective BACE1 inhibitor with IC50 of 23.6 uM, about 14-fold selectivity over BACE2, also a β-secretase enzyme inhibitor.

Not Intended for Therapeutic Use. For research use only.

CAS: 1227163-84-9 Category

AZD3839 (1227163-84-9) Description

AZD3839 (free base) is a potent and selective BACE1 inhibitor with IC50 of 23.6 uM, about 14-fold selectivity over BACE2, also a β-secretase enzyme inhibitor. target: BACE1, β-secretase enzyme [1] IC50: 23.6 uM [1] AZD3839 dissolved in 0.33% dimethylsulfoxide In vitro: AZD3839 and its metabolites M1 and M2 inhibited CYP3A4 in a reversible and an irreversible manner, which could affect not only the metabolism of other CYP3A4 substrates but also the metabolism of AZD3839 itself. [1] In vivo: AZD3839 is dissolved in 0.3 M gluconic acid, adjusted to pH 3. Solutions of 0.75, 2.5, and 7.5 mg/ml are prepared and are administered orally by gavage at 2 ml body weight at 1.5, 5, and 15 mg (study 1) and 15 mg (study 2). [1]AZD3839 effectively reduces the levels of Aβ in brain, CSF, and plasma in several preclinical species.

AZD3839 is a potent and selective BACE1 inhibitor. AZD3839 is clinical candidate for the treatment of Alzheimer disease. AZD3839 inhibits BACE1 activity, Aβ and sAPPβ release from modified and wild-type human SH-SY5Y cells and mouse N2A cells as well as from mouse and guinea pig primary cortical neurons. Selectivity against BACE2 and cathepsin D was 14 and >1000-fold, respectively. AZD3839 exhibits dose- and time-dependent lowering of plasma, brain, and cerebrospinal fluid Aβ levels in mouse, guinea pig, and non-human primate. AZD3839 effectively reduces the levels of Aβ in brain, CSF, and plasma in several preclinical species.

 

AZD3839 (1227163-84-9) Specifications

Product Name AZD3839
Synonym AZD3839; AZD-3839; AZD 3839.
Chemical Name (S)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine
Drug Class N/A
Purity ≥ >98% (or refer to the Certificate of Analysis)
CAS Number 1227163-84-9
Molecular Formula C24H16F3N5
Molecular Weight 431.4222
Monoisotopic Mass 431.136 g/mol
MDL number N/A
InChIKey MRXBCEQZNKUUIP-DEOSSOPVSA-N
InChi Code InChI=1S/C24H16F3N5/c25-19-6-2-5-18-21(19)23(28)32-24(18,17-7-8-31-20(10-17)22(26)27)16-4-1-3-14(9-16)15-11-29-13-30-12-15/h1-13,22H,(H2,28,32)/t24-/m0/s1
SMILES NC1=N[[email protected]@](C2=CC=CC(C3=CN=CN=C3)=C2)(C4=CC(C(F)F)=NC=C4)C5=C1C(F)=CC=C5
Form Solid powder
Color N/A
Solubility  Soluble in DMSO
Storage Temp.  0 – 4 C for short term (days to weeks), or -20 C for long term (months)
Shelf life > >2 years if stored properly
Handling Protect from air and light
Application AZD3839 (free base) is a potent and selective BACE1 inhibitor with IC50 of 23.6 uM, about 14-fold selectivity over BACE2, also a β-secretase enzyme inhibitor.

 


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RIDADR NONH for all modes of transport

References:

  • 1: Sparve E, Quartino AL, Lüttgen M, Tunblad K, Gårdlund AT, Fälting J, Alexander R, Kågström J, Sjödin L, Bulgak A, Al-Saffar A, Bridgland-Taylor M, Pollard C, Swedberg MD, Vik T, Paulsson B. Prediction and modeling of effects on the QTc interval for clinical safety margin assessment, based on single-ascending-dose study data with AZD3839. J Pharmacol Exp Ther. 2014 Aug;350(2):469-78. doi: 10.1124/jpet.114.215202. Epub 2014 Jun 10. PubMed PMID: 24917547.
  • 2: Lindgren A, Eklund G, Turek D, Malmquist J, Swahn BM, Holenz J, von Berg S, Karlström S, Bueters T. Biotransformation of two β-secretase inhibitors including ring opening and contraction of a pyrimidine ring. Drug Metab Dispos. 2013 May;41(5):1134-47. doi: 10.1124/dmd.112.050351. Epub 2013 Mar 8. PubMed PMID: 23474650.
  • 3: Aasa J, Hu Y, Eklund G, Lindgren A, Baranczewski P, Malmquist J, Turek D, Bueters T. Effect of solvents on the time-dependent inhibition of CYP3A4 and the biotransformation of AZD3839 in human liver microsomes and hepatocytes. Drug Metab Dispos. 2013 Jan;41(1):159-69. doi: 10.1124/dmd.112.047597. Epub 2012 Oct 16. PubMed PMID: 23073735.
  • 4: Jeppsson F, Eketjäll S, Janson J, Karlström S, Gustavsson S, Olsson LL, Radesäter AC, Ploeger B, Cebers G, Kolmodin K, Swahn BM, von Berg S, Bueters T, Fälting J. Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease. J Biol Chem. 2012 Nov 30;287(49):41245-57. doi: 10.1074/jbc.M112.409110. Epub 2012 Oct 9. PubMed PMID: 23048024; PubMed Central PMCID: PMC3510823.
  • 5: Swahn BM, Kolmodin K, Karlström S, von Berg S, Söderman P, Holenz J, Berg S, Lindström J, Sundström M, Turek D, Kihlström J, Slivo C, Andersson L, Pyring D, Rotticci D, Ohberg L, Kers A, Bogar K, von Kieseritzky F, Bergh M, Olsson LL, Janson J, Eketjäll S, Georgievska B, Jeppsson F, Fälting J. Design and synthesis of β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors with in vivo brain reduction of β-amyloid peptides. J Med Chem. 2012 Nov 8;55(21):9346-61. doi: 10.1021/jm3009025. Epub 2012 Sep 17. PubMed PMID: 22924815.