Cofttek holdings limited

Gamma Secretase

YO-01027 (Dibenzazepine) (209984-56-5)

YO-01027 (Dibenzazepine) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively.

Not Intended for Therapeutic Use. For research use only.

CAS: 209984-56-5 Category

YO-01027 (Dibenzazepine) (209984-56-5) Description:

Dibenzazepine, also known as YO-01027 and Iminostilbene, is a potent γ-secretase inhibitor. Dibenzazepine also potently blocks amyloid precursor protein-like (APPL) and Notch cleavage. γ-Secretase is a fascinating, multi-subunit, intramembrane cleaving protease that is now being considered as a therapeutic target for a number of diseases. Potent, orally bioavailable γ-secretase inhibitors (GSIs) have been developed and tested in humans with Alzheimer’s disease (AD) and cancer.

YO-01027 is a dipeptidic gamma-secretase inhibitor with IC50 of 2.6 and 2.9 nM for the proteolysis of APPL and Notch, respectively. YO-01027 is used as an anti-Alzheimer agent. YO-01027 directly interact with the gamma-secretase complex. Unlike other gamma-secretase inhibitors,YO-01027 targets different functional domain of the complex. YO-01027 targets the N-terminal Presenilin fragment as well as another gamma-secretase inhibitor Compound E (Cpn E), whereas DFK167 and DAPT, another two gamma-secretase inhibitors, bind to the catalytic site of the Presenilin aspartyl protease subunit and the C-terminal Presenilin fragment, respectively. In a study, YO-01027 and CpnE indicated no apparent discrimination in blocking APPL and Notch cleavages, displaying statistically equivalent IC50 values for both substrates.

YO-01027 (Dibenzazepine) (209984-56-5) Specifications:

Product Name YO-01027(Dibenzazepine)
Synonyms YO-01027; YO 01027; YO01027; Dibenzazepine; DBZ; Iminostilbene; Deshydroxy LY-411575.
Chemical Names (S)-2-(2-(3,5-difluorophenyl)acetamido)-N-((S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)propanamide
Purity >98% (or refer to the Certificate of Analysis)
CAS Number 209984-56-5
Molecular Formula C26H23F2N3O3
Molecular Weight 463.48
Monoisotopic Mass 463.171 g/mol
MDL number N/A
InChIKey QSHGISMANBKLQL-OWJWWREXSA-N
InChi Code InChI=1S/C26H23F2N3O3/c1-15(29-23(32)13-16-11-17(27)14-18(28)12-16)25(33)30-24-21-9-4-3-7-19(21)20-8-5-6-10-22(20)31(2)26(24)34/h3-12,14-15,24H,13H2,1-2H3,(H,29,32)(H,30,33)/t15-,24-/m0/s1
SMILES C[[email protected]](NC(CC1=CC(F)=CC(F)=C1)=O)C(N[[email protected]@H]2C(N(C)C3=CC=CC=C3C4=CC=CC=C24)=O)=O
Form Powder
Color Yellow to orange
Solubility  Soluble in DMSO, not in water
Storage Temp.  Dry, dark and at 0 – 4 C for short term (days to weeks) or -20 C for long term (months to years).
Shelf life >2 years if stored properly
Handling Protect from air and light
Application Inhibits γ-secretase and Notch signaling

 


=

RIDADR NONH for all modes of transport

References:

  • 1: Sanabría CM, Palma A, Cobo J, Glidewell C. Three closely related dibenzazepine carboxylic acids: hydrogen-bonded aggregation in one, two and three dimensions. Acta Crystallogr C Struct Chem. 2014 Mar;70(Pt 3):332-7. doi: 10.1107/S2053229614003568. Epub 2014 Feb 22. PubMed PMID: 24594729.
  • 2: Zheng YH, Li FD, Tian C, Ren HL, Du J, Li HH. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One. 2013 Dec 16;8(12):e83310. doi: 10.1371/journal.pone.0083310. eCollection 2013. PubMed PMID: 24358274; PubMed Central PMCID: PMC3865307.
  • 3: Tsoung J, Panteleev J, Tesch M, Lautens M. Multicomponent-multicatalyst reactions (MC)(2)R: efficient dibenzazepine synthesis. Org Lett. 2014 Jan 3;16(1):110-3. doi: 10.1021/ol4030925. Epub 2013 Dec 13. PubMed PMID: 24328339.
  • 4: Al-Tel TH, Al-Qawasmeh RA, Schmidt MF, Al-Aboudi A, Rao SN, Sabri SS, Voelter W. Rational design and synthesis of potent dibenzazepine motifs as beta-secretase inhibitors. J Med Chem. 2009 Oct 22;52(20):6484-8. doi: 10.1021/jm9008482. PubMed PMID: 19788239.
  • 5: Al-Qawasmeh RA, Lee Y, Cao MY, Gu X, Viau S, Lightfoot J, Wright JA, Young AH. 11-Phenyl-[b,e]-dibenzazepine compounds: novel antitumor agents. Bioorg Med Chem Lett. 2009 Jan 1;19(1):104-7. doi: 10.1016/j.bmcl.2008.11.001. Epub 2008 Nov 6. PubMed PMID: 19027297.