Description
Key facts
CAS number:209986-17-4,
Purity:>99%,
Form:SolidSee storage information,
Molecular weight:490.5 Da,
Molecular formula:C27H24F2N4O3,
PubChem:11306390,
Nature:Synthetic,
Solubility:Soluble in DMSO to 100 mM,
Biochemical name:gamma-Secretase Inhibitor XXI,
Biological description:Cell-permeable, selective, non-competitive, potent γ-secretase inhibitor (IC50 = 0.3 nM). Active in vitro and in vivo.,
Canonical smiles:CC(C(=O)NC1C(=O)N(C2=CC=CC=C2C(=N1)C3=CC=CC=C3)C)NC(=O)CC4=CC(=CC(=C4)F)F,
Isomeric smiles:C[C@@H](C(=O)N[C@@H]1C(=O)N(C2=CC=CC=C2C(=N1)C3=CC=CC=C3)C)NC(=O)CC4=CC(=CC(=C4)F)F,
InChi:InChI=1S/C27H24F2N4O3/c1-16(30-23(34)14-17-12-19(28)15-20(29)13-17)26(35)32-25-27(36)33(2)22-11-7-6-10-21(22)24(31-25)18-8-4-3-5-9-18/h3-13,15-16,25H,14H2,1-2H3,(H,30,34)(H,32,35)/t16-,25+/m0/s1,
InChiKey:JNGZXGGOCLZBFB-IVCQMTBJSA-N,
IUPAC Name:(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]propanamide
Product details:
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Properties and Storage Information:
Shipped at conditions-Ambient - Can Ship with Ice, Appropriate short-term storage conditions--20°C, Appropriate long-term storage conditions--20°C, Storage information-Store under desiccating conditions, The product can be stored for up to 12 months
Supplementary Information:
This supplementary information is collated from multiple sources and compiled automatically.
PS-1 and PS-2 have strong associations with Alzheimer's disease and familial early-onset Alzheimer's patients. Mutations in the presenilin genes lead to altered gamma-secretase activity resulting in increased production of amyloid-beta 42 a toxic form that is more prone to aggregation. These malfunctions are often observed in people with Alzheimer's and highlight the pathogenic role of altered presenilin activity alongside the amyloid precursor protein and tau another protein commonly associated with Alzheimer-related neurodegeneration.
Pathways
PS-1 and PS-2 are central to the Notch signaling pathway and amyloid precursor protein processing. Within these pathways gamma-secretase plays an essential role in cleaving substrates which allows for proper signaling and cellular communication. Here APP and Notch are critical substrates processed by this proteolytic activity. Other related proteins include the ligands for Notch signaling which presenilins help process through their enzymatic function in the gamma-secretase complex.
Biological function summary
Presenilins are important for the intramembrane proteolysis of various type 1 transmembrane proteins. They function as part of the gamma-secretase complex to facilitate the cleavage of amyloid precursor protein (APP) which is an essential process for generating amyloid-beta peptides. These peptides can aggregate and form plaques linked to neurodegeneration. The gamma-secretase complex includes other important proteins like PEN2 Aph1a and Aph1b which together with presenilins execute the proteolytic process.
Presenilin 1 (PS-1) and Presenilin 2 (PS-2) also known as AD5 are integral membrane proteins that act mechanically as the catalytic core of the gamma-secretase complex. PS-1 has a molecular mass of about 467 amino acids while PS-2 is 448 amino acids. These proteins are expressed primarily in the endoplasmic reticulum and the Golgi apparatus across many tissues including neurons. They form a complex with accessory proteins such as PEN2 and either Aph1a or Aph1b which are necessary for the gamma-secretase activity.
