γ-Secretase

γ-secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1 and PEN-2. γ-secretase is involved in the processing of Notch.

Products
Background
Literature
Gene Data

Modulators

Cat. No. Product Name / Activity
5550 E 2012
γ-secretase modulator; Notch-sparing
4898 TC-E 5006
γ-secretase modulator; reduces Aβ42 levels

Inhibitors

Cat. No. Product Name / Activity
6363 Avagacestat
Highly potent γ-secretase inhibitor; orally bioavailable
4283 Begacestat
γ-secretase inhibitor; lowers Aβ40 and Aβ42 levels
2870 BMS 299897
Potent γ-secretase inhibitor
6476 Compound E
γ-secretase inhibitor; induces neuronal differentiation
2654 Compound W
γ-secretase inhibitor
2634 DAPT
γ-secretase inhibitor
4489 DBZ
γ-secretase inhibitor; inhibits Notch pathway
4495 Flurizan
γ-secretase inhibitor; lowers Aβ42 levels in vitro
2677 JLK 6
Inhibitor of γ-secretase-mediated βAPP processing
2627 L-685,458
Potent and selective γ-secretase inhibitor
6559 LY 450139
γ-secretase pseudo-inhibitor
4000 MRK 560
γ-secretase inhibitor; attenuates amyloid plaque deposition
5751 PF 3084014 hydrobromide
Potent γ-secretase inhibitor

Related Targets

    γ-secretase is a multi-subunit internal protease that cleaves within the transmembrane domain of its substrates. It is an integral membrane protein and minimally consists of four proteins; presenilin, nicastrin, APH-1 and PEN-2. Presenilin is an aspartic protease and the catalytic subunit of the complex.

    γ-secretase is involved in the processing of Notch. The Notch receptor is a single transmembrane spanning protein involved in angiogenesis and cell differentiation during embryonic and adult life. Upon ligand binding, the extracellular domain is cleaved by a metalloprotease named TACE. Following this initial cleavage, γ-secretase cleaves within the transmembrane domain of the remaining Notch protein, releasing the intracellular domain (Nβ) into the cytoplasm. Nβ moves to the nucleus where it upregulates transcription of target genes such as Hes1, Hey1 and Hey2. Deficient Notch signaling impairs developmental angiogenesis in the embryo and prevents wound healing in adult tissues.

    External sources of pharmacological information for γ-Secretase :

      Literature for γ-Secretase

      Tocris offers the following scientific literature for γ-Secretase to showcase our products. We invite you to request* or download your copy today!

      *Please note that Tocris will only send literature to established scientific business / institute addresses.


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      γ-Secretase Gene Data

      Gene Species Gene Symbol Gene Accession No. Protein Accession No.
      Presenilin-1 Human PSEN1 NM_000021 P49768
      Mouse Psen1 NM_008943 P49769
      Rat Psen1 NM_019163 P97887
      Presenilin-2 Human PSEN2 NM_000447 P49810
      Mouse Psen2 NM_001128605 Q61144
      Rat Psen2 NM_031087 O88777
      Nicastrin Human NCSTN NM_015331 Q92542
      Mouse Ncstn NM_021607 P57716
      Rat Ncstn NM_174864 Q8CGU6
      APH1A Human APH1A NM_016022 Q96BI3
      Mouse Aph1a NM_146104 Q8BVF7
      Rat Aph1a NM_001014255 Q5PQQ3
      APH1B Human APH1B NM_031301 Q8WW43
      Mouse Aph1b NM_177583 Q8C7N7
      Rat Aph1b NM_001047090 Q0PY50
      PEN-2 Human PSENEN NM_172341 Q9NZ42
      Mouse Psenen NM_025498 Q9CQR7
      Rat Psenen NM_001008764 Q6QI68
      CD147 Human BSG NM_001728 P35613
      Mouse Bsg NM_009768 P18572