Gamma-secretase

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Gamma-secretase Signaling Pathway Map

Gamma-secretase Signaling Pathways

Gamma-secretase Products

  • All (15)
  • Gamma-secretase Inhibitors (12)
  • Gamma-secretase Antibodies (1)
  • Gamma-secretase Modulators (2)
  • New Gamma-secretase Products
Catalog No. Product Name Information Product Use Citations Product Validations
S1262 Avagacestat (BMS-708163) Avagacestat (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.
Cell, 2021, 184(2):521-533.e14
Biochem Biophys Res Commun, 2021, 570:137-142
Carcinogenesis, 2020, 41(7):993-1004
S1575 RO4929097 RO4929097 (RG-4733) is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.
Proc Natl Acad Sci U S A, 2021, 118(22)e2026184118
Cell Rep, 2021, 37(1):109774
Cell Death Differ, 2021, 10.1038/s41418-021-00861-5
S1594 Semagacestat (LY450139) Semagacestat (LY450139) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM in H4 human glioma cell. Phase 3.
Life Sci Alliance, 2021, 4(4)e202000844
Cancer Cell, 2020, 13;37(1):104-122e12
Carcinogenesis, 2020, 41(7):993-1004
S2215 DAPT (GSI-IX) DAPT (GSI-IX, LY-374973) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells. DAPT enhances the apoptosis of human tongue carcinoma cells and regulates autophagy.
Immunity, 2021, S1074-7613(21)00344-7
Neuron, 2021, 109(12):1949-1962.e6
Sci Adv, 2021, 7(5)eabc9781
S2660 MK-0752 MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM. Phase 1/2.
Carcinogenesis, 2020, 41(7):993-1004
Mol Cancer Ther, 2020, molcanther.0654.2020
Sci Rep, 2019, 9(1):1897
S2711 Dibenzazepine (YO-01027) Dibenzazepine (YO-01027, DBZ) 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.
Nature, 2021, 598(7881):510-514
Signal Transduct Target Ther, 2021, 6(1):148
ACS Nano, 2020, 22
S2714 LY411575 LY411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells. LY411575 induces apoptosis.
Nat Commun, 2021, 12(1):6839
J Endocrinol, 2021, JOE-21-0016.R1
Nature, 2020, 10.1038/s41586-020-2946-9
S7169 Crenigacestat (LY3039478) Crenigacestat (LY3039478) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch.
Nucleic Acids Res, 2021, gkab800
Cancer Res, 2021, canres.0524.2021
Oncoimmunology, 2021, 10(1):1881268
S7394 MDL-28170 MDL-28170 (Calpain Inhibitor III) is a potent and selective calpain inhibitor of calpain that penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. MDL-28170 is also an inhibitor of γ-secretase.
S7673 L-685,458 L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.
Biochem Biophys Res Commun, 2021, 570:137-142
Aging (Albany NY), 2020, 12(1):481-501
J Cell Biol, 2019, 218(2):644-663
S8018 Nirogacestat (PF-03084014) Nirogacestat (PF-03084014, PF-3084014) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Nirogacestat (PF-03084014, PF-3084014) induces apoptosis. Phase 2.
Stem Cell Res Ther, 2020, 11(1):258
Pharm Res, 2020, 37(10):185
Mol Ther Oncolytics, 2019, 13:58-66
S8185 FPS-ZM1 FPS-ZM1 is a blood-brain-barrier permeant, non-toxic, tertiary amide compound which is a high affinity RAGE-specific inhibitor, blocking Aβ binding to the V domain of RAGE.
Cell Death Discov, 2021, 7(1):337
J Cancer, 2021, 12(2):518-529
Ann Transl Med, 2021, 9(6):494
A5298 ADAM10 Rabbit Recombinant mAb ADAM10 Rabbit Recombinant mAb detects endogenous level of total ADAM10.
S7323 Itanapraced (CHF 5074) Itanapraced (CHF 5074, CSP-1103) is a gamma-secretase modulator that reduces Aβ42 and Aβ40 secretion. The IC50s of CHF5074 for inhibition of COX-1 and COX-2 is above 100 μmol/L.
S8603 NGP 555 NGP 555 is a small-molecule modulator of γ-secretase and has been successful in achieving good oral absorption, brain penetration, CNS activity, and specificity for a lipid-based membrane target preclinically.
S1262 Avagacestat (BMS-708163) Avagacestat (BMS-708163) is a potent, selective, orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 of 0.3 nM and 0.27 nM, demonstrating a 193-fold selectivity against Notch. Phase 2.
Cell, 2021, 184(2):521-533.e14
Biochem Biophys Res Commun, 2021, 570:137-142
Carcinogenesis, 2020, 41(7):993-1004
S1575 RO4929097 RO4929097 (RG-4733) is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.
Proc Natl Acad Sci U S A, 2021, 118(22)e2026184118
Cell Rep, 2021, 37(1):109774
Cell Death Differ, 2021, 10.1038/s41418-021-00861-5
S1594 Semagacestat (LY450139) Semagacestat (LY450139) is a γ-secretase blocker for Aβ42, Aβ40 and Aβ38 with IC50 of 10.9 nM, 12.1 nM and 12.0 nM, also inhibits Notch signaling with IC50 of 14.1 nM in H4 human glioma cell. Phase 3.
Life Sci Alliance, 2021, 4(4)e202000844
Cancer Cell, 2020, 13;37(1):104-122e12
Carcinogenesis, 2020, 41(7):993-1004
S2215 DAPT (GSI-IX) DAPT (GSI-IX, LY-374973) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells. DAPT enhances the apoptosis of human tongue carcinoma cells and regulates autophagy.
Immunity, 2021, S1074-7613(21)00344-7
Neuron, 2021, 109(12):1949-1962.e6
Sci Adv, 2021, 7(5)eabc9781
S2660 MK-0752 MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM. Phase 1/2.
Carcinogenesis, 2020, 41(7):993-1004
Mol Cancer Ther, 2020, molcanther.0654.2020
Sci Rep, 2019, 9(1):1897
S2711 Dibenzazepine (YO-01027) Dibenzazepine (YO-01027, DBZ) 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.
Nature, 2021, 598(7881):510-514
Signal Transduct Target Ther, 2021, 6(1):148
ACS Nano, 2020, 22
S2714 LY411575 LY411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells. LY411575 induces apoptosis.
Nat Commun, 2021, 12(1):6839
J Endocrinol, 2021, JOE-21-0016.R1
Nature, 2020, 10.1038/s41586-020-2946-9
S7169 Crenigacestat (LY3039478) Crenigacestat (LY3039478) is an oral Notch and gamma-secretase inhibitor with IC50 of 0.41 nM for Notch.
Nucleic Acids Res, 2021, gkab800
Cancer Res, 2021, canres.0524.2021
Oncoimmunology, 2021, 10(1):1881268
S7394 MDL-28170 MDL-28170 (Calpain Inhibitor III) is a potent and selective calpain inhibitor of calpain that penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. MDL-28170 is also an inhibitor of γ-secretase.
S7673 L-685,458 L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.
Biochem Biophys Res Commun, 2021, 570:137-142
Aging (Albany NY), 2020, 12(1):481-501
J Cell Biol, 2019, 218(2):644-663
S8018 Nirogacestat (PF-03084014) Nirogacestat (PF-03084014, PF-3084014) is a selective gamma-secretase inhibitor with IC50 of 6.2 nM in a cell-free assay. Nirogacestat (PF-03084014, PF-3084014) induces apoptosis. Phase 2.
Stem Cell Res Ther, 2020, 11(1):258
Pharm Res, 2020, 37(10):185
Mol Ther Oncolytics, 2019, 13:58-66
S8185 FPS-ZM1 FPS-ZM1 is a blood-brain-barrier permeant, non-toxic, tertiary amide compound which is a high affinity RAGE-specific inhibitor, blocking Aβ binding to the V domain of RAGE.
Cell Death Discov, 2021, 7(1):337
J Cancer, 2021, 12(2):518-529
Ann Transl Med, 2021, 9(6):494
A5298 ADAM10 Rabbit Recombinant mAb ADAM10 Rabbit Recombinant mAb detects endogenous level of total ADAM10.
S7323 Itanapraced (CHF 5074) Itanapraced (CHF 5074, CSP-1103) is a gamma-secretase modulator that reduces Aβ42 and Aβ40 secretion. The IC50s of CHF5074 for inhibition of COX-1 and COX-2 is above 100 μmol/L.
S8603 NGP 555 NGP 555 is a small-molecule modulator of γ-secretase and has been successful in achieving good oral absorption, brain penetration, CNS activity, and specificity for a lipid-based membrane target preclinically.
Tags: Gamma-secretase inhibition | Gamma-secretase inhibitor Notch | Gamma-secretase activity | Gamma-secretase assay | Gamma-secretase cleavage | Gamma-secretase inhibitor in clinical trial | Gamma-secretase inhibitor review