Secretase inhibitors

Other Neuronal Signaling Inhibitors

• Featured Inhibitors
• Inhibitors (13)
• Modulators (2)

Cat.No.	Product Name	Information	Product Use Citations	Product Validations
S2215	DAPT	DAPT 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.	Signal Transduct Target Ther, 2025, 10(1):334 Cell Host Microbe, 2025, 33(3):408-419.e8 Nat Commun, 2025, 16(1):8693
S1575	RO4929097 (RG-4733)	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.	Nat Commun, 2025, 16(1):10435 Cell Rep Med, 2025, S2666-3791(25)00102-8 Cell Death Dis, 2025, 16(1):150
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, 2025, 16(1):5913 Dev Cell, 2025, S1534-5807(25)00468-X Cell Rep, 2025, 44(6):115781
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, and it induces apoptosis. Phase 2.	J Cell Biol, 2024, 223(10)e202305093 Biochem Pharmacol, 2024, 230(Pt 2):116577 Neurooncol Adv, 2024, 6(1):vdae188
S2711	Dibenzazepine (YO-01027)	DBZ (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.	Acta Neuropathol Commun, 2025, 13(1):87 Sci Rep, 2025, 15(1):12154 Nat Commun, 2024, 15(1):9771
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, respectively. It also inhibits Notch signalling with IC50 of 14.1 nM in H4 human glioma cell. This compound has reached Phase 3 clinical trials.	Cell Rep Med, 2025, S2666-3791(25)00102-8 Biochim Biophys Acta Mol Basis Dis, 2025, 1871(8):167992 Cancers (Basel), 2023, 15(6)1883
S2660	MK-0752	MK-0752 is a moderately potent γ-secretase inhibitor, which reduces Aβ40 production with IC50 of 5 nM. Phase 1/2.	Nat Cell Biol, 2024, 26(3):353-365 Cancers (Basel), 2023, 15(6)1883 J Cancer Res Clin Oncol, 2023, 149(16):14691-14699
S1262	Avagacestat (BMS-708163)	Avagacestat (BMS-708163) is a potent, selective, and orally bioavailable γ-secretase inhibitor of Aβ40 and Aβ42 with IC50 values of 0.3 nM and 0.27 nM, respectively. This compound demonstrates a 193-fold selectivity against Notch and has reached Phase 2 clinical trials.	Nat Commun, 2022, 13(1):6345 Sci Rep, 2022, 12(1):7 Cell, 2021, 184(2):521-533.e14
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.	iScience, 2022, 25(10):105182 Biochem Biophys Res Commun, 2021, 570:137-142 Aging (Albany NY), 2020, 12(1):481-501
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 are above 100 μmol/L.
1 2