Notch Inhibitors

Cat.No.	Product Name	Information	Product Use Citations
S0225	IMR-1A	IMR-1A, an acid metabolite of IMR-1, is a potent inhibitor of Notch with IC50 of 0.5 μM and Kd of 2.9 μM. This compound exhibits anti-tumor activity.
S3944	VPA (Valproic acid)	Valproic acid (VPA) is a fatty acid with anticonvulsant properties used in the treatment of epilepsy. It is also a histone deacetylase (HDAC) inhibitor and is under investigation for treatment of HIV and various cancers. This compound induces autophagy and mitophagy by upregulation of BNIP3 and mitochondrial biogenesis by upregulating PGC-1α. Additionally, it activates Notch-1 signaling.	Cell, 2025, S0092-8674(25)00406-4 Nat Commun, 2025, 16(1):8267 Stem Cell Res Ther, 2025, 16(1):426
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
S1168	Valproic Acid sodium	Valproic Acid sodium is a HDAC inhibitor by selectively inducing proteasomal degradation of HDAC2, used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches. Valproic acid induces Notch1 signaling in small cell lung cancer (SCLC) cells. Valproic acid is under investigation for treatment of HIV and various cancers. Valproic acid (VPA) induces autophagy and mitophagy by upregulation of BNIP3 and mitochondrial biogenesis by upregulating PGC-1α.	J Exp Clin Cancer Res, 2024, 43(1):152 J Immunother Cancer, 2024, 12(11)e009805 Front Pharmacol, 2024, 15:1534772
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 signaling 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
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
S0058	Compound E	Compound E (γ-Secretase-IN-1) is a potent inhibitor of γ-secretase, which blocks γ-secretase-mediated cleavage of Notch with an IC50 of 0.32 nM. It also suppresses the production of β-amyloid(40) and β-amyloid(42) with IC50 values of 0.24 nM and 0.37 nM, respectively. It also inhibits Notch signalling, significantly disrupting gonadotropin-dependent follicle growth and halting progression to the preovulatory stage of development.
E6426^New	Sulindac sulfide	Sulindac sulfide is a potent, reversible and noncompetitive inhibitor of γ42-secretase with an IC50 of 20.2 μM. It preferentially reduces Aβ42 generation, inhibits Aβ40 and Notch intracellular domain production, and can be used in Alzheimer's disease research.