γ secretase(aβ42)

DAPT (LY-374973) is a γ-secretase inhibitor that inhibits total Aβ and Aβ42 (IC50=115/200 nM) and is orally active. DAPT is also a Notch inhibitor. DAPT induces cell differentiation, autophagy and apoptosis.

BI-1408 is a modulator potent of γ secretase (IC50: 0.04 μM for Aβ42).

Ro 90-7501 is an amyloid β42 (Aβ42) protofibrillar and TPR-dependent PP5 inhibitor, a novel radiosensitizer for cervical cancer cells, which inhibits ATM phosphorylation, promotes apoptosis, and induces cell-cycle arrest. Ro 90-7501 also exhibits antiviral activity and potential anticancer activity by inhibiting ATM phosphorylation and DNA repair, and by inhibiting HCMV.

γ-Secretase modulator 13 is a γ-secretase modulator (GSMs) that inhibits the production of amyloid β-peptide Aβ42 and can be used to study Alzheimer's disease and tumors.

Aβ-IN-1 is a novel, potent and orally active γ-secretase modulator (GSM). Aβ-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ-IN-1 shows a sustained pharmacokinetic profile.

Aβ42-IN-2, a γ-secretase modulator with an IC50 of 6.5 nM for Αβ42, can be used for Alzheimer's disease research [1].

3,5-Bis(4-nitrophenoxy)benzoic acid (Compound W) is a γ-secretase inhibitor that reduces the levels of released Aβ42 and notch-1 Aβ-like peptide 25 (Nβ25).

Aftin-4, an amyloid forty-two inducer, activates γ-secretase, promoting the generation of amyloid-β-1-42 (Aβ1-42) from amyloid-β protein precursor. Aftin-4(Aftin4) increased Aβ-1-42, but not Aβ-1-40 in mouse hipppocampus, accompanied by learning deficits and mitochondrial ultrastructural changes similar to those found in the brains of patients with AD. Aftin-4(Aftin4) can thus be used to induce a rapid, acute Alzheimer's disease-like toxicity in the rodent brain.

Avagacestat (BMS-708163) (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.

Aβ42-IN-1, compound 1v, is a novel, potent and orally active γ-secretase modulator (GSM). Aβ42-IN-1 potently reduced Aβ42 levels with an IC 50 value of 0.091 μM in cultured cells without inhibiting CYP3A4. Aβ42-IN-1 shows a sustained pharmacokinetic profile.

Aβ42-IN-1 free base (compound 1v), an orally active γ-secretase modulator with high brain exposure, effectively lowers Aβ42 levels with an IC50 of 0.091 μM, and significantly diminishes brain Aβ42 levels in mice. Given these properties, Aβ42-IN-1 free base represents a potential disease-modifying agent for Alzheimer's disease [1].

BPN-15606 besylate is a highly potent, orally active γ-secretase modulator, attenuates the production of Aβ40 and Aβ42 by SHSY5Y neuroblastoma cells (IC50s: 7 nM and 17nM).

BPN-15606, an orally active γ-secretase modulator (GSM), significantly reduces Aβ42 and Aβ40 production in SHSY5Y neuroblastoma cells, demonstrating IC50 values of 7 nM and 17 nM, respectively. This compound exhibits favorable pharmacokinetic/pharmacodynamic (PK/PD) properties, such as bioavailability, half-life, and clearance. Importantly, BPN-15606 markedly decreases Aβ42 and Aβ40 levels in the central nervous system of both rats and mice[1].

γ-Secretase modulator 4 is a potent γ-secretase modulator that reduces Aβ42 levels with IC50s of 0.017 μM in mice and 0.014 μM in humans.

Amyloid-β-IN-3 (EX.113) is a selective inhibitor of γ-secretase. It demonstrates inhibitory activity on Aβ42 secretion in H4 cells, with an EC50 value of 148 nM. By modulating the catalytic activity of γ-secretase, Amyloid-β-IN-3 decreases Aβ42 production, thereby alleviating neurotoxicity caused by Aβ deposition. It holds potential for Alzheimer's disease (AD) research.

Amyloid-β-IN-2 (Compound EX.112) is a selective inhibitor of γ-secretase. In H4 cells, it demonstrates inhibitory activity on Aβ42 secretion, with an EC50 value of 226 nM. Amyloid-β-IN-2 holds potential for research in Alzheimer's disease (AD) and diseases associated with Aβ deposition.

PF-06442609 is an orally active γ-secretase modulator with an IC50 value of 6 nM for Aβ42. It exhibits good CNS permeability.

AZ1136 is a highly selective γ-secretase modulator (GSM) that reduces the levels of Aβ42 and Aβ40, with IC50 values of 990 and 1400 nM, respectively. It increases the levels of Aβ39 and Aβ37 without affecting Aβ38. AZ1136 is utilized in Alzheimer's disease research.

Itanapraced (CHF5074), a γ-secretase modulator, reduces Aβ42/40 secretion (IC50: 3.6/18.4 μM).

GSK-B, a potent γ-secretase modulator, decreases Aβ42, increases Aβ38 with no effect on Aβ40 levels.

HDAC6-IN-9 is an orally active and highly effective γ-secretase modulator that can significantly reduce the level of Aβ42 in mouse brain and can be used to study neurological diseases.

Semagacestat (LY450139) (LY450139) is a γ-secretase blocker for Aβ42/Aβ40/Aβ38 (IC50: 10.9/12.1/12.0 nM) and also inhibits Notch signaling (IC50: 14.1 nM).

γ-Secretase modulator 12 (Compound 1a) is a selective compound that effectively reduces amyloid-β42 (Aβ42) levels with an IC50 of 0.39 μM, specifically designed for Alzheimer's disease research. Notably, γ-Secretase modulator 12 exhibits a favorable brain/plasma ratio (Kp, brain = 0.72) in mice [1].

γ-Secretase modulator 11 hydrochloride is a potent, orally active γ-secretase modulator (IC50: 0.029 μM). γ-Secretase modulator 11 hydrochloride significantly reduces brain Aβ42 levels and rescues the cognitive deficits exhibited by AD model mice. γ-Secretase modulator 11 hydrochloride has shown research potential in Alzheimer's disease.