Notch Inhibitor

DAPT (GSI-IX) is a potent and orally active γ-secretase inhibitor with IC₅₀s of 115 nM and 200 nM for total amyloid-β (Aβ) and Aβ₄₂, respectively. DAPT inhibits the activation of Notch 1 signaling and induces cell differentiation. DAPT also induces autophagy and apoptosis. DAPT has neuroprotection activity and has the potential for autoimmune and lymphoproliferative diseases, degenerative disease and cancers treatment.

Tarlatamab (AMG-757) is a bispecific T-cell engager (BiTE) antibody targeting delta-like ligand 3 (DLL3). DLL3 is a target that is selectively expressed in small-cell lung cancer (SCLC) tumors, but with minimal normal tissue expression. Tarlatamab has the K_Ds of 0.64 nM and 0.50 nM for human and nonhuman primate (NHP) DLL3, respectively. Tarlatamab has the K_Ds of 14.9 nM and 12 nM for human and NHP CD3, respectively. Tarlatamab is a first-in-class HLE BiTE immuno-oncology therapy targeting DLL3 and has the potential for SCLC research.

LY-411575 is a potent γ-secretase inhibitor with IC₅₀ of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with an IC₅₀ of 0.39 nM.

YO-01027 (Dibenzazepine;DBZ) is a potent γ-secretase inhibitor with IC₅₀ values of 2.92 and 2.64 nM for Notch and APPL cleavage, respectively.

RO4929097 is an orally active γ secretase inhibitor with an IC₅₀ of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC₅₀ of 14 nM and 5 nM, respectively.

Tangeretin (Tangeritin), a flavonoid from citrus fruit peels, has been proven to play an important role in anti-inflammatory responses and neuroprotective effects in several disease models, and is a Notch-1 inhibitor.

Carvacrol is an orally active and blood-brain barrier-permeable monoterpenic phenol that can be extract from an abundant number of aromatic plants, including thyme and oregano, possessing antioxidant, antibacterial, antifungal, anticancer, anti-inflammatory, hepatoprotective, spasmolytic, and vasorelaxant properties. Carvacrol also causes cell cycle arrest in G0/G1, downregulates Notch-1, and Jagged-1, and induces apoptosis. Carvacrol is used in low concentrations as a food flavoring ingredient and preservative, as well as a fragrance ingredient in cosmetic formulations.

Rovalpituzumab is a humanized monoclonal antibody against delta-like protein 3 (DLL3). Rovalpituzumab can be used in the synthesis of antibody-drug conjugate (ADC), Rovalpituzumab Tesirine. Rovalpituzumab has activity against small cell lung cancer (SCLC).

RBPJ Inhibitor-1 (RIN1), the first RBPJ inhibitor, blocks the functional interaction of RBPJ with SHARP. RBPJ Inhibitor-1 (RIN1) inhibits NOTCH-dependent tumor cell proliferation.

Limantrafin (CB-103) is a first-in-class, orally active protein-protein interaction (PPI) inhibitor of the NOTCH transcriptional activation complex. Limantrafin has anti-tumor activity.

Crenigacestat (LY3039478) is an orally active Notch and γ-secretase inhibitor, with an IC₅₀ of 1 nM in most of the tumor cell lines tested.

Lumiflavin (Lumiflavine), a riboflavine analog, causes significant inhibition of riboflavine uptake. Lumiflavin can effectively reduce the riboflavin enrichment in cancer stem-like cells (CSCs) and sensitize the effect of cisplatin Diamminedichloroplatinum (DDP) on CSCs. Lumiflavin is promising for research of ovarian cancer.

Bruceine D is a Notch inhibitor with anti-cancer activity and induces apoptosis in several human cancer cells. Bruceine D is an effective botanical insect antifeedant with outstanding systemic properties, causing potent pest growth inhibitory activity. Bruceine D has strong anthelmintic activity against D. intermedius with an EC₅₀ value of 0.57 mg/L.

IMR-1 is a novel class of Notch inhibitor targeting the transcriptional activation with an IC₅₀ of 26 μM. IMR-1 prevents the recruitment of Mastermind-like 1 (Maml1) to the Notch Ternary Complex (NTC) on chromatin, inhibits Notch target gene transcription and dramatically inhibits tumor growth.

Semagacestat is a γ-secretase inhibitor, inhibits β-amyloid (Aβ42), Aβ38 and Aβ40 with IC₅₀s of 10.9, 12 and 12.1 nM, respectively; also inhibits Notch signaling with IC₅₀ of 14.1 nM. Semagacestat can be used for the research of alzheimer's disease.

Anti-DLL3 Antibody (anti-DLL3 arm derived from AMG-757) is the anti-DLL3 arm of the bispecific T-cell engager (BiTE) antibody-Tarlatamab (AMG-757) (HY-P99575). Tarlatamab targets both DLL3 and CD3.

Psoralidin is a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation.Anti-cancer, anti-bacterial, and anti-inflammatory properties. Psoralidin significantly downregulates NOTCH1 signaling. Psoralidin also greatly induces ROS generation.

Hexamethylene bisacetamide (HMBA) is a differentiation inducer and selective bromine domain inhibitor that can differentiate across the blood-brain barrier. Hexamethylene bisacetamide can induce tumor cell differentiation and inhibit cell proliferation, showing antitumor activity. Hexamethylene bisacetamide induces apoptosis by Notch1, Bcl-2 and p53 signaling pathways. In addition, Hexamethylene bisacetamide improves the obesity phenotype of mice.

Avagacestat (BMS-708163) is a potent inhibitor of γ-secretase, with IC₅₀s of 0.27 nM and 0.30 nM for Aβ42 and Aβ40 inhibition; Avagacestat (BMS-708163) also inhibits NICD (Notch IntraCellular Domain) with IC₅₀ of 0.84 nM and shows weak inhibition of CYP2C19, with IC₅₀ of 20 μM. Avagacestat can be used for Alzheimer disease research.

Tarextumab (OMP-59R5) is a cross-reactive, fully human IgG2 antibody that selectively inhibits Notch2 and Notch3 signaling. Tarextumab demonstrates broad-spectrum antitumor efficacy in xenograft models of epithelial tumors. Tarextumab can be used for the study of pancreatic cancer.