BMS-983970 is an oral pan-Notch inhibitor for the treatment of cancer.
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 KDs of 0.64 nM and 0.50 nM for human and nonhuman primate (NHP) DLL3, respectively. Tarlatamab has the KDs 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[1].
Crenigacestat (LY3039478) is a novel and potent Notch inhibitor.
Carvacrol is a monoterpenoid phenol isolated from Lamiaceae family plants, with antioxidant, anti-inflammatory and anticancer properties. Carvacrol causes cell cycle arrest in G0/G1, downregulates Notch-1, and Jagged-1, and induces apoptosis[1].
Enoticumab (REGN421, SAR153192) is an IgG1κ antibody targeting human Dll4. DLL4 is a ligand of the Notch signaling pathway and regulates fatty acid uptake through non-transcriptional regulation of macropinocytosis-dependent long-chain fatty acid uptake. Specific in vivo activity of Enoticumab in an ovarian xenograft model. EGN421 (2.5 mg/kg once weekly) resulted in 86% and 83% tumor growth inhibition in mouse subcutaneous TOV-112D or intraperitoneal A2780 human tumor xenograft models, respectively[1].
Notch inhibitor 1 is a potent Notch inhibitor, with IC50s of 7.8 and 8.5 nM for Notch 1 and Notch 3, respectively. Used in the research of cancer[1].
Psoralidin, a natural furanocoumarin, is isolated from Psoralea corylifolia L. possessing anti-cancer properties.IC50 value:Target: Anticancer natural compoundin vitro: PSO dramatically decreased the cell viabilities in dose- and time-dependent manner. Autophagy inhibitor 3-MA blocked the production of LC3-II and reduced the cytotoxicity in response to PSO. Furthermore, PSO increased intracellular ROS level which was correlated to the elevation of LC3-II [1]. Psoralidin at 10 μM was able to induce the maximum reporter gene expression corresponding to that of E2-treated cells and such activation of the ERE-reporter gene by psoralidin was completely abolished by the cotreatment of a pure ER antagonist, implying that the biological activities of psoralidin are mediated by ER [2]. Psoralidin enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and depolarization of mitochondrial membrane potential [3]. Psoralidin inhibited the IR-induced COX-2 expression and PGE(2) production through regulation of PI3K/Akt and NF-κB pathway. Also, psoralidin blocked IR-induced LTB(4) production, and it was due to direct interaction of psoralidin and 5-lipoxygenase activating protein (FLAP) in 5-LOX pathway. IR-induced fibroblast migration was notably attenuated in the presence of psoralidin [4].in vivo: Moreover, in vivo results from mouse lung indicate that psoralidin suppresses IR-induced expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-6 and IL-1 α/β) and ICAM-1[4].
Yhhu-3792 is a novel small molecule that enhances the self-renewal capability of neural stem cells (NSCs) in vitro and in vivo via activating the Notch signaling pathway; activates Notch signaling pathway and promotes the expression of Notch target genes, Hes3 and Hes5; expands the NSCs pool and promotes endogenous neurogenesis in the hippocampal dentate gyrus (DG) after chronic administration in mice.
Brontictuzumab (OMP 52M51) is a monoclonal antibody (MAb) that inhibits Notch1 signal. Brontictuzumab selectively binds the negative regulatory region of the Notch1. Brontictuzumab inhibits tumor cell proliferation. Brontictuzumab can be used in the research of leukemia and lymphoma[1][2][3].
Tangeretin, 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 was also selected as a Notch-1 inhibitor.IC50 value:Target: Notch-1In vitro: Tangeretin enhanced the radiosensitivity of GC cells as demonstrated by MTT and colony formation assays. Tangeretin also attenuated radiation-induced EMT, invasion and migration in GC cells, accompanied by a decrease in Notch-1, Jagged1/2, Hey-1 and Hes-1 expressions. Tangeretin triggered the upregulation of miR-410, a tumor-suppressive microRNA. Furthermore, re-expression of miR-410 prevented radiation-induced EMT and cell invasion [1]. In vivo: In this study, we investigated the in vivo anti-RSV activity of tangeretin in 3-week-old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) showed that tangeretin inhibited RSV replication in the lung of mice [2].
ZLDI-8 (IAC-8) is a novel Notch signaling pathway inhibitor for Notch activating/cleaving enzyme ADAM-17, significantly decreases the level of NICD and accumulation of NICD in the nucleus; exhibits cytotoxic acitviity against MHCC97-H cells with IC50 of 5.32 uM, reduces the expression of pro-survival/anti-apoptosis regulators, Survivin and cIAP1/2, also increases the expression of epithelial marker E-Cadherin and reduces mesenchymal markers N-Cadherin and Vimentin in HCC cells; significantly disrupted the activity of Notch pathway in HCC cells and inhibits the epithelial-mesenchymal transition (EMT) process of HCC cells; ZLDI-8 treatment enhances the susceptibility of HCC cells to Sorafenib, Etoposide, and Paclitaxel both in vitro and in vivo.
RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively.
BMS-906024 is an oral and selective gamma secretase inhibitor (GSI) that is a small molecule Notch inhibitor[1]. BMS-906024 prevents the activation of all four Notch receptors with a high oral bioavailability with IC50s of 1.6, 0.7, 3.4, and 2.9 nM for Notch1, -2, -3, and -4 receptors, respectively. BMS-906024 demonstrates broad-spectrum antineoplastic activity against a wide array of human cancer xenografts[2].
JI051 is a stabilizer for the Hes1-PHB2 interaction, interacts with a cancer-associated protein chaperone prohibitin 2 (PHB2), induces cell-cycle arrest by inhibiting the Notch downstream effector gene Hes1. Anti-cancer activity[1].
JI130 (JI-130) is a specific Hse1 inhibitor that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone, blocks Hes1-mediated transcriptional repression; interacts with prohibitin 2 (PHB2), stabilizes PHB2's interaction with Hes1 outside the nucleus, inducing G2/M cell cycle arrest; dose-dependently reduces cell growth of the human pancreatic cancer cell line MIA PaCa-2 (IC50=49 nM); significantly reduces tumor volume in murine pancreatic tumor xenograft models.
Tarextumab (OMP-59R5) is an anti-Notch2/3 fully human IgG2 monoclonal antibody. Tarextumab shows anti-tumor activity[1].
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[1][2].
IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 6 μmol/L.target: NotchIC 50: 6 μmol/LIn vitro: IMR-1 prevents the recruitment of Maml1 to the NTC on chromatin, inhibits Notch target gene transcription, and dramatically inhibits tumor growth .A decrease in colony formation of Notch-dependent cell lines is observed upon treatment with IMR-1 when compared with the control (DMSO). In vivo : The reference for intraperitoneal injection is 15 mg/kg. IMR-1 inhibits Notch-dependent somite development in zebrafish.
YO-01027 (Dibenzazepine;DBZ) is a potent γ-secretase inhibitor with IC50 values of 2.92±0.22 and 2.64±0.30 nM for Notch and APPL cleavage, respectively.
Z-Ile-Leu-aldehyde(Z-IL-CHO; GSI-XII) is a potent gamma-Secretase inhibitor; Notch signaling inhibitor.IC50 value:Target: gamma-Secretase inhibitorin vitro: GSI-XII induces apoptosis of murine MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells in vitro [1]. Notch-signaling inhibition in HRS cells by the γ-secretase inhibitor (GSI) XII results in decreased alternative p52/RelB NF-κB signaling, interfering with processing of the NF-κB2 gene product p100 into its active form p52 [2]. GSI treatment induced morphologic erythroid differentiation and promoted hemoglobin production. GSI treatment suppressed short-term growth and colony formation, while treatment with GSI-XXI promoted the growth of AA cells [3].in vivo: In the murine MOPC315.BM myeloma model GSI XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and quantitative assessment of bone structure changes via high-resolution microcomputed tomography scans [1].
Semagacestat is a γ-secretase inhibitor, inhibits β-amyloid (Aβ42), Aβ38 and Aβ40 with IC50 of 10.9, 12 and 12.1 nM, respectively; also inhibits Notch signaling with IC50 of 14.1 nM.
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 IC50 of 0.39 nM.
FLI-06 is an inhibitor of Notch signaling with an EC50 of 2.3 μM.
Navicixizumab (OMP-305B83) is a bispecific anti-VEGF and anti-DLL4 inhibitory antibody. Navicixizumab can combine with Paclitaxel (HY-B0015) for cancer research. Navicixizumab can be used in the research of ovarian, primary peritoneal, or fallopian tube cancer[1][2][3].
BMS-708163 is a potent inhibitor of γ-secretase, with IC50s of 0.27 nM and 0.30 nM for Aβ42 and Aβ40 inhibition; 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.
IMR-1A is the metabolite of IMR-1. IMR-1 is a novel class of Notch inhibitors targeting the transcriptional activation with IC50 of 6 μmol/L.target: NotchIC 50: 6 μmol/LIn vitro: IMR-1 prevents the recruitment of Maml1 to the NTC on chromatin, inhibits Notch target gene transcription, and dramatically inhibits tumor growth .A decrease in colony formation of Notch-dependent cell lines is observed upon treatment with IMR-1 when compared with the control (DMSO).In vivo : The reference for intraperitoneal injection is 15 mg/kg. IMR-1 inhibits Notch-dependent somite development in zebrafish.
SAHM1 is a Notch pathway inhibitor. SAHM1 stabilizes hydrocarbon-stapled alpha helical peptide. SAHM1 targets the protein-protein interface and prevents Notch complex assembly.
tCFA15 is a trimethyl cyclohexenonic long chain fatty alcohol containing 15 carbon atoms on the side chain, promotes the differentiation of neurons, and may regulates Notch signaling.
RA-V is a cyclic hexapeptide. RA-V has activity against Wnt, Myc and Notch with IC50 values of 50, 75, and 93 ng/mL, respectively. RA-V can be used for the research of cancer-related signaling pathways.
Valproic acid (VPA) sodium (2:1) is an orally active HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2. Valproic acid sodium (2:1) activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid sodium (2:1) is used in the treatment of epilepsy, bipolar disorder, metabolic disease, HIV infection and prevention of migraine headaches[1][2][3][4][5][6][7].