Skip to main content

Table 1 Agents targeting NOTCH1 pathway in T-ALL

From: Advances of target therapy on NOTCH1 signaling pathway in T-cell acute lymphoblastic leukemia

Name Target Mechanism Type of cancer Phase NCT number/publication date Assessment
MK-0752 γ-Secretase Induce G0/G1 cell cycle arrest and inhibit cell proliferation T-ALL I 2006 Transient anti-leukemia effect but severe diarrhea
PF-03084014 γ-Secretase Inhibit ICN1 levels and the expression of Notch target genes T-ALL or T-cell lymphoblastic lymphoma I NCT00878189 1/8 achieved complete remission lasting about 3 months and the most common adverse effects were nausea and vomiting
BMS-906024 γ-Secretase γ-Secretase inhibitor screened by efficacy/tolerance profile T-ALL or T-cell lymphoblastic lymphoma I NCT01363817 32% showed at least a 50% reduction in bone marrow blasts and had tolerable side effects
MRK-560 PSEN1 of γ-Secretase Selective γ-Secretase inhibitor, mainly target PSEN1 in the γ-secretase complex T-ALL Preclinical July 1, 2019 Improved survival and did not show obvious gastrointestinal pathological
G1254023X ADAM Prevent ADAM protease cleavage Notch receptor at the S2 site T-ALL Preclinical August 20, 2015 Inhibited the activation of NOTCH1 signaling pathway and induce apoptosis
OMP-52M51 NRR Prevent ligand-free activation of NOTCH1 receptors T-ALL Preclinical July 23, 2013 Prolonged survival time but had drug resistance
MAb 604.107 NRR Distinguish the conformation of the NRR region between mutant NOTCH1 and wild-type NOTCH1 T-ALL Preclinical June 5, 2015 Inhibited T-ALL leukemia-initiating cells
SAHM1 ICN1-CSL-MAML complex Block the formation of ICN1-CSL-MAML complex, and inhibit the activation of NOTCH1 target gene expression T-ALL Preclinical November 12, 2009 Inhibited leukemic progression and NOTCH1 signaling
Thapsigargicin SERCA Induce the depletion of endoplasmic reticulum calcium ions and oxidative stress, which ultimately leads to apoptosis T-ALL Preclinical March 18, 2013 Effective but severe cardiotoxicity
JQ-FT SERCA Combine folic acid and thapsigargicin with a cleavable bond to achieve leukemia-specific delivery of thapsigargicin T-ALL Preclinical January 2, 2018 Dual selectivity: targeting NOTCH1 mutations and targeting leukemia cells, but Complex process and poor practicality
CJ SERCA Target NOTCH1 HD domain mutant T-ALL, induce T-ALL cell death T-ALL Preclinical January 28, 2016 Mainly target NOTCH1 HD domain mutation but weak effect on cells with mutations in other domains of NOTCH1
CAD204520 SERCA Retain the anti-NOTCH1 tumor characteristics while inhibiting thapsigargicin-resistant cell lines T-ALL Preclinical June 18, 2020 Effective and had tolerable side effects