Table 1.

Agents targeting NOTCH1 pathway in T-ALL

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