U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Status:
Investigational
Source:
NCT04142749: Phase 3 Interventional Completed Non-Alcoholic Fatty Liver Disease
(2019)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Oltipraz is an organosulfur compound belonging to the dithiolethione class. It acts as a schistosomicide and has been shown in rodent models to inhibit the formation of cancers in the bladder, blood, colon, kidney, liver, lung, pancreas, stomach, and trachea, skin, and mammary tissue. Oltipraz and other 1,2-dithiole-3-thiones inactivate protein tyrosine phosphatases under physiologically-relevant conditions. Clinical trials of oltipraz have failed to demonstrate efficacy and have shown significant side effects, including neurotoxicity and gastrointestinal toxicity.
NSC-87877 is a potent inhibitor shp2 and shp1 protein tyrosine phosphatases (PTP). Molecular modeling and site-directed mutagenesis studies suggested that NSC-87877 binds to the catalytic cleft of Shp2. In addition, NSC-87877 inhibits EGF-induced Erk1/2 activation in HEK293 cells and significantly reduces MDA-MB-468 cell viability/proliferation. In addition, NSC-87877 possesses ability to inhibit the dual-specificity protein phosphatase 26 (DUSP26). Active DUSP26 causes inactivation of p38 and p53 with their respective downstream proapoptic proteins, resulting in tumor growth. The addition of NSC-87877 results in competitive inhibition of DUSP26 activity and removes the inhibitory effect of DUSP26 on p38 and p53. Because DUSP26 is involved in survival of anaplastic thyroid cancer (ATC) cells, NSC-87877 could be a therapeutic reagent for treating ATC. In addition was shown on animal models, that NSC-87877 could be effective strategy against neuroblastoma.