Fat mass and obesity-associated protein (FTO), an RNA N6-methyladenosine (m6A) demethylase, plays oncogenic roles in various cancers, presenting an opportunity for the development of effective targeted therapeutics. Here, we report two potent small-molecule FTO inhibitors that exhibit strong anti-tumor effects in multiple types of cancers. We show that genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially LILRB4. FTO inhibition sensitizes leukemia cells to T cell cytotoxicity and overcomes hypomethylating agent-induced immune evasion. Our study demonstrates that FTO plays critical roles in cancer stem cell self-renewal and immune evasion and highlights the broad potential of targeting FTO for cancer therapy.
Pubmed ID: 32531268 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Portal for preclinical information and research materials, including web-accessible data and tools, NCI-60 Tumor Cell Line Screen, compounds in vials and plates, tumor cells, animals, and bulk drugs for investigational new drug (IND)-directed studies. DTP has been involved in the discovery or development of more than 70 percent of the anticancer therapeutics on the market today, and will continue helping the academic and private sectors to overcome various therapeutic development barriers, particularly through supporting high-risk projects and therapeutic development for rare cancers. Initially DTP made its drug discovery and development services and the results from the human tumor cell line assay publicly accessible to researchers worldwide. At first, the site offered in vitro human cell line data for a few thousand compounds and in vitro anti-HIV screening data for roughly 42,000 compounds. Today, visitors can find: * Downloadable in vitro human tumor cell line data for some 43,500 compounds and 15,000 natural product extracts * Results for 60,000 compounds evaluated in the yeast assay * In vivo animal model results for 30,000 compounds * 2-D and 3-D chemical structures for more than 200,000 compounds * Molecular target data, including characterizations for at least 1,200 targets, plus data from multiple cDNA microarray projects In addition to browsing DTP's databases and downloading data, researchers can request individual samples or sets of compounds on 96-well plates for research, or they can submit their own compounds for consideration for screening via DTP's online submission form. Once a compound is submitted for screening, researchers can follow its progress and retrieve data using a secure web interface. The NCI has collected information on almost half a million chemical structures in the past 50 years. DTP has made this information accessible and useful for investigators through its 3-D database, a collection of three-dimensional structures for more than 200,000 drugs. Investigators use the 3-D database to screen compounds for anticancer therapeutic activity. Also available on DTP's website are 127,000 connection tables for anticancer agents. A connection table is a convenient way of depicting molecular structures without relying on drawn chemical structures. As unique lists of atoms and their connections, the connection tables can be indexed and stored in computer databases where they can be used for patent searches, toxicology studies, and precursor searching, for example.
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD85k
View all literature mentionsThis monoclonal targets CD117 (c-Kit)
View all literature mentionsThis monoclonal targets CD85k
View all literature mentionsThis monoclonal targets CD86
View all literature mentionsThis monoclonal targets CD209
View all literature mentionsThis monoclonal targets CD45.2
View all literature mentionsThis monoclonal targets CD85k (ILT3)
View all literature mentionsThis monoclonal targets CD45.1
View all literature mentionsThis monoclonal targets CD15
View all literature mentionsThis monoclonal targets CD14
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis unknown targets rabbit IgG (H+L) F(ab) 2 Fragment
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis monoclonal targets CD33
View all literature mentionsThis polyclonal secondary targets not applicable
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets beta-actin
View all literature mentionsThis polyclonal targets Mouse Mouse IgG secondary - H&L
View all literature mentionsThis polyclonal targets Rabbit Rabbit IgG secondary - H&L
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets FTO antibody [EPR6895]
View all literature mentionsThis polyclonal targets 5-Hydroxymethylcytosine (5-hmC)
View all literature mentionsCell line ZR-75-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ML-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NOMO-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line TF-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U-937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name B6.SJL-PtprcaPepc/BoyCrCrl from IMSR.
View all literature mentions
Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Mus musculus with name NOD.Cg-Rag1tm1Mom Il2rg
Cell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NB4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Mono-Mac-6 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line K-562 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Kasumi-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentions