BIOMAT Database Logo BIOMAT Database Logo

The Small-Molecule E26-Transformation-Specific Inhibitor TK216 Attenuates the Oncogenic Properties of Pediatric Leukemia. 2023

Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Department of Oncology, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr NW, Calgary, AB T2N 4N1, Canada.

The E26-transformation-specific (ETS) transcription factors regulate multiple aspects of the normal hematopoietic system. There is an increasing body of evidence suggesting aberrant ETS activity and its contribution to leukemia initiation and progression. In this study, we evaluated the small-molecule ETS inhibitor TK216 and demonstrated its anti-tumor activity in pediatric leukemia. We found TK216 induced growth inhibition, cell cycle arrest and apoptosis and inhibited the migratory capability of leukemic cells, without significantly inhibiting the cell viability of normal blood mononuclear cells. Priming the leukemic cells with 5-Azacitidine enhanced the cytotoxic effects of TK216 on pediatric leukemia cells. Importantly, we found purine-rich box1 (PU.1) to be a potential target of TK216 in myeloid and B-lymphoid leukemic cells. In addition, TK216 sharply decreased Mcl-1 protein levels in a dose-dependent manner. Consistent with this, TK216 also potentiated the cytotoxic effects of Bcl-2 inhibition in venetoclax-resistant cells. The sustained survival benefit provided to leukemic cells in the presence of bone-marrow-derived conditioned media is also found to be modulated by TK216. Taken together, our data indicates that TK216 could be a promising targeted therapeutic agent for the treatment of acute myeloid and B-lymphoid leukemia.

UI MeSH Term Description Entries
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D001374 Azacitidine A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. Azacytidine,5-Azacytidine,NSC-102816,Vidaza,5 Azacytidine,NSC 102816,NSC102816
D015470 Leukemia, Myeloid, Acute Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES. Leukemia, Myelogenous, Acute,Leukemia, Nonlymphocytic, Acute,Myeloid Leukemia, Acute,Nonlymphocytic Leukemia, Acute,ANLL,Acute Myelogenous Leukemia,Acute Myeloid Leukemia,Acute Myeloid Leukemia with Maturation,Acute Myeloid Leukemia without Maturation,Leukemia, Acute Myelogenous,Leukemia, Acute Myeloid,Leukemia, Myeloblastic, Acute,Leukemia, Myelocytic, Acute,Leukemia, Myeloid, Acute, M1,Leukemia, Myeloid, Acute, M2,Leukemia, Nonlymphoblastic, Acute,Myeloblastic Leukemia, Acute,Myelocytic Leukemia, Acute,Myelogenous Leukemia, Acute,Myeloid Leukemia, Acute, M1,Myeloid Leukemia, Acute, M2,Nonlymphoblastic Leukemia, Acute,Acute Myeloblastic Leukemia,Acute Myeloblastic Leukemias,Acute Myelocytic Leukemia,Acute Myelocytic Leukemias,Acute Myelogenous Leukemias,Acute Myeloid Leukemias,Acute Nonlymphoblastic Leukemia,Acute Nonlymphoblastic Leukemias,Acute Nonlymphocytic Leukemia,Acute Nonlymphocytic Leukemias,Leukemia, Acute Myeloblastic,Leukemia, Acute Myelocytic,Leukemia, Acute Nonlymphoblastic,Leukemia, Acute Nonlymphocytic,Leukemias, Acute Myeloblastic,Leukemias, Acute Myelocytic,Leukemias, Acute Myelogenous,Leukemias, Acute Myeloid,Leukemias, Acute Nonlymphoblastic,Leukemias, Acute Nonlymphocytic,Myeloblastic Leukemias, Acute,Myelocytic Leukemias, Acute,Myelogenous Leukemias, Acute,Myeloid Leukemias, Acute,Nonlymphoblastic Leukemias, Acute,Nonlymphocytic Leukemias, Acute
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis

Related Publications

Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Acute leukemia viruses E26 and avian myeloblastosis virus have related transformation-specific RNA sequences but different genetic structures, gene products, and oncogenic properties.
June 1982, Proceedings of the National Academy of Sciences of the United States of America,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells.
October 2016, Cancer science,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Small-Molecule Protein-Protein Interaction Inhibitor of Oncogenic Rho Signaling.
September 2016, Cell chemical biology,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Small-Molecule Targeting of Oncogenic FTO Demethylase in Acute Myeloid Leukemia.
April 2019, Cancer cell,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Small-molecule inhibitor of HlyU attenuates virulence of Vibrio species.
March 2019, Scientific reports,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Targeting PELP1 oncogenic signaling in TNBC with the small molecule inhibitor SMIP34.
July 2023, Breast cancer research and treatment,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA.
March 2017, ACS central science,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice.
June 2018, Scientific reports,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Small Molecule Inhibitor that Stabilizes the Autoinhibited Conformation of the Oncogenic Tyrosine Phosphatase SHP2.
February 2019, Journal of medicinal chemistry,
Ritul Sharma, and Chunfen Zhang, and Aru Narendran
Suppression of RUNX1/ETO oncogenic activity by a small molecule inhibitor of tetramerization.
May 2017, Haematologica,
Copied contents to your clipboard!