Table 2 small-molecule inhibitors of m6A regulators

METTL3

inhibitor

Compound 1 and 2

Suppress m6A modification, exerts anti-tumor effects in AML models

[148]

STM2457

Suppress m6A modification, reduce AML growth and increase differentiation and apoptosis

[128]

UZH2

Suppress m6A modification in vitro

[129]

UZH1a

Suppress m6A modification in vitro

[127]

FTO

inhibitor

Rhein

Competitively binds the FTO catalytic domain and disrupts FTO from binding m6A-modified RNAs.

[133]

Meclofenamic acid (MA)

Competes with FTO binding for the m6A-containing RNA, increase m6A levels

[134]

MA2

Binds FTO active surface, induces m6A methylation, inhibits glioblastoma progression in mice

[135]

FB23-2

Reduces expression of c-Myc and CEBPA and promotes RARA and ASB2, represses leukemia cell proliferation, survival, and leukemia progression in mice

[136]

R-2HG

Induces degradation of c-Myc and CEBPA, promotes leukemia cell apoptosis, and inhibits leukemia growth in mice.

[108]

CS1 and CS2

Attenuate LSC self-renewal, reprogram immune response by reducing LILRB4, sensitize leukemia cells to T-cell cytotoxicity, and show potent anti-leukemic efficacy in mouse models

[136]

acrylonitrile derivative 1a

Binding FTO with chlorine atom, inhibits proliferation of leukemia cells

[137]

Saikosaponin D

Inhibites AML cells proliferation, induce apoptosis and cell cycle arrest both in vitro and vivo, particularly in TKIs-resistant cells

[138]

let-7b-5p mimic

Downregulate the expression of FTO and upregulate c-MYC level in AML line cells

[139]

ALKBH5

inhibitor

Compound 1 and 2

Bioactive peptide

Reduces leukemia cell viability

inhibit AML cell proliferation and promote apoptosis in vitro, and reduce tumor growth in vivo

[143, 144]