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Table 4 The functions of small-molecules targeting m6A regulators

From: Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy

Targeting

Compounds

Role

Functions

References

METTL3-METTL14-WTAP complex

Asp295

Activator

Promotes mRNA m6A modification

[159]

METTL3-METTL14-WTAP complex

Phe534

Activator

Promotes mRNA m6A modification

[159]

METTL3-METTL14-WTAP complex

Arg536

Activator

Promotes mRNA m6A modification

[159]

METTL3-METTL14-WTAP complex

Asn539

Activator

Promotes mRNA m6A modification

[159]

METTL3

molecule 1

Inhibitor

Reduces the abundance of mRNA targeted by METTL3 and suppresses the proliferation of leukemia cell

[146]

METTL3

molecule 2

Inhibitor

Reduces the abundance of mRNA targeted by METTL3 and suppresses the proliferation of leukemia cell

[146]

METTL3

STM2457

Inhibitor

Shows antitumor capacity against leukemia in vitro and in vivo

[160]

FTO

R-2HG

Inhibitor

Downregulates the expression of oncogene c-Myc and CEBPA, and increases the expression of antioncogene RARA and ASB2 expression; represses AML cell proliferation/viability

[144]

FTO

MO-I-50

Inhibitor

Suppresses the survival or colony forming ability of cancer cells in triple-negative inflammatory breast cancer cell lines

[153]

FTO

Rhein

Inhibitor

Competitively binds with the FTO catalytic domain and suppresses FTO function

[154]

FTO

CHTB

Inhibitor

Suppresses FTO function by binding with FTO between an antiparallel sheet and the extended C-terminal of the long loop of FTO

[155]

FTO

N-CDPCB

Inhibitor

Suppresses FTO function by binding with FTO between an antiparallel b-sheet and the L1 loop of FTO

[156]

FTO

Meclofenamic acid (MA)

Inhibitor

Specially integrates with the active surface of FTO to inhibit the activity of FTO and increase m6A abundance

[31, 105, 145, 147, 148]

FTO

FB23

Inhibitor

Downregulates the expression of oncogene c-Myc and CEBPA, and increases the expression of anti-oncogene RARA and ASB2 expression

[149]

FTO

FB23-2

Inhibitor

Downregulates the expression of oncogene c-Myc and CEBPA, and increases the expression of anti-oncogene RARA and ASB2 expression

[149]

FTO

CS1

Inhibitor

Directly binds to the enzymatic reaction center of FTO, interfere with its binding with target mRNA; reprograms the immune response, conquers immune escape by suppressing the expression of immune checkpoint gene LILRB4, and sensitizes leukemia cells to cytotoxic T cells

[101]

FTO

CS2

Inhibitor

Directly binds to the enzymatic reaction center of FTO, interfere its binding to target mRNA; reprograms the immune response, conquers immune escape by suppressing the expression of immune checkpoint gene LILRB4, and sensitizes leukemia cells to cytotoxic T cells

[101]

FTO

Entacapone

Inhibitor

Suppresses the function of FTO by directly binding with FTO at its cofactor and substrate binding sites

[150]

ALKBH5

ALK-04

Inhibitor

Functions synergistically with PD-1 inhibitor to inhibit melanoma

[105]

ALKBH5

MV1035

Inhibitor

Shows a favorable antitumor potency in GBM

[157]

ALKBH5

2-[(1-hydroxy-2-oxo-2- phenylethyl)sulfanyl]acetic acid

Inhibitor

Suppresses the proliferation of leukemia

[158]

ALKBH5

4-[(furan-2-yl)methyl]amino-1,2-diazinane-3,6-dione,

Inhibitor

suppresses the proliferation of leukemia

[158]

IGF2BP1

BTYNB

Inhibitor

Suppresses the proliferation of melanoma and ovarian cancer cells by downregulating the expression of targeted mRNAs

[161, 162]

  1. AML Acute myeloid leukemia, GBM Glioblastoma, BC Breast cancer