Table 3 Identified m6A-targeted compounds
From: Biological and pharmacological roles of m6A modifications in cancer drug resistance
Molecule | Target | Activity | IC50 (of target) (μM) | Mechanism in cancer/ cell line | Validated cancer type/ cell line type | Identified year | Ref |
|---|---|---|---|---|---|---|---|
rhein | FTO, ALKBH2, ALKBH3 | inhibit | 21 (FTO) | rhein restored nilotinib resistance by inhibiting the activity of FTO | leukemia | 2012 | |
MO-I-500 | FTO | inhibit | 8.7 | MO-I-500 inhibited BC cells survival and colony-forming | BC | 2014 | |
MA2 | FTO | inhibit | 7 | MA2 treatment inhibited GSCs growth and self-renewal | GBM | 2014 | |
FB23–2 | FTO | inhibit | 0.06 | FB23–2 suppressed proliferation and promoted the differentiation and apoptosis of AML cells | AML | 2019 | [165] |
Dac51 | FTO | inhibit | 0.4 | Dac51 increased CD8 + T cell infiltration and synergized with anti-PD-L1 blockade | SKCM, lung cancer | 2021 | [105] |
FTO-04 | FTO, ALKBH5 | inhibit | 3.39 (FTO) | prevented neurosphere formation in patient-derived GSCs | GBM | 2021 | [166] |
R-2HG | FTO | inhibit | 133.3 | R-2HG inhibited cancer cells proliferation/survival by targeting FTO/m6A/MYC/CEBPA pathway | AML | 2018 | [168] |
CS1 | FTO FTO | inhibit | 0.143 | CS1 and CS2 exerted anti-leukemic effects by activating apoptosis signaling and inhibition of MYC pathways | AML AML | 2020 | [103] |
CS2 | inhibit | 0.713 | 2020 | [103] | |||
adenosine | METTL3 | inhibit | 500 | NA | NA | 2020 | [170] |
STM2457 | METTL3 | inhibit | 0.0169 | STM2457 reduced AML growth and increased differentiation and apoptosis | AML | 2021 | [171] |
U2H1a | METTL3 | inhibit | 7 | U2H1a reduced m6A/A levels in mRNA fraction | AML, osteosarcoma, HEK293T | 2021 | [172] |
ALK-04 | ALKBH5 | inhibit | NA | ALK-04 reduced tumor growth and enhanced the efficacy of anti–PD-1 therapy | melanoma, CRC | 2019 | [106] |
BTYNB | IGF2BP1 | inhibit | 6 | BTYNB impaired tumor cell proliferation and inhibited E2F-driven gene expression | HepG2, A549, ES-2, PANC-1, MV3 | 2017 | [175] |
METTL3/14-WTAP compounds | METTL3 | activate | 0.281 | The compounds increased the mRNA m6A levels and regulated the cell cycle | HEK293 cell | 2019 | [173] |
MPCH | METTL3/14 | activate | NA | MPCH activated METTL3/14 and resulted in considerable m6A hypermethylation after short UV light exposure | A549, MCF-7, HeLa | 2021 | [176] |
IDH2 | FTO | activate | NA | IDH2 elevated FTO activity and contributed to tumorigenesis and progression in MM | MM | 2021 | [177] |