METTL3
gene geneOn this page
Also known as Spo8M6AMT-A70
Summary
METTL3 (methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit, HGNC:17563) is a protein-coding gene on chromosome 14q11.2, encoding N(6)-adenosine-methyltransferase catalytic subunit METTL3 (Q86U44). The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis,…. It is a selective cancer dependency (DepMap: 79.5% of cell lines).
This gene encodes the 70 kDa subunit of MT-A which is part of N6-adenosine-methyltransferase. This enzyme is involved in the posttranscriptional methylation of internal adenosine residues in eukaryotic mRNAs, forming N6-methyladenosine.
Source: NCBI Gene 56339 — RefSeq curated summary.
At a glance
- GWAS associations: 1
- Clinical variants (ClinVar): 53 total
- Druggable target: yes — 6 molecules with ChEMBL bioactivity
- Cancer dependency (DepMap): dependent in 79.5% of screened cell lines
- MANE Select transcript:
NM_019852
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:17563 |
| Approved symbol | METTL3 |
| Name | methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit |
| Location | 14q11.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | Spo8, M6A, MT-A70 |
| Ensembl gene | ENSG00000165819 |
| Ensembl biotype | protein_coding |
| OMIM | 612472 |
| Entrez | 56339 |
Gene structure
Transcript identifiers
Ensembl transcripts: 28 — 16 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined
ENST00000298717, ENST00000367606, ENST00000377543, ENST00000396522, ENST00000536201, ENST00000537163, ENST00000538267, ENST00000539760, ENST00000542054, ENST00000543235, ENST00000544248, ENST00000544500, ENST00000545319, ENST00000545788, ENST00000894032, ENST00000894034, ENST00000894036, ENST00000912042, ENST00000912043, ENST00000912044, ENST00000912045, ENST00000912046, ENST00000912047, ENST00000912048, ENST00000912049, ENST00000967377, ENST00000967378, ENST00000967379
RefSeq mRNA: 1 — MANE Select: NM_019852
NM_019852
CCDS: CCDS32044
Canonical transcript exons
ENST00000298717 — 11 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001263795 | 21498138 | 21498369 |
| ENSE00003474656 | 21501728 | 21501903 |
| ENSE00003486807 | 21499492 | 21499600 |
| ENSE00003503270 | 21511124 | 21511340 |
| ENSE00003523956 | 21499025 | 21499137 |
| ENSE00003541279 | 21499764 | 21499802 |
| ENSE00003542100 | 21500495 | 21500682 |
| ENSE00003582041 | 21503173 | 21503577 |
| ENSE00003594789 | 21500913 | 21501129 |
| ENSE00003621932 | 21503664 | 21503881 |
| ENSE00003671920 | 21499306 | 21499371 |
Expression profiles
Bgee: expression breadth ubiquitous, 297 present calls, max score 97.47.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.1088 / max 165.0067, expressed in 1811 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 142181 | 14.3165 | 1802 |
| 142180 | 4.7138 | 1537 |
| 142179 | 0.0785 | 13 |
Top tissues by expression
300 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right uterine tube | UBERON:0001302 | 97.47 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 96.17 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 95.98 | gold quality |
| body of uterus | UBERON:0009853 | 95.96 | gold quality |
| cerebellar cortex | UBERON:0002129 | 95.93 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 95.89 | gold quality |
| left ovary | UBERON:0002119 | 95.84 | gold quality |
| right ovary | UBERON:0002118 | 95.81 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 95.79 | gold quality |
| thyroid gland | UBERON:0002046 | 95.52 | gold quality |
| body of pancreas | UBERON:0001150 | 95.40 | gold quality |
| tibial nerve | UBERON:0001323 | 95.28 | gold quality |
| endocervix | UBERON:0000458 | 95.18 | gold quality |
| endothelial cell | CL:0000115 | 95.16 | gold quality |
| cerebellum | UBERON:0002037 | 95.14 | gold quality |
| middle temporal gyrus | UBERON:0002771 | 95.14 | gold quality |
| left uterine tube | UBERON:0001303 | 95.09 | gold quality |
| ectocervix | UBERON:0012249 | 94.95 | gold quality |
| lymph node | UBERON:0000029 | 94.83 | gold quality |
| minor salivary gland | UBERON:0001830 | 94.82 | gold quality |
| right lung | UBERON:0002167 | 94.72 | gold quality |
| spleen | UBERON:0002106 | 94.70 | gold quality |
| ovary | UBERON:0000992 | 94.42 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 94.41 | gold quality |
| metanephros cortex | UBERON:0010533 | 94.30 | gold quality |
| skin of abdomen | UBERON:0001416 | 94.24 | gold quality |
| granulocyte | CL:0000094 | 94.17 | gold quality |
| saliva-secreting gland | UBERON:0001044 | 94.16 | gold quality |
| mucosa of stomach | UBERON:0001199 | 94.12 | gold quality |
| vagina | UBERON:0000996 | 94.09 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 8.78 |
Regulation
Is transcription factor: yes
Downstream targets (CollecTRI)
2 targets.
| Target | Regulation |
|---|---|
| EGFR | Activation |
| WWTR1 | Activation |
Upstream regulators (CollecTRI, top): E2F4
miRNA regulators (miRDB)
6 targeting METTL3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-LET-7C-3P | 99.95 | 73.42 | 2862 |
| HSA-MIR-338-5P | 99.92 | 72.34 | 2951 |
| HSA-MIR-4320 | 99.75 | 65.80 | 793 |
| HSA-MIR-33A-3P | 99.70 | 70.27 | 3362 |
| HSA-MIR-1246 | 98.54 | 66.21 | 959 |
| HSA-MIR-5579-3P | 97.00 | 68.81 | 1111 |
Functional genomics
DepMap (CRISPR cell-line fitness): dependent in 79.5% of screened cell lines.
Literature-anchored findings (GeneRIF, showing 40)
- Study identifies m(6)A methylation sites on many clock gene transcripts and shows that specific inhibition of m(6)A methylation by silencing of the m(6)A methylase Mettl3 is sufficient to elicit circadian period elongation and RNA processing delay. (PMID:24209618)
- genetic inactivation impaired embryonic stem cells differentiation (PMID:25456834)
- METTL3 enhances mRNA translation through an interaction with the translation initiation machinery in lung adenocarcinoma cells. (PMID:27117702)
- Structure of the METTL3-METTL14 complex (PMID:27281194)
- For the methylation of adenosine in RNA, Mettl3 is the catalytically active subunit, while Mettl14 plays a structural role critical for substrate recognition. (PMID:27373337)
- The structure reveals the heterodimeric architecture of the complex and donor substrate binding by METTL3. Structure-guided mutagenesis indicates that METTL3 is the catalytic subunit of the complex, whereas METTL14 has a degenerate active site and plays non-catalytic roles in maintaining complex integrity and substrate RNA binding. (PMID:27627798)
- miR-33a can attenuatenon-small-cell lung carcinoma cells proliferation via targeting to the 3’-untranslated region of METTL3 mRNA. (PMID:27856248)
- methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2-mediated m5C and METTL3/METTL14-mediated m6A methylation synergistically enhance p21 expression at the translational level (PMID:28247949)
- loss of METTL3 leads to increased levels of phosphorylated AKT, which contributes to the differentiation-promoting effects of METTL3 depletion. Overall, these results provide a rationale for the therapeutic targeting of METTL3 in myeloid leukemia (PMID:28920958)
- Study reports the importance of m6A modification in glioma stem-like cells and uncovers METTL3 as a potential molecular target in glioblastoma therapy. (PMID:28991227)
- Data show that hepatitis B X-interacting protein (HBXIP) modulated Methyltransferase-like 3 (METTL3) by inhibiting miRNA let-7g, which down-regulated the expression of METTL3 by targeting its 3’UTR. (PMID:29174803)
- data define METTL3 as a regulator of a chromatin-based pathway that is necessary for maintenance of the leukaemic state and identify this enzyme as a potential therapeutic target for acute myeloid leukaemia (PMID:29186125)
- The role of METTL3 in pancreatic cancer cells drug resistance and radiation resistance.METTL3 was associated with mitogen-activated protein kinase cascades, ubiquitin-dependent process and RNA splicing and regulation of cellular process. (PMID:29345285)
- METTL3 is soluble and inactive while the catalytic center of METTL14 is degenerated and thus also inactive. In addition, the C-terminal RGG repeats of METTL14 are required for METTL3/14 activity by contributing to RNA substrate binding. (PMID:29348140)
- METTL3 might inhibit the LPS-induced inflammatory response of human dental pulp cells by regulating alternative splicing of MyD88. (PMID:29502358)
- An important mechanism for SUMOylation of METTL3 regulating its m6A RNA methyltransferase activity.Lysine 177/211/212/215 are major SUMOylation-sites of METTL3.METTL3 role in tumorigenesis. (PMID:29506078)
- METTL3 acts as an oncogene in myeloid leukemia MOLM13 cells by upregulating MYC expression. (PMID:29978784)
- METTL3-eIF3h interaction is required for enhanced translation, formation of densely packed polyribosomes and oncogenic transformation; findings uncover a mechanism of translation control that is based on mRNA looping and identify METTL3-eIF3h as a potential therapeutic target for patients with cancer (PMID:30232453)
- Findings suggest that METTL3 plays very important oncogenic roles in ovarian carcinoma development and/or aggressiveness by stimulating AXL translation and EMT. (PMID:30249526)
- we found that METTL3 interacted with viral RNA-dependent RNA polymerase 3D and induced enhanced sumoylation and ubiquitination of the 3D polymerase that boosted viral replication. Taken together, our findings demonstrated that the host m6A modification complex interacts with viral proteins to modulate EV71 replication. (PMID:30364964)
- METTL3 expression is elevated in bladder cancer.MYC, AFF4, RELA and IKBKB are functionally important target genes of METTL3 in bladder cancer. (PMID:30659266)
- Results for the first time uncover the role of mA modification in melanoma cell biology. Authors show that METTL3 is upregulated in human melanoma and plays a role in invasion/migration through MMP2. (PMID:30762711)
- We conclude that METTL3 plays a vital role in many steps of RNA processing and orchestrates successful execution of oncogenic pathways in glioma stem-like cells . (PMID:30781903)
- Genetic alterations of m6A regulatory genes in clear cell renal cell carcinoma indicate a relationship between the alterations resulting in decreased m6A level and worse clinical characteristics including survival. (PMID:30877265)
- main writer of N6-methyladenosine modification in germ cell tumors (PMID:30903744)
- Study demonstrates that oncogenic miR-25 in pancreatic duct epithelial cells can be excessively maturated by cigarette smoke condensate (CSC) via enhanced N(6)-methyladenosine modification that is mediated by NF-kappaB associated protein NKAP. This modification is catalyzed by overexpressed METTL3 due to hypomethylation of the METTL3 promoter also caused by CSC. (PMID:31015415)
- The m(6)A methyltransferase METTL3 is a critical gene in regulating tumorigeneis of cutaneous squamous cell carcinoma. METTL3 knock down decreased m(6)A levels and the expression of DeltaNp63. (PMID:31153635)
- Results showed that METTL3 was significantly increased in bladder cancer and correlated with poor prognosis of bladder cancer patients. Moreover, METTL3 could promote cell proliferation both in vitro and tumorigenesis in vivo. (PMID:31228940)
- Higher METTL3 expression was found in colorectal carcinoma (CRC) metastatic tissues and was associated with a poor prognosis. Further data revealed that METTL3, acting as an oncogene, maintained SOX2 expression through an m6A-IGF2BP2-dependent mechanism in CRC cells, and indicated a potential biomarker panel for prognostic prediction in CRC. (PMID:31230592)
- Dysregulated N6-methyladenosine methylation writer METTL3 contributes to the proliferation and migration of gastric cancer. (PMID:31232471)
- In silico genome-wide identification of m6A-associated SNPs as potential functional variants for periodontitis. (PMID:31245852)
- Data suggest that methyltransferase-like protein 3 (METTL3) silence decreased the m6A methylation and total mRNA level of lymphoid enhancer-binding factor 1 (LEF1), followed by inhibited the activity of Wnt/beta-catenin signaling pathway. (PMID:31253399)
- miR-4429 prevented gastric cancer progression through targeting METTL3 to inhibit m(6)A-caused stabilization of SEC62 (PMID:31395342)
- METTL3 inhibits hepatic insulin sensitivity via N6-methylation of Fasn mRNA and promoting fatty acid metabolism. (PMID:31405565)
- METTL3 was up-regulated in the breast cancer tissue and cells. And, METTL3 could install the methylation of Bcl-2 and promote its translation, thereby regulating the proliferation and apoptosis of breast cancer. (PMID:31454538)
- our findings provide a totally different mechanism of METTL3 in regulating CRC metastasis. Our study demonstrates that aberrant m6A modification in CRC was responsible for the upregulated METTL3 expression, which marks pri-miR-1246 for further processing (PMID:31492150)
- METTL3-mediated m(6)A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance. (PMID:31582403)
- A Mass Spectrometric Assay of METTL3/METTL14 Methyltransferase Activity. (PMID:31585521)
- METTL3 is probably involved in pancreatic carcinogenesis (PMID:31606241)
- our findings indicate the critical role of m6A modification in GC and uncover METTL3/ZMYM1/E-cadherin signaling as a potential therapeutic target in anti-metastatic strategy against GC. (PMID:31607270)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | mettl3 | ENSDARG00000012827 |
| mus_musculus | Mettl3 | ENSMUSG00000022160 |
| rattus_norvegicus | Mettl3 | ENSRNOG00000013111 |
| drosophila_melanogaster | Mettl3 | FBGN0039139 |
Protein
Protein identifiers
N(6)-adenosine-methyltransferase catalytic subunit METTL3 — Q86U44 (reviewed: Q86U44)
Alternative names: Methyltransferase-like protein 3, N(6)-adenosine-methyltransferase 70 kDa subunit
All UniProt accessions (6): A0A0G2JH39, B4DTN4, B4E349, Q86U44, F5H6D8, H0YFV6
UniProt curated annotations — full annotation on UniProt →
Function. The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing. In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core. N6-methyladenosine (m6A), which takes place at the 5’-[AG]GAC-3’ consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing. M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation. In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs. M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop. M6A also regulates circadian regulation of hepatic lipid metabolism. M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis. Also required for oogenesis. Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites. M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation. Inhibits the type I interferon response by mediating m6A methylation of IFNB. M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist. M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells. METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8. Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm. Its overexpression in a number of cancer cells suggests that it may participate in cancer cell proliferation by promoting mRNA translation. During human coronavirus SARS-CoV-2 infection, adds m6A modifications in SARS-CoV-2 RNA leading to decreased RIGI binding and subsequently dampening the sensing and activation of innate immune responses.
Subunit / interactions. Heterodimer; heterodimerizes with METTL14 to form an antiparallel heterodimer that constitutes an active methyltransferase. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B). Interacts with NCBP1/CBP80. Interacts with EIF4E. Interacts with EIF3B.
Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.
Tissue specificity. Widely expressed at low level. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.
Post-translational modifications. Sumoylation inhibits the N6-adenosine-methyltransferase activity. Sumoylation does not affect subcellular location or interaction with METTL14. Desumoylated by SENP1.
Activity regulation. Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism. Methyltransferase activity is inhibited by sumoylation.
Domain organisation. Gate loop 1 and gate loop 2 regions are adjacent to the S-adenosyl-L-homocysteine-binding site and display large conformational changes upon ligand-binding. They may play an important role in adenosine recognition. The interface loop contributes to the heterodimer interaction.
Induction. Overexpressed in a number of cancer tissues, such as lung adenocarcinoma and colon adenocarcinoma.
Similarity. Belongs to the MT-A70-like family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q86U44-1 | 1 | yes |
| Q86U44-2 | 2 |
RefSeq proteins (1): NP_062826* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR007757 | MT-A70-like | Family |
| IPR025848 | MT-A70 | Family |
| IPR029063 | SAM-dependent_MTases_sf | Homologous_superfamily |
Pfam: PF05063
Enzyme classification (BRENDA):
- EC 2.1.1.348 — mRNA m6A methyltransferase (BRENDA: 11 organisms, 24 substrates, 64 inhibitors, 6 Km, 5 kcat entries)
Substrate kinetics (BRENDA)
3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ADENINE IN DOUBLE-STRANDED DNA CONTAINING A CYCL | 0.0006–0.0007 | 2 |
| ADENINE IN MRNA | 0.0002–0.023 | 2 |
| ADENINE IN SINGLE-STRANDED DNA | 0.0032–0.0077 | 2 |
Catalyzed reactions (Rhea), 1 shown:
- an adenosine in mRNA + S-adenosyl-L-methionine = an N(6)-methyladenosine in mRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:55584)
UniProt features (87 total): mutagenesis site 25, strand 13, modified residue 9, region of interest 8, helix 7, binding site 5, cross-link 4, sequence conflict 4, splice variant 3, site 2, turn 2, initiator methionine 1, chain 1, short sequence motif 1, compositionally biased region 1, sequence variant 1
Structure
Experimental structures (PDB)
77 structures, top 30 by resolution.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 5IL2 | X-RAY DIFFRACTION | 1.61 |
| 7RX7 | X-RAY DIFFRACTION | 1.65 |
| 5K7M | X-RAY DIFFRACTION | 1.65 |
| 5K7W | X-RAY DIFFRACTION | 1.65 |
| 5K7U | X-RAY DIFFRACTION | 1.7 |
| 5IL1 | X-RAY DIFFRACTION | 1.71 |
| 9RS1 | X-RAY DIFFRACTION | 1.73 |
| 9Q8G | X-RAY DIFFRACTION | 1.75 |
| 5TEY | X-RAY DIFFRACTION | 1.8 |
| 7O09 | X-RAY DIFFRACTION | 1.8 |
| 7RX6 | X-RAY DIFFRACTION | 1.8 |
| 7NHI | X-RAY DIFFRACTION | 1.85 |
| 7RX8 | X-RAY DIFFRACTION | 1.85 |
| 9G4W | X-RAY DIFFRACTION | 1.85 |
| 9IH5 | X-RAY DIFFRACTION | 1.85 |
| 5L6D | X-RAY DIFFRACTION | 1.85 |
| 7OEL | X-RAY DIFFRACTION | 1.86 |
| 5IL0 | X-RAY DIFFRACTION | 1.88 |
| 6Y4G | X-RAY DIFFRACTION | 1.9 |
| 7O0L | X-RAY DIFFRACTION | 1.9 |
| 7OEK | X-RAY DIFFRACTION | 1.9 |
| 5L6E | X-RAY DIFFRACTION | 1.9 |
| 7NHV | X-RAY DIFFRACTION | 1.91 |
| 9RRY | X-RAY DIFFRACTION | 1.91 |
| 9G4S | X-RAY DIFFRACTION | 1.95 |
| 9Q89 | X-RAY DIFFRACTION | 1.95 |
| 9Q8A | X-RAY DIFFRACTION | 1.95 |
| 6TTP | X-RAY DIFFRACTION | 2 |
| 6TTX | X-RAY DIFFRACTION | 2 |
| 7O08 | X-RAY DIFFRACTION | 2 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q86U44-F1 | 76.71 | 0.35 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (2): 438 (interaction with mettl14); 441 (interaction with mettl14)
Ligand- & substrate-binding residues (5): 377–378; 395; 513; 536–539; 549–550
Post-translational modifications (13): 2, 2, 43, 48, 50, 219, 243, 348, 350, 177, 211, 212, 215
Mutagenesis-validated functional residues (25):
| Position | Phenotype |
|---|---|
| 2 | does not affect nuclear localization, interaction with mettl14 or wtap or catalytic activity; when associated with a-43; |
| 43 | does not affect nuclear localization, interaction with mettl14 or wtap or catalytic activity; when associated with a-2; |
| 48 | does not affect nuclear localization, interaction with mettl14 or wtap or catalytic activity; when associated with a-2; |
| 50 | does not affect nuclear localization, interaction with mettl14 or wtap or catalytic activity; when associated with a-2; |
| 177 | in 4kr; strongly decreased sumoylation; when associated with 211-r–r-215. |
| 211–215 | abolishes localization to the nucleus. |
| 211–215 | in 3kr; decreased sumoylation. in 4kr; strongly decreased sumoylation; when associated with r-177. |
| 219 | does not affect nuclear localization, interaction with mettl14 or wtap or catalytic activity; when associated with a-243 |
| 243 | does not affect nuclear localization, interaction with mettl14 or wtap or catalytic activity; when associated with a-219 |
| 294 | abolishes methyltransferase activity. |
| 326 | abolishes methyltransferase activity. |
| 348–350 | does not affect nuclear localization, interaction with mettl14 or wtap or catalytic activity; when associated with a-219 |
| 377 | abolishes methyltransferase activity. |
| 395–398 | loss of function. abolishes ability to regulate primary mirna processing. does not affect ability to promote mrna transl |
| 395 | abolishes methyltransferase activity. |
| 406 | strong reduction in methyltransferase activity. |
| 462–479 | impaired rna-binding and methyltransferase activities. |
| 475 | decreased methyltransferase activity. |
| 477 | decreased methyltransferase activity. |
| 532 | abolishes methyltransferase activity. |
| 536 | slight reduction in methyltransferase activity. |
| 538 | slight reduction in methyltransferase activity. |
| 539 | abolishes methyltransferase activity. |
| 549 | slight reduction in methyltransferase activity. strong reduction in methyltransferase activity; when associated with a-5 |
| 550 | slight reduction in methyltransferase activity. strong reduction in methyltransferase activity; when associated with a-5 |
Function
Pathways and Gene Ontology
Reactome pathways
2 pathways
| ID | Pathway |
|---|---|
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA |
| R-HSA-8953854 | Metabolism of RNA |
MSigDB gene sets: 331 (showing top):
GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_CIRCADIAN_RHYTHM, GOBP_CYTOPLASMIC_TRANSLATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_UV, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_OOGENESIS, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION
GO Biological Process (29): mRNA splicing, via spliceosome (GO:0000398), RNA methylation (GO:0001510), mRNA processing (GO:0006397), DNA damage response (GO:0006974), spermatogenesis (GO:0007283), circadian rhythm (GO:0007623), dosage compensation by inactivation of X chromosome (GO:0009048), mRNA modification (GO:0016556), stem cell population maintenance (GO:0019827), forebrain radial glial cell differentiation (GO:0021861), primary miRNA processing (GO:0031053), cellular response to UV (GO:0034644), gliogenesis (GO:0042063), innate immune response (GO:0045087), regulation of T cell differentiation (GO:0045580), positive regulation of translation (GO:0045727), negative regulation of Notch signaling pathway (GO:0045746), oogenesis (GO:0048477), regulation of meiotic cell cycle (GO:0051445), negative regulation of type I interferon-mediated signaling pathway (GO:0060339), mRNA destabilization (GO:0061157), endothelial to hematopoietic transition (GO:0098508), regulation of hematopoietic stem cell differentiation (GO:1902036), positive regulation of cap-independent translational initiation (GO:1903679), immune system process (GO:0002376), mRNA export from nucleus (GO:0006406), cell differentiation (GO:0030154), methylation (GO:0032259), rhythmic process (GO:0048511)
GO Molecular Function (11): mRNA m(6)A methyltransferase activity (GO:0001734), mRNA binding (GO:0003729), RNA methyltransferase activity (GO:0008173), protein heterodimerization activity (GO:0046982), S-adenosyl-L-methionine binding (GO:1904047), RNA binding (GO:0003723), protein binding (GO:0005515), methyltransferase activity (GO:0008168), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740), catalytic activity, acting on a nucleic acid (GO:0140640)
GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), nuclear body (GO:0016604), nuclear speck (GO:0016607), RNA N6-methyladenosine methyltransferase complex (GO:0036396), cytoplasm (GO:0005737), oxidoreductase complex (GO:1990204)
Reactome top-level categories
Rollup of top-1 pathways:
| Category | Pathways |
|---|---|
| Metabolism of RNA | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| RNA modification | 2 |
| mRNA metabolic process | 2 |
| methyltransferase activity | 2 |
| catalytic activity | 2 |
| intracellular membrane-bounded organelle | 2 |
| cytoplasm | 2 |
| RNA splicing, via transesterification reactions with bulged adenosine as nucleophile | 1 |
| mRNA processing | 1 |
| macromolecule methylation | 1 |
| RNA processing | 1 |
| cellular response to stress | 1 |
| developmental process involved in reproduction | 1 |
| male gamete generation | 1 |
| rhythmic process | 1 |
| sex-chromosome dosage compensation | 1 |
| heterochromatin formation | 1 |
| multicellular organismal process | 1 |
| maintenance of cell number | 1 |
| forebrain generation of neurons | 1 |
| radial glial cell differentiation | 1 |
| miRNA processing | 1 |
| response to UV | 1 |
| cellular response to light stimulus | 1 |
| neurogenesis | 1 |
| immune response | 1 |
| defense response to symbiont | 1 |
| T cell differentiation | 1 |
| regulation of lymphocyte differentiation | 1 |
| regulation of T cell activation | 1 |
| translation | 1 |
| regulation of translation | 1 |
| positive regulation of gene expression | 1 |
| positive regulation of protein metabolic process | 1 |
| Notch signaling pathway | 1 |
| regulation of Notch signaling pathway | 1 |
| negative regulation of signal transduction | 1 |
| germ cell development | 1 |
| female gamete generation | 1 |
| meiotic cell cycle | 1 |
Protein interactions and networks
STRING
2399 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| METTL3 | VIRMA | Q69YN4 | 999 |
| METTL3 | WTAP | Q15007 | 999 |
| METTL3 | METTL4 | Q8N3J2 | 999 |
| METTL3 | ZC3H13 | Q5T200 | 998 |
| METTL3 | RBM15 | Q96T37 | 998 |
| METTL3 | RBM15B | Q8NDT2 | 997 |
| METTL3 | CBLL1 | Q75N03 | 996 |
| METTL3 | METTL14 | Q9HCE5 | 993 |
| METTL3 | METTL16 | Q86W50 | 990 |
| METTL3 | EIF3H | O15372 | 989 |
| METTL3 | YTHDF3 | Q7Z739 | 988 |
| METTL3 | DGCR8 | Q8WYQ5 | 985 |
| METTL3 | SMAD2 | Q15796 | 969 |
| METTL3 | YTHDC1 | Q96MU7 | 951 |
| METTL3 | YTHDC2 | Q9H6S0 | 942 |
IntAct
68 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| METTL14 | METTL3 | psi-mi:“MI:0915”(physical association) | 0.940 |
| METTL14 | METTL3 | psi-mi:“MI:0407”(direct interaction) | 0.940 |
| METTL3 | METTL14 | psi-mi:“MI:0407”(direct interaction) | 0.940 |
| METTL3 | METTL14 | psi-mi:“MI:0914”(association) | 0.940 |
| BMAL2 | CLOCK | psi-mi:“MI:0914”(association) | 0.670 |
| EIF3H | METTL3 | psi-mi:“MI:0407”(direct interaction) | 0.560 |
| EIF3H | METTL3 | psi-mi:“MI:2364”(proximity) | 0.560 |
| METTL3 | EIF3H | psi-mi:“MI:0914”(association) | 0.560 |
| METTL3 | WTAP | psi-mi:“MI:0914”(association) | 0.530 |
| METTL14 | WTAP | psi-mi:“MI:0914”(association) | 0.530 |
| NSUN2 | LIN7A | psi-mi:“MI:0914”(association) | 0.530 |
| CPSF6 | DDX39A | psi-mi:“MI:0914”(association) | 0.480 |
| METTL14 | psi-mi:“MI:0213”(methylation reaction) | 0.440 | |
| MYC | TARS3 | psi-mi:“MI:0914”(association) | 0.350 |
| MPP1 | DKC1 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (337): METTL3 (Affinity Capture-RNA), METTL3 (Co-fractionation), METTL3 (Proximity Label-MS), METTL3 (Proximity Label-MS), ROBO2 (Affinity Capture-MS), SEL1L (Affinity Capture-MS), WTAP (Affinity Capture-MS), RBM15B (Affinity Capture-MS), PPHLN1 (Affinity Capture-MS), METTL3 (Affinity Capture-MS), METTL3 (Affinity Capture-MS), METTL3 (Affinity Capture-MS), METTL14 (Affinity Capture-MS), METTL3 (Affinity Capture-MS), METTL3 (Affinity Capture-MS)
ESM2 similar proteins: A0A1D3PCM3, A0A1U8QYZ5, A0A2Z4HPY5, A0A384JRP0, A1D3I1, A2QCJ2, A4RE47, A7EYY7, B0XQ16, C0SGJ2, C1G2I2, C1GP85, C5P635, C8V9Y5, C8VP37, E3QDT3, E9CS37, E9ESM3, G9NNY7, J4W6X9, O42783, O47881, O94069, P08465, P0CQ16, P0CQ17, P12917, P21334, P38092, Q06736, Q10341, Q2QXY1, Q2RAP0, Q2U9G3, Q2URJ0, Q4HVQ9, Q4IQC1, Q4WTK9, Q4X0Z7, Q5AT15
Diamond homologs: A4IFD8, F1R777, O82486, Q3UIK4, Q5R5N4, Q5ZK35, Q66KJ9, Q6EU10, Q6NU56, Q6NZ22, Q86U44, Q8C3P7, Q94AI4, Q9HCE5, Q9VCE6, Q9VLP7, P41833, Q2HVD6
SIGNOR signaling
16 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| MAPK3 | “up-regulates quantity by stabilization” | METTL3 | phosphorylation |
| MAPK1 | “up-regulates quantity by stabilization” | METTL3 | phosphorylation |
| ERK1/2 | “up-regulates quantity by stabilization” | METTL3 | phosphorylation |
| METTL3 | “up-regulates quantity by expression” | EGFR | “transcriptional regulation” |
| METTL3 | “up-regulates quantity by expression” | WWTR1 | “transcriptional regulation” |
| Gbeta | “up-regulates quantity by stabilization” | METTL3 | phosphorylation |
| TBK1 | “up-regulates activity” | METTL3 | phosphorylation |
| ATM | “up-regulates activity” | METTL3 | phosphorylation |
| METTL3 | “up-regulates quantity by stabilization” | USP13 | “post transcriptional regulation” |
| METTL3 | “up-regulates quantity by stabilization” | UCK2 | “post transcriptional regulation” |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 67 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| circadian regulation of gene expression | 5 | 18.9× | 4e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
53 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 38 |
| Likely benign | 0 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1786 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 14:21499506:T:TA | donor_gain | 1.0000 |
| 14:21499507:C:A | donor_gain | 1.0000 |
| 14:21499596:CATAC:C | acceptor_gain | 1.0000 |
| 14:21499598:TAC:T | acceptor_gain | 1.0000 |
| 14:21499599:AC:A | acceptor_gain | 1.0000 |
| 14:21499599:ACC:A | acceptor_loss | 1.0000 |
| 14:21499600:CC:C | acceptor_gain | 1.0000 |
| 14:21499601:C:CA | acceptor_loss | 1.0000 |
| 14:21500528:T:TA | donor_gain | 1.0000 |
| 14:21500681:CA:C | acceptor_gain | 1.0000 |
| 14:21500683:C:CC | acceptor_gain | 1.0000 |
| 14:21501059:CCA:C | acceptor_gain | 1.0000 |
| 14:21501060:CA:C | acceptor_gain | 1.0000 |
| 14:21501061:A:C | acceptor_gain | 1.0000 |
| 14:21501071:A:C | acceptor_gain | 1.0000 |
| 14:21501125:TTCGT:T | acceptor_gain | 1.0000 |
| 14:21501126:TCGT:T | acceptor_gain | 1.0000 |
| 14:21501127:CGT:C | acceptor_gain | 1.0000 |
| 14:21501127:CGTC:C | acceptor_gain | 1.0000 |
| 14:21501130:C:CC | acceptor_gain | 1.0000 |
| 14:21503167:CCCTA:C | donor_loss | 1.0000 |
| 14:21503168:CCTAC:C | donor_loss | 1.0000 |
| 14:21503169:CTAC:C | donor_loss | 1.0000 |
| 14:21503170:TAC:T | donor_loss | 1.0000 |
| 14:21503172:CCTT:C | donor_gain | 1.0000 |
| 14:21511138:T:TA | donor_gain | 1.0000 |
| 14:21511145:T:TA | donor_gain | 1.0000 |
| 14:21499019:CCTTA:C | donor_loss | 0.9900 |
| 14:21499020:CTTA:C | donor_loss | 0.9900 |
| 14:21499022:TACC:T | donor_loss | 0.9900 |
AlphaMissense
3807 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 14:21498358:C:A | G548V | 1.000 |
| 14:21498358:C:T | G548E | 1.000 |
| 14:21498359:C:G | G548R | 1.000 |
| 14:21498359:C:T | G548R | 1.000 |
| 14:21499026:A:G | W544R | 1.000 |
| 14:21499026:A:T | W544R | 1.000 |
| 14:21499039:A:C | N539K | 1.000 |
| 14:21499039:A:T | N539K | 1.000 |
| 14:21499052:C:T | G535E | 1.000 |
| 14:21499053:C:G | G535R | 1.000 |
| 14:21499053:C:T | G535R | 1.000 |
| 14:21499054:A:C | F534L | 1.000 |
| 14:21499054:A:T | F534L | 1.000 |
| 14:21499056:A:G | F534L | 1.000 |
| 14:21499056:A:T | F534I | 1.000 |
| 14:21499085:A:G | L524P | 1.000 |
| 14:21499115:G:C | P514R | 1.000 |
| 14:21499115:G:T | P514Q | 1.000 |
| 14:21499116:G:A | P514S | 1.000 |
| 14:21499117:T:A | K513N | 1.000 |
| 14:21499117:T:G | K513N | 1.000 |
| 14:21499118:T:A | K513I | 1.000 |
| 14:21499119:T:C | K513E | 1.000 |
| 14:21499119:T:G | K513Q | 1.000 |
| 14:21499123:A:C | S511R | 1.000 |
| 14:21499123:A:T | S511R | 1.000 |
| 14:21499124:C:A | S511I | 1.000 |
| 14:21499124:C:T | S511N | 1.000 |
| 14:21499125:T:G | S511R | 1.000 |
| 14:21499311:C:G | A505P | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000165463 (14:21505465 A>G), RS1000174585 (14:21510483 A>T), RS1000219668 (14:21505790 C>T), RS1000373945 (14:21498838 C>T), RS1000723956 (14:21498492 G>A,C), RS1000769783 (14:21508665 C>A,T), RS1000781812 (14:21511591 T>C), RS1001119760 (14:21506508 C>G,T), RS1001130481 (14:21511423 G>C), RS1001280877 (14:21507930 AAG>A), RS1001311875 (14:21507501 C>T), RS1001732096 (14:21512720 C>T), RS1001775762 (14:21500765 C>T), RS1002119876 (14:21503431 G>A), RS1002184492 (14:21512976 C>A)
Disease associations
OMIM: gene MIM:612472 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
1 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST002749_4 | Response to Homoharringtonine (cytotoxicity) | 9.000000e-07 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0006952 | cytotoxicity measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (4): CHEMBL4106140 (PROTEIN COMPLEX), CHEMBL4739695 (SINGLE PROTEIN), CHEMBL6195524 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195539 (PROTEIN-PROTEIN INTERACTION)
Molecules with ChEMBL bioactivity
6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 149,602 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL461101 | ELTROMBOPAG | 4 | 602 |
| CHEMBL204656 | ELVITEGRAVIR | 4 | 2,944 |
| CHEMBL509 | MECLOFENAMIC ACID | 4 | 45,809 |
| CHEMBL50 | QUERCETIN | 3 | 74,559 |
| CHEMBL1214186 | SINEFUNGIN | 2 | 2,165 |
| CHEMBL151 | LUTEOLIN | 2 | 23,523 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB variants
1 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs1139130 | METTL3 | 0.00 | 0 |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — 2.1.1.- Methyltransferases
Most potent curated ligand interactions (3 total), top 3:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| UZH2 | Inhibition | 8.3 | pIC50 |
| STC-15 | Inhibition | 8.21 | pIC50 |
| STM2457 | Inhibition | 7.77 | pIC50 |
Binding affinities (BindingDB)
135 measured of 135 human assays (135 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| US20250214997, Compound E-57 | IC50 | 0.1 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 5-[1-[[2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indol-6-yl]methyl]triazol-4-yl]-N,N-dimethylpyridin-3-amine | IC50 | 0.12 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-[5-(3-fluoropyrrolidin-1-yl)-3-pyridinyl]triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine | IC50 | 0.16 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-(5-pyrrolidin-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine | IC50 | 0.16 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-140 | IC50 | 0.17 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-87 | IC50 | 0.19 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-121 | IC50 | 0.2 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-84 | IC50 | 0.24 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-111 | IC50 | 0.24 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-51 | IC50 | 0.25 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-101 | IC50 | 0.25 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-50 | IC50 | 0.29 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-105 | IC50 | 0.29 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-119 | IC50 | 0.29 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-2-[(1-methylpiperidin-4-yl)amino]-4-(4-phenylmethoxyanilino)-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochloride | IC50 | 0.3 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-(5-pyrrol-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine | IC50 | 0.31 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-56 | IC50 | 0.32 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| N-[[6-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]imidazo[1,2-a]pyridin-2-yl]methyl]-5-pyrrolidin-1-ylpyridine-3-carboxamide | IC50 | 0.33 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 2-[[4-[5-(2,5-dihydropyrrol-1-yl)-3-pyridinyl]triazol-1-yl]methyl]-6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridine | IC50 | 0.36 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-49 | IC50 | 0.37 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 6-(aziridin-1-yl)-4-[1-[[2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indol-6-yl]methyl]triazol-4-yl]-1H-indazole | IC50 | 0.4 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 6-[(4,4-dimethylpiperidin-1-yl)methyl]-2-[[4-(5-pyrrolidin-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridine | IC50 | 0.4 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 1-[2-[[4-[5-(3,3-difluoropyrrolidin-1-yl)-3-pyridinyl]triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]-N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]methanamine | IC50 | 0.41 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-106 | IC50 | 0.48 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 6-[[4-[5-(azetidin-1-yl)-3-pyridinyl]triazol-1-yl]methyl]-2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indole | IC50 | 0.5 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-79 | IC50 | 0.54 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-4-(4-phenoxyanilino)-2-[[1-(2,2,2-trifluoroethyl)piperidin-4-yl]amino]-6H-pyrido[4,3-d]pyrimidin-5-one | IC50 | 0.56 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-59 | IC50 | 0.59 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-4-(3-methyl-4-phenoxyanilino)-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochloride | IC50 | 0.61 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-4-[4-(3,5-difluorophenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochloride | IC50 | 0.69 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 1-cyclobutyl-N-[[2-[[4-[5-(2,5-dihydropyrrol-1-yl)-3-pyridinyl]triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine | IC50 | 0.74 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-2-[(1-methylpiperidin-4-yl)amino]-4-(4-phenylmethoxyanilino)-6H-pyrido[4,3-d]pyrimidin-5-one | IC50 | 0.75 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-39 | IC50 | 0.75 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-143 | IC50 | 0.77 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-4-[3-fluoro-4-(3-fluorophenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochloride | IC50 | 0.8 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-chloro-4-(4-cyclohexyloxyanilino)-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one | IC50 | 0.9 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 1-cyclobutyl-N-[[2-[[4-(5-pyrrolidin-1-yl-3-pyridinyl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine | IC50 | 1.02 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 5-[1-[[6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl]methyl]triazol-4-yl]-N,N-dimethylpyridin-3-amine | IC50 | 1.06 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 5-(dimethylamino)-N-[[2-[(4,4-dimethylpiperidin-1-yl)methyl]-1H-indol-6-yl]methyl]pyridine-3-carboxamide | IC50 | 1.09 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 2-[[(3S)-pyrrolidin-3-yl]amino]-4-[4-(trifluoromethyl)anilino]-6H-pyrido[4,3-d]pyrimidin-5-one | IC50 | 1.17 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-58 | IC50 | 1.18 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-4-[4-(4-chlorophenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochloride | IC50 | 1.21 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 4-[1-[[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]methyl]triazol-4-yl]-6-methylsulfanyl-1H-indazole | IC50 | 1.23 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 1-cyclobutyl-N-[[2-[[4-(6-iodo-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine | IC50 | 1.24 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-112 | IC50 | 1.25 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 4-[1-[[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]methyl]triazol-4-yl]-6-bromo-1H-indazole | IC50 | 1.37 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-4-[4-(4-methylphenoxy)anilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one | IC50 | 1.38 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-60 | IC50 | 1.39 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| 8-bromo-4-[4-(3-fluorophenoxy)-3-methylanilino]-2-[(1-methylpiperidin-4-yl)amino]-6H-pyrido[4,3-d]pyrimidin-5-one;hydrochloride | IC50 | 1.4 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| US20250214997, Compound E-43 | IC50 | 1.4 nM | US-20250214997: METTL3 INHIBITOR COMPOUND, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF |
ChEMBL bioactivities
1054 potent at pChembl≥5 of 1076 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
144 with measured affinity, of 267 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| N-[[6-[(cyclohexylmethylamino)methyl]imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide | 1939568: Binding affinity to METTL3 (unknown origin) by SPR method | kd | 0.0014 | uM |
| 1-cyclobutyl-N-[[2-[[4-(6-methoxy-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0036 | uM |
| N-[[2-[[4-(6-chloro-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]-1-cyclobutylmethanamine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0043 | uM |
| 6-[(3-chloro-2-fluorophenyl)methyl]-1-[(2S)-1-hydroxy-3-methylbutan-2-yl]-7-methoxy-4-oxoquinoline-3-carboxylic acid | 1986930: Binding affinity to METTL3 (unknown origin) assessed as dissociation constant by SPR analysis | kd | 0.0048 | uM |
| 4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]-2,5-difluorophenyl]-9-[6-(methylamino)pyrimidin-4-yl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0050 | uM |
| (1R,2S,3R,5R)-3-(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]cyclopentane-1,2-diol | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0060 | uM |
| N-[(1-methoxycyclobutyl)methyl]-1-[2-[[4-(6-methoxy-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[[6-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]imidazo[1,2-a]pyridin-2-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| 1-cyclobutyl-N-[[2-[[4-(5-methoxy-1H-indazol-4-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]methyl]-5-oxo-[1,3]thiazolo[3,2-a]pyrimidine-7-carboxamide | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[[2-[(cyclobutylmethylamino)methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[[2-[(cyclobutylmethylamino)methyl]-5-fluoro-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[[2-[(3,3-diethylazetidin-1-yl)methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[[2-[[1-(3-fluoro-1-bicyclo[1.1.1]pentanyl)ethylamino]methyl]-1H-indol-6-yl]methyl]-4-oxopyrido[1,2-a]pyrimidine-2-carboxamide | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-(1-bicyclo[1.1.1]pentanylmethyl)-1-[2-[[4-(6-methoxyimidazo[1,5-a]pyridin-8-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| 1-cyclobutyl-N-[[2-[[4-(6-methoxyimidazo[1,5-a]pyridin-8-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methyl]methanamine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| N-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methyl]-1-[2-[[4-(6-methoxyimidazo[1,5-a]pyridin-8-yl)triazol-1-yl]methyl]imidazo[1,2-a]pyridin-6-yl]methanamine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| (1R,2S,3R,5R)-3-(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]cyclopentane-1,2-diol | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| (1R,2S,3R,5R)-3-(4-amino-5-chloropyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-[[(3-fluoro-1-bicyclo[1.1.1]pentanyl)methylamino]methyl]-1H-indol-6-yl]cyclopentane-1,2-diol | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0061 | uM |
| (1R,2S,3R,5R)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-azaspiro[3.4]octan-6-ylmethyl)-1H-indol-6-yl]cyclopentane-1,2-diol | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0062 | uM |
| 2-[[4-(6-bromo-1H-indazol-4-yl)triazol-1-yl]methyl]-6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridine | 1986899: Inhibition of full-length His-tagged METTL3/full length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using synthetic RNA 5’P-uacacucgaucuggacuaaagcugcuc-3’ and SAM as substrate preincubated for 10 mins followed by substrate addition and measured after 60 mins by RF/MS analysis | ic50 | 0.0079 | uM |
| 7-[2-[5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]ethyl]-N-methylquinolin-2-amine | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| 7-[2-[5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]ethyl]-2-ethyl-N-(2-methoxyethyl)-N-methylquinolin-4-amine | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| 7-[2-[5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]ethyl]-2-ethyl-N-(2-methoxyethyl)quinolin-4-amine | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| 7-[[5-[4-amino-5-[(2S)-oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-7-yl]-3-pyridinyl]methoxy]-N-methylquinolin-2-amine | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-5-[4-amino-5-(5-methylfuran-2-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-4-fluoro-2-[[2-(methylamino)quinolin-7-yl]oxymethyl]oxolan-3-ol | 1768407: Inhibition of METTL3 (unknown origin) using 3’ biotinylated RNA (UCUGGACUAAA) and 3H-SAM as a substrate preincubated for 5 mins followed by substrate addition incubated for 30 mins by scintillation counting method | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| (2R,3S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]oxolan-3-ol | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-5-(4-amino-5-pyrazol-1-ylpyrrolo[2,3-d]pyrimidin-7-yl)-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol | 1768407: Inhibition of METTL3 (unknown origin) using 3’ biotinylated RNA (UCUGGACUAAA) and 3H-SAM as a substrate preincubated for 5 mins followed by substrate addition incubated for 30 mins by scintillation counting method | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-5-[4-amino-5-(4-methyl-1,3-oxazol-2-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol | 1768407: Inhibition of METTL3 (unknown origin) using 3’ biotinylated RNA (UCUGGACUAAA) and 3H-SAM as a substrate preincubated for 5 mins followed by substrate addition incubated for 30 mins by scintillation counting method | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(cyclobutylamino)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-2-(4-amino-5-cyclopentylpyrrolo[2,3-d]pyrimidin-7-yl)-5-[[2-(ethylamino)quinolin-7-yl]oxymethyl]oxolane-3,4-diol | 1768407: Inhibition of METTL3 (unknown origin) using 3’ biotinylated RNA (UCUGGACUAAA) and 3H-SAM as a substrate preincubated for 5 mins followed by substrate addition incubated for 30 mins by scintillation counting method | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-2-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-5-[[2-(methylamino)quinolin-7-yl]oxymethyl]oxolane-3,4-diol | 1768407: Inhibition of METTL3 (unknown origin) using 3’ biotinylated RNA (UCUGGACUAAA) and 3H-SAM as a substrate preincubated for 5 mins followed by substrate addition incubated for 30 mins by scintillation counting method | ic50 | 0.0100 | uM |
| (2R,3S,5R)-5-(4-amino-5-pyrazol-1-ylpyrrolo[2,3-d]pyrimidin-7-yl)-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]oxolan-3-ol | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-5-[4-amino-5-[(2S)-oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-7-yl]-2-[[2-(azetidin-1-yl)quinolin-7-yl]oxymethyl]-4-fluorooxolan-3-ol | 1768407: Inhibition of METTL3 (unknown origin) using 3’ biotinylated RNA (UCUGGACUAAA) and 3H-SAM as a substrate preincubated for 5 mins followed by substrate addition incubated for 30 mins by scintillation counting method | ic50 | 0.0100 | uM |
| (2R,3R,4S,5R)-5-[4-amino-5-[(2S)-oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-7-yl]-4-fluoro-2-[[2-(methylamino)quinolin-7-yl]oxymethyl]oxolan-3-ol | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| (2S,3R,4S,5R)-5-[4-amino-5-(1-methylpyrazol-3-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-N-[2-(azetidin-1-yl)quinolin-7-yl]-4-fluoro-3-hydroxyoxolane-2-carboxamide | 1986933: Inhibition of METTL3/METTL14 (unknown origin) using biotinylated RNA (UCUGGACUAAA-biotin) and 3H-SAM as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by scintillation counter analysis | ic50 | 0.0100 | uM |
| N-[[(3R)-1-[6-(benzylamino)pyrimidin-4-yl]-3-hydroxypiperidin-3-yl]methyl]-4-[(4,4-dimethylpiperidin-1-yl)methyl]-2-hydroxybenzamide | 1939567: Inhibition of METTL3 in human MOLM-13 cells assessed as reduction in m6A methylation level | ic50 | 0.0170 | uM |
| 9-(2-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0240 | uM |
| 9-[6-(benzylamino)pyrimidin-4-yl]-4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0260 | uM |
| 4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]-3-fluorophenyl]-9-[6-(methylamino)pyrimidin-4-yl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0320 | uM |
| 9-[6-(benzylamino)pyrimidin-4-yl]-4-[6-[(4,4-dimethylpiperidin-1-yl)methyl]-3-pyridinyl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0370 | uM |
| 4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]-2-fluorophenyl]-9-[6-(methylamino)pyrimidin-4-yl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0380 | uM |
| 4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]-9-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0610 | uM |
| 9-[6-(cyclopropylamino)pyrimidin-4-yl]-4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0840 | uM |
| 4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]-9-[6-(methylamino)pyrimidin-4-yl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.0890 | uM |
| N-benzyl-6-[4-[6-[(4,4-dimethylpiperidin-1-yl)methyl]-3-pyridinyl]-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl]pyrimidin-4-amine | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.2800 | uM |
| 4-[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]-9-[6-(propan-2-ylamino)pyrimidin-4-yl]-1,4,9-triazaspiro[5.5]undecan-2-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.3300 | uM |
| 8-[4-[(4,4-dimethylpiperidin-1-yl)methyl]phenyl]-2-[6-(methylamino)pyrimidin-4-yl]-2,5,8-triazaspiro[3.5]nonan-6-one | 1829989: Inhibition of recombinant METLL3 (unknown origin) expressed in baculovirus infected Sf9 cells assessed as decrease in N6-methyladenosine level in oligonucleotide substrate by TR-FRET assay | ic50 | 0.4400 | uM |
CTD chemical–gene interactions
49 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | decreases expression, increases methylation, increases reaction, affects expression, decreases reaction (+7 more) | 13 |
| Benzo(a)pyrene | decreases methylation, increases expression, affects cotreatment, increases reaction | 3 |
| Valproic Acid | affects cotreatment, increases expression, decreases expression | 3 |
| bisphenol A | decreases expression | 2 |
| N-methyladenosine | affects abundance, affects expression, affects methylation, increases abundance, increases methylation | 2 |
| Arsenic Trioxide | decreases expression | 2 |
| Arsenic | affects methylation, increases expression | 2 |
| Tobacco Smoke Pollution | affects reaction, increases expression, affects binding, increases reaction, decreases expression | 2 |
| Cadmium Chloride | decreases expression, increases abundance, increases expression | 2 |
| FR900359 | affects phosphorylation | 1 |
| quinone | increases expression | 1 |
| sodium arsenate | decreases expression, increases reaction, increases expression | 1 |
| trichostatin A | affects expression | 1 |
| beta-lapachone | decreases expression | 1 |
| 3-deazaadenosine | decreases reaction, increases expression | 1 |
| 2,4,6-trichlorophenol | increases expression | 1 |
| thallium acetate | decreases reaction, increases expression, affects reaction | 1 |
| coumarin | increases phosphorylation | 1 |
| cadmium sulfate | increases expression | 1 |
| beta-methylcholine | affects expression | 1 |
| fumonisin B1 | increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| chromium hexavalent ion | increases expression, increases response to substance | 1 |
| ICG 001 | decreases expression | 1 |
| stattic | decreases reaction, increases expression, increases reaction, increases phosphorylation | 1 |
| jinfukang | increases expression | 1 |
| Sunitinib | increases expression | 1 |
| Leflunomide | decreases expression | 1 |
| Acetaminophen | decreases expression | 1 |
| Acetylcysteine | decreases reaction, increases expression | 1 |
ChEMBL screening assays
141 unique, capped per target: 139 binding, 2 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL4005637 | Binding | Inhibition of METTL3-14 (unknown origin) at 10 uM using biotin-labeled peptide as substrate and [3H]-SAM measured after 1 hr by scintillation proximity assay | Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase. — J Med Chem |
| CHEMBL5723072 | Functional | Affinity Biochemical interaction: (METTL3/14 RF/MS methyltransferase assay) EUB0001097a METTL3 | Affinity Biochemical Literature for EUbOPEN Chemogenomic Library |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.