TET1

Summary

TET1 (tet methylcytosine dioxygenase 1, HGNC:29484) is a protein-coding gene on chromosome 10q21.3, encoding Methylcytosine dioxygenase TET1 (Q8NFU7). Dioxygenase that plays a key role in active DNA demethylation, by catalyzing the sequential oxidation of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC).

DNA methylation is an epigenetic mechanism that is important for controlling gene expression. The protein encoded by this gene is a demethylase that belongs to the TET (ten-eleven translocation) family. Members of the TET protein family play a role in the DNA methylation process and gene activation.

Source: NCBI Gene 80312 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 271 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 8 cancer types
• Transcription factor: yes — 16 downstream targets (CollecTRI)
• MANE Select transcript: NM_030625

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29484
Approved symbol	TET1
Name	tet methylcytosine dioxygenase 1
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	LCX, KIAA1676, bA119F7.1
Ensembl gene	ENSG00000138336
Ensembl biotype	protein_coding
OMIM	607790
Entrez	80312

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000373644, ENST00000929763, ENST00000929764, ENST00000929765

RefSeq mRNA: 12 — MANE Select: NM_030625 NM_001406365, NM_001406367, NM_001406368, NM_001406369, NM_001406370, NM_001406371, NM_001406372, NM_001406373, NM_001406374, NM_001406375, NM_001406376, NM_030625

CCDS: CCDS7281

Canonical transcript exons

ENST00000373644 — 12 exons

Exon	Start	End
ENSE00000933676	68681399	68681488
ENSE00000933677	68682836	68682973
ENSE00000986277	68672895	68673045
ENSE00000986278	68686356	68686707
ENSE00001267275	68644698	68647005
ENSE00001267283	68600981	68601034
ENSE00001267287	68560337	68560742
ENSE00001461113	68690808	68694487
ENSE00001461117	68572217	68574252
ENSE00002437458	68651846	68651936
ENSE00002485692	68652501	68652594
ENSE00002499414	68667045	68667256

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 84.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2062 / max 339.0751, expressed in 992 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105244	4.9915	913
105243	0.6769	296
105245	0.3742	191
105246	0.1636	96

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.41	gold quality
ventricular zone	UBERON:0003053	83.24	gold quality
calcaneal tendon	UBERON:0003701	80.77	gold quality
ganglionic eminence	UBERON:0004023	80.34	gold quality
pancreatic ductal cell	CL:0002079	79.79	gold quality
cortical plate	UBERON:0005343	76.91	gold quality
tibialis anterior	UBERON:0001385	75.86	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.83	gold quality
adrenal tissue	UBERON:0018303	74.53	gold quality
pigmented layer of retina	UBERON:0001782	74.45	gold quality
deltoid	UBERON:0001476	69.32	silver quality
sural nerve	UBERON:0015488	69.15	gold quality
cartilage tissue	UBERON:0002418	68.61	gold quality
stromal cell of endometrium	CL:0002255	68.36	gold quality
tendon	UBERON:0000043	67.53	gold quality
colonic epithelium	UBERON:0000397	67.37	silver quality
bone marrow cell	CL:0002092	67.12	silver quality
ileal mucosa	UBERON:0000331	65.01	silver quality
tibia	UBERON:0000979	64.16	gold quality
corpus callosum	UBERON:0002336	62.25	gold quality
tonsil	UBERON:0002372	60.88	gold quality
quadriceps femoris	UBERON:0001377	60.84	silver quality
smooth muscle tissue	UBERON:0001135	60.09	gold quality
endometrium	UBERON:0001295	59.20	gold quality
vastus lateralis	UBERON:0001379	59.16	silver quality
oviduct epithelium	UBERON:0004804	58.56	gold quality
tibial nerve	UBERON:0001323	58.20	gold quality
ovary	UBERON:0000992	57.94	gold quality
placenta	UBERON:0001987	57.66	gold quality
upper leg skin	UBERON:0004262	57.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.09
E-MTAB-6524	no	143.21

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

16 targets.

Target	Regulation
APOBEC3A
APOBEC3C
FOXP3
HOXA7
HOXA9	Activation
IL1B
KDM1A
KEAP1
NOTCH1
OGT
PRM1
PTEN	Activation
SLIT2	Activation
TET2
TET3
ZNF382	Activation

Upstream regulators (CollecTRI, top): POU5F1

miRNA regulators (miRDB)

260 targeting TET1, 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-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-507	99.97	70.11	1915

Literature-anchored findings (GeneRIF, showing 40)

• demonstrated that TET1 is fused to MLL in a case of pediatric acute myeloid leukemia containing the t(10;11)(q22;q23) (PMID:12646957)
• Significant association with late-onset Alzheimer’s disease for 4 SNPs: rs1881747 near DKK1, rs2279420 in ANK3, rs2306402 in CTNNA3, and rs5030882 in CXXC6 in 1,160 cases and 1,389 controls. (PMID:18163421)
• findings show TET1 catalyzes conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC) in cultured cells & in vitro; TET proteins have potential roles in epigenetic regulation by modification of 5mC to hmC (PMID:19372391)
• mutational status of TET1, TET2, and TET3 in myeloproliferative neoplasms (MPNs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) (PMID:19420352)
• TET family influences DNA methylation in hematopoietic malignancy (PMID:19923888)
• The oncometabolite 2-hydroxyglutarate is a competitive inhibitor of multiple alpha-ketoglutarate-dependent dioxygenases, including histone demethylases, prolyl hydroxylases, and the TET family of 5-methlycytosine hydroxylases. (PMID:21251613)
• Different binding properties and function of CXXC zinc finger domains in Dnmt1 and Tet1. (PMID:21311766)
• Study suggests a TET1-induced oxidation-deamination mechanism for active DNA demethylation in mammals. (PMID:21496894)
• These findings suggest that the amount of 5-hmC in tumors is often reduced via various mechanisms, including the downregulation of TET1. (PMID:22320381)
• The loss of 5-hydroxymethylcytosine is a frequent event in gliomas, independent of IDH1 mutation, and may be influenced by the nuclear exclusion of TET1 from the nuclei of glioma cells. (PMID:22688054)
• TET1 (mRNA and protein) is markedly increased (two- to threefold) in the parietal cortex of psychotic patients. (PMID:22948384)
• these results illustrate a mechanism by which TET1 suppresses tumor development and invasion partly through downregulation of critical gene methylation. (PMID:22999938)
• Data indicate that MLL-TET1 rearrangement was confirmed in 3 new cases of acute myeloid leukemia. (PMID:23100278)
• OAC1 increases transcription of the Oct4-Nanog-Sox2 triad and Tet1, a gene known to be involved in DNA demethylation (PMID:23213213)
• Results suggest a TET1-dependent anti-inflammatory pathway, which may include TET2. In particular, IL-1beta transcriptional regulation is likely to depend on TET1-regulated chromatin domains. (PMID:23328087)
• Data show 5-hydroxymethylcytosine (5 hmC) may be served as a prognostic marker for hepatocellular carcinoma (HCC) and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC. (PMID:23671639)
• TET1-mediated 5-hydroxymethylcytosine modification could contribute to the epigenetic variation of induced pluripotent stem cells and induced pluripotent stem cell-human embryonic stem cell differences. (PMID:23685628)
• Data indicate that the genes comprising the HMGA2-TET1-HOXA9 pathway are coordinately regulated in breast cancer and together encompass a prognostic signature for patient survival. (PMID:23716660)
• TET1 plays an essential oncogenic role in MLL-rearranged leukemia. (PMID:23818607)
• An miR-29a mimic consistently decreases Tet1 and Tet3 transcripts while the miR-29a inhibitor increases Tet1 and Tet3 levels consistent with a pattern of direct targeting. (PMID:23820384)
• This study demonistrated that the expressions of DNMT1 and TET1 are increased in patient with schizophrenia. (PMID:23938174)
• A MLL-TET1 translocation is described in a case of T-cell lymphoblastic lymphoma with subsequent switch to acute myelomonocytic myeloid leukemia. (PMID:24323992)
• There was no statistical significance in TET1 rs150689919 genotype or allele frequencies between the PD cases and healthy controls, even after being stratified by gender and age at onset. (PMID:24325350)
• 5-hmC in human chondrocytes is suppressed by proinflammatory cytokines IL-1beta and TNF-alpha, and this suppression involves downregulation of TET1 and IDH expression and activity. (PMID:24469454)
• Decrease in TET1 transcript and protein levels is associated with some clinicopathological features in gastric cancer. (PMID:24507562)
• the mechanism underlying the acquisition of 5-fluorouracil resistance in colorectal cancer involves the upregulation of Nrf2 and HO-1 expression via epigenetic modifications of DNA demethylation. (PMID:24743738)
• TET1 suppresses cancer formation by coupling DNA demethylation with DNA-PK activation of p53 and suppression of oncogenic protein EZH2. (PMID:24804542)
• Hypoxia results in transcriptional activation of TET1, and full induction of hypoxia-responsive genes and global 5-hmC increases require TET1. (PMID:24835990)
• the results identify TET1 as a maintenance DNA demethylase that does not purposely decrease methylation levels, but specifically prevents aberrant methylation spreading into unmethylated CpG islands in differentiated cells. (PMID:24875481)
• These results indicate that IGF2BP1 and TET1/2 contribute to the stemness of MSCs, at least regarding their proliferative potential. (PMID:24915579)
• TET1 depletion yields widespread reduction of 5hmC, while depletion of TET2 and TET3 reduces 5hmC at a subset of TET1 targets suggesting functional co-dependence. (PMID:24958354)
• GABRA3 also carries a microRNA (miR-767) with predicted target sites in TET1 and TET3, two members of the ten-eleven-translocation family of tumor suppressor genes, involved in the conversion of 5-methylcytosines to 5-hydroxymethylcytosines in DNA. (PMID:25089631)
• TET1 partially mediates HDAC inhibitor elicited suppression of breast cancer invasion. (PMID:25175940)
• Data indicate that tet oncogene 1 protein (TET1) silencing in primary epithelial colon cells increase their cellular proliferation. (PMID:25362856)
• Potentiation of TET1 expression was linked to hepatocellular carcinogenesis and disease progression. (PMID:25367851)
• Suppression of TET1-dependent DNA demethylation is critical for KRAS-mediated transformation. (PMID:25466250)
• The expression (mRNA and protein levels) of DNMT1 and TET1 is increased in PFC of SZ and BP disorder patients. (PMID:25476119)
• Findings show that TET1 serves as a transcription co-activator that interacts with HIF-1alpha and HIF-2alpha to enhance their transactivation activity as well as INSIG1 in addition to its role in demethylating 5-methylcytosine. (PMID:25517638)
• TET1, TET2, and TET3 are highly phosphorylated. (PMID:25568311)
• Downregulation of TET1 due to hypermethylation is associated with breast cancer metastasis. (PMID:25735355)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tet1	ENSDARG00000075230
mus_musculus	Tet1	ENSMUSG00000047146
rattus_norvegicus	Tet1	ENSRNOG00000000277

Paralogs (2): TET2 (ENSG00000168769), TET3 (ENSG00000187605)

Protein

Protein identifiers

Methylcytosine dioxygenase TET1 — Q8NFU7 (reviewed: Q8NFU7)

Alternative names: CXXC-type zinc finger protein 6, Leukemia-associated protein with a CXXC domain, Ten-eleven translocation 1 gene protein

All UniProt accessions (1): Q8NFU7

UniProt curated annotations — full annotation on UniProt →

Function. Dioxygenase that plays a key role in active DNA demethylation, by catalyzing the sequential oxidation of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression. Plays therefore a role in many biological processes, including stem cell maintenance, T- and B-cell development, inflammation regulation, genomic imprinting, neural activity or DNA repair. Involved in the balance between pluripotency and lineage commitment of cells and plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Together with QSER1, plays an essential role in the protection and maintenance of transcriptional and developmental programs to inhibit the binding of DNMT3A/3B and therefore de novo methylation. May play a role in pancreatic beta-cell specification during development. In this context, may function as an upstream epigenetic regulator of PAX4 presumably through direct recruitment by FOXA2 to a PAX4 enhancer to preserve its unmethylated status, thereby potentiating PAX4 expression to adopt beta-cell fate during endocrine lineage commitment. Under DNA hypomethylation conditions, such as in female meiotic germ cells, may induce epigenetic reprogramming of pericentromeric heterochromatin (PCH), the constitutive heterochromatin of pericentromeric regions. PCH forms chromocenters in the interphase nucleus and chromocenters cluster at the prophase of meiosis. In this context, may also be essential for chromocenter clustering in a catalytic activity-independent manner, possibly through the recruitment polycomb repressive complex 1 (PRC1) to the chromocenters. During embryonic development, may be required for normal meiotic progression in oocytes and meiotic gene activation. Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG. Dioxygenase that plays a key role in active DNA demethylation. Binds to promoters, particularly to those with high CG content. In hippocampal neurons, isoform 1 regulates the expression of a unique subset of genes compared to isoform 2, although some overlap exists between both isoforms, hence differentially regulates excitatory synaptic transmission. In hippocampal neuron cell cultures, isoform 1 controls both miniature excitatory postsynaptic current amplitude and frequency. Isoform 1 may regulate genes involved in hippocampal-dependent memory, leading to positive regulation of memory, contrary to isoform 2 that may decrease memory. Dioxygenase that plays a key role in active DNA demethylation. As isoform 1, binds to promoters, particularly to those with high CG content, however displays reduced global chromatin affinity compared with isoform 1, leading to decreased global DNA demethylation compared with isoform 1. Contrary to isoform 1, isoform 2 localizes during S phase to sites of ongoing DNA replication in heterochromatin, causing a significant de novo 5hmC formation, globally, and more so in heterochromatin, including LINE 1 interspersed DNA repeats leading to their activation. In hippocampal neurons, isoform 2 regulates the expression of a unique subset of genes compared to isoform 1, although some overlap between both isoforms, hence differentially regulates excitatory synaptic transmission. In hippocampal neuron cell cultures, isoform 2 controls miniature excitatory postsynaptic current frequency, but not amplitude. Isoform 2 may regulate genes involved in hippocampal-dependent memory, leading to negative regulation of memory, contrary to isoform 1 that may improve memory. In immature and partially differentiated gonadotrope cells, directly represses luteinizing hormone gene LHB expression and does not catalyze 5hmC at the gene promoter.

Subunit / interactions. Interacts with SIN3A; recruits the transcriptional corepressor SIN3A to gene promoters. Interacts with HCFC1. Interacts (via C-terminus) with OGT. Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with QSER1. Interacts with NONO (via DNA-binding domain); this interaction recruits TET1 to genomic loci. Interacts with FOXA2; this interaction may recruit TET1 to specific enhancers to preserve their unmethylated status and hence allowing gene expression. Interacts with RNF2. Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex. Interacts with UHRF1; this interaction induces the recruitment of TET1 to replicating heterochromatin. Interacts with DCAF1.

Subcellular location. Nucleus. Chromosome Nucleus. Chromosome.

Tissue specificity. Expressed in fetal heart, lung and brain, and in adult skeletal muscle, thymus and ovary. Not detected in adult heart, lung or brain. Up-regulated in glioblastoma cells (at protein level). Expressed in embryonic stem cells (at protein level).

Post-translational modifications. Glycosylated. Interaction with OGT leads to GlcNAcylation. Monoubiquitinated at Lys-1589 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.

Disease relevance. A chromosomal aberration involving TET1 may be a cause of acute leukemias. Translocation t(10;11)(q22;q23) with KMT2A/MLL1. This is a rare chromosomal translocation 5’ KMT2A/MLL1-TET1 3’. Plays an important role in the tumorigenicity of glioblastoma cells. TET1-mediated production of 5hmC acts as a recruitment signal for the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastoma genesis.

Cofactor. Binds 1 Fe(2+) ion per subunit. Binds 3 zinc ions per subunit. The zinc ions have a structural role.

Domain organisation. The CXXC zinc finger plays a role in TET1 chromatin loading and participates in binding to CpG-DNA. However, the global chromatin binding can be mediated by the entire N-terminus and occurs even in the absence of the CXXC domain. The zinc finger domain impedes association DNA replication sites and prevents aberrant 5mC oxidation.

Miscellaneous. Produced by alternative promoter usage. Produced by alternative splicing. Produced by alternative splicing.

Similarity. Belongs to the TET family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q8NFU7-1	1, TET1-FL	yes
Q8NFU7-2	2, TET1s, TET1-ALT
Q8NFU7-3	3
Q8NFU7-4	4

RefSeq proteins (12): NP_001393294, NP_001393296, NP_001393297, NP_001393298, NP_001393299, NP_001393300, NP_001393301, NP_001393302, NP_001393303, NP_001393304, NP_001393305, NP_085128* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002857	Znf_CXXC	Domain
IPR024779	2OGFeDO_JBP1/TET_oxygenase_dom	Domain
IPR040175	TET1/2/3	Family
IPR046942	TET_oxygenase	Domain

Pfam: PF02008, PF12851

Catalyzed reactions (Rhea), 3 shown:

• a 5-methyl-2’-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-hydroxymethyl-2’-deoxycytidine in DNA + succinate + CO2 (RHEA:52636)
• a 5-hydroxymethyl-2’-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-formyl-2’-deoxycytidine in DNA + succinate + CO2 + H2O (RHEA:53828)
• a 5-formyl-2’-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-carboxyl-2’-deoxycytidine in DNA + succinate + CO2 + H(+) (RHEA:53832)

UniProt features (77 total): binding site 29, compositionally biased region 14, region of interest 10, sequence variant 6, splice variant 4, helix 3, mutagenesis site 2, turn 2, chain 1, zinc finger region 1, site 1, modified residue 1, cross-link 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ASD	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFU7-F1	46.86	0.17

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 (1): 1608–1609 (breakpoint for translocation to form kmt2a/mll1-tet1 oncogene)

Ligand- & substrate-binding residues (29): 591; 594; 597; 603; 606; 609; 619; 624; 1422; 1424; 1482; 1508 …

Post-translational modifications (2): 871, 1589

Mutagenesis-validated functional residues (2):

Position	Phenotype
1672	loss of catalytic activity and loss of the ability to induce dna demethylation; when associated with a-1674. when transf
1674	loss of catalytic activity and loss of the ability to induce dna demethylation; when associated with y-1672. when transf

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5221030	TET1,2,3 and TDG demethylate DNA
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 304 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, NKX25_02, chr10q21, GOBP_BLASTOCYST_FORMATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_BLASTOCYST_DEVELOPMENT

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), inner cell mass cell differentiation (GO:0001826), chromatin remodeling (GO:0006338), protein O-linked glycosylation (GO:0006493), stem cell population maintenance (GO:0019827), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), cellular response to reactive oxygen species (GO:0034614), positive regulation of gene expression via chromosomal CpG island demethylation (GO:0044029), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), chromatin organization (GO:0006325), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), epigenetic regulation of gene expression (GO:0040029), chromosomal 5-methylcytosine DNA demethylation, oxidation pathway (GO:0141167)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), iron ion binding (GO:0005506), zinc ion binding (GO:0008270), methyl-CpG binding (GO:0008327), DNA 5-methylcytosine dioxygenase activity (GO:0070579), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (3): nucleus (GO:0005634), Sin3-type complex (GO:0070822), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
stem cell population maintenance	2
regulation of stem cell population maintenance	2
regulation of macromolecule biosynthetic process	2
transition metal ion binding	2
negative regulation of DNA-templated transcription	1
blastocyst formation	1
cell differentiation	1
chromatin organization	1
glycoprotein biosynthetic process	1
multicellular organismal process	1
maintenance of cell number	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
response to reactive oxygen species	1
cellular response to oxidative stress	1
cellular response to oxygen-containing compound	1
transcription initiation-coupled chromatin remodeling	1
positive regulation of DNA-templated transcription	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
cellular component organization	1
gene expression	1
macromolecule biosynthetic process	1
positive regulation of biosynthetic process	1
positive regulation of macromolecule metabolic process	1
chromatin remodeling	1
regulation of gene expression	1
positive regulation of gene expression, epigenetic	1
chromosomal 5-methylcytosine DNA demethylation pathway	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1

Protein interactions and networks

STRING

2232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TET1	NANOG	Q9H9S0	991
TET1	GADD45A	P24522	947
TET1	DNMT1	P26358	900
TET1	HDAC1	Q13547	893
TET1	PRMT5	O14744	886
TET1	TDG	Q13569	886
TET1	SIN3A	Q96ST3	884
TET1	DNMT3A	Q9Y6K1	883
TET1	PRDM14	Q9GZV8	880
TET1	PPARG	P37231	842
TET1	DNMT3B	Q9UBC3	800
TET1	MECP2	P51608	782
TET1	POU5F1	P31359	761
TET1	EZH2	Q15910	754
TET1	KDM1A	O60341	744

IntAct

15 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
TET1	OGT	psi-mi:“MI:0914”(association)	0.530
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	MCRIP1	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
OGT	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): VPRBP (Affinity Capture-Western), DDB1 (Affinity Capture-Western), TET1 (Affinity Capture-MS), TET1 (Affinity Capture-MS), TET1 (Co-localization), TET1 (Affinity Capture-Western), HIF1A (Affinity Capture-Western), OGT (Affinity Capture-Western), EPAS1 (Affinity Capture-Western), TET1 (Affinity Capture-Western), TET1 (Affinity Capture-Western), TET1 (Affinity Capture-RNA), TET1 (Proximity Label-MS), RELN (Co-localization), GAD1 (Co-localization)

ESM2 similar proteins: A0A087WXM9, A0A2K1JJ00, A0JM83, A4IGL8, E1BC15, E9Q5F9, O14513, O35923, O60673, O88491, P46013, P97929, Q14B71, Q28DZ0, Q29RT4, Q3MHH3, Q3TNU4, Q3ZBP0, Q4QY64, Q4V7J0, Q5DTT3, Q5E9A0, Q5F2C3, Q5RD08, Q5VWN6, Q5VYV7, Q61493, Q69YH5, Q6NS59, Q703I1, Q80U59, Q86XD8, Q8IXS0, Q8IYL3, Q8L7I1, Q8N7Z5, Q8NFU7, Q8TEP8, Q92628, Q96BU1

Diamond homologs: A0A1L8GSA2, A0JP82, K9JHZ4, M9NEY8, O43151, Q0VFP6, Q32LB3, Q4JK59, Q5R7N4, Q5XIQ3, Q6N021, Q6NXI8, Q7LFL8, Q800L6, Q8BG87, Q8NFU7, Q91WA4, Q9EQC9, Q9H2H0, Q3URK3

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
TET1	“up-regulates quantity by expression”	SLIT2	“transcriptional regulation”
TET1	“up-regulates quantity by expression”	HOXA9	“transcriptional regulation”
TET1	“up-regulates quantity by expression”	ZNF382	“transcriptional regulation”
TET1	“up-regulates quantity by expression”	PTEN	“transcriptional regulation”
OGT	“up-regulates activity”	TET1	glycosylation
hsa-miR-183-5p	“down-regulates quantity by destabilization”	TET1	“post transcriptional regulation”
MECP2	“up-regulates activity”	TET1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
G2/M DNA damage checkpoint	5	40.1×	4e-06
Signaling by Rho GTPases	5	11.4×	6e-04
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	5	11.2×	6e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 8 cancer types — COAD, GBM, HCC, MBL, MGCT, NPC, PRCC, STAD.

Clinical variants and AI predictions

ClinVar

271 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	207
Likely benign	30
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

2784 predictions. Top by Δscore:

Variant	Effect	Δscore
10:68560740:GCG:G	donor_gain	1.0000
10:68600975:TTTTA:T	acceptor_loss	1.0000
10:68600976:TTTA:T	acceptor_loss	1.0000
10:68600980:G:GT	acceptor_loss	1.0000
10:68601031:AAAGG:A	donor_loss	1.0000
10:68601032:AAG:A	donor_loss	1.0000
10:68601033:AG:A	donor_loss	1.0000
10:68601034:GG:G	donor_loss	1.0000
10:68601036:T:A	donor_loss	1.0000
10:68644697:GGCA:G	acceptor_gain	1.0000
10:68667040:TTCA:T	acceptor_loss	1.0000
10:68667042:CAG:C	acceptor_loss	1.0000
10:68667252:GAAAA:G	donor_gain	1.0000
10:68667257:G:GG	donor_gain	1.0000
10:68672885:A:AG	acceptor_gain	1.0000
10:68672893:A:AG	acceptor_gain	1.0000
10:68672894:G:GG	acceptor_gain	1.0000
10:68672894:GTC:G	acceptor_gain	1.0000
10:68673046:G:GG	donor_gain	1.0000
10:68681393:CTATA:C	acceptor_loss	1.0000
10:68681394:TATAG:T	acceptor_loss	1.0000
10:68681395:ATAG:A	acceptor_gain	1.0000
10:68681395:ATAGG:A	acceptor_loss	1.0000
10:68681396:TA:T	acceptor_loss	1.0000
10:68681397:A:AC	acceptor_loss	1.0000
10:68681397:A:AG	acceptor_gain	1.0000
10:68681397:AG:A	acceptor_gain	1.0000
10:68681398:G:GG	acceptor_gain	1.0000
10:68681398:GG:G	acceptor_gain	1.0000
10:68681398:GGA:G	acceptor_gain	1.0000

AlphaMissense

14040 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:68574109:T:A	C591S	1.000
10:68574109:T:C	C591R	1.000
10:68574110:G:C	C591S	1.000
10:68574118:T:C	C594R	1.000
10:68574127:T:C	C597R	1.000
10:68574154:T:C	C606R	1.000
10:68574163:T:C	C609R	1.000
10:68574193:T:A	C619S	1.000
10:68574193:T:C	C619R	1.000
10:68574194:G:C	C619S	1.000
10:68574195:T:G	C619W	1.000
10:68574204:A:C	R622S	1.000
10:68574204:A:T	R622S	1.000
10:68574208:T:C	C624R	1.000
10:68667111:T:C	C1510R	1.000
10:68672953:G:C	G1578R	1.000
10:68672954:G:A	G1578D	1.000
10:68672956:T:C	C1579R	1.000
10:68672962:T:A	W1581R	1.000
10:68672962:T:C	W1581R	1.000
10:68672964:G:C	W1581C	1.000
10:68672964:G:T	W1581C	1.000
10:68672965:A:C	S1582R	1.000
10:68672967:T:A	S1582R	1.000
10:68672967:T:G	S1582R	1.000
10:68672989:T:C	F1590L	1.000
10:68672991:T:A	F1590L	1.000
10:68672991:T:G	F1590L	1.000
10:68673016:T:C	F1599L	1.000
10:68673017:T:C	F1599S	1.000

dbSNP variants (sampled 300 via entrez): RS1000014014 (10:68655129 C>G,T), RS1000027123 (10:68683526 C>T), RS1000036299 (10:68675760 T>C), RS1000068022 (10:68655470 A>G), RS1000072776 (10:68633432 G>A), RS1000073961 (10:68610843 A>G), RS1000077394 (10:68564595 C>A), RS1000108622 (10:68585796 T>G), RS1000124649 (10:68690570 G>A), RS1000143656 (10:68665804 C>G), RS1000157211 (10:68690892 C>G), RS1000181456 (10:68595751 G>A), RS1000202478 (10:68618755 G>A), RS1000219064 (10:68682237 G>A,T), RS1000233596 (10:68688866 A>C)

Disease associations

OMIM: gene MIM:607790 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): hearing loss disorder (MONDO:0005365), hypothyroidism (MONDO:0005420)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST006613_40	Triglycerides	2.000000e-09
GCST006626_19	Pulse pressure	2.000000e-09
GCST007576_145	Chronotype	4.000000e-09
GCST008839_377	Height	1.000000e-17
GCST012227_610	Hip circumference adjusted for BMI	7.000000e-09
GCST012227_611	Hip circumference adjusted for BMI	2.000000e-09
GCST90000025_437	Appendicular lean mass	8.000000e-45
GCST90002409_33	Childhood body mass index	2.000000e-07
GCST90020028_79	Hip circumference adjusted for BMI	7.000000e-12
GCST90020028_80	Hip circumference adjusted for BMI	1.000000e-09
GCST90020028_81	Hip circumference adjusted for BMI	5.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005763	pulse pressure measurement
EFO:0008328	chronotype measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004340	body mass index

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D007037	Hypothyroidism	C19.874.482

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523402 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,199 (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
CHEMBL3646221	VADADUSTAT	4	533
CHEMBL483254	PANOBINOSTAT	4	11,666

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

46 potent at pChembl≥5 of 71 total, top 46 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.74	IC50	18.2	nM	CHEMBL5527999
6.76	IC50	173.8	nM	CHEMBL5557793
6.71	IC50	195	nM	CHEMBL5559263
6.69	IC50	204.2	nM	CHEMBL5549950
6.62	IC50	239.9	nM	CHEMBL5532540
6.60	IC50	250	nM	CHEMBL5527999
6.60	IC50	250	nM	CHEMBL5565375
6.60	IC50	251.2	nM	CHEMBL3785455
6.59	IC50	257	nM	CHEMBL5557372
6.58	IC50	260	nM	CHEMBL5557372
6.57	IC50	269.1	nM	CHEMBL5557587
6.44	IC50	363.1	nM	CHEMBL5561497
6.39	IC50	407.4	nM	CHEMBL5562605
6.38	IC50	416.9	nM	CHEMBL5556063
6.36	EC50	436.5	nM	CHEMBL1982368
6.36	EC50	440	nM	CHEMBL1982368
6.33	IC50	467.7	nM	CHEMBL5567655
6.25	IC50	562.3	nM	CHEMBL1230640
6.22	IC50	602.6	nM	CHEMBL5562105
6.16	IC50	691.8	nM	CHEMBL5561894
6.11	IC50	776.2	nM	CHEMBL5561920
6.10	IC50	794.3	nM	CHEMBL5549844
6.10	IC50	794.3	nM	CHEMBL5564944
6.08	IC50	831.8	nM	CHEMBL1230640
5.96	IC50	1096	nM	CHEMBL5558323
5.94	IC50	1148	nM	CHEMBL4203498
5.94	IC50	1148	nM	CHEMBL5557957
5.91	IC50	1230	nM	CHEMBL5563922
5.89	IC50	1288	nM	CHEMBL1398529
5.87	IC50	1349	nM	CHEMBL5563232
5.82	IC50	1500	nM	CHEMBL4851104
5.77	IC50	1698	nM	CHEMBL316034
5.76	IC50	1738	nM	CHEMBL5561450
5.73	IC50	1862	nM	CHEMBL5560200
5.54	IC50	2884	nM	CHEMBL5566835
5.51	IC50	3090	nM	CHEMBL5564005
5.46	IC50	3480	nM	CHEMBL4872206
5.42	IC50	3802	nM	CHEMBL4475458
5.38	IC50	4169	nM	PANOBINOSTAT
5.38	IC50	4200	nM	PANOBINOSTAT
5.20	IC50	6300	nM	CHEMBL5189434
5.20	IC50	6310	nM	VADADUSTAT
5.16	IC50	6918	nM	CHEMBL5563415
5.13	IC50	7413	nM	CHEMBL1982368
5.02	IC50	9550	nM	CHEMBL5557758
5.00	EC50	1e+04	nM	CHEMBL1230640

PubChem BioAssay actives

46 with measured affinity, of 173 total; 39 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
3-[(3S,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-3-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]-36-[(2S)-butan-2-yl]-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30-methyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.0182	uM
(3S,6S,9S,12S,15S,21S,24S,27S,30R,36R,39S,42S,45S)-39-benzyl-6-(3-carbamimidamidopropyl)-12-(hydroxymethyl)-9,24,30-tris[(4-hydroxyphenyl)methyl]-27,42-bis(1H-indol-3-ylmethyl)-21-(2-methylpropyl)-2,5,8,11,14,20,23,26,29,32,38,41,44-tridecaoxo-3-propan-2-yl-34-thia-1,4,7,10,13,19,22,25,28,31,37,40,43-tridecazatricyclo[43.3.0.015,19]octatetracontane-36-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.1738	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-15,18-bis(1H-indol-3-ylmethyl)-9,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.1950	uM
3-[(5R,8S,11S,14S,17S,20S,23S,26S,29S,32S,35S,38S,41S,44R)-41-(3-amino-3-oxopropyl)-38-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-44-carbamoyl-26-[(1R)-1-hydroxyethyl]-5,14,23-tris[(4-hydroxyphenyl)methyl]-29,32-bis(1H-indol-3-ylmethyl)-17-methyl-20,35-bis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33,36,39,42-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-11-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.2042	uM
(3S,6S,9R,12S,15R,21S,27S,30S,33S,36S,39S,42S,45S,48S,51S)-12-(4-aminobutyl)-9,30-dibenzyl-27-[(2S)-butan-2-yl]-39-(3-carbamimidamidopropyl)-6,15,33-tris[(4-hydroxyphenyl)methyl]-45,48-bis(1H-indol-3-ylmethyl)-42-methyl-36-(2-methylpropyl)-2,5,8,11,14,17,23,26,29,32,35,38,41,44,47,50-hexadecaoxo-3-propan-2-yl-19-thia-1,4,7,10,13,16,22,25,28,31,34,37,40,43,46,49-hexadecazabicyclo[49.3.0]tetrapentacontane-21-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.2399	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-3-[[N-[(4S)-4-amino-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-oxopentyl]carbamimidoyl]carbamoyl]-36-[(2S)-butan-2-yl]-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30-methyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.2500	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.2512	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-12-(3-amino-3-oxopropyl)-36-[(2S)-butan-2-yl]-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30-methyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxylic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.2570	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-33-[(2S)-butan-2-yl]-6,24-bis(3-carbamimidamidopropyl)-15-[(1R)-1-hydroxyethyl]-18,21,27,36-tetrakis[(4-hydroxyphenyl)methyl]-9,12-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-30-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.2692	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-21-(2-amino-2-oxoethyl)-30,33-bis[(2S)-butan-2-yl]-6-(3-carbamimidamidopropyl)-15-[(1R)-1-hydroxyethyl]-18,27-bis[(4-hydroxyphenyl)methyl]-24-(1H-imidazol-4-ylmethyl)-9,12,36-tris(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.3631	uM
(3S)-3-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[2-[[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-12-(2-carboxyethyl)-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30-methyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carbonyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]hexanoyl]amino]-4-[[(2S)-3-carboxy-1-[[(2S)-3-carboxy-1-[[(2S)-3-carboxy-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.4074	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-6,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.4169	uM
5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine	1984359: Inhibition of tetracyclin/Dox-inducible N-terminal 3xFLAG/C-terminal GFP tagged human TET1 catalytic domain (1481 to 2136 residues) expressed in human U2OS cells assessed as reduction in 5-hydroxymethylcytosine level incubated for 24 hrs by immunofluorescence analysis	ec50	0.4365	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-24-benzyl-33-(3-carbamimidamidopropyl)-15-[(1R)-1-hydroxyethyl]-18,27,30,36-tetrakis[(4-hydroxyphenyl)methyl]-9,12-bis(1H-indol-3-ylmethyl)-6,21-dimethyl-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.4677	uM
8-hydroxyquinoline-5-carboxylic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.5623	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-33-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-6-[(2S)-butan-2-yl]-15-[(1R)-1-hydroxyethyl]-18,24,27-tris[(4-hydroxyphenyl)methyl]-9,12,36-tris(1H-indol-3-ylmethyl)-30-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.6026	uM
(3S,6R,12R,15S,18S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51S,54S)-24-(2-amino-2-oxoethyl)-3,36-bis[(2S)-butan-2-yl]-18,42-bis(3-carbamimidamidopropyl)-15,39-bis(hydroxymethyl)-27-[(4-hydroxyphenyl)methyl]-48-(1H-imidazol-4-ylmethyl)-6-(1H-indol-3-ylmethyl)-30-methyl-33,45,51-tris(2-methylpropyl)-2,5,8,14,17,20,23,26,29,32,35,38,41,44,47,50,53-heptadecaoxo-10-thia-1,4,7,13,16,19,22,25,28,31,34,37,40,43,46,49,52-heptadecazabicyclo[52.3.0]heptapentacontane-12-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.6918	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51R)-39-(4-aminobutyl)-27-(3-amino-3-oxopropyl)-24-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-21,36-bis[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-12,18,33,48,51-pentakis[(4-hydroxyphenyl)methyl]-30-(1H-imidazol-4-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53-heptadecaoxo-9,15,42-tri(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46,49,52-heptadecazacyclotetrapentacontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.7762	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51R)-39-(4-aminobutyl)-27-(3-amino-3-oxopropyl)-24-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-21,36-bis[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-12,18,30,33,48,51-hexakis[(4-hydroxyphenyl)methyl]-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53-heptadecaoxo-15,42-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46,49,52-heptadecazacyclotetrapentacontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.7943	uM
2-[(5R,8S,11S,14S,17S,20S,23S,26S,29S,32S,35S,38S,41S,44R)-14-(4-aminobutyl)-44-carbamoyl-8,32-bis[(1R)-1-hydroxyethyl]-41-(hydroxymethyl)-17,20,29-tris[(4-hydroxyphenyl)methyl]-5,23,35,38-tetrakis(1H-indol-3-ylmethyl)-26-methyl-3,6,9,12,15,18,21,24,27,30,33,36,39,42-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-11-yl]acetic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	0.7943	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,33,42-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-27,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	1.0965	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-12-(2-amino-2-oxoethyl)-27-benzyl-36-[(2S)-butan-2-yl]-39-(3-carbamimidamidopropyl)-21-[(1R)-1-hydroxyethyl]-6,24,33,42-tetrakis[(4-hydroxyphenyl)methyl]-15,18-bis(1H-indol-3-ylmethyl)-30-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-9-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	1.1482	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	1.1482	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30,36-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	1.2303	uM
N-[3-(dimethylamino)propyl]-4-(8-hydroxyquinolin-6-yl)benzamide	1984345: Inhibition of N-terminal 3xFlag-tagged human TET1 catalytic domain (E1418 to V2136 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 30 mins by Alphascreen assay	ic50	1.2882	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51R)-39-(4-aminobutyl)-27-(3-amino-3-oxopropyl)-24-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-21,36-bis[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-12,18,30,33,48,51-hexakis[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53-heptadecaoxo-9,15,42-tri(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46,49,52-heptadecazacyclotetrapentacontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	1.3490	uM
2-hydroxy-4-methylidenepentanedioic acid	1763204: Inhibition of recombinant human N-terminal Flag-tagged TET1 (1418 to 2136 residues) expressed in Baculovirus infected Sf9 cells assessed as reduction in 5hmc level incubated for 2 hrs by ELISA	ic50	1.5000	uM
pyridine-2,4-dicarboxylic acid	1984345: Inhibition of N-terminal 3xFlag-tagged human TET1 catalytic domain (E1418 to V2136 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 30 mins by Alphascreen assay	ic50	1.6982	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-12,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	1.7378	uM
(3S,6R,12R,15S,18S,21S,24S,27S,30S,33S,36S,39S)-27-(2-amino-2-oxoethyl)-21-[(1R)-1-hydroxyethyl]-6,24,33-tris[(4-hydroxyphenyl)methyl]-15,18,30-tris(1H-indol-3-ylmethyl)-3-methyl-2,5,8,14,17,20,23,26,29,32,35,38-dodecaoxo-36-propan-2-yl-10-thia-1,4,7,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-12-carboxamide	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	1.8621	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-21,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	2.8840	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30,39-dimethyl-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	3.0903	uM
[(2R,3R)-3-(3,4-dihydroxyphenyl)-6,8-dihydroxy-1,2,3,4-tetrahydronaphthalen-2-yl] (3S)-5-(3,4-dihydroxyphenyl)-3-hydroxypentanoate	1763192: Inhibition of TET1 (unknown origin)	ic50	3.4800	uM
4-oxo-1H-1,10-phenanthroline-3-carboxylic acid	1984345: Inhibition of N-terminal 3xFlag-tagged human TET1 catalytic domain (E1418 to V2136 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 30 mins by Alphascreen assay	ic50	3.8019	uM
Panobinostat	1984345: Inhibition of N-terminal 3xFlag-tagged human TET1 catalytic domain (E1418 to V2136 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 30 mins by Alphascreen assay	ic50	4.1687	uM
4-(4-ethoxyphenyl)-1-prop-2-enoylpiperidine-4-carboxylic acid	1871098: Inhibition of GST-tagged human TET1 (583 to 633 residues) expressed in Escherichia coli BL21 cells incubated for 30 mins by fluorescence polarization assay	ic50	6.3000	uM
Vadadustat	1984345: Inhibition of N-terminal 3xFlag-tagged human TET1 catalytic domain (E1418 to V2136 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 30 mins by Alphascreen assay	ic50	6.3096	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15-(1H-indol-3-ylmethyl)-18,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	6.9183	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-27,33,42-tris[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-24,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083783: Inhibition of N-terminal 3xFlag-tagged recombinant human TET1 catalytic domain (E1418 to V2136 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 30 mins by Alphascreen assay	ic50	9.5499	uM

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, affects expression, affects binding, affects cotreatment, decreases expression (+4 more)	4
Valproic Acid	affects expression, decreases expression	4
Particulate Matter	increases activity, affects expression, increases expression, increases reaction, decreases reaction (+4 more)	4
Vehicle Emissions	affects binding, increases abundance, increases reaction, increases expression, affects reaction (+3 more)	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
Cyclosporine	decreases expression	3
methylmercuric chloride	decreases expression	2
perfluorooctanoic acid	affects cotreatment, increases expression, decreases expression	2
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, decreases expression	2
Acetylcysteine	increases reaction, decreases reaction, increases expression, affects binding, increases abundance	2
Hydrogen Peroxide	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Antigens, Dermatophagoides	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
geniposide	affects cotreatment, decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
nickel chloride	affects reaction, increases abundance, increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
resorcinol	increases expression	1
hydroquinone	increases activity, increases expression, affects reaction	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334313	Binding	Inhibition of recombinant human N-terminal FLAG-tagged TET1 (1418 to 2136 residues) expressed in baculovirus infected sf9 cells assessed as reduction in oxidation of methylated dsDNA at 100 uM after 2 hrs by chemiluminescence assay relative	Cytosine-Based TET Enzyme Inhibitors. — ACS Med Chem Lett

Cellosaurus cell lines

8 cell lines: 8 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8V1	sHPT-1/TET1	Cancer cell line	Sex unspecified
CVCL_B8QM	Abcam HCT 116 TET1 KO	Cancer cell line	Male
CVCL_B9T3	Abcam A-549 TET1 KO	Cancer cell line	Male
CVCL_DX62	HAP1 TET1 (-) TET2 (-) 1	Cancer cell line	Male
CVCL_DX63	HAP1 TET1 (-) TET2 (-) 2	Cancer cell line	Male
CVCL_DX64	HAP1 TET1 (-) TET2 (-) 3	Cancer cell line	Male
CVCL_TS03	HAP1 TET1 (-) 1	Cancer cell line	Male
CVCL_TS04	HAP1 TET1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss