EIF4E

Summary

EIF4E (eukaryotic translation initiation factor 4E, HGNC:3287) is a protein-coding gene on chromosome 4q23, encoding Eukaryotic translation initiation factor 4E (P06730). Acts in the cytoplasm to initiate and regulate protein synthesis and is required in the nucleus for export of a subset of mRNAs from the nucleus to the cytoplasm which promotes processes such as RNA capping, processing and splicing. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

The protein encoded by this gene is a component of the eukaryotic translation initiation factor 4F complex, which recognizes the 7-methylguanosine cap structure at the 5’ end of messenger RNAs. The encoded protein aids in translation initiation by recruiting ribosomes to the 5’-cap structure. Association of this protein with the 4F complex is the rate-limiting step in translation initiation. This gene acts as a proto-oncogene, and its expression and activation is associated with transformation and tumorigenesis. Several pseudogenes of this gene are found on other chromosomes. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1977 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism, susceptibility to, 19 (Limited, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 33 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_001968

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3287
Approved symbol	EIF4E
Name	eukaryotic translation initiation factor 4E
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	EIF4E1
Ensembl gene	ENSG00000151247
Ensembl biotype	protein_coding
OMIM	133440
Entrez	1977

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000280892, ENST00000418385, ENST00000450253, ENST00000504432, ENST00000504472, ENST00000505194, ENST00000505829, ENST00000505992, ENST00000507665, ENST00000511644, ENST00000515638, ENST00000887787, ENST00000928990, ENST00000928991, ENST00000950872

RefSeq mRNA: 4 — MANE Select: NM_001968 NM_001130678, NM_001130679, NM_001331017, NM_001968

CCDS: CCDS34031, CCDS47109, CCDS54779, CCDS82940

Canonical transcript exons

ENST00000450253 — 7 exons

Exon	Start	End
ENSE00001982115	98879276	98881142
ENSE00003506126	98901876	98901982
ENSE00003576703	98929095	98929133
ENSE00003605710	98891237	98891332
ENSE00003660412	98884922	98885061
ENSE00003664428	98887079	98887192
ENSE00003666453	98887889	98887952

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.9807 / max 819.9124, expressed in 1816 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53230	33.0423	1815
53231	0.9568	635
53236	0.8184	145
53238	0.4881	110
53234	0.3725	69
53233	0.1565	40
53232	0.0597	25
53235	0.0412	25
53237	0.0297	8
53239	0.0089	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.46	gold quality
calcaneal tendon	UBERON:0003701	98.64	gold quality
oocyte	CL:0000023	97.60	gold quality
ventricular zone	UBERON:0003053	97.43	gold quality
ganglionic eminence	UBERON:0004023	97.39	gold quality
cortical plate	UBERON:0005343	97.27	gold quality
adrenal tissue	UBERON:0018303	97.20	gold quality
secondary oocyte	CL:0000655	97.08	gold quality
right testis	UBERON:0004534	96.70	gold quality
rectum	UBERON:0001052	96.68	gold quality
left testis	UBERON:0004533	96.56	gold quality
colonic epithelium	UBERON:0000397	96.38	gold quality
islet of Langerhans	UBERON:0000006	95.86	gold quality
stromal cell of endometrium	CL:0002255	95.74	gold quality
testis	UBERON:0000473	95.41	gold quality
male germ cell	CL:0000015	95.14	gold quality
esophagus mucosa	UBERON:0002469	94.85	gold quality
gall bladder	UBERON:0002110	94.62	gold quality
substantia nigra pars compacta	UBERON:0001965	94.49	gold quality
monocyte	CL:0000576	94.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.38	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.04	gold quality
medial globus pallidus	UBERON:0002477	93.97	gold quality
prefrontal cortex	UBERON:0000451	93.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.42	gold quality
left adrenal gland	UBERON:0001234	93.41	gold quality
right adrenal gland cortex	UBERON:0035827	93.37	gold quality
globus pallidus	UBERON:0001875	93.35	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10137	no	594.35
E-CURD-112	no	2.76
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, DDIT3, DLX4, HIF1A, HNRNPK, HOXA9, MYC, NFKB1, PAX1, PRKAA1, PRKAA2, TBP, TBXT, TP53

miRNA regulators (miRDB)

172 targeting EIF4E, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Ectopic expression of eIF-4E in human colon cancer cells promotes the stimulation of adhesion molecules by transforming growth factorbeta (PMID:11771728)
• 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. (PMID:11847216)
• The crystal structures of the full-length human eukaryotic initiation factor (eIF) 4E complexed with two mRNA cap analogues (PMID:11879179)
• Mutations in the S4-H2 loop of eIF4E which increase the affinity for m7GTP (PMID:11959093)
• Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation (Integrin alpha6beta4) (PMID:12105188)
• eIF4E phosphorylation during hypertonic shock is not required for protein synthesis (PMID:12138083)
• Data show that H2O2 increased eIF4E and 4E-BP1 expression and eIF4E phosphorylation, and shifted distribution of 4E-BP1 phosphorylation. These oxidant-mediated alterations occur in concert with changes in factors known to regulate translation kinetics. (PMID:12151318)
• Overexpression of PML and eIF4E mutants showed that PML-eIF4E interaction is required for the effects of cadmium and interferon treatment. This provides the first evidence that physiological factors modulate the mRNA transport functions of eIF4E. (PMID:12167712)
• increased expression of both eIF-4E and eIF-2alpha in aggresive thyroid carcinoma compared to conventional papillary carcinoma suggesting a role in the progression of thyroid cancer (PMID:12186496)
• Vesicular stomatitis virus infection alters the eIF4F translation initiation complex and causes dephosphorylation of the eIF4E binding protein 4E-BP1 (PMID:12239292)
• progressive increases of tumoral and stromal eIF4E may be part of a positive feedback loop for malignant progression in peripheral lung adenocarcinoma (PMID:12374671)
• eIF4E is associated with 4E-BP3 in the cell nucleus and cytoplasm (PMID:12482586)
• PRH is a negative regulator of eIF4E in myeloid cells, interacting with eIF4E through a conserved binding site typically found in translational regulators (PMID:12554669)
• structural features were investigated by X-ray crystal analyses of its cap analog (m(7)GTP and m(7)GpppA) complexes and molecular dynamics simulations of cap-free and cap-bound eIF4Es (PMID:12691746)
• While phosphorylation of eIF4E was sensitive to SB203580 in cells expressing WT-SAPK2a, these responses to SB203580 were abrogated in cells expressing DR-SAPK2a. (PMID:12781867)
• EIF-4E is involved in regulation of heparanase production in colon adenocarcinoma cell line LS-174T, and its critical function makes it a particularly interesting target for heparanase regulation. (PMID:12918105)
• eIF-4E play an important role in translational regulation of NF-kappaB expression in LS-174T cells. (PMID:14558943)
• nuclear function of eIF4E can contribute to leukemogenesis by promoting growth and by impeding differentiation (PMID:14645512)
• Both eIF4E and TLK1B are elevated in breast cancer specimens but not in benign breast specimens from noncancer patients. Degree of TLK1B elevation is correlated with degree of IF4E overexpression. (PMID:14732354)
• eIF4E functions as a pleiotropic regulator of cell viability and that integration of critical organelle-mediated checkpoints for apoptosis can be controlled by the cap-dependent translation apparatus. (PMID:14990584)
• Results obtained with mutants of eIF4E and the phosphorylated protein clearly show that electrostatic repulsion is the main factor that reduces the binding affinity of the phosphorylated protein for capped mRNAs. (PMID:15122903)
• Adenovirus 100K protein blocks cellular protein synthesis by coopting eIF4G and cap-initiation complexes and displacing or blocking binding by Mnk1, which occurs only on preassembled complexes, resulting in dephosphorylation of eIF4E. (PMID:15220445)
• Overexpressed eIF4E is associated with head and neck cancer patients via activation of the Akt/mammalian target of rapamycin pathway (PMID:15355912)
• A dramatic increase of phosphorylated eIF4E is found in Alzheimer brains compared to controls, especially in those cases with late stages of neurofibrillary changes. (PMID:15371741)
• Review of IF4E binding to mRNA and overexpression results in upregulation of proteins essential for cell growth and division. (PMID:15375804)
• results show that LK6 binds to ERK and is activated by ERK signalling and it is responsible for phosphorylating eIF4E in Drosophila (PMID:15487973)
• These findings suggest that hyperoxia diminishes protein synthesis by increasing eIF4E phosphorylation and enhancing the affinity of 4E-BP1 for eIF4E. (PMID:15542544)
• human P bodies contain the cap-binding protein eIF4E and the related factor eIF4E-transporter (eIF4E-T), suggesting novel roles for these proteins in targeting mRNAs for 5’ –> 3’ degradation (PMID:15840819)
• exposure of cells to cadmium chloride results in cytotoxicity and cell death due to enhanced ubiquitination and consequent proteolysis of eIF4E protein, which in turn diminishes cellular levels of critical genes such as cyclin D1 (PMID:15878868)
• Members of the herpesvirus family can enhance eIF4F activity during their replicative cycle. (PMID:15956551)
• FN has a role in controlling translation through beta1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways (PMID:15961545)
• These results suggest that the expression of eIF4E is reciprocally regulated by p53. (PMID:16112647)
• Overexpression of eIF4E may be a molecular marker of malignant transformation and progression in laryngeal squamous cell carcinoma. (PMID:16124648)
• a novel signaling pathway involving MKK-2 and ERK1/2 may down-regulate the activity of PABP and eIF4E by controlling their phosphorylation and compensates for the effect of excess cellular PABP (PMID:16332685)
• kinetic analysis of eIF4E and phosphorylated eIF4E binding to cap analogs and capped oligoribonucleotides (PMID:16540463)
• Chip may be at least one ubiquitin E3 ligase responsible for eIF4E ubiquitination (PMID:16720573)
• Overexpression of eIF4E may play an important role in tumor progression & microneoangiogenesis. Specifically, eIF4E may be an important regulator of angiogenic factor(IL-8 & VEGF) production, associated with poor prognosis in breast cancer. (PMID:17010208)
• eIF4E is a critical node in an RNA regulon impacting cell cycle progression. eIF4E coordinately promotes mRNA export of cell cycle genes. (PMID:17074885)
• eIF4E, along with VEGF and cyclin D1, has a role in translational regulation of proteins related to angiogenesis and growth (PMID:17203162)
• This review summarizes recent studies depicting the role of eIF4E as a central node of an RNA regulon that plays an essential role in normal differentiation and development and is frequently dysregulated in cancer. (PMID:17245113)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif4eb	ENSDARG00000013274
danio_rerio	eif4ea	ENSDARG00000077012
mus_musculus	Eif4e	ENSMUSG00000028156
rattus_norvegicus	Eif4e	ENSRNOG00000052343
drosophila_melanogaster	eIF4E1	FBGN0015218
drosophila_melanogaster	eIF4E4	FBGN0035709
drosophila_melanogaster	eIF4E5	FBGN0035823
drosophila_melanogaster	eIF4E6	FBGN0039622
drosophila_melanogaster	eIF4E7	FBGN0040368
drosophila_melanogaster	eIF4EHP	FBGN0053100
drosophila_melanogaster	eIF4E3	FBGN0265089
caenorhabditis_elegans		WBGENE00002059
caenorhabditis_elegans		WBGENE00002062
caenorhabditis_elegans		WBGENE00002063

Paralogs (3): EIF4E2 (ENSG00000135930), EIF4E3 (ENSG00000163412), EIF4E1B (ENSG00000175766)

Protein

Protein identifiers

Eukaryotic translation initiation factor 4E — P06730 (reviewed: P06730)

Alternative names: eIF-4F 25 kDa subunit, mRNA cap-binding protein

All UniProt accessions (5): P06730, D6RBW1, D6RFJ3, H0Y8J7, X5D7E3

UniProt curated annotations — full annotation on UniProt →

Function. Acts in the cytoplasm to initiate and regulate protein synthesis and is required in the nucleus for export of a subset of mRNAs from the nucleus to the cytoplasm which promotes processes such as RNA capping, processing and splicing. Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5’-terminal secondary structure and recruitment of mRNA to the ribosome. This protein recognizes and binds the 7-methylguanosine (m7G)-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Together with EIF4G1, antagonizes the scanning promoted by EIF1-EIF4G1 and is required for TISU translation, a process where the TISU element recognition makes scanning unnecessary. In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap. Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis. In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation. May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development. As well as its roles in translation, also involved in mRNA nucleocytoplasmic transport. Its role in mRNA export from the nucleus to the cytoplasm relies on its ability to bind the m7G cap of RNAs and on the presence of the 50-nucleotide EIF4E sensitivity element (4ESE) in the 3’UTR of sensitive transcripts. Interaction with the 4ESE is mediated by LRPPRC which binds simultaneously to both EIF4E and the 4ESE, thereby acting as a platform for assembly for the RNA export complex. EIF4E-dependent mRNA export is independent of ongoing protein or RNA synthesis and is also NFX1-independent but is XPO1-dependent with LRPPRC interacting with XPO1 to form an EIF4E-dependent mRNA export complex. Alters the composition of the cytoplasmic face of the nuclear pore to promote RNA export by reducing RANBP2 expression, relocalizing nucleoporin NUP214 and increasing expression of RANBP1 and RNA export factors DDX19 and GLE1. Promotes the nuclear export of cyclin CCND1 mRNA. Promotes the nuclear export of NOS2/iNOS mRNA. Promotes the nuclear export of MDM2 mRNA. Promotes the export of additional mRNAs, including others involved in the cell cycle. In the nucleus, binds to capped splice factor-encoding mRNAs and stimulates their nuclear export to enhance splice factor production by increasing their cytoplasmic availability to the translation machinery. May also regulate splicing through interaction with the spliceosome in an RNA and m7G cap-dependent manner. Also binds to some pre-mRNAs and may play a role in their recruitment to the spliceosome. Promotes steady-state capping of a subset of coding and non-coding RNAs by mediating nuclear export of capping machinery mRNAs including RNMT, RNGTT and RAMAC to enhance their translation. Stimulates mRNA 3’-end processing by promoting the expression of several core cleavage complex factors required for mRNA cleavage and polyadenylation, and may also have a direct effect through its interaction with the CPSF3 cleavage enzyme. Rescues cells from apoptosis by promoting activation of serine/threonine-protein kinase AKT1 through mRNA export of NBS1 which potentiates AKT1 phosphorylation and also through mRNA export of AKT1 effectors, allowing for increased production of these proteins.

Subunit / interactions. eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4E is also known to interact with other partners. Interacts with EIF4ENIF1/4E-T; promotes recruitment to P-bodies and import into the nucleus. Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Interacts mutually exclusive with EIF4A1 or EIF4A2. Interacts with NGDN and PIWIL2. Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts directly with CYFIP1. Interacts with CLOCK. Binds to MKNK2 in nucleus. Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with LARP1. Interacts with METTL3. Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex. Interacts with DDX3X; interaction is direct and in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability and is required for the repression of cap-dependent translation and the increase of IRES-mediated translation. DDX3X competes with EIF4G1 for interaction with EIF4E. Interacts with EIF4G1; which in a mutual exclusive interaction associates either with EIF1 or with EIF4E on a common binding site. Interacts with BTG4 and CNOT7. Interacts with LRPPRC (via N-terminus); the interaction promotes association of EIF4E with 4ESE-containing mRNAs. Interacts with mRNA cleavage enzyme CPSF3 and its cofactor CPSF1. Interacts (via RING-type zinc finger) with PML; the interaction results in conformational changes of both interacting proteins and reduces EIF4E affinity for the 5’ m7G cap of mRNA, thus reducing EIF4E-mediated mRNA nuclear export. Interacts with homeobox protein HHEX/PRH; the interaction inhibits EIF4E-mediated mRNA nuclear export. Interacts with homeobox protein HOXA9; the interaction positively regulates EIF4E-mediated mRNA nuclear export. Interacts with homeobox protein EMX2. Interacts with ANGEL1. (Microbial infection) Interacts with Lassa virus Z protein. (Microbial infection) Interacts with Lymphocytic choriomeningitis virus (LCMV) Z protein (via RING-type zinc finger); the interaction results in conformational changes of both interacting proteins and reduces EIF4E affinity for the m7G mRNA cap structure. (Microbial infection) Interacts (via cap-binding region) with potato virus Y VPg; this interaction mediates the translation of the VPg-viral RNA conjugates and interferes with the cellular EIF4E-dependent mRNA export and translation.

Subcellular location. Cytoplasm. P-body. Stress granule. Nucleus. Nucleus speckle. Nuclear body.

Post-translational modifications. Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex. Phosphorylation also enhances its mRNA transport function. Phosphorylation at Ser-209 is not essential for protein synthesis.

Disease relevance. Autism 19 (AUTS19) [MIM:615091] A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability. Disease susceptibility is associated with variants affecting the gene represented in this entry. A heterozygous single-nucleotide insertion has been found in families affected by autism. The variant results in increased promoter activity and is involved in disease pathogenesis through EIF4E deregulation. A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t(45)(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E.

Miscellaneous. The antiviral drug ribavirin relocalizes nuclear EIF4E to the cytoplasm and reduces the elevated EIF4E levels found in acute myeloid leukemia patients, suggesting its potential use as a therapeutic agent. Ribavirin suppresses EIF4E-mediated oncogenic transformation by binding to EIF4E at the functional site used by the m7G mRNA cap and competing with the mRNA cap for binding to EIF4E which leads to relocalization of the majority of EIF4E to the cytoplasm and inhibition of nucleocytoplasmic mRNA transport.

Similarity. Belongs to the eukaryotic initiation factor 4E family.

Isoforms (3)

UniProt ID	Names	Canonical?
P06730-1	1	yes
P06730-2	2
P06730-3	3

RefSeq proteins (4): NP_001124150, NP_001124151, NP_001317946, NP_001959* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001040	TIF_eIF_4E	Family
IPR019770	TIF_eIF_4E_CS	Conserved_site
IPR023398	TIF_eIF4e-like	Homologous_superfamily

Pfam: PF01652

UniProt features (52 total): strand 12, mutagenesis site 11, helix 8, region of interest 4, turn 4, binding site 4, modified residue 3, splice variant 2, initiator methionine 1, chain 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

45 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4TPW	X-RAY DIFFRACTION	1.5
5T46	X-RAY DIFFRACTION	1.53
8QM8	X-RAY DIFFRACTION	1.58
4TQB	X-RAY DIFFRACTION	1.59
5ZJY	X-RAY DIFFRACTION	1.59
7D6Y	X-RAY DIFFRACTION	1.67
5ZJZ	X-RAY DIFFRACTION	1.67
5EI3	X-RAY DIFFRACTION	1.71
4UED	X-RAY DIFFRACTION	1.75
5ZK9	X-RAY DIFFRACTION	1.76
4TQC	X-RAY DIFFRACTION	1.8
5ZML	X-RAY DIFFRACTION	1.8
7XTP	X-RAY DIFFRACTION	1.83
8QM4	X-RAY DIFFRACTION	1.85
8QM5	X-RAY DIFFRACTION	1.89
7MEU	X-RAY DIFFRACTION	1.91
8QM6	X-RAY DIFFRACTION	1.93
5GW6	X-RAY DIFFRACTION	1.97
8QM9	X-RAY DIFFRACTION	1.97
8SX4	X-RAY DIFFRACTION	1.99
1IPB	X-RAY DIFFRACTION	2
1IPC	X-RAY DIFFRACTION	2
9DON	X-RAY DIFFRACTION	2.09
1WKW	X-RAY DIFFRACTION	2.1
2V8Y	X-RAY DIFFRACTION	2.1
3TF2	X-RAY DIFFRACTION	2.1
3U7X	X-RAY DIFFRACTION	2.1
5ZK7	X-RAY DIFFRACTION	2.12
4AZA	X-RAY DIFFRACTION	2.16
8QM7	X-RAY DIFFRACTION	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06730-F1	91.48	0.83

Antibody-complex structures (SAbDab): 4 — 7D6Y, 7D8B, 7F07, 7XTP

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): 159 ((microbial infection) interaction with potato virus y vpg)

Ligand- & substrate-binding residues (4): 56–57; 102–103; 157–162; 205–207

Post-translational modifications (3): 2, 22, 209

Mutagenesis-validated functional residues (11):

Position	Phenotype
53	no effect on phosphorylation level nor incorporation into eif4f complex.
53	does not affect ability to rescue growth of yeast lacking a functional eif4e/cdc33 gene.
56	impairs mrna nuclear export. reduces affinity for ribavirin.
73	abolishes binding to eif4ebp1. impairs interaction with ddx3x. does not impair mrna nuclear export. does not affect affi
102	decrease in mrna cap binding; when associated with a-105.
103	no effect.
104	no effect.
105	decrease in mrna cap binding; when associated with l-102.
119	higher affinity for eif4g1.
209	abolishes resistance to cellular stress and dna-damaging agents. does not affect ability to rescue growth of yeast lacki
209	phosphomimetic mutant; confers resistance to cellular stress and dna-damaging agents. does not affect ability to rescue

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-166208	mTORC1-mediated signalling
R-HSA-429947	Deadenylation of mRNA
R-HSA-72649	Translation initiation complex formation
R-HSA-72662	Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S
R-HSA-72702	Ribosomal scanning and start codon recognition
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors
R-HSA-9820865	Z-decay: degradation of maternal mRNAs by zygotically expressed factors
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 462 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_BEHAVIOR, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, NKX25_02, GOBP_RESPONSE_TO_CORTICOSTEROID, SHEPARD_CRASH_AND_BURN_MUTANT_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, CAIRO_PML_TARGETS_BOUND_BY_MYC_UP, GOBP_TRANSLATIONAL_INITIATION

GO Biological Process (15): G1/S transition of mitotic cell cycle (GO:0000082), behavioral fear response (GO:0001662), mRNA export from nucleus (GO:0006406), translational initiation (GO:0006413), regulation of translation (GO:0006417), negative regulation of translation (GO:0017148), stem cell population maintenance (GO:0019827), neuron differentiation (GO:0030182), negative regulation of neuron differentiation (GO:0045665), positive regulation of mitotic cell cycle (GO:0045931), cellular response to dexamethasone stimulus (GO:0071549), regulation of translation at postsynapse, modulating synaptic transmission (GO:0099578), translation (GO:0006412), mRNA transport (GO:0051028), nuclear export (GO:0051168)

GO Molecular Function (9): RNA cap binding (GO:0000339), RNA 7-methylguanosine cap binding (GO:0000340), RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), enzyme binding (GO:0019899), eukaryotic initiation factor 4G binding (GO:0031370), mRNA cap binding (GO:0098808), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (15): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic stress granule (GO:0010494), eukaryotic translation initiation factor 4F complex (GO:0016281), RISC complex (GO:0016442), nuclear speck (GO:0016607), chromatoid body (GO:0033391), cytoplasmic ribonucleoprotein granule (GO:0036464), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Cap-dependent Translation Initiation	3
Maternal to zygotic transition (MZT)	2
Antimicrobial mechanism of IFN-stimulated genes	1
Eukaryotic Translation Initiation	1
MTOR signalling	1
Deadenylation-dependent mRNA decay	1
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	4
cellular anatomical structure	4
cytoplasm	4
cytoplasmic ribonucleoprotein granule	3
mitotic cell cycle	2
translational initiation	2
RNA cap binding	2
synapse	2
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
behavioral defense response	1
fear response	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
formation of translation initiation ternary complex	1
metabolic process	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
multicellular organismal process	1
maintenance of cell number	1
cell differentiation	1
generation of neurons	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
cellular response to glucocorticoid stimulus	1
response to dexamethasone	1
cellular response to ketone	1
chemical synaptic transmission	1
postsynapse	1
postsynaptic modulation of chemical synaptic transmission	1
regulation of translation at synapse, modulating synaptic transmission	1
regulation of translation at postsynapse	1
peptidyltransferase activity	1

Protein interactions and networks

STRING

5170 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF4E	EIF4A1	P04765	999
EIF4E	EIF4A2	Q14240	999
EIF4E	EIF4EBP1	Q13541	999
EIF4E	EIF4B	P23588	999
EIF4E	EIF4G1	Q04637	999
EIF4E	PABPC1	P11940	998
EIF4E	EIF4EBP2	Q13542	998
EIF4E	NGDN	Q8NEJ9	998
EIF4E	EIF4ENIF1	Q9NRA8	997
EIF4E	EIF4G3	O43432	993
EIF4E	CYFIP1	Q7L576	988
EIF4E	EIF4A3	P38919	984
EIF4E	EIF4G2	P78344	983
EIF4E	RPS6KB1	P23443	980
EIF4E	DDX3X	O00571	979

IntAct

308 interactions, top by confidence:

A	B	Type	Score
EIF4EBP1	EIF4E	psi-mi:“MI:0915”(physical association)	0.980
EIF4E	EIF4EBP1	psi-mi:“MI:0915”(physical association)	0.980
EIF4EBP1	EIF4E	psi-mi:“MI:0407”(direct interaction)	0.980
EIF4E	EIF4EBP1	psi-mi:“MI:0407”(direct interaction)	0.980
EIF4EBP2	EIF4E	psi-mi:“MI:0915”(physical association)	0.960
EIF4E	EIF4EBP2	psi-mi:“MI:0915”(physical association)	0.960
EIF4EBP2	EIF4E	psi-mi:“MI:0407”(direct interaction)	0.960
EIF4E	EIF4ENIF1	psi-mi:“MI:0915”(physical association)	0.940
EIF4ENIF1	EIF4E	psi-mi:“MI:0915”(physical association)	0.940
EIF4E	EIF4G1	psi-mi:“MI:0915”(physical association)	0.940
EIF4E	EIF4G1	psi-mi:“MI:0407”(direct interaction)	0.940
EIF4G1	EIF4E	psi-mi:“MI:0407”(direct interaction)	0.940

BioGRID (410): EIF4EBP1 (Affinity Capture-Western), EIF4E (Affinity Capture-Western), RPS6KB1 (Affinity Capture-Western), MTOR (Affinity Capture-Western), EIF3B (Affinity Capture-Western), EIF4G1 (Affinity Capture-Western), EIF4E (Affinity Capture-Western), TRIM22 (Affinity Capture-Western), EIF4G1 (Affinity Capture-Western), EIF4EBP1 (Affinity Capture-Western), EIF4EBP1 (Two-hybrid), EIF4EBP2 (Two-hybrid), TRIM27 (Two-hybrid), TDO2 (Two-hybrid), EIF4EBP3 (Two-hybrid)

ESM2 similar proteins: A0A8I6G705, A1L3K1, B5DFF2, B5DFI8, G3MWR8, O19048, O19137, O88508, P06730, P29338, P57721, P57722, P60335, Q12800, Q13888, Q15365, Q15366, Q16763, Q1LZ53, Q1RML1, Q28D01, Q2TBV5, Q4W5Z4, Q5E9A3, Q5FVR7, Q5NVP9, Q5TDH0, Q61990, Q6AYU1, Q6DH13, Q6P1K8, Q6ZRY4, Q7RTP6, Q8C6G8, Q8CCI5, Q8CJ19, Q8IY57, Q8N488, Q8VC52, Q921J4

Diamond homologs: A0A075QQ08, A0A1D8EJF9, A0A1U8F5V2, A0A1U8GR65, A0A2J6L8Y7, A0A3Q7FGP1, A0A3Q7I7R4, A0A445AGS0, A3RCV9, A6NMX2, A7KWF8, C6ZJZ3, C7SG33, D3UW26, K0P2S0, M1J8U6, M1JJT8, O04663, O23252, O45551, O60573, O61955, O74743, O77210, O81481, O81482, P06730, P07260, P0DXI0, P0DXI5, P29338, P29557, P48597, P48598, P48599, P48600, P56570, P63073, P63074, P78954

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
EIF4E	“form complex”	eIF4F_complex	binding
MKNK1	up-regulates	EIF4E	phosphorylation
MKNK2	up-regulates	EIF4E	phosphorylation
EIF4EBP1	“down-regulates activity”	EIF4E	binding
PPP2CA	down-regulates	EIF4E	dephosphorylation
EIF4E	up-regulates	Protein_synthesis
4E2RCat	“down-regulates activity”	EIF4E	“chemical inhibition”
PABPC1	“up-regulates activity”	EIF4E	binding
EIF4E	up-regulates	Translational_regulation
DDX3X	“down-regulates activity”	EIF4E	binding
STUB1	“down-regulates quantity by destabilization”	EIF4E	ubiquitination
BIRC2	“down-regulates quantity by destabilization”	EIF4E	ubiquitination
MTOR	“down-regulates activity”	EIF4E	phosphorylation
AURKA	“up-regulates activity”	EIF4E	phosphorylation
PRKCA	up-regulates	EIF4E	phosphorylation
PRKCB	up-regulates	EIF4E	phosphorylation
PRKCG	unknown	EIF4E	phosphorylation
EIF4E	“up-regulates activity”	MTFP1	“translation regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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
Translation initiation complex formation	13	32.6×	2e-14
Ribosomal scanning and start codon recognition	13	32.6×	2e-14
Deadenylation of mRNA	5	28.9×	4e-05
Formation of the ternary complex, and subsequently, the 43S complex	9	25.5×	6e-09
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	7	25.0×	9e-07
M-decay: degradation of maternal mRNAs by maternally stored factors	5	21.5×	1e-04
Dengue Virus Genome Translation and Replication	5	20.9×	1e-04
L13a-mediated translational silencing of Ceruloplasmin expression	14	18.6×	2e-12

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	6	71.0×	4e-08
translational initiation	15	56.6×	3e-20
miRNA-mediated gene silencing by inhibition of translation	5	46.7×	7e-06
negative regulation of translational initiation	5	46.7×	7e-06
TOR signaling	5	40.3×	1e-05
regulation of translational initiation	7	34.5×	2e-07
stress granule assembly	5	31.7×	4e-05
negative regulation of translation	11	22.7×	8e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	3
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1479 predictions. Top by Δscore:

Variant	Effect	Δscore
4:98884915:AACTT:A	donor_loss	1.0000
4:98884916:ACTTA:A	donor_loss	1.0000
4:98884917:CTTAC:C	donor_loss	1.0000
4:98884918:TTA:T	donor_loss	1.0000
4:98884919:T:TG	donor_loss	1.0000
4:98884920:A:AC	donor_gain	1.0000
4:98884920:AC:A	donor_gain	1.0000
4:98884920:ACC:A	donor_gain	1.0000
4:98884921:C:CC	donor_gain	1.0000
4:98884921:CC:C	donor_gain	1.0000
4:98884921:CCC:C	donor_gain	1.0000
4:98884921:CCCTA:C	donor_gain	1.0000
4:98885063:T:C	acceptor_gain	1.0000
4:98885063:T:TC	acceptor_gain	1.0000
4:98887077:A:AC	donor_gain	1.0000
4:98887078:C:CA	donor_gain	1.0000
4:98887078:CT:C	donor_gain	1.0000
4:98887078:CTGT:C	donor_gain	1.0000
4:98887109:T:TA	donor_gain	1.0000
4:98887949:CAGA:C	acceptor_gain	1.0000
4:98887953:C:CC	acceptor_gain	1.0000
4:98891229:TTAC:T	donor_loss	1.0000
4:98891230:TACT:T	donor_loss	1.0000
4:98891231:ACTT:A	donor_loss	1.0000
4:98891233:T:TA	donor_loss	1.0000
4:98891234:T:TC	donor_loss	1.0000
4:98891235:A:AC	donor_gain	1.0000
4:98891235:ACG:A	donor_gain	1.0000
4:98891235:ACGC:A	donor_gain	1.0000
4:98891235:ACGCC:A	donor_gain	1.0000

AlphaMissense

1438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:98881082:G:C	H200Q	1.000
4:98881082:G:T	H200Q	1.000
4:98881084:G:C	H200D	1.000
4:98881093:A:C	Y197D	1.000
4:98881130:C:A	K184N	1.000
4:98881130:C:G	K184N	1.000
4:98884922:C:T	G180E	1.000
4:98884923:C:A	G180W	1.000
4:98884963:C:A	W166C	1.000
4:98884963:C:G	W166C	1.000
4:98884965:A:G	W166R	1.000
4:98884965:A:T	W166R	1.000
4:98884967:A:T	I165K	1.000
4:98884971:C:G	A164P	1.000
4:98884975:C:A	K162N	1.000
4:98884975:C:G	K162N	1.000
4:98884977:T:C	K162E	1.000
4:98884990:T:A	R157S	1.000
4:98884990:T:G	R157S	1.000
4:98884991:C:A	R157I	1.000
4:98884991:C:G	R157T	1.000
4:98884996:A:C	N155K	1.000
4:98884996:A:T	N155K	1.000
4:98885000:A:T	V154D	1.000
4:98885006:G:T	A152D	1.000
4:98885009:C:A	G151V	1.000
4:98885009:C:T	G151D	1.000
4:98885010:C:A	G151C	1.000
4:98885010:C:G	G151R	1.000
4:98885045:C:T	G139E	1.000

dbSNP variants (sampled 300 via entrez): RS1000054757 (4:98905927 A>T), RS1000102685 (4:98887546 C>A,G), RS1000276458 (4:98905447 G>C), RS1000323107 (4:98911740 T>C), RS1000399511 (4:98917691 A>G), RS10004975 (4:98895076 C>A,G,T), RS1000535553 (4:98882269 G>A), RS1000537709 (4:98919263 C>T), RS1000582702 (4:98912850 G>GT), RS1000618297 (4:98913078 C>A,G,T), RS1000653998 (4:98911369 G>A), RS10007957 (4:98925811 G>A,C,T), RS1000809069 (4:98895015 C>A), RS10008093 (4:98926089 C>A,G), RS1000839032 (4:98900025 T>C)

Disease associations

OMIM: gene MIM:133440 | disease phenotypes: MIM:615091

GenCC curated gene-disease

Disease	Classification	Inheritance
autism, susceptibility to, 19	Limited	Unknown

Mondo (1): autism, susceptibility to, 19 (MONDO:0014041)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST003518_99	Daytime sleep phenotypes	8.000000e-06
GCST005863_12	Menopause (age at onset)	3.000000e-08
GCST005863_5	Menopause (age at onset)	1.000000e-08
GCST007328_18	Alcohol consumption (drinks per week)	4.000000e-15
GCST007328_26	Alcohol consumption (drinks per week)	2.000000e-11
GCST007328_42	Alcohol consumption (drinks per week)	2.000000e-08
GCST007328_6	Alcohol consumption (drinks per week)	9.000000e-24
GCST007621_1	Sensation seeking	1.000000e-07
GCST008811_14	Alcohol consumption (drinks per week)	4.000000e-68
GCST010242_49	HDL cholesterol levels	1.000000e-14
GCST010421_1	Mean arterial pressure x educational attainment (graduated college) interaction (2df)	7.000000e-09
GCST010421_2	Mean arterial pressure x educational attainment (graduated college) interaction (2df)	2.000000e-07
GCST011955_6	Alcohol dependence	7.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0004704	age at menopause
EFO:0006946	behavioural disinhibition measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004784	self reported educational attainment
EFO:0006340	mean arterial pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL4296088 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523621 (PROTEIN COMPLEX), CHEMBL4848 (SINGLE PROTEIN), CHEMBL4879530 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 251,373 (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
CHEMBL1643	RIBAVIRIN	4	78,049
CHEMBL413	SIROLIMUS	4	172,798
CHEMBL4073443	TOMIVOSERTIB	2	473
CHEMBL4211649	TINODASERTIB	2	53

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

Binding affinities (BindingDB)

136 measured of 149 human assays (149 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[2-chloro-5-(trifluoromethoxy)phenyl]-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	600 nM	US-9073881: Benzoic acid derivatives
2-(6-chloro-2-fluoro-3-methylphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	700 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-fluoro-2-(trifluoromethyl)phenyl]benzoic acid	IC50	800 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-(1-phenylethylcarbamoyl)phenyl]benzoic acid	IC50	970 nM	US-9073881: Benzoic acid derivatives
2-[2-chloro-5-(trifluoromethyl)phenyl]-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1100 nM	US-9073881: Benzoic acid derivatives
2-(2-chloro-5-methylphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1100 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(2-oxo-1H-pyrimidin-5-yl)benzoic acid	IC50	1200 nM	US-9073881: Benzoic acid derivatives
2-(5-chloro-2-nitrophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1300 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-[(3-methoxyphenyl)methylcarbamoyl]phenyl]benzoic acid	IC50	1300 nM	US-9073881: Benzoic acid derivatives
2-(2-carbamoyl-3-pyridinyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1300 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-methoxy-2-(trifluoromethyl)phenyl]benzoic acid	IC50	1300 nM	US-9073881: Benzoic acid derivatives
2-(4-cyano-2-methylphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1300 nM	US-9073881: Benzoic acid derivatives
2-(2-chloro-4-fluorophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1400 nM	US-9073881: Benzoic acid derivatives
2-(2,4-dichlorophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1400 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-[(4-fluorophenyl)methylcarbamoyl]phenyl]benzoic acid	IC50	1500 nM	US-9073881: Benzoic acid derivatives
2-(2-chloro-4-methoxyphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1500 nM	US-9073881: Benzoic acid derivatives
2-(5-acetyl-2-chlorophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1500 nM	US-9073881: Benzoic acid derivatives
2-[2-chloro-4-(trifluoromethyl)phenyl]-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1600 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(2,3,5-trifluorophenyl)benzoic acid	IC50	1600 nM	US-9073881: Benzoic acid derivatives
2-(2-chloro-6-fluoro-3-methylphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1600 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-[(3-methylphenyl)methylcarbamoyl]phenyl]benzoic acid	IC50	1700 nM	US-9073881: Benzoic acid derivatives
2-(5-chloro-2-cyanophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1700 nM	US-9073881: Benzoic acid derivatives
2-(3-chloro-4-cyanophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1700 nM	US-9073881: Benzoic acid derivatives
2-(3-chlorothiophen-2-yl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1700 nM	US-9073881: Benzoic acid derivatives
2-(4-chlorophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1700 nM	US-9073881: Benzoic acid derivatives
2-(2,5-dichlorophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1700 nM	US-9073881: Benzoic acid derivatives
2-(2-chloro-6-methoxyphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1800 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(2,5-difluorophenyl)benzoic acid	IC50	1800 nM	US-9073881: Benzoic acid derivatives
2-(4-carboxy-2-methylphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1900 nM	US-9073881: Benzoic acid derivatives
2-(4-chloro-3-cyanophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	1900 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(2,3-difluorophenyl)benzoic acid	IC50	1900 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[2-nitro-5-(trifluoromethyl)phenyl]benzoic acid	IC50	2000 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-[(4-methoxyphenyl)methylcarbamoyl]phenyl]benzoic acid	IC50	2000 nM	US-9073881: Benzoic acid derivatives
2-(2-chloro-4-ethoxyphenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	2000 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-[(3-fluorophenyl)methylcarbamoyl]phenyl]benzoic acid	IC50	2100 nM	US-9073881: Benzoic acid derivatives
2-(2,3-dichlorophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	2100 nM	US-9073881: Benzoic acid derivatives
2-(2-chlorothiophen-3-yl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	2200 nM	US-9073881: Benzoic acid derivatives
2-(2-chlorophenyl)-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	2200 nM	US-9073881: Benzoic acid derivatives
2-[4-(benzylcarbamoyl)phenyl]-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	2300 nM	US-9073881: Benzoic acid derivatives
2-(2-nitrophenyl)-5-[4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]benzoic acid	IC50	2400 nM	US-9073881: Benzoic acid derivatives
5-[4-[3,5-bis(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]-2-(2-nitrophenyl)benzoic acid	IC50	2500 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-[(2-fluorophenyl)methylcarbamoyl]phenyl]benzoic acid	IC50	2500 nM	US-9073881: Benzoic acid derivatives
2-(2-nitrophenyl)-5-[4-[4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl]benzoic acid	IC50	2600 nM	US-9073881: Benzoic acid derivatives
5-[4-(3-fluorophenyl)-1,3-thiazol-2-yl]-2-(2-nitrophenyl)benzoic acid	IC50	2600 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(4-fluorophenyl)benzoic acid	IC50	2600 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-(2-nitrophenyl)benzoic acid	IC50	2800 nM	US-9073881: Benzoic acid derivatives
2-[2-chloro-3-(trifluoromethyl)phenyl]-5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]benzoic acid	IC50	2800 nM	US-9073881: Benzoic acid derivatives
5-[4-(2,5-dichlorophenyl)-1,3-thiazol-2-yl]-2-(2-nitrophenyl)benzoic acid	IC50	2900 nM	US-9073881: Benzoic acid derivatives
5-[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]-2-[4-(2-phenylethylcarbamoyl)phenyl]benzoic acid	IC50	2900 nM	US-9073881: Benzoic acid derivatives
5-[4-(3-bromophenyl)-1,3-thiazol-2-yl]-2-(2-nitrophenyl)benzoic acid	IC50	3000 nM	US-9073881: Benzoic acid derivatives

ChEMBL bioactivities

212 potent at pChembl≥5 of 302 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	Kd	0.5	nM	SIROLIMUS
8.85	IC50	1.4	nM	TOMIVOSERTIB
8.66	Kd	2.2	nM	CHEMBL4780117
8.51	IC50	3.1	nM	CHEMBL4577429
8.50	IC50	3.162	nM	CHEMBL5183975
8.27	IC50	5.4	nM	TOMIVOSERTIB
8.22	IC50	6	nM	TOMIVOSERTIB
8.19	IC50	6.5	nM	CHEMBL4780117
8.14	Kd	7.2	nM	CHEMBL4777401
8.10	IC50	7.943	nM	CHEMBL5203720
8.10	IC50	7.943	nM	CHEMBL5181488
7.80	IC50	16	nM	CHEMBL2046918
7.80	IC50	15.85	nM	CHEMBL5206647
7.78	IC50	16.6	nM	CHEMBL4447089
7.77	Kd	17	nM	CHEMBL4461497
7.70	IC50	20.1	nM	CHEMBL4461497
7.70	IC50	19.95	nM	CHEMBL5175341
7.70	IC50	19.95	nM	CHEMBL5187414
7.70	IC50	19.95	nM	CHEMBL5184155
7.68	IC50	21	nM	CHEMBL6149494
7.66	IC50	22	nM	CHEMBL4777401
7.60	IC50	25.12	nM	CHEMBL5196084
7.60	IC50	25.12	nM	CHEMBL5195407
7.58	IC50	26	nM	CHEMBL6120909
7.55	Ki	28	nM	CHEMBL1094973
7.50	IC50	31.62	nM	CHEMBL5195560
7.50	IC50	31.62	nM	CHEMBL5171562
7.50	IC50	31.62	nM	CHEMBL5180948
7.42	IC50	38	nM	CHEMBL6145107
7.40	IC50	39.81	nM	CHEMBL5186068
7.40	IC50	39.81	nM	CHEMBL5205835
7.39	IC50	41	nM	CHEMBL2046906
7.35	IC50	45	nM	CHEMBL6163769
7.34	IC50	46	nM	CHEMBL6172372
7.30	IC50	50.12	nM	CHEMBL5183411
7.29	IC50	51	nM	CHEMBL2046915
7.28	IC50	52.5	nM	CHEMBL5561277
7.27	IC50	54	nM	CHEMBL6145107
7.25	IC50	56	nM	CHEMBL2046910
7.23	IC50	59	nM	CHEMBL2046905
7.22	IC50	60	nM	CHEMBL4461497
7.22	IC50	60	nM	CHEMBL6149494
7.16	IC50	70	nM	CHEMBL6172372
7.15	IC50	71.5	nM	CHEMBL5561300
7.10	IC50	79.43	nM	CHEMBL5197975
7.04	IC50	91.5	nM	CHEMBL5561635
7.04	IC50	90.5	nM	CHEMBL5559028
7.02	IC50	95	nM	CHEMBL2046916
6.96	IC50	110.8	nM	CHEMBL5532369
6.93	IC50	117	nM	CHEMBL2046912

PubChem BioAssay actives

96 with measured affinity, of 537 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
Sirolimus	548276: Binding affinity to purified elF4E	kd	0.0005	uM
6-[(6-aminopyrimidin-4-yl)amino]-8-methylspiro[2H-imidazo[1,5-a]pyridine-3,1’-cyclohexane]-1,5-dione	1881777: Inhibition of Ser 209 phosphorylation of eIF4E (unknown origin)	ic50	0.0014	uM
(3S)-3-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[[(2S)-1-[[(3S,6S,9S,12S,21S)-21-[[(2R)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]-9-benzyl-6-(2-methylpropyl)-3-(2-methylsulfanylethyl)-2,5,8,11,15-pentaoxo-1,4,7,10,16-pentazacyclohenicos-12-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1741913: Binding affinity to recombinant human 10His-tagged eIF4E expressed in Escherichia coli BL21 (DE3) cells assessed as binding constant by surface plasmon resonance analysis	kd	0.0022	uM
(3S)-3-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[(2-acetamidoacetyl)amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[[(2S)-1-[[(3S,6S,9S,12S,16Z,21S)-9-benzyl-21-[[(2R)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]-12,21-dimethyl-6-(2-methylpropyl)-3-(2-methylsulfanylethyl)-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohenicos-16-en-12-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.0031	uM
7-(3,3-dimethyl-2H-indol-1-yl)-N-(piperidin-4-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0032	uM
(3S)-3-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-acetamido-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[[(2S)-1-[[(2S,5S,8S,11S,20S)-11-[[(2R)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]-2-benzyl-5-(2-methylpropyl)-8-(2-methylsulfanylethyl)-3,6,9,14,21-pentaoxo-1,4,7,10,15-pentazacyclohenicos-20-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-oxobutanoic acid	1741913: Binding affinity to recombinant human 10His-tagged eIF4E expressed in Escherichia coli BL21 (DE3) cells assessed as binding constant by surface plasmon resonance analysis	kd	0.0072	uM
N-[3-(dimethylamino)propyl]-7-(5-fluoro-2,3-dihydroindol-1-yl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0079	uM
7-(5-fluoro-2,3-dihydroindol-1-yl)-N-(piperidin-4-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0079	uM
N-[3-(dimethylamino)propyl]-7-(3,3-dimethyl-2H-indol-1-yl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0158	uM
[[4-[7-[2-(4-chlorophenoxy)ethyl]-2-(methylamino)-6-oxo-1H-purin-8-yl]phenyl]-difluoromethyl]phosphonic acid	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.0160	uM
(2S,5S,8S,11S,15Z,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-N-[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]-2-(3-amino-3-oxopropyl)-11,20-dimethyl-5,8-bis(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carboxamide	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.0166	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[(2-acetamidoacetyl)amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-6-aminohexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[(2R)-1-[[(2S)-5-carbamimidamido-1-[[(2S)-1,4-diamino-1,4-dioxobutan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid	1741913: Binding affinity to recombinant human 10His-tagged eIF4E expressed in Escherichia coli BL21 (DE3) cells assessed as binding constant by surface plasmon resonance analysis	kd	0.0170	uM
N-(2-cyclopentyloxy-4-fluorophenyl)-5-methylpyrrolo[3,2-d]pyrimidin-4-amine	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.0199	uM
N-[2-(1,3-difluoropropan-2-yloxy)-4-fluorophenyl]-5-methylpyrrolo[3,2-d]pyrimidin-4-amine	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.0199	uM
N-[4-fluoro-2-[(3R)-oxan-3-yl]oxyphenyl]-5-methylpyrrolo[3,2-d]pyrimidin-4-amine	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.0199	uM
7-(4-fluoro-2-propan-2-yloxyanilino)-N-methyl-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0251	uM
N-[3-(dimethylamino)propyl]-4-(5-fluoro-2,3-dihydroindol-1-yl)-5-methylpyrrolo[3,2-d]pyrimidine-6-carboxamide	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.0251	uM
[(2R,3S,4R,5R)-5-(2-amino-7-methyl-6-oxo-1H-purin-9-ium-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl [hydroxy(phosphonooxy)phosphoryl] phosphate	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ki	0.0280	uM
7-(5-chloro-2,3-dihydroindol-1-yl)-N-(piperidin-4-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0316	uM
7-(2,3-dihydroindol-1-yl)-N-[3-(dimethylamino)propyl]-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0316	uM
4-[(5-methylpyrrolo[3,2-d]pyrimidin-4-yl)amino]-3-propan-2-yloxybenzonitrile	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.0316	uM
7-(4-fluoro-2-propan-2-yloxyanilino)-N-(2-piperazin-1-ylethyl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0398	uM
N-[3-(dimethylamino)propyl]-4-(4-fluoro-2-propan-2-yloxyanilino)-5-methylpyrrolo[3,2-d]pyrimidine-6-carboxamide	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.0398	uM
[(2R,3S,4R,5R)-5-[2-amino-7-[2-(4-bromophenoxy)ethyl]-6-oxo-1H-purin-9-ium-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.0410	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-[[(2R)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid	548276: Binding affinity to purified elF4E	kd	0.0500	uM
4-(5-fluoro-2,3-dihydroindol-1-yl)-5H-pyrrolo[3,2-d]pyrimidine	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.0501	uM
[(3aR,4R,6R,6aR)-4-[2-amino-7-[2-(4-chlorophenoxy)ethyl]-6-oxo-1H-purin-9-ium-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl hydrogen phosphate	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.0510	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-[4-(dimethylamino)piperidin-1-yl]methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.0525	uM
[(2R,3S,4R,5R)-5-[2-amino-7-[2-(4-chloro-3-fluorophenoxy)ethyl]-6-oxo-1H-purin-9-ium-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.0560	uM
[(2R,3S,4R,5R)-5-[2-amino-7-[2-(4-chlorophenoxy)ethyl]-6-oxo-1H-purin-9-ium-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.0590	uM
1-[4-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]benzoyl]piperazin-1-yl]ethanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.0715	uM
7-(4-fluoro-2-propan-2-yloxyanilino)-N-(piperidin-4-ylmethyl)-[1,3]thiazolo[5,4-d]pyrimidine-2-carboxamide	1881804: Inhibition of phosphorylation of eIF4E (unknown origin)	ic50	0.0794	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-(4-piperidin-1-ylpiperidin-1-yl)methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.0905	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-(4-methylpiperazin-1-yl)methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.0915	uM
[4-[7-[2-(4-chlorophenoxy)ethyl]-2-(methylamino)-6-oxo-1H-purin-8-yl]phenyl]phosphonic acid	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.0950	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-(4-piperidin-1-ylpiperidin-1-yl)methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.1108	uM
[(2R,3S,4R,5R)-5-[2-amino-7-[(5-chloro-1-benzofuran-2-yl)methyl]-6-oxo-1H-purin-9-ium-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.1170	uM
(4-aminopiperidin-1-yl)-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.1186	uM
1-[4-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]benzoyl]piperazin-1-yl]ethanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.1222	uM
[(2R,3S,4R,5R)-5-[2-amino-7-[2-(4-cyanophenoxy)ethyl]-6-oxo-1H-purin-9-ium-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.1250	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-[4-(dimethylamino)piperidin-1-yl]methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.1289	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-5-oxopentanoic acid	1598541: Inhibition of Halo-tagged biotinylated human eIF4E expressed in Escherichia coli/Halo-tagged methyltetrazine-labelled human 4E-BP1 expressed in Escherichia coli protein-protein interaction incubated for 1 hr by catalytic enzyme-linked click chemistry assay	ic50	0.1370	uM
(4-aminopiperidin-1-yl)-[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.1460	uM
[4-[7-[2-(4-chlorophenoxy)ethyl]-2-(methylamino)-6-oxo-1H-purin-8-yl]phenyl]methylphosphonic acid	669612: Competitive inhibition of [3H]m7-GTP binding to human FLAG-His6 tagged eIF4E expressed in Escherichia coli by scintillation proximity assay	ic50	0.1600	uM
4-(4-fluoro-2-propan-2-yloxyanilino)-5-methyl-N-(piperidin-4-ylmethyl)pyrrolo[3,2-d]pyrimidine-6-carboxamide	1881800: Inhibition of eIF4E (unknown origin)	ic50	0.1995	uM
4-[5-[1-(oxetan-3-yl)pyrazol-4-yl]-3-pyridinyl]-2-propan-2-yloxybenzamide	2003774: Inhibition of eIF4E phosphorylation in human HeLa cells	ic50	0.2000	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-(4-morpholin-4-ylpiperidin-1-yl)methanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.2131	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-a]pyridin-6-yl]phenyl]-morpholin-4-ylmethanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.2617	uM
[4-[3-(1-benzofuran-2-yl)imidazo[1,2-b]pyridazin-6-yl]phenyl]-morpholin-4-ylmethanone	2083036: Inhibition of eIF4E phosphorylation at ser209 residue in human HeLa cells incubated for 2 hrs by HTRF assay	ic50	0.2694	uM
N-[5-[3-fluoro-4-[[2-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)anilino]-2-oxoethyl]amino]phenyl]-2-pyridinyl]cyclopropanecarboxamide	2003774: Inhibition of eIF4E phosphorylation in human HeLa cells	ic50	0.2800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression, affects binding, decreases reaction, increases reaction (+7 more)	9
CGP 57380	decreases phosphorylation, decreases reaction, increases activity, increases phosphorylation, affects binding (+1 more)	4
Cisplatin	affects reaction, decreases expression, affects cotreatment, decreases reaction, increases phosphorylation	4
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	affects cotreatment, decreases reaction, increases phosphorylation, increases reaction, decreases phosphorylation	3
Arsenic Trioxide	affects expression, increases activity, increases phosphorylation, decreases reaction, increases reaction (+1 more)	3
Estradiol	affects expression, decreases phosphorylation, increases expression, decreases reaction	3
Fluorouracil	decreases expression, affects binding, affects cotreatment, decreases reaction, increases expression (+1 more)	3
Ribavirin	decreases phosphorylation, affects binding, decreases reaction, increases phosphorylation, decreases expression	3
Cadmium Chloride	decreases expression, decreases reaction, increases expression, increases ubiquitination, decreases response to substance	3
bisphenol A	affects expression, increases expression	2
arsenite	affects reaction, decreases reaction, increases phosphorylation, affects binding, increases reaction	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, decreases phosphorylation	2
SB 203580	affects cotreatment, decreases reaction, increases phosphorylation, increases reaction	2
U 0126	increases activity, increases phosphorylation, decreases reaction	2
Sorafenib	decreases reaction, increases phosphorylation, decreases phosphorylation, decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Doxorubicin	decreases expression, increases phosphorylation, decreases reaction	2
Quercetin	affects cotreatment, decreases expression, affects binding, decreases reaction	2
Tetradecanoylphorbol Acetate	increases reaction, affects binding, affects cotreatment, decreases reaction, increases phosphorylation	2
Tretinoin	decreases expression, increases reaction	2
Sirolimus	decreases expression, decreases reaction, decreases activity, increases phosphorylation	2
afuresertib	decreases expression	1
squaramide	affects binding	1
bisphenol F	increases expression, affects cotreatment	1
moringin	affects cotreatment, increases expression	1
mivebresib	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dihydrotanshinone I	decreases phosphorylation	1
EGPI-1 compound	affects binding, decreases reaction, decreases phosphorylation	1
dicrotophos	decreases expression	1

ChEMBL screening assays

136 unique, capped per target: 136 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4150513	Binding	Inhibition of eIF4E-4E-BP1 (unknown origin) interaction at 100 uM by cat-ELCCA	Expansion of cat-ELCCA for the Discovery of Small Molecule Inhibitors of the Pre-let-7-Lin28 RNA-Protein Interaction. — ACS Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1G3	SEES3-1V human EIF4E, clone1	Embryonic stem cell	Male
CVCL_A1G4	SEES3-1V human EIF4E, clone2	Embryonic stem cell	Male
CVCL_A1G5	SEES3-1V human EIF4E, clone3	Embryonic stem cell	Male
CVCL_IN94	HLY-1 eIF4E1	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

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