EPHA2

Summary

EPHA2 (EPH receptor A2, HGNC:3386) is a protein-coding gene on chromosome 1p36.13, encoding Ephrin type-A receptor 2 (P29317). Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.

Source: NCBI Gene 1969 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 6 multiple types (Definitive, GenCC) — +6 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 446 total — 12 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 50 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_004431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3386
Approved symbol	EPHA2
Name	EPH receptor A2
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142627
Ensembl biotype	protein_coding
OMIM	176946
Entrez	1969

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000358432, ENST00000461614, ENST00000462805, ENST00000480202, ENST00000863593, ENST00000863594, ENST00000917106

RefSeq mRNA: 2 — MANE Select: NM_004431 NM_001329090, NM_004431

CCDS: CCDS169

Canonical transcript exons

ENST00000358432 — 17 exons

Exon	Start	End
ENSE00000827996	16150896	16150963
ENSE00000955400	16133860	16133915
ENSE00000955402	16133180	16133368
ENSE00000955403	16132378	16132439
ENSE00000955404	16132064	16132273
ENSE00000955405	16131721	16131870
ENSE00000955406	16130226	16130419
ENSE00001031771	16133481	16133606
ENSE00001031795	16134468	16134567
ENSE00001031824	16129434	16129589
ENSE00001840165	16124337	16125320
ENSE00001954971	16155848	16156069
ENSE00003523386	16135655	16135770
ENSE00003543184	16138275	16138430
ENSE00003546123	16148378	16149047
ENSE00003577899	16137853	16138185
ENSE00003593176	16135036	16135189

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.8392 / max 177.8033, expressed in 1353 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10523	11.6438	1307
10522	2.7595	976
10521	0.4359	265

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.89	gold quality
esophagus mucosa	UBERON:0002469	96.98	gold quality
pharyngeal mucosa	UBERON:0000355	96.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.48	gold quality
esophagus squamous epithelium	UBERON:0006920	93.05	gold quality
epithelium of esophagus	UBERON:0001976	92.81	gold quality
vagina	UBERON:0000996	91.38	gold quality
squamous epithelium	UBERON:0006914	91.35	gold quality
gall bladder	UBERON:0002110	91.34	gold quality
skin of abdomen	UBERON:0001416	90.77	gold quality
cervix epithelium	UBERON:0004801	90.66	gold quality
cervix squamous epithelium	UBERON:0006922	90.51	silver quality
buccal mucosa cell	CL:0002336	90.39	gold quality
skin of leg	UBERON:0001511	89.62	gold quality
cartilage tissue	UBERON:0002418	89.53	gold quality
saliva-secreting gland	UBERON:0001044	89.50	gold quality
minor salivary gland	UBERON:0001830	89.02	gold quality
mouth mucosa	UBERON:0003729	88.99	gold quality
trachea	UBERON:0003126	88.58	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.51	gold quality
esophagus	UBERON:0001043	87.95	gold quality
metanephros cortex	UBERON:0010533	87.71	gold quality
oral cavity	UBERON:0000167	87.56	gold quality
zone of skin	UBERON:0000014	87.51	gold quality
omental fat pad	UBERON:0010414	86.55	gold quality
gingiva	UBERON:0001828	86.51	gold quality
peritoneum	UBERON:0002358	86.49	gold quality
parotid gland	UBERON:0001831	86.42	gold quality
gingival epithelium	UBERON:0001949	86.19	gold quality
nasal cavity epithelium	UBERON:0005384	86.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	56.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, HIC1, MTA1, PAX3, TP53, TP63, TP73

miRNA regulators (miRDB)

65 targeting EPHA2, 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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676

Literature-anchored findings (GeneRIF, showing 40)

• estrogen and Myc negatively regulate EphA2 expression in mammary epithelial cells (PMID:11968011)
• negative regulation by Cbl (PMID:12147253)
• EphA2 receptor tyrosine kinase is a substrate for low molecular weight tyrosine phosphatase and has a role in neoplastic transformation progression (PMID:12167657)
• a peptide has been identified which has ephrin-like activity in that it stimulates EphA2 tyrosine phosphorylation and signaling (PMID:12351647)
• Eph A receptors inhibit tumor angiogenesis and progression in vivo. (PMID:12370823)
• We demonstrate that tyrosine phosphorylated EphA2 interacts with the PTB and SH2 domains of SHC. We show that the interaction of EphA2 with GRB2 is mediated by SHC and that this complex is necessary for EphA2-mediated activation of ERK kinases. (PMID:12400011)
• Patients with EphA2 overexpression have a poorer prognosis than those without. (PMID:12494475)
• Blockade of EphA2 activation inhibits vascular endothelial growth factor-induced angiogenesis. (PMID:12496364)
• c-Cbl-dependent EphA2 protein degradation is induced by ligand binding. (PMID:12496371)
• Levels predict lung cancer (NSCLC) recurrence and survival. (PMID:12576426)
• Recent studies have demonstrated that the EphA2 receptor tyrosine kinase is frequently overexpressed and functionally altered in aggressive tumor cells, and that these changes promote metastatic character (PMID:12650608)
• differentially regulated in normal and malignant cells. (PMID:12651595)
• Overexpression of EphA2 decreases estrogen dependence. EphA2-transfected cells show increased growth in vitro & larger & more aggressive tumors in vivo. Overexpression decreases tamoxifen’s ability to inhibit breast cancer cell growth & tumorigenesis. (PMID:12810680)
• EphA2/ephrin-A3 interactions may play a role in the localization and network of Langerhans cells in the epithelium and in the regulation of their trafficking. (PMID:12907451)
• EphA2 increases as prostatic epithelial cells have more aggressive phenotype. EphA2 functions as a powerful oncogene. Presence of high levels of EphA2 suggests opportunities for prostate cancer prevention and treatment. (PMID:14633601)
• EphA2 is a tumor rejection antigen. Two immunogenic HLA-A*0201 restricted peptides identified by reverse immunology approach. (PMID:14679012)
• EphA2 and E-cadherin may play an important role in tumor metastasis in colorectal cancer (PMID:14767510)
• involvement of EPHA2 in colon carcinogenesis, mainly in stages I and II, and probably through their effect on microvessel induction. (PMID:14965363)
• found the prototype ephrin-A1 receptor, EphA2, localized in several placental cell types (PMID:15193868)
• We show that EphA2 overexpression induces a FAK-dependent increase in MMP-2 expression and invasiveness. (PMID:15249202)
• EPHA2 may have a role in progression of ovarian cancer (PMID:15297418)
• EphA2 selectively inhibits cell-cell adhesions by increasing cell attachment and up-regulating the extracellular matrix protein fibronectin (PMID:15498927)
• Renal medullary EphA2 expression may represent an adaptive response to medullary hypertonicity or urea exposure (PMID:15561974)
• EPHA2 and EFNA1 expression may influence the behavior of human gastric cancer. (PMID:15649254)
• EphA2 may have a role in progression of surgically treated renal cell carcinoma (PMID:15671550)
• low molecular weight protein-tyrosine phosphatase acts as terminator of EphA2 signaling causing efficient negative feedback loop on biological response mediated by ephrinA1; tyrosine phosphorylation main event orchestrating repulsive response (PMID:16051609)
• EphA2 attenuates the growth factor-induced activation of Ras and a negative feedback loop is created that regulates Ras activity. (PMID:16098464)
• receptor phosphorylation and kinase activity of the EphA2 receptor, at least in part, contribute to tumor malignancy (PMID:16103880)
• EphA2 moderates the function of tight junctions via phosphorylation of claudin-4 (PMID:16236711)
• High expression of EphA2 is associated with urinary bladder carcinoma. (PMID:16428472)
• VE-cadherin and EphA2 act in a coordinated manner as a key regulatory element in the process of melanoma vasculogenic mimicry. (PMID:16481735)
• increased levels of ephrins A1 and A5 in the presence of high expression of Ephs A1 and A2 lead to a more aggressive ovarian cancer phenotype (PMID:16737551)
• p53 appears to regulate EphA2 expression and clinical outcome in ovarian cancer. (PMID:16969087)
• Our findings show that p53 is a transcriptional regulator of ECK in mediating apoptosis. The discovery of the novel p53-binding motif in the promoter may lead to the identification of a new class of p53 target genes. (PMID:17050670)
• EphA2 was overexpressed in 76% of tumors and was associated with advanced-stage disease and high-grade histology. (PMID:17154180)
• Ephrin-A1 serves as a critical negative regulator in the tumorigenesis of gliomas by down-regulating EphA2 and FAK. (PMID:17332925)
• Ligand activation of EphA2 and EphA2 knockdown by small interfering RNA inhibit EGF-induced cell motility of EGFR-overexpressing human cancer cells, indicating a functional role of EphA2 in EGFR-expressing cancer cells. (PMID:17374733)
• EphA2 may be a new biomarker for astrocytic tumors and may also affect the proliferation and apoptosis of tumor cells and be an attractive therapy target for astrocytic tumors. (PMID:17519535)
• Increasing ephrin-A expression enhances T-cell interactions not only with purified integrin ligands but also endothelial cells, while EphA activation down-regulates these interactions. (PMID:17980912)
• Required for Raf-induced AKT inhibition and cell cycle arrest. (PMID:18059341)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Epha2	ENSMUSG00000006445
rattus_norvegicus	Epha2	ENSRNOG00000009222

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Ephrin type-A receptor 2 — P29317 (reviewed: P29317)

Alternative names: Epithelial cell kinase, Tyrosine-protein kinase receptor ECK

All UniProt accessions (1): P29317

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells.

Subunit / interactions. Homodimer. Interacts with SLA. Interacts (phosphorylated form) with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3); critical for the EFNA1-induced activation of RAC1 which stimulates cell migration. Interacts with INPPL1; regulates activated EPHA2 endocytosis and degradation. Interacts (inactivated form) with PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with PTPN11; regulates integrin-mediated adhesion. Interacts with ARHGEF16, DOCK4 and ELMO2; mediates ligand-independent activation of RAC1 which stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4 and may regulate tight junctions. Interacts with ACP1. Interacts (via SAM domain) with ANKS1A (via SAM domain). Interacts with CEMIP. Interacts with NCK1; may regulate EPHA2 activity in cell migration and adhesion. Interacts with TIMD4. (Microbial infection) Interacts with human herpes virus 8/HHV-8 glycoprotein L/gL and glycoprotein H/gH heterodimer; this interaction triggers EPHA2 phosphorylation and endocytosis, allowing virus entry. (Microbial infection) Interacts with human cytomegalovirus (HCMV) glycoprotein L/gL and glycoprotein H/gH heterodimer. (Microbial infection) Interacts with Epstein-Barr virus/HHV-4 glycoprotein L/gL and glycoprotein H/gH heterodimer; this interaction facilitates virus internalization and fusion.

Subcellular location. Cell membrane. Cell projection. Ruffle membrane. Lamellipodium membrane. Cell junction. Focal adhesion.

Tissue specificity. Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g. skin, intestine, lung, and ovary.

Post-translational modifications. Autophosphorylates. Phosphorylated on tyrosine upon binding and activation by EFNA1. Phosphorylated residues Tyr-588 and Tyr-594 are required for binding VAV2 and VAV3 while phosphorylated residues Tyr-735 and Tyr-930 are required for binding PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3). These phosphorylated residues are critical for recruitment of VAV2 and VAV3 and PI3-kinase p85 subunit which transduce downstream signaling to activate RAC1 GTPase and cell migration. Dephosphorylation of Tyr-930 by PTPRF prevents the interaction of EPHA2 with NCK1. Phosphorylated at Ser-897 by PKB; serum-induced phosphorylation which targets EPHA2 to the cell leading edge and stimulates cell migration. Phosphorylation by PKB is inhibited by EFNA1-activated EPHA2 which regulates PKB activity via a reciprocal regulatory loop. Phosphorylated at Ser-897 in response to TNF by RPS6KA1 and RPS6KA3; RPS6KA-EPHA2 signaling pathway controls cell migration. Phosphorylated at Ser-897 by PKA; blocks cell retraction induced by EPHA2 kinase activity. Dephosphorylated by ACP1. Ubiquitinated by CHIP/STUB1. Ubiquitination is regulated by the HSP90 chaperone and regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation.

Disease relevance. Cataract 6, multiple types (CTRCT6) [MIM:116600] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT6 includes posterior polar and age-related cortical cataracts, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Age-related cortical cataract is a developmental punctate opacity restricted to the cortex. The cataract is white or cerulean, increases in number with age, but rarely affects vision. The disease is caused by variants affecting the gene represented in this entry. Overexpressed in several cancer types and promotes malignancy.

Induction. Up-regulated by UV irradiation via a TP53-independent, MAPK-dependent mechanism.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P29317-1	1	yes
P29317-2	2

RefSeq proteins (2): NP_001316019, NP_004422* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001090	EPH_LBD	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001426	Tyr_kinase_rcpt_V_CS	Conserved_site
IPR001660	SAM	Domain
IPR003961	FN3_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR016257	EPH	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR027936	EPH_TM	Domain
IPR034263	EphA2_rcpt_lig-bd	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR050449	Ephrin_rcpt_TKs	Family

Pfam: PF00041, PF00536, PF01404, PF07714, PF14575, PF25599

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (142 total): strand 52, helix 31, modified residue 15, sequence variant 10, turn 6, domain 5, mutagenesis site 4, region of interest 3, binding site 2, topological domain 2, glycosylation site 2, disulfide bond 2, splice variant 2, signal peptide 1, chain 1, short sequence motif 1, active site 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

103 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6Q7D	X-RAY DIFFRACTION	0.98
6Q7B	X-RAY DIFFRACTION	1.01
6FNG	X-RAY DIFFRACTION	1.04
6Q7G	X-RAY DIFFRACTION	1.05
6Q7C	X-RAY DIFFRACTION	1.05
6Q7E	X-RAY DIFFRACTION	1.06
5NKF	X-RAY DIFFRACTION	1.1
5NKG	X-RAY DIFFRACTION	1.1
8BOM	X-RAY DIFFRACTION	1.12
6HES	X-RAY DIFFRACTION	1.13
6Q7F	X-RAY DIFFRACTION	1.2
6HET	X-RAY DIFFRACTION	1.21
5I9Y	X-RAY DIFFRACTION	1.23
5NK6	X-RAY DIFFRACTION	1.27
6HEW	X-RAY DIFFRACTION	1.27
6HEV	X-RAY DIFFRACTION	1.28
5NKH	X-RAY DIFFRACTION	1.29
5NK5	X-RAY DIFFRACTION	1.33
5I9W	X-RAY DIFFRACTION	1.36
6HEY	X-RAY DIFFRACTION	1.37
5NKA	X-RAY DIFFRACTION	1.38
6FNH	X-RAY DIFFRACTION	1.38
5NKE	X-RAY DIFFRACTION	1.39
5NKD	X-RAY DIFFRACTION	1.41
6HEX	X-RAY DIFFRACTION	1.41
8BOH	X-RAY DIFFRACTION	1.42
5I9X	X-RAY DIFFRACTION	1.43
5NKC	X-RAY DIFFRACTION	1.45
5NK4	X-RAY DIFFRACTION	1.45
5I9V	X-RAY DIFFRACTION	1.46

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29317-F1	82.73	0.48

Antibody-complex structures (SAbDab): 6 — 3SKJ, 8T9B, 8TRS, 8TRT, 8TRV, 8TV1

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): 739 (proton acceptor)

Ligand- & substrate-binding residues (2): 619–627; 646

Post-translational modifications (15): 570, 575, 579, 588, 594, 628, 647, 735, 772, 869, 892, 897, 901, 921, 930

Disulfide bonds (2): 70–188, 105–115

Glycosylation sites (2): 407, 435

Mutagenesis-validated functional residues (4):

Position	Phenotype
103	significantly reduced response to efna1.
646	loss of kinase activity.
739	increases serum-induced chemotaxis. loss of efna1-dependent regulation of cell migration.
897	loss of serum-induced phosphorylation by pkb. loss of serum-induced chemotaxis.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle

MSigDB gene sets: 499 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, ATF_B, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MODULE_52, AP1_01, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_MAMMARY_GLAND_MORPHOGENESIS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MYOGENIN_Q6, GOBP_GLAND_MORPHOGENESIS, GOBP_CELL_CHEMOTAXIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (56): skeletal system development (GO:0001501), angiogenesis (GO:0001525), vasculogenesis (GO:0001570), osteoblast differentiation (GO:0001649), blood vessel endothelial cell proliferation involved in sprouting angiogenesis (GO:0002043), inflammatory response (GO:0006954), cell adhesion (GO:0007155), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), regulation of lamellipodium assembly (GO:0010591), notochord formation (GO:0014028), cell migration (GO:0016477), negative regulation of angiogenesis (GO:0016525), neural tube development (GO:0021915), central nervous system neuron differentiation (GO:0021953), keratinocyte differentiation (GO:0030216), osteoclast differentiation (GO:0030316), positive regulation of cell migration (GO:0030335), negative regulation of chemokine production (GO:0032682), mammary gland epithelial cell proliferation (GO:0033598), negative regulation of cell adhesion mediated by integrin (GO:0033629), post-anal tail morphogenesis (GO:0036342), regulation of blood vessel endothelial cell migration (GO:0043535), regulation of angiogenesis (GO:0045765), cAMP metabolic process (GO:0046058), bone remodeling (GO:0046849), ephrin receptor signaling pathway (GO:0048013), axial mesoderm formation (GO:0048320), cell motility (GO:0048870), defense response to Gram-positive bacterium (GO:0050830), notochord cell development (GO:0060035), cell chemotaxis (GO:0060326), branching involved in mammary gland duct morphogenesis (GO:0060444), lens fiber cell morphogenesis (GO:0070309), regulation of ERK1 and ERK2 cascade (GO:0070372), response to growth factor (GO:0070848), protein localization to plasma membrane (GO:0072659), activation of GTPase activity (GO:0090630), negative regulation of lymphangiogenesis (GO:1901491), positive regulation of protein localization to plasma membrane (GO:1903078)

GO Molecular Function (13): virus receptor activity (GO:0001618), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ephrin receptor activity (GO:0005003), ATP binding (GO:0005524), growth factor binding (GO:0019838), cadherin binding (GO:0045296), molecular function activator activity (GO:0140677), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (12): plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), lamellipodium (GO:0030027), leading edge membrane (GO:0031256), lamellipodium membrane (GO:0031258), ruffle membrane (GO:0032587), signaling receptor complex (GO:0043235), tight junction (GO:0070160), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	9
EPH-Ephrin signaling	2
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
blood vessel morphogenesis	2
anatomical structure formation involved in morphogenesis	2
cell differentiation	2
nervous system development	2
cell leading edge	2
cell projection membrane	2
leading edge membrane	2
system development	1
ossification	1
endothelial cell proliferation	1
sprouting angiogenesis	1
defense response	1
cellular process	1
enzyme-linked receptor protein signaling pathway	1
DNA damage response	1
intrinsic apoptotic signaling pathway	1
lamellipodium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of lamellipodium organization	1
notochord morphogenesis	1
cell motility	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
tube development	1
chordate embryonic development	1
epithelium development	1
central nervous system development	1
neuron differentiation	1
epidermal cell differentiation	1
skin development	1
myeloid leukocyte differentiation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
negative regulation of cytokine production	1
chemokine production	1
regulation of chemokine production	1
epithelial cell proliferation	1

Protein interactions and networks

STRING

3665 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPHA2	EFNA1	P20827	999
EPHA2	EFNA2	O43921	998
EPHA2	EFNA5	P52803	997
EPHA2	EFNA3	P52797	993
EPHA2	EFNA4	P52798	993
EPHA2	INPPL1	O15357	982
EPHA2	EFNB2	P52799	924
EPHA2	EFNB3	Q15768	858
EPHA2	CLDN4	O14493	839
EPHA2	EFNB1	P98172	818
EPHA2	EGFR	P00533	806
EPHA2	IL13RA2	Q14627	800
EPHA2	EPHA1	P21709	795
EPHA2	PTPN11	Q06124	773
EPHA2	LYN	P07948	762

IntAct

203 interactions, top by confidence:

A	B	Type	Score
EPHA2	EFNA1	psi-mi:“MI:0407”(direct interaction)	0.820
EFNA1	EPHA2	psi-mi:“MI:0915”(physical association)	0.820
EPHA2	EFNA1	psi-mi:“MI:0915”(physical association)	0.820
EFNA1	EPHA2	psi-mi:“MI:0407”(direct interaction)	0.820
EPHA2	EFNA5	psi-mi:“MI:0407”(direct interaction)	0.810
EPHA2	EFNA5	psi-mi:“MI:0915”(physical association)	0.810
EPHA7	EPHA2	psi-mi:“MI:0915”(physical association)	0.780
EPHA2	EPHA7	psi-mi:“MI:0915”(physical association)	0.780
EPHA2	EPHA7	psi-mi:“MI:0407”(direct interaction)	0.780
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PTPN11	EPHA2	psi-mi:“MI:0915”(physical association)	0.660
EPHA2	PTPN11	psi-mi:“MI:0915”(physical association)	0.660
EPHA2	EPHA6	psi-mi:“MI:0915”(physical association)	0.650
EFNB1	EPHA2	psi-mi:“MI:0407”(direct interaction)	0.600
EPHA2	EFNB1	psi-mi:“MI:0407”(direct interaction)	0.600
EPHA2	EFNB1	psi-mi:“MI:0403”(colocalization)	0.600
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570

BioGRID (926): EPHA2 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), EPHA2 (Proximity Label-MS), EPHA2 (Proximity Label-MS), FANCD2 (Affinity Capture-MS), SSR3 (Affinity Capture-MS), TGFBR1 (Affinity Capture-MS), ZBTB14 (Affinity Capture-MS), VPS4B (Affinity Capture-MS), SCAMP3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RPR8, O02740, O08644, O09127, O15197, O19179, O73875, O73878, P0C0K6, P0C0K7, P14616, P16067, P20594, P21709, P26770, P29317, P29322, P35590, P46197, P51839, P51840, P51841, P51842, P52333, P52785, P54753, P54754, P54760, P54761, P55203, P55205, Q02846, Q03146, Q06805, Q06806, Q08345, Q1KL86, Q5JZY3, Q5SDA5, Q60750

Diamond homologs: A0A2R6XIK6, A2VDU3, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, F4JTP5, G5EE56, O01700, O22558, O35346, O43283, O43318, O64768, P08630, P0C8E4, P0CD62, P18106, P18160, P18161, P29317, P32577, P34152, P41239, P41240, P41241, P42680, P42686, P42690, P51813, P80192, P97504, Q00944, Q02779, Q02977, Q03145, Q05397, Q05609, Q0VBZ0

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
EPHA2	up-regulates	EPHA2	phosphorylation
EPHA2	“up-regulates activity”	EPHA2	phosphorylation
SRC	“up-regulates activity”	EPHA2	phosphorylation
HIC1	“down-regulates quantity by repression”	EPHA2	“transcriptional regulation”
MTA1	“down-regulates quantity by repression”	EPHA2	“transcriptional regulation”
regorafenib	“down-regulates activity”	EPHA2	“chemical inhibition”
SLA	“down-regulates quantity by destabilization”	EPHA2	binding
CBL	“down-regulates quantity by destabilization”	EPHA2	binding
EPHB6	“down-regulates activity”	EPHA2	binding
EPHA2	“up-regulates activity”	YES1	phosphorylation
EPHA2	“up-regulates activity”	PLCG1	phosphorylation
AKT1	“up-regulates activity”	EPHA2	phosphorylation
RPS6KA1	“up-regulates activity”	EPHA2	phosphorylation
EPHA2	up-regulates	PIK3R2
EFNA1	up-regulates	EPHA2	binding
EFNA3	up-regulates	EPHA2	binding
EFNA5	up-regulates	EPHA2	binding
EFNA2	up-regulates	EPHA2	binding
EPHA2	up-regulates	SHC1	binding
ACP1	“down-regulates activity”	EPHA2	dephosphorylation
EPHA2	“down-regulates activity”	CLDN4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 189 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
EPHA-mediated growth cone collapse	10	27.8×	4e-10
EPH-ephrin mediated repulsion of cells	14	22.4×	6e-13
Tie2 Signaling	5	21.9×	1e-04
FRS-mediated FGFR3 signaling	5	19.9×	2e-04
Downstream signal transduction	7	19.4×	6e-06
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	18.9×	2e-04
FRS-mediated FGFR4 signaling	5	18.1×	2e-04
SHC1 events in ERBB2 signaling	5	17.4×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	15	31.5×	6e-16
peptidyl-tyrosine phosphorylation	10	25.7×	1e-09
regulation of GTPase activity	6	18.7×	8e-05
cell surface receptor protein tyrosine kinase signaling pathway	14	14.8×	2e-10
protein autophosphorylation	15	13.3×	2e-10
symbiont entry into host cell	5	12.2×	3e-03
negative regulation of MAPK cascade	6	11.0×	1e-03
negative regulation of ERK1 and ERK2 cascade	8	10.5×	9e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — CHOL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	6
Uncertain significance	225
Likely benign	73
Benign	77

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1213988	NM_004431.5(EPHA2):c.2815_2825+9del	Pathogenic
13258	NM_004431.5(EPHA2):c.2842G>T (p.Gly948Trp)	Pathogenic
13259	NM_004431.5(EPHA2):c.2819C>T (p.Thr940Ile)	Pathogenic
1341682	NM_004431.5(EPHA2):c.41G>A (p.Trp14Ter)	Pathogenic
1704213	NM_004431.5(EPHA2):c.2825+2del	Pathogenic
2066016	NM_004431.5(EPHA2):c.988dup (p.Ser330fs)	Pathogenic
2153735	NM_004431.5(EPHA2):c.2426_2427dup (p.Val810fs)	Pathogenic
280146	NM_004431.5(EPHA2):c.2826-9G>A	Pathogenic
3661807	NM_004431.5(EPHA2):c.2903_2904del (p.Gln968fs)	Pathogenic
665755	NM_004431.5(EPHA2):c.759G>A (p.Trp253Ter)	Pathogenic
849920	NM_004431.5(EPHA2):c.2915_2916del (p.Val972fs)	Pathogenic
916205	NM_004431.5(EPHA2):c.2891del (p.Gly964fs)	Pathogenic
1687229	NM_004431.5(EPHA2):c.2353G>A (p.Ala785Thr)	Likely pathogenic
190978	NM_004431.5(EPHA2):c.2007G>T (p.Gln669His)	Likely pathogenic
2633255	NM_004431.5(EPHA2):c.2928_2929del (p.Ile976fs)	Likely pathogenic
4081374	NM_004431.5(EPHA2):c.2475+1G>A	Likely pathogenic
4820296	NM_004431.5(EPHA2):c.2890G>T (p.Gly964Ter)	Likely pathogenic
647226	NM_004431.5(EPHA2):c.1582+1G>A	Likely pathogenic

SpliceAI

2937 predictions. Top by Δscore:

Variant	Effect	Δscore
1:16125316:TGTCG:T	acceptor_gain	1.0000
1:16125317:GTCG:G	acceptor_gain	1.0000
1:16125318:TCG:T	acceptor_gain	1.0000
1:16125319:CG:C	acceptor_gain	1.0000
1:16125319:CGC:C	acceptor_gain	1.0000
1:16125321:C:CC	acceptor_gain	1.0000
1:16125329:C:CT	acceptor_gain	1.0000
1:16125329:C:T	acceptor_gain	1.0000
1:16125330:G:T	acceptor_gain	1.0000
1:16129428:A:AC	donor_gain	1.0000
1:16129429:C:CC	donor_gain	1.0000
1:16129429:CTT:C	donor_loss	1.0000
1:16129429:CTTA:C	donor_gain	1.0000
1:16129430:TTA:T	donor_loss	1.0000
1:16129431:TACT:T	donor_loss	1.0000
1:16129432:A:AC	donor_gain	1.0000
1:16129432:ACT:A	donor_gain	1.0000
1:16129433:C:CA	donor_gain	1.0000
1:16129433:CT:C	donor_gain	1.0000
1:16129433:CTC:C	donor_gain	1.0000
1:16129433:CTCG:C	donor_gain	1.0000
1:16129433:CTCGT:C	donor_gain	1.0000
1:16129585:ACACG:A	acceptor_gain	1.0000
1:16129586:CACG:C	acceptor_gain	1.0000
1:16129586:CACGC:C	acceptor_gain	1.0000
1:16129587:ACG:A	acceptor_gain	1.0000
1:16129588:CG:C	acceptor_gain	1.0000
1:16129588:CGC:C	acceptor_gain	1.0000
1:16129590:C:CC	acceptor_gain	1.0000
1:16130221:CTCA:C	donor_loss	1.0000

AlphaMissense

6404 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:16129525:A:G	W912R	1.000
1:16129525:A:T	W912R	1.000
1:16130314:G:T	R861S	1.000
1:16130335:A:G	W854R	1.000
1:16130335:A:T	W854R	1.000
1:16131727:G:C	N823K	1.000
1:16131727:G:T	N823K	1.000
1:16131774:A:G	W808R	1.000
1:16131774:A:T	W808R	1.000
1:16131785:C:T	G804D	1.000
1:16131786:C:G	G804R	1.000
1:16131790:G:C	S802R	1.000
1:16131790:G:T	S802R	1.000
1:16131792:T:G	S802R	1.000
1:16131793:C:A	W801C	1.000
1:16131793:C:G	W801C	1.000
1:16131795:A:G	W801R	1.000
1:16131795:A:T	W801R	1.000
1:16131801:C:G	D799H	1.000
1:16131802:G:C	S798R	1.000
1:16131802:G:T	S798R	1.000
1:16131803:C:A	S798I	1.000
1:16131804:T:G	S798R	1.000
1:16131814:G:C	F794L	1.000
1:16131814:G:T	F794L	1.000
1:16131815:A:G	F794S	1.000
1:16131816:A:G	F794L	1.000
1:16131847:C:A	W783C	1.000
1:16131847:C:G	W783C	1.000
1:16131848:C:G	W783S	1.000

dbSNP variants (sampled 300 via entrez): RS1000035403 (1:16143481 C>T), RS1000067504 (1:16137220 A>G), RS1000181733 (1:16143992 T>A,C), RS1000185956 (1:16137547 G>A,T), RS1000430607 (1:16132607 G>A,T), RS1000639974 (1:16126518 C>T), RS1000686130 (1:16126471 A>G), RS1000741113 (1:16126277 A>G), RS1000753669 (1:16153084 G>A,T), RS1000994588 (1:16143963 G>A,C), RS1001015683 (1:16147699 T>C), RS1001043173 (1:16132040 T>G), RS1001156295 (1:16142168 C>T), RS1001384762 (1:16147509 T>A,C), RS1001503686 (1:16153843 C>T)

Disease associations

OMIM: gene MIM:176946 | disease phenotypes: MIM:116600, MIM:156000, MIM:116200

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 6 multiple types	Definitive	Autosomal dominant
eye disorder	Strong	Autosomal recessive
early-onset non-syndromic cataract	Moderate	Autosomal recessive
early-onset posterior subcapsular cataract	Supportive	Autosomal dominant
early-onset nuclear cataract	Supportive	Autosomal dominant
early-onset posterior polar cataract	Supportive	Autosomal dominant
total early-onset cataract	Supportive	Autosomal dominant

Mondo (10): cataract 6 multiple types (MONDO:0007288), Meniere disease (MONDO:0007972), cataract (MONDO:0005129), aniridia (MONDO:0019172), early-onset non-syndromic cataract (MONDO:0011060), early-onset posterior subcapsular cataract (MONDO:0018610), early-onset nuclear cataract (MONDO:0020376), early-onset posterior polar cataract (MONDO:0020378), total early-onset cataract (MONDO:0021548), eye disorder (MONDO:0005328)

Orphanet (3): Early onset non-syndromic cataract (Orphanet:91492), NON RARE IN EUROPE: Menière disease (Orphanet:45360), OBSOLETE: Aniridia (Orphanet:77)

HPO phenotypes

5 total (6 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0001115	Posterior polar cataract
HP:0001139	Chorioretinal scalloped atrophy
HP:0000518	Cataract

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001277_7	Liver enzyme levels (gamma-glutamyl transferase)	3.000000e-19
GCST006019_43	Gamma glutamyl transferase levels	1.000000e-36
GCST006585_1704	Blood protein levels	2.000000e-10
GCST011349_33	Gamma glutamyl transferase levels	7.000000e-44
GCST011352_15	Alanine aminotransferase levels	5.000000e-09
GCST90011898_30	Alanine aminotransferase levels	1.000000e-54
GCST90011899_178	Aspartate aminotransferase levels	1.000000e-39
GCST90013663_101	Alanine aminotransferase levels	2.000000e-66
GCST90013664_61	Aspartate aminotransferase levels	8.000000e-45

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D015783	Aniridia	C11.250.060; C11.270.060; C11.941.375.060; C16.131.384.079; C16.320.290.078
D002386	Cataract	C11.510.245
D005128	Eye Diseases	C11
D008575	Meniere Disease	C09.218.568.217.500
C563333	Cataract, Age-Related Nuclear (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2068 (SINGLE PROTEIN), CHEMBL2363043 (PROTEIN FAMILY), CHEMBL5291975 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

50 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 340,243 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3544983	TESEVATINIB	3	2,819
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL119385	NEFLAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL2029988	CEP-32496	2
CHEMBL206834	BAFETINIB	2
CHEMBL2408045	SAPITINIB	2
CHEMBL253969	OSI-632	2
CHEMBL3039525	GOLVATINIB	2
CHEMBL3991932	PEXMETINIB	2

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type XIII RTKs: Ephrin receptor family

Most potent curated ligand interactions (8 total), top 8:

Ligand	Action	Affinity	Parameter
compound 8h [PMID: 21561767]	Inhibition	9.22	pIC50
compound 66 [PMID: 19788238]	Inhibition	8.64	pIC50
dorsomorphin	Inhibition	7.96	pIC50
NVP-BHG712	Inhibition	7.89	pKd
NVP-BHG712 isomer	Inhibition	7.14	pKd
DDR1/2 inhibitor 5n	Inhibition	6.59	pKd
compound 20 [PMID: 23489211]	Inhibition	5.66	pIC50
cilofexor	Inhibition	5.07	pKi

Binding affinities (BindingDB)

288 measured of 328 human assays (329 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
4-(9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-ylamino)-2-methoxybenzoic acid	IC50	0.6 nM	US-9346787: Piperidine compound or salt thereof
8-(2-Methoxyphenyl)-1-methyl-7-(2’-methyl-5’-hydroxyphenyl-1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione	IC50	1 nM
3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	IC50	1.3 nM
Staurosporine	KD	1.7 nM
FORETINIB	IC50	1.9 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile	IC50	2 nM
US12486270, Compound @1	KD	3 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	IC50	4 nM
4-methyl-3-[(1-methyl-6-pyrimidin-5-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	KD	4 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
LDN-211904	IC50	4.1 nM
Danusertib	IC50	4.4 nM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	IC50	4.8 nM
6-(2,6-dichlorophenyl)-8-methyl-2-{[3-(methylsulfanyl)phenyl]amino}-7H,8H-pyrido[2,3-d]pyrimidin-7-one	IC50	7.9 nM
tert-butyl 4-amino-3-[2-[2-methyl-5-[[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]phenyl]ethynyl]pyrazolo[3,4-d]pyrimidine-1-carboxylate	IC50	11 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
E-7050	IC50	13 nM
4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(5-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	IC50	17 nM
N-[3-[2-[4-amino-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	IC50	18 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
US12486270, Compound @6	KD	24 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
BMS-354825	KD	27 nM
CEP-32496	IC50	28 nM
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	IC50	33 nM
US12486270, Compound @9	KD	34 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
US12486270, Compound NVP-Iso	KD	73 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
US12486270, Compound @4	KD	86 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
US12486270, Compound @13	KD	97 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
US12486270, Compound @2	KD	132 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
US12486270, Compound @12	KD	132 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
US12486270, Compound @10	KD	191 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
US12486270, Compound @5	KD	225 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
Tivozanib	KD	259 nM
4-(3-chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)pyridin-2-yl]methyl]cyclohexane-1-carboxylic acid	KD	265 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
AZD0530	KD	338 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
US12486270, Compound @11	KD	443 nM	US-12486270: Receptor tyrosine kinase inhibitors for treatment of protein kinase modulation-responsive disease or disorder
7-[[(3aS,6aR)-2-methyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-yl]methoxy]-N-(3,4-dichloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine	KD	458 nM
2-[(1R)-1-[(6-amino-5-chloropyrimidine-4-carbonyl)amino]ethyl]-N-[5-chloro-4-(trifluoromethyl)pyridin-2-yl]-1,3-thiazole-5-carboxamide	KD	484 nM
N-(3,4-dichloro-2-fluorophenyl)-7- ({[(3aR,5r,6aS)-2-(1- methylethyl)octahydrocyclopenta[c]pyrrol-5- yl]methyl}oxy)-6-(methyloxy)quinazolin-4- amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(3,4-dichloro-2-fluorophenyl)-7- ({[(3aR,5s,6aS)-2- methyloctahydrocyclopenta[c]pyrrol-5- yl]methyl}oxy)-6-(methyloxy)quinazolin-4- amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(4-bromo-3-chloro-2-fluorophenyl)-7- ({[(3aR,5r,6aS)-2- ethyloctahydrocyclopenta[c]pyrrol-5- yl]methyl}oxy)-6-(methyloxy)quinazolin-4- amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(4-bromo-3-chloro-2-fluorophenyl)-6- (methyloxy)-7-({[(3aR,5r,6aS)-2-(2- methylpropyl)octahydrocyclopenta[c]pyrrol-5- yl]methyl}oxy)quinazolin-4-amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(4-bromo-2,3-dichlorophenyl)-7- {[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4- c][1,4]oxazin-3-ylmethyl]oxy}-6- (methyloxy)quinazolin-4-amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(4,5-dichloro-2-fluorophenyl)-7-{[(3R,9aS)- hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin- 3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4- amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(4-bromo-5-chloro-2-fluorophenyl)-7- {[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4- c][1,4]oxazin-3-ylmethyl]oxy}-6- (methyloxy)quinazolin-4-amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(3-chloro-2,4-difluorophenyl)-7-{[(3R,9aS)- hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin- 3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4- amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(4-bromo-5-chloro-2-fluorophenyl)-7- {[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4- c][1,4]oxazin-3-ylmethyl]oxy}-6- (methyloxy)quinazolin-4-amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(3,4-dichloro-2-fluorophenyl)-7-{[(3R,9aS)- hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin- 3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4- amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors
N-(4-bromo-3-chloro-2-fluorophenyl)-7- {[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4- c][1,4]oxazin-3-ylmethyl]oxy}-6- (methyloxy)quinazolin-4-amine	IC50	525 nM	US-9796704: Substituted quinazolines as receptor-type kinase inhibitors

ChEMBL bioactivities

870 potent at pChembl≥5 of 1001 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.27	Ki	0.54	nM	CHEMBL4642167
9.22	IC50	0.6	nM	CHEMBL1784637
9.07	Kd	0.85	nM	DASATINIB
9.00	Kd	1	nM	CHEMBL400402
8.82	Ki	1.5	nM	CHEMBL4649686
8.70	Ki	2	nM	CHEMBL4641389
8.64	IC50	2.3	nM	CHEMBL566515
8.55	Ki	2.83	nM	CHEMBL4642849
8.55	Ki	2.8	nM	CHEMBL4634220
8.52	IC50	3	nM	CHEMBL3752910
8.51	Ki	3.1	nM	CHEMBL4634551
8.50	Ki	3.162	nM	CHEMBL1994938
8.49	Kd	3.26	nM	DASATINIB ANHYDROUS
8.48	IC50	3.3	nM	CHEMBL3752910
8.44	Kd	3.6	nM	FORETINIB
8.42	Kd	3.8	nM	CHEMBL386051
8.40	Ki	3.981	nM	DASATINIB
8.35	IC50	4.5	nM	DASATINIB ANHYDROUS
8.32	Ki	4.8	nM	CHEMBL4636597
8.29	Ki	5.07	nM	CHEMBL4637644
8.28	Ki	5.2	nM	CHEMBL4643355
8.28	IC50	5.3	nM	CHEMBL5180264
8.26	Ki	5.5	nM	CHEMBL4634880
8.24	Ki	5.78	nM	CHEMBL4640044
8.24	Ki	5.8	nM	CHEMBL4648601
8.24	Ki	5.74	nM	CHEMBL4636032
8.23	Kd	5.9	nM	DASATINIB ANHYDROUS
8.23	Kd	5.929	nM	DASATINIB ANHYDROUS
8.22	Kd	6	nM	DASATINIB
8.20	Ki	6.31	nM	CHEMBL1993661
8.19	IC50	6.5	nM	CHEMBL5180519
8.17	Ki	6.8	nM	CHEMBL4643893
8.12	IC50	7.6	nM	CHEMBL5178807
8.10	Kd	8	nM	CHEMBL249097
8.05	Ki	9	nM	CHEMBL4637500
8.03	IC50	9.3	nM	CHEMBL5177810
8.00	Ki	10	nM	CHEMBL1982476
7.97	IC50	10.8	nM	CHEMBL5192123
7.96	IC50	11	nM	CHEMBL556140
7.96	IC50	11	nM	DORSOMORPHIN
7.96	IC50	11	nM	CHEMBL1688861
7.90	Ki	12.59	nM	CHEMBL1974664
7.90	Ki	12.59	nM	CHEMBL1988717
7.89	Ki	12.9	nM	CHEMBL4643498
7.89	IC50	13	nM	CHEMBL3752910
7.89	IC50	12.82	nM	CHEMBL5423601
7.89	Kd	13	nM	CHEMBL3752910
7.89	IC50	13	nM	CHEMBL5910397
7.87	IC50	13.5	nM	CHEMBL4466555
7.85	Kd	14	nM	CEP-32496

PubChem BioAssay actives

322 with measured affinity, of 1807 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
(3S)-4-[[(2S)-1-[2-[[(1R,7S,10S,13S,16S,22S,28R,40R,46S,49S,58S,61S,64S)-13-(2-amino-2-oxoethyl)-28-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-61-benzyl-16-(3-carbamimidamidopropyl)-49,64-bis(1H-indol-3-ylmethyl)-2,8,11,14,17,23,26,41,47,50,53,59,62,65-tetradecaoxo-10-propan-2-yl-30,38,68-trithia-3,9,12,15,18,24,27,42,48,51,54,60,63,66-tetradecazaheptacyclo[32.32.3.132,36.03,7.018,22.042,46.054,58]heptaconta-32,34,36(70)-trien-40-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0005	uM
5-[2-[5-[[4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-3-(trifluoromethyl)phenyl]carbamoyl]-2-methylphenyl]ethynyl]-N,1-dimethylimidazole-2-carboxamide	601671: Inhibition of human EPHA2 using poly[Glu:Tyr] peptide substrate by Hotspot assay	ic50	0.0006	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435908: Binding constant for EPHA2 kinase domain	kd	0.0008	uM
Dasatinib	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0008	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1424988: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0010	uM
7-(5-hydroxy-2-methylphenyl)-6-(2-methoxyphenyl)-4-methylpurino[7,8-a]imidazole-1,3-dione	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0010	uM
Ponatinib	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0013	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-42-benzhydryl-57-[(1R)-1-hydroxyethyl]-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0015	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0019	uM
(3S)-4-[[(9R,13S,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,51R,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-57-(4-carbamimidamidobutyl)-51-(carboxymethyl)-13-hydroxy-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-6-carbamimidamidohexanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0020	uM
Bosutinib	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0020	uM
(3S)-4-[[(9R,13R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-13-hydroxy-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0028	uM
(3R)-4-[[(2S)-1-[(2S)-2-[[(1R,7S,10S,13S,16S,22S,25R,28S,40S,46S,55S,58S)-13-(2-amino-2-oxoethyl)-55-benzyl-10-tert-butyl-16-(4-carbamimidamidobutyl)-28-carbamoyl-25-(carboxymethyl)-43,43,52,52-tetramethyl-46,58-bis(naphthalen-1-ylmethyl)-2,8,11,14,17,23,26,41,44,47,50,53,56,59-tetradecaoxo-30,38,62-trithia-3,9,12,15,18,24,27,42,45,48,51,54,57,60-tetradecazapentacyclo[32.26.3.132,36.03,7.018,22]tetrahexaconta-32,34,36(64)-trien-40-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-[[(2S)-2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[3-aminopropanoyl(methyl)amino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0028	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,51R,54S,60R)-24-(2-amino-2-oxoethyl)-57-(4-carbamimidamidobutyl)-60-carbamoyl-51-(carboxymethyl)-54-(2,3-dihydro-1H-inden-1-ylmethyl)-42-(1H-imidazol-4-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[3-[4-[[3-[[(2R)-1-[[(1R,2S,3R,5R,6R,16E,18E,20S,21R)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl]oxy]-1-oxopropan-2-yl]-methylamino]-3-oxopropyl]disulfanyl]butanoylamino]propanoyl-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]amino]propanoyl]amino]pentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0031	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147740: Inhibition of Nano Luc-fused full length C-terminal EPHA2 (unknown origin) expressed in HEK293T cells using NanoGlo as substrate incubated for 2 hrs in presence of tracer by NanoBRET assay	ic50	0.0033	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624951: Binding constant for EPHA2 kinase domain	kd	0.0038	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0040	uM
N-(2-chlorophenyl)-6-piperidin-4-ylimidazo[1,2-a]pyridine-3-carboxamide	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0041	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0044	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,51R,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-51-methyl-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0048	uM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0048	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,51R,54S,60R)-24-(2-amino-2-oxoethyl)-57-(4-carbamimidamidobutyl)-60-carbamoyl-51-(carboxymethyl)-54-(2,3-dihydro-1H-inden-1-ylmethyl)-42-(1H-imidazol-4-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-5-carbamimidamido-2-[[(2S)-2-[[2-[methyl-[2-[methyl-[2-[methyl-[2-[methyl-[2-[methyl-[2-[methyl-[2-[methyl-[2-[methyl-[2-[methyl-[2-[methyl-[3-[2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetyl]oxypropanoyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]propanoyl]amino]pentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0051	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-57-(4-carbamimidamidobutyl)-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0052	uM
(3S)-4-[[(2S)-1-[[(1S)-2-[(2S)-2-[[(2S)-1-[[(2S)-1-[(2S)-2-[[4-[[(5S)-6-amino-5-[4-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-2-cyclohexylacetyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]butanoylamino]-6-oxohexyl]amino]-4-oxobutyl]carbamoyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	1848891: Inhibition of EPHA2 (unknown origin) by DELFIA assay	ic50	0.0053	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-18-(cyclobutylmethyl)-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-33,39-bis(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0055	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,51R,54S,60R)-24-(2-amino-2-oxoethyl)-57-(4-carbamimidamidobutyl)-60-carbamoyl-51-(carboxymethyl)-54-(2,3-dihydro-1H-inden-1-ylmethyl)-42-(1H-imidazol-4-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[3-aminopropanoyl(methyl)amino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0057	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2R)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0058	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0058	uM
(3S)-4-[[(2S)-1-[[(1S)-2-[(2S)-2-[[(2S)-1-[[(2S)-1-[(2S)-2-[[2-[[(5S)-6-amino-5-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-2-cyclohexylacetyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-6-oxohexyl]amino]-2-oxoethyl]carbamoyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	1848891: Inhibition of EPHA2 (unknown origin) by DELFIA assay	ic50	0.0065	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,51S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-51-(carboxymethyl)-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0068	uM
(3S)-4-[[(2S)-1-[[(1S)-2-[(2S)-2-[[(2S)-1-[[(2S)-1-[(2S)-2-[[3-[[(5S)-6-amino-5-[3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]propanoyl]amino]-2-cyclohexylacetyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]propanoylamino]-6-oxohexyl]amino]-3-oxopropyl]carbamoyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	1848891: Inhibition of EPHA2 (unknown origin) by DELFIA assay	ic50	0.0076	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389077: Binding affinity to human EPHA2	kd	0.0080	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-6-carbamimidamidohexanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0090	uM
(3S)-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-4-[[(2S)-1-[[(1S)-2-[(2S)-2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1848891: Inhibition of EPHA2 (unknown origin) by DELFIA assay	ic50	0.0093	uM
(3S)-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-4-[[(2S)-1-[[(1S)-2-[(2S)-2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1848891: Inhibition of EPHA2 (unknown origin) by DELFIA assay	ic50	0.0108	uM
6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine	527865: Inhibition of EphA2 by Hot Spot filtration binding assay	ic50	0.0110	uM
N-[5-[[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]-2-methylphenyl]-5-thiophen-2-ylpyridine-3-carboxamide	2098570: Inhibition of human EphA2 by FRET assay	ic50	0.0110	uM
3-(2-aminopropan-2-yl)-N-[(2R)-7-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalen-2-yl]-5-(trifluoromethyl)benzamide	586444: Inhibition of EPHA2	ic50	0.0110	uM
N-[3-cyclopropyl-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-5-methyl-18-oxo-9-oxa-17,23,25,26-tetrazatetracyclo[17.5.2.14,8.022,25]heptacosa-1(24),4,6,8(27),19(26),20,22-heptaen-2-yne-6-carboxamide	2014044: Inhibition of EphA2 (unknown origin)	ic50	0.0128	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-42-(2-carboxyethyl)-57-[(1R)-1-hydroxyethyl]-54-(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0129	uM
1-N’-[2-fluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0130	uM
N-[4-chloro-3-(trifluoromethyl)phenyl]-4-methyl-3-[[1-(7H-purin-6-yl)cyclopropanecarbonyl]amino]benzamide	1534563: Inhibition of human EPHA2 using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0135	uM
1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea	660895: Inhibition of EPHA2 in human HEK293 cells after 1 hr by competition binding assay	kd	0.0140	uM
(3S)-4-[[(9R,15S,18S,21S,24S,30S,33S,36R,39S,42S,48S,54S,57S,60R)-24-(2-amino-2-oxoethyl)-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-57-[(1R)-1-hydroxyethyl]-42-(1H-imidazol-4-ylmethyl)-54-(1H-indol-3-ylmethyl)-33,39-bis(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,65,68-heptadecaoxo-18-(2-phenylethyl)-21-propan-2-yl-7,62,71-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.011,15.026,30.044,48]triheptacontan-9-yl]amino]-3-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	1648457: Binding affinity to 6x-His-tagged human EphA2 ecto-domain residues (Lys27 to Asn529 residues) expressed in HEK293 cells incubated for 60 mins by fluorescence polarization assay	ki	0.0145	uM
(3S)-4-[[(2S)-1-[[(1S)-2-[(2S)-2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-4-methyl-2-[[(2S)-3-naphthalen-2-yl-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]pentanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid	1848891: Inhibition of EPHA2 (unknown origin) by DELFIA assay	ic50	0.0150	uM
3-[2-(4-amino-1-ethylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1206228: Inhibition of human EphA2	ic50	0.0160	uM
4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(5-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	1802324: HotSpot Kinase Activity Assay from Article 10.1021/acschembio.6b00709: “Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.”	ic50	0.0170	uM
(3S)-3-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-aminophenyl)-2-[(2-piperazin-1-ylacetyl)amino]propanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-3-[4-[2-(trifluoromethyl)phenyl]phenyl]propanoyl]pyrrolidine-2-carbonyl]amino]-4-[[(2S)-1-[[(1S)-2-[(2S)-2-[[(2S)-1-[[(2S)-5-carbamimidamido-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-cyclohexyl-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1848890: Inhibition of EPHA2 (unknown origin) by ITC	kd	0.0180	uM
3-[(dimethylamino)methyl]-N-[(2R)-7-[(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-4-yl)oxy]-1,2,3,4-tetrahydronaphthalen-2-yl]-5-(trifluoromethyl)benzamide	586444: Inhibition of EPHA2	ic50	0.0180	uM
1-(3,3-dimethylbutyl)-3-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea	1226896: Competitive binding affinity to EphA2 in human A375 cells after 15 mins in presence of ATP analogue	ic50	0.0200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, affects cotreatment, increases expression, increases methylation	6
sodium arsenite	decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
Arsenic	affects methylation, increases abundance, increases expression	3
Lithocholic Acid	decreases activity, decreases phosphorylation, decreases reaction, increases phosphorylation, affects binding	3
Silver	increases expression	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
bisphenol A	decreases expression	2
sodium arsenate	decreases expression, increases abundance, increases expression	2
ponatinib	decreases activity	2
(+)-JQ1 compound	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Doxorubicin	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Quercetin	increases expression, decreases phosphorylation	2
Valproic Acid	affects expression	2
1-Methyl-4-phenylpyridinium	increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
2-methoxy-5-((3,4,5-trimethosyphenyl)seleninyl)phenol	decreases expression	1
tetrabromobisphenol S	decreases expression	1
propionaldehyde	increases expression	1
cholanic acid	affects binding, decreases activity, decreases reaction, increases activity, increases phosphorylation	1
deoxynivalenol	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1

ChEMBL screening assays

567 unique, capped per target: 565 binding, 1 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011753	Binding	Binding affinity to EPHA2 at 10 uM	Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK? — Bioorg Med Chem Lett
CHEMBL1963791	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: EPHA2	PubChem BioAssay data set
CHEMBL4313081	ADMET	Inhibition of human EPHA2 using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA relative to control	Discovery and Development of a Series of Pyrazolo[3,4-d]pyridazinone Compounds as the Novel Covalent Fibroblast Growth Factor Receptor Inhibitors by the Rational Drug Design. — J Med Chem

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1DG	Abcam HCT 116 EPHA2 KO	Cancer cell line	Male
CVCL_B1RC	Abcam HeLa EPHA2 KO	Cancer cell line	Female
CVCL_D7PE	Ubigene A-549 EPHA2 KO	Cancer cell line	Male
CVCL_D8KW	Ubigene HCT 116 EPHA2 KO	Cancer cell line	Male
CVCL_D9EC	Ubigene HEK293 EPHA2 KO	Transformed cell line	Female
CVCL_E0CN	Ubigene HeLa EPHA2 KO	Cancer cell line	Female
CVCL_HG05	HCT 116 EphA2 KO Tet-inducible	Cancer cell line	Male
CVCL_SM12	HAP1 EPHA2 (-)	Cancer cell line	Male
CVCL_WR52	VR-ALL	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00911924	PHASE4	COMPLETED	A Prospective, Unmasked Evaluation of the iStent in Patients With Primary Open-Angle Glaucoma
NCT00913029	PHASE4	COMPLETED	Evaluation of the iStent Versus Two Ocular Hypotensive Agents in Patients With Primary Open-angle Glaucoma (POAG)
NCT00957190	PHASE4	COMPLETED	The DIOXXACT Trial(Diurnal IOP and OBF Xalatan vs Xalatan And Cosopt Trial)
NCT03148132	PHASE4	COMPLETED	VEGF Concentrations After Intravitreal Bevacizumab vs Ranibizumab as a Treatment for Type 1 ROP
NCT07266948	PHASE4	RECRUITING	Impact of TRYPTYR on a Patient’s Quality of Life and Ability to Perform Work
NCT07267299	PHASE4	NOT_YET_RECRUITING	Switching From Restasis to TRYPTYR
NCT07267481	PHASE4	NOT_YET_RECRUITING	Switching From Xiidra to TRYPTYR
NCT07434635	PHASE4	RECRUITING	APPRAISE: Assessment of Pain and Posterior Synechiae Reduction With Atropine, an Investigation of Post-Surgical Eyes
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00312299	PHASE4	COMPLETED	Posterior Capsule Opacification Study
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00347243	PHASE4	COMPLETED	Wavefront Analisys and Contrast Sensitivity of Spherical and Aspherical Intraocular Lenses
NCT00347503	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients
NCT00348244	PHASE4	COMPLETED	Ketorolac vs. Steroid in the Prevention of CME
NCT00348270	PHASE4	COMPLETED	Comparison of the Quality of Vision Provided by AMO Tecnis Z9000 and Alcon Laboratories MA60 Acrysof Posterior Chamber Intraocular Lenses
NCT00348582	PHASE4	COMPLETED	Acular LS vs. Nevanac in Post op Inflammation Following Cataract Surgery
NCT00348621	PHASE4	COMPLETED	A Study of Interventions to Reduce Disability From Visual Loss in Nursing Home Residents
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00355446	PHASE4	COMPLETED	Bioavailability of Bimatoprost Ophthalmic Solution in Human Aqueous.
NCT00386438	PHASE4	COMPLETED	Efficacy of Honan Balloon in Intraocular Pressure Reduction Before Phacoemulsification
NCT00392275	PHASE4	COMPLETED	Penetrance of Third Generation Fluoroquinolones in Eyes With Functioning Filtering Blebs
NCT00428363	PHASE4	COMPLETED	Effect of Optic Edge Design in a Silicone Intraocular Lens on Posterior Capsule Opacification
NCT00449267	PHASE4	COMPLETED	Aurolab Hydrophobic Foldable Intraocular Lens Study
NCT00459303	PHASE4	COMPLETED	Comparison of Functional Vision Provided by AMO Tecnis Z9000 and Alcon SA60AT Acrysof
NCT00469690	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients: Trough Drug Effects
NCT00576485	PHASE4	COMPLETED	Spherical Aberration and Contrast Sensitivity in IOLs
NCT00612729	PHASE4	COMPLETED	Light Filters in Intraocular Lenses (IOLs) and Its Influence on Colour and Contrast Vision.
NCT00612781	PHASE4	COMPLETED	Yellow Versus White Study
NCT00630019	PHASE4	COMPLETED	Ocular Tissue Levels of 1.5% Levofloxacin Ophthalmic Solution Compared to an Active Comparator
NCT00673803	PHASE4	COMPLETED	Influence of Two Different Preloaded Intraocular Lens (IOLs) on Posterior Capsule Opacification
NCT00684138	PHASE4	COMPLETED	ACRYSOF® ReSTOR® Aspheric +3.0 D Add Power Intraocular Lens (IOL)
NCT00698724	PHASE4	COMPLETED	Comparing Optical Coherence Tomography (OCT) and Visual Acuity Outcomes in Subjects Undergoing Cataract Surgery, Who Receive Xibrom Ophthalmic Solution and Standard Presurgical Care vs. Xibrom Ophthalmic Solution Plus Prednisolone Acetate 1% and Standard Presurgical Care
NCT00710905	PHASE4	TERMINATED	Visual Function With Contralateral AcrySof® ReSTOR® Aspheric SN6AD1 and SN6AD3
NCT00710931	PHASE4	COMPLETED	Visual Function With Bilateral AcrySof® ReSTOR® Aspheric SN6AD1
NCT00711347	PHASE4	COMPLETED	Intraoperative Floppy Iris Syndrome
NCT00712244	PHASE4	COMPLETED	DisCoVisc Versus DuoVisc, Healon5 and AmVisc Plus
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction