AXL

Summary

AXL (AXL receptor tyrosine kinase, HGNC:905) is a protein-coding gene on chromosome 19q13.2, encoding Tyrosine-protein kinase receptor UFO (P30530). Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation.

The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. It transduces signals from the extracellular matrix into the cytoplasm by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. The encoded protein acts as a host cell receptor for multiple viruses, including Marburg, Ebola and Lassa viruses and is a candidate receptor for the SARS-CoV2 virus.

Source: NCBI Gene 558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Kallmann syndrome (Limited, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 303 total — 1 likely-pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes — 59 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:905
Approved symbol	AXL
Name	AXL receptor tyrosine kinase
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	UFO, JTK11, Tyro7, ARK
Ensembl gene	ENSG00000167601
Ensembl biotype	protein_coding
OMIM	109135
Entrez	558

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000301178, ENST00000359092, ENST00000593513, ENST00000594880, ENST00000599659, ENST00000898512, ENST00000915596, ENST00000915597, ENST00000915598, ENST00000915599, ENST00000915600

RefSeq mRNA: 3 — MANE Select: NM_021913 NM_001278599, NM_001699, NM_021913

CCDS: CCDS12574, CCDS12575, CCDS62677

Canonical transcript exons

ENST00000301178 — 20 exons

Exon	Start	End
ENSE00001114774	41243616	41243707
ENSE00001114775	41256452	41256611
ENSE00001114780	41248514	41248609
ENSE00001114784	41253599	41253708
ENSE00001114792	41252846	41252967
ENSE00001114794	41257493	41257629
ENSE00001114797	41248743	41248820
ENSE00001114801	41252351	41252443
ENSE00001361520	41259553	41261766
ENSE00001361543	41219223	41219477
ENSE00003518744	41237944	41238154
ENSE00003533736	41239164	41239314
ENSE00003547478	41221146	41221246
ENSE00003548162	41231183	41231298
ENSE00003565990	41221880	41222056
ENSE00003576856	41242883	41243015
ENSE00003638151	41239694	41239720
ENSE00003650369	41220636	41220858
ENSE00003657173	41230967	41231047
ENSE00003676850	41238470	41238609

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.8572 / max 810.3034, expressed in 1417 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175931	43.2852	1374
175930	6.2763	1231
175933	4.2395	955
175932	3.9721	919
208821	1.1640	591
175950	0.6917	362
175946	0.6666	382
175951	0.6013	192
175947	0.4623	270
208822	0.3925	227

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	99.00	gold quality
saphenous vein	UBERON:0007318	98.27	gold quality
stromal cell of endometrium	CL:0002255	97.81	gold quality
cartilage tissue	UBERON:0002418	97.39	gold quality
vein	UBERON:0001638	97.24	gold quality
layer of synovial tissue	UBERON:0007616	97.24	gold quality
urethra	UBERON:0000057	97.22	gold quality
pericardium	UBERON:0002407	96.57	gold quality
decidua	UBERON:0002450	96.21	gold quality
popliteal artery	UBERON:0002250	96.02	gold quality
tibial artery	UBERON:0007610	96.01	gold quality
tendon of biceps brachii	UBERON:0008188	95.61	gold quality
right coronary artery	UBERON:0001625	95.26	gold quality
aorta	UBERON:0000947	94.83	gold quality
coronary artery	UBERON:0001621	94.70	gold quality
left coronary artery	UBERON:0001626	94.61	gold quality
descending thoracic aorta	UBERON:0002345	94.55	gold quality
vena cava	UBERON:0004087	94.25	gold quality
mucosa of stomach	UBERON:0001199	94.23	gold quality
blood vessel layer	UBERON:0004797	94.02	gold quality
nipple	UBERON:0002030	93.51	gold quality
tendon	UBERON:0000043	93.32	gold quality
smooth muscle tissue	UBERON:0001135	93.32	gold quality
thoracic aorta	UBERON:0001515	93.25	gold quality
penis	UBERON:0000989	93.24	gold quality
endocervix	UBERON:0000458	93.22	gold quality
skin of hip	UBERON:0001554	93.20	gold quality
ascending aorta	UBERON:0001496	93.16	gold quality
calcaneal tendon	UBERON:0003701	92.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.52	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	19843.77
E-GEOD-86618	yes	2971.95
E-CURD-11	yes	2485.90
E-GEOD-109979	yes	1509.26
E-MTAB-7008	yes	666.47
E-MTAB-8205	yes	305.96
E-MTAB-8142	yes	104.41
E-MTAB-6701	yes	42.51
E-GEOD-135922	yes	33.51
E-MTAB-6678	yes	26.78
E-MTAB-10553	yes	24.78
E-HCAD-9	yes	15.66
E-GEOD-81547	yes	9.73
E-CURD-112	yes	5.74
E-MTAB-7381	no	1216.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, EZH2, FOXC1, GAS6, KLF9, MEF2B, MZF1, NFKBIA, PAX3, SP1, SP3, TFAP2A, TP53, TP63

miRNA regulators (miRDB)

114 targeting AXL, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-574-5P	100.00	66.01	989
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431

Literature-anchored findings (GeneRIF, showing 40)

• Data suggest that Gas6 and Axl signal transduction is aberrantly stimulated in endometriotic endometria, and is plausibly related to its growth potential. (PMID:12029073)
• Acidification prevents vascular endothelial cell apoptosis by Axl activation (PMID:12364394)
• Interaction of Axl receptor tyrosine kinase with C1-TEN (C1 domain-containing phosphatase and TENsin homologue). (PMID:12470648)
• Axl and Gas6 expression might be involved in childhood thyroid tumorigenesis around Chernobyl. (PMID:12490074)
• Gas6 receptors were not upregulated in any of the allograft groups, except for the Axl receptor, which increased only in acute tubular necrosis. (PMID:12768229)
• We found that there was a significant increase in the steady-state levels of Axl mRNA in the RCC compared with the normal kidney pair (PMID:14565870)
• Axl pathway mediates increased survival of uveal melanoma cells (PMID:14729616)
• GAS6/Axl signaling is involved in human renal disease. (PMID:14750094)
• Gas6-Axl interactions can rescue endothelial cells from apoptosis. (PMID:15130893)
• Axl stimulation by GAS6 results in inhibition of the ligand-dependent activation of vascular endothelial growth factor (VEGF) receptor 2 and the consequent activation of an angiogenic program in vascular endothelial cells (PMID:15507525)
• Axl overexpression and activation by Gas6 could be involved in progression of prostate neoplastic disease (PMID:15605394)
• Axl, Sky and Mer are Gas6 receptors that enhance platelet activation and regulate thrombotic responses (PMID:15733062)
• This report demonstrates that Gas6-induced downregulation of Axl is blocked by inhibitors of endocytosis and lysosomal degradation, but not by inhibitors of proteosomal activity. (PMID:15958209)
• Results identify and characterise a novel interaction between RanBPM and the related receptor tyrosine kinases, Axl and Sky. (PMID:15964779)
• Over-expression of axl is associated with lung adenocarcinoma and with tumor progression (PMID:16354588)
• The crystal structure at 3.3 A resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry. (PMID:16362042)
• Suppression of Gas6 using small interfering RNA and the Axl-extracellular domain abolished the preventive effect of statins on Pi-induced apoptosis and calcification. (PMID:16556867)
• Identification, functional manipulation, in vitro and in vivo validation, and preclinical therapeutic inhibition of a target receptor tyrosine kinase mediating glioma growth and invasion. (PMID:16585512)
• Overexpression of the Axl tyrosine kinase receptor is associated with the development of squamous cell skin cancers (PMID:16641895)
• These results implicate Twist proteins in regulation of TNFalpha production by antiinflammatory factors and pathways, and provide a mechanism by which type I IFNs and Axl receptors suppress inflammatory cytokine production. (PMID:16831897)
• Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family-Axl, Dtk, and Mer-in cell entry of filoviruses. (PMID:17005688)
• Signaling through Axl inhibits vascular calcification in vitro. (PMID:17255529)
• Axl and Gas6 are frequently overexpressed in both glioma and vascular cells and predict poor prognosis in GBM patients. (PMID:18172262)
• coordination of ERK signaling and NF-kappaB and Brg-1 activation are indispensable to regulation of Axl-dependent MMP-9 gene transcription (PMID:18345028)
• Axl gene expression in cancer cells is constitutively driven by Sp1/Sp3 bound to five core promoter motifs, and restricted by methylation within/around Sp-binding sites. (PMID:18522535)
• Possible strategies for targeted inhibition of the TAM family in the treatment of human cancer. (PMID:18620092)
• Activation of Axl may be a protective mechanism against hypertonicity-induced apoptosis. Our results identify Axl as an important element of osmotic stress-induced signalling. (PMID:18673450)
• The Axl/Gas6 pathway contributes to normal human NK-cell development via an effect on the master regulatory transcription factor T-BET. (PMID:18840707)
• In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. (PMID:19055724)
• there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin (PMID:19541935)
• Data show that Axl and Gas6 expression in RCC are associated with tumor advancement and patient survival. (PMID:19567592)
• Data demonstrates that Axl plays multiple roles in tumorigenesis. (PMID:19633687)
• Results identify several receptor tyrosine kinases, including Axl, that can bind to the ACK1/MIG6 homology region. (PMID:19815557)
• Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, have a role in progression of clear cell RCC (ccRCC) derived cells (PMID:19888345)
• findings suggest that Axl is a downstream effector of the tumor cell EMT that is required for breast cancer metastasis. Thus, the detection and targeted treatment of Axl-expressing tumors represents an important new therapeutic strategy for breast cancer (PMID:20080645)
• Gas6 in circulation is bound to sAxl suggesting circulating Gas6 to be inhibited and incapable of stimulating the TAM receptors. (PMID:20088931)
• Taken together, this is the first study to show that MZF1 induces invasion and in vivo metastasis in colorectal and cervical cancer, at least in part by regulating Axl gene expression. (PMID:20145042)
• Gas6 and soluble Axl have a role in critical limb ischemia, presumably connected to the inflammatory process (PMID:20417630)
• Axl has a potential role in Kaposi sarcoma pathogenesis (PMID:20442363)
• Gas6 and Tyro3, Axl and Mer (TAM) receptors have roles in human and murine platelet activation and thrombus stabilization (PMID:20546121)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	AXL	ENSDARG00000112045
mus_musculus	Axl	ENSMUSG00000002602
rattus_norvegicus	Axl	ENSRNOG00000020716

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), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078)

Protein

Protein identifiers

Tyrosine-protein kinase receptor UFO — P30530 (reviewed: P30530)

Alternative names: AXL oncogene

All UniProt accessions (2): P30530, M0R0W6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. (Microbial infection) Promotes Zika virus entry in glial cells, Sertoli cells and astrocytes. Additionally, Zika virus potentiates AXL kinase activity to antagonize type I interferon signaling and thereby promotes infection. Interferon signaling inhibition occurs via an SOCS1-dependent mechanism.

Subunit / interactions. Heterodimer and heterotetramer with ligand GAS6. Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TNS2. Part of a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.

Post-translational modifications. Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion. Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.

Disease relevance. AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.

Activity regulation. Activated by GAS6-binding and subsequent autophosphorylation.

Induction. (Microbial infection) Up-regulated by Aedes aegypti lymphotoxin beta receptor inhibitor during Zika virus infection.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P30530-1	Long	yes
P30530-2	Short

RefSeq proteins (3): NP_001265528, NP_001690, NP_068713* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00041, PF07714, PF13927

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 (90 total): strand 31, helix 14, glycosylation site 6, sequence conflict 6, modified residue 5, sequence variant 5, domain 5, mutagenesis site 4, region of interest 3, binding site 2, topological domain 2, disulfide bond 2, signal peptide 1, chain 1, active site 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5VXZ	X-RAY DIFFRACTION	2.3
5U6B	X-RAY DIFFRACTION	2.84
4RA0	X-RAY DIFFRACTION	3.07
2C5D	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30530-F1	75.57	0.39

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): 672 (proton acceptor)

Ligand- & substrate-binding residues (2): 542–550; 567

Post-translational modifications (5): 703, 779, 821, 866, 884

Disulfide bonds (2): 56–117, 160–205

Glycosylation sites (6): 43, 157, 198, 339, 345, 401

Mutagenesis-validated functional residues (4):

Position	Phenotype
63	slightly reduced affinity for gas6.
66	reduced affinity for gas6.
84	reduced affinity for gas6.
567	catalytically inactive mutant.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 485 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, FREAC2_01, GOBP_PINOCYTOSIS, JI_RESPONSE_TO_FSH_UP, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, MYOGENIN_Q6, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS

GO Biological Process (50): neuron migration (GO:0001764), natural killer cell differentiation (GO:0001779), positive regulation of cytokine-mediated signaling pathway (GO:0001961), blood vessel remodeling (GO:0001974), phagocytosis (GO:0006909), inflammatory response (GO:0006954), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), spermatogenesis (GO:0007283), nervous system development (GO:0007399), negative regulation of macrophage cytokine production (GO:0010936), cell migration (GO:0016477), forebrain cell migration (GO:0021885), platelet activation (GO:0030168), negative regulation of type II interferon production (GO:0032689), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of natural killer cell differentiation (GO:0032825), secretion by cell (GO:0032940), erythrocyte homeostasis (GO:0034101), substrate adhesion-dependent cell spreading (GO:0034446), cellular response to interferon-alpha (GO:0035457), ovulation cycle (GO:0042698), negative regulation of apoptotic process (GO:0043066), negative regulation of neuron apoptotic process (GO:0043524), innate immune response (GO:0045087), symbiont entry into host cell (GO:0046718), vascular endothelial growth factor receptor signaling pathway (GO:0048010), cell maturation (GO:0048469), positive regulation of pinocytosis (GO:0048549), negative regulation of lymphocyte activation (GO:0051250), neuron apoptotic process (GO:0051402), establishment of localization in cell (GO:0051649), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), vagina development (GO:0060068), cellular response to lipopolysaccharide (GO:0071222), dendritic cell differentiation (GO:0097028), neutrophil clearance (GO:0097350), positive regulation of viral life cycle (GO:1903902), negative regulation of dendritic cell apoptotic process (GO:2000669), negative regulation of cytokine production (GO:0001818)

GO Molecular Function (10): virus receptor activity (GO:0001618), phosphatidylserine binding (GO:0001786), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), cell surface (GO:0009986), actin cytoskeleton (GO:0015629), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by VEGF	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	2
cellular anatomical structure	2
generation of neurons	1
lymphocyte differentiation	1
natural killer cell activation	1
regulation of cytokine-mediated signaling pathway	1
positive regulation of signal transduction	1
cytokine-mediated signaling pathway	1
positive regulation of response to cytokine stimulus	1
tissue remodeling	1
endocytosis	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
developmental process involved in reproduction	1
male gamete generation	1
system development	1
negative regulation of cytokine production involved in immune response	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
cell motility	1
forebrain development	1
cell activation	1
blood coagulation	1
negative regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
natural killer cell differentiation	1
positive regulation of natural killer cell activation	1
regulation of natural killer cell differentiation	1
positive regulation of lymphocyte differentiation	1
secretion	1
export from cell	1

Protein interactions and networks

STRING

3916 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AXL	GAS6	Q14393	999
AXL	PROS1	P07225	997
AXL	IFNAR1	P17181	921
AXL	TNS2	Q63HR2	866
AXL	GRB2	P29354	839
AXL	RANBP9	Q96S59	831
AXL	SOCS1	O15524	808
AXL	LRP1	Q07954	767
AXL	ERBB2	P04626	751
AXL	SOCS3	O14543	727
AXL	ERBB3	P21860	715
AXL	ELMO2	Q96JJ3	708
AXL	TULP1	O00294	707
AXL	CD209	Q9NNX6	701
AXL	SRC	P12931	694

IntAct

126 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
S	AXL	psi-mi:“MI:0915”(physical association)	0.650
S	AXL	psi-mi:“MI:0403”(colocalization)	0.650
S	AXL	psi-mi:“MI:0407”(direct interaction)	0.650
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
AXL	GRB2	psi-mi:“MI:0914”(association)	0.600
PIK3R1	AXL	psi-mi:“MI:0914”(association)	0.600
GRB2	AXL	psi-mi:“MI:0914”(association)	0.600
AXL	EGFR	psi-mi:“MI:0915”(physical association)	0.580
EGFR	AXL	psi-mi:“MI:2364”(proximity)	0.580
AXL	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.560
S	EGFR	psi-mi:“MI:0914”(association)	0.540
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
TMEM200A	STX6	psi-mi:“MI:0914”(association)	0.530
AXL	EPHA2	psi-mi:“MI:0915”(physical association)	0.500
PLCG1	AXL	psi-mi:“MI:0914”(association)	0.460
SPOP	AXL	psi-mi:“MI:0915”(physical association)	0.450
SPOP	AXL	psi-mi:“MI:2364”(proximity)	0.450

BioGRID (401): RANBP9 (Affinity Capture-Western), RANBP9 (Two-hybrid), TYRO3 (Two-hybrid), RANBP9 (Reconstituted Complex), PIK3R1 (Affinity Capture-Western), ABL2 (Affinity Capture-Western), GRB2 (Affinity Capture-Western), GRB2 (Reconstituted Complex), AXL (Affinity Capture-MS), AXL (Affinity Capture-MS), AXL (Affinity Capture-MS), AXL (Biochemical Activity), AXL (Biochemical Activity), AXL (Affinity Capture-Western), EGFR (Affinity Capture-Western)

ESM2 similar proteins: A6QLW8, O08966, O35308, O35956, O70461, O94956, O95528, P14672, P19357, P29376, P30530, P30935, P30936, P31388, P32745, P50406, Q05B81, Q1RPP5, Q27994, Q2YDU8, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A3, Q5IS65, Q5R540, Q5RCH6, Q5RLM2, Q6DFR1, Q6NUB3, Q6NWF1, Q6ZMD2, Q863T6, Q864Z3, Q8CFZ5, Q8IY34, Q8MK48, Q8R0G7, Q8VC69, Q8VHD6

Diamond homologs: A0JM20, A0M8R7, A0M8S8, A1X150, F1QVU0, G3V9H8, O02466, O35346, P00519, P00520, P00521, P00522, P00529, P06213, P07949, P08069, P08581, P08941, P09760, P0DV84, P10447, P13368, P14617, P16056, P20806, P22182, P23049, P30530, P33497, P34152, P34925, P35546, P35590, P42684, P55144, P55146, P57097, P70451, P97523, P97793

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
GAS6	up-regulates	AXL	binding
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxo-3-pyridinecarboxamide	down-regulates	AXL	“chemical inhibition”
cabozantinib	“down-regulates activity”	AXL	“chemical inhibition”
AXL	“up-regulates quantity by stabilization”	MLKL	phosphorylation
AXL	“up-regulates activity”	YES1	phosphorylation
GAS6	“up-regulates activity”	AXL	binding
AXL	“up-regulates activity”	Epithelial-mesenchymal_transition	binding
AXL	up-regulates	Metastasis
AXL	“up-regulates quantity”	TNS2	phosphorylation
AXL	“up-regulates activity”	NEDD9	phosphorylation
AXL	“up-regulates activity”	EGFR	phosphorylation
EGFR	“up-regulates activity”	AXL	phosphorylation
AXL	“down-regulates activity”	ERBB2	phosphorylation
PROS1	up-regulates	AXL	binding
AXL	“up-regulates activity”	AXL	phosphorylation
N1’-[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	“down-regulates activity”	AXL	“chemical inhibition”

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
Signaling by ERBB2 ECD mutants	5	44.2×	3e-05
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	34.1×	5e-05
Signaling by ERBB2 KD Mutants	5	27.8×	1e-04
Downstream signal transduction	5	25.0×	1e-04
DAP12 signaling	5	24.2×	1e-04
Signaling by ERBB2	5	22.8×	2e-04
RHOU GTPase cycle	6	22.0×	5e-05
RET signaling	5	17.1×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	7	17.5×	2e-04
positive regulation of protein localization to plasma membrane	6	16.5×	1e-03
cellular response to growth factor stimulus	5	16.1×	3e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	12.8×	2e-03
transforming growth factor beta receptor signaling pathway	7	11.2×	1e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	137
Likely benign	81
Benign	62

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
638632	NM_021913.5(AXL):c.2161C>G (p.Leu721Val)	Likely pathogenic

SpliceAI

2733 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41220634:A:AC	acceptor_loss	1.0000
19:41220634:A:AG	acceptor_gain	1.0000
19:41220635:G:GG	acceptor_gain	1.0000
19:41220635:G:GT	acceptor_loss	1.0000
19:41220830:G:GT	donor_gain	1.0000
19:41222054:CAGGT:C	donor_loss	1.0000
19:41222055:AGG:A	donor_loss	1.0000
19:41222056:GGT:G	donor_loss	1.0000
19:41222057:G:C	donor_loss	1.0000
19:41222058:T:G	donor_loss	1.0000
19:41231181:A:AG	acceptor_gain	1.0000
19:41231181:AGT:A	acceptor_gain	1.0000
19:41231182:G:GA	acceptor_gain	1.0000
19:41231182:GT:G	acceptor_gain	1.0000
19:41231182:GTG:G	acceptor_gain	1.0000
19:41231299:G:GA	donor_loss	1.0000
19:41231300:T:G	donor_loss	1.0000
19:41237943:GGCT:G	acceptor_gain	1.0000
19:41243615:GAGAA:G	acceptor_gain	1.0000
19:41248446:T:A	acceptor_gain	1.0000
19:41248500:A:AG	acceptor_gain	1.0000
19:41248508:A:AG	acceptor_gain	1.0000
19:41248508:AT:A	acceptor_gain	1.0000
19:41248509:T:G	acceptor_gain	1.0000
19:41248510:GCAGT:G	acceptor_loss	1.0000
19:41248511:CA:C	acceptor_loss	1.0000
19:41248512:A:AC	acceptor_loss	1.0000
19:41248512:A:AG	acceptor_gain	1.0000
19:41248513:G:GT	acceptor_gain	1.0000
19:41248513:GT:G	acceptor_gain	1.0000

AlphaMissense

5784 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41248553:T:C	L526P	1.000
19:41248609:G:A	G545R	1.000
19:41248609:G:C	G545R	1.000
19:41248748:T:A	F547I	1.000
19:41248748:T:C	F547L	1.000
19:41248748:T:G	F547V	1.000
19:41248749:T:C	F547S	1.000
19:41248749:T:G	F547C	1.000
19:41248750:T:A	F547L	1.000
19:41248750:T:G	F547L	1.000
19:41248752:G:A	G548E	1.000
19:41248758:T:A	V550E	1.000
19:41248766:G:C	G553R	1.000
19:41248803:C:A	A565D	1.000
19:41248808:A:C	K567Q	1.000
19:41248808:A:G	K567E	1.000
19:41248809:A:C	K567T	1.000
19:41248809:A:T	K567M	1.000
19:41248810:G:C	K567N	1.000
19:41248810:G:T	K567N	1.000
19:41252387:T:C	L583P	1.000
19:41252394:A:C	E585D	1.000
19:41252394:A:T	E585D	1.000
19:41252395:G:C	A586P	1.000
19:41252405:T:C	M589T	1.000
19:41252429:T:A	V597D	1.000
19:41252438:T:A	L600H	1.000
19:41252438:T:C	L600P	1.000
19:41252894:T:A	V618D	1.000
19:41252910:G:A	M623I	1.000

dbSNP variants (sampled 300 via entrez): RS1000072986 (19:41261862 C>A), RS1000076660 (19:41219472 C>A,T), RS1000124895 (19:41262078 T>C), RS1000125301 (19:41220611 C>T), RS1000204994 (19:41225852 T>C,G), RS1000220997 (19:41235131 C>A,T), RS1000276982 (19:41226037 G>A), RS1000300632 (19:41254979 T>G), RS1000497395 (19:41220502 G>A), RS1000575029 (19:41230403 C>T), RS1000607848 (19:41225004 T>G), RS1000711745 (19:41242695 A>G), RS1000788072 (19:41225564 G>A), RS1000983198 (19:41259052 G>C), RS1001011621 (19:41249151 G>A,C)

Disease associations

OMIM: gene MIM:109135 | disease phenotypes: MIM:146110

GenCC curated gene-disease

Disease	Classification	Inheritance
Kallmann syndrome	Limited	Autosomal dominant

Mondo (4): amenorrhea (MONDO:0001836), hypogonadotropic hypogonadism 7 with or without anosmia (MONDO:0007794), NK-cell enteropathy (MONDO:0016996), Kallmann syndrome (MONDO:0018800)

Orphanet (3): Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), Rare genetic premature ovarian failure (Orphanet:485382), NK-cell enteropathy (Orphanet:263665)

HPO phenotypes

12 total (13 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000054	Micropenis
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000789	Infertility
HP:0002215	Sparse axillary hair
HP:0002225	Sparse pubic hair
HP:0003621	Juvenile onset
HP:0004408	Abnormality of the sense of smell
HP:0008734	Decreased testicular size
HP:0000141	Amenorrhea

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST006979_680	Heel bone mineral density	9.000000e-30
GCST006979_681	Heel bone mineral density	1.000000e-21
GCST008141_6	HDL cholesterol	1.000000e-06
GCST010173_155	Triglyceride levels	4.000000e-08
GCST010244_430	Triglyceride levels	1.000000e-09
GCST010796_5293	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST90002390_657	Mean corpuscular hemoglobin	4.000000e-16
GCST90002392_75	Mean corpuscular volume	4.000000e-14
GCST90002397_432	Mean spheric corpuscular volume	2.000000e-10
GCST90002403_300	Red blood cell count	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004327	electrocardiography
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000568	Amenorrhea	C23.550.568.500
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600
C562785	Idiopathic Hypogonadotropic Hypogonadism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL4523666 (CHIMERIC PROTEIN), CHEMBL4895 (SINGLE PROTEIN), CHEMBL5169079 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465244 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066566 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

59 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 549,023 (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
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL31965	CANERTINIB	3
CHEMBL3622820	ITACITINIB	3
CHEMBL3989926	SITRAVATINIB	3
CHEMBL428690	ALVOCIDIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL50	QUERCETIN	3
CHEMBL5095079	POVORCITINIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL5314428	ZANZALINTINIB	3
CHEMBL603469	LESTAURTINIB	3

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12459996	AXL	3	0.00	1	glatiramer acetate

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family

Most potent curated ligand interactions (22 total), top 22:

Ligand	Action	Affinity	Parameter
canlitinib	Inhibition	9.62	pIC50
gilteritinib	Inhibition	9.1	pIC50
BMS-777607	Inhibition	8.96	pIC50
sitravatinib	Inhibition	8.82	pIC50
compound 6li [Chan et al., 2022]	Inhibition	8.8	pIC50
ligritinib	Inhibition	8.74	pIC50
compound 8i [PMID: 22765894]	Inhibition	8.34	pIC50
UNC8969	Inhibition	8.28	pIC50
A-910	Inhibition	8.09	pIC50
zanzalintinib	Inhibition	8.0	pIC50
ningetinib	Inhibition	7.96	pIC50
merestinib	Inhibition	7.96	pIC50
bemcentinib	Inhibition	7.85	pIC50
dubermatinib	Inhibition	7.57	pIC50
belizatinib	Inhibition	7.54	pKd
LDC1267	Inhibition	7.54	pIC50
RIPK1 inhibitor 22b	Inhibition	7.46	pIC50
UNC4203	Inhibition	7.4	pKi
compound 19a [PMID: 30503936]	Inhibition	7.28	pIC50
adrixetinib	Inhibition	7.0	pKd
SLC-391	Inhibition	6.3	pIC50
compound 1 [Cruz-López et al., 2019]	Inhibition	4.89	pIC50

Binding affinities (BindingDB)

1240 measured of 2459 human assays (2459 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- (bicyclo[1.1.1]pent- 1-yl)-6-[(1- cyanocyclopropyl) methoxy]-1,3,5- triazine-2- carboxamide	KI	0.01 nM	US-9593097: Axl inhibitors
4-[4-[[2-amino-5-(1-methylimidazol-4-yl)-3-pyridinyl]oxymethyl]piperidin-1-yl]-N-[(2R)-1-hydroxypropan-2-yl]-6-[[(2R)-oxolan-2-yl]methoxy]-1,3,5-triazine-2-carboxamide	KI	0.012 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-(1- methylcyclobutyl)- 1,3,5-triazine-2- carboxamide	KI	0.012 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-2-[(2R)-2- methoxypropoxy]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.014 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6- {[(1R)-2,2- difluoro- cyclopropyl] methoxy}-N- (propan-2-yl)- 1,3,5-triazine-2- carboxamide	KI	0.015 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 2-[{2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.015 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N- cyclobutyl-1,3,5- triazine-2- carboxamide	KI	0.016 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]- 6-[(2R)- tetrahydrofuran-2- ylmethoxy]-N- [(2S)-1,1,1- trifluoropropan-2- yl]-1,3,5-triazine- 2-carboxamide	KI	0.016 nM	US-9593097: Axl inhibitors
N-(2- methoxyethyl)-6- [4-(4-methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-2- [(2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.016 nM	US-9593097: Axl inhibitors
(3,3- difluoroazetidin-1- yl)(2-{[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidin-4- yl)methanone	KI	0.018 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-[(1R)- 1-cyclopropylethyl]- 1,3,5-triazine-2- carboxamide	KI	0.019 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- tert-butyl-6-[(1- cyanocyclopropyl) methoxy]-1,3,5- triazine-2- carboxamide	KI	0.02 nM	US-9593097: Axl inhibitors
N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 4-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-6- [(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.02 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-2-[(2S)-2- methoxypropoxy]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.02 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-N-tert- butyl-6-{[(1S,2R)- 2- cyanocyclopropyl] methoxy}-1,3,5- triazine-2- carboxamide	KI	0.021 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- N-[(2S)-1,1,1- trifluoropropan-2- yl]-1,3,5-triazine- 2-carboxamide	KI	0.021 nM	US-9593097: Axl inhibitors
N-cyclobutyl-4- {[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.021 nM	US-9593097: Axl inhibitors
4-(benzyloxy)-N- [(2R)-1- hydroxypropan-2- yl]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.025 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- [(2R)- butan-2-yl]-6-[(1- cyanocyclopropyl) methoxy]-1,3,5- triazine-2- carboxamide	KI	0.026 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- (bicyclo[1.1.1]pent- 1-yl)-6-{[(1S,2R)- 2- cyanocyclopropyl] methoxy}-1,3,5- triazine-2- carboxamide	KI	0.028 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-(2,2- dimethylpropyl)- 1,3,5-triazine-2- carboxamide	KI	0.028 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-4-{[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.028 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6- {[(1R)-2,2- difluoro- cyclopropyl] methoxy}-N- [(2R)-1- hydroxypropan-2- yl]-1,3,5-triazine- 2-carboxamide	KI	0.029 nM	US-9593097: Axl inhibitors
N- (bicyclo[1.1.1]pent- 1-yl)-4-{[(1S,2R)- 2- cyanocyclopropyl] methoxy}-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.03 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-4-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-6- [(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.03 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-N-[(2R)- 1-hydroxypropan- 2-yl]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.03 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6-[(1- cyanocyclopropyl) methoxy]-N- (cyclo- propylmethyl)- 1,3,5-triazine-2- carboxamide	KI	0.032 nM	US-9593097: Axl inhibitors
4-{[(1S,2R)-2- cyanocyclopropyl] methoxy}-N-[(2R)- 3-hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.032 nM	US-9593097: Axl inhibitors
6-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-2- {[(1S)-2,2- difluoro- cyclopropyl] methoxy}-N- [(2R)-1- hydroxypropan-2- yl]pyrimidine-4- carboxamide	KI	0.033 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- [(2R)-3-hydroxy-3- methylbutan-2-yl]- 6-[(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.034 nM	US-9593097: Axl inhibitors
N-(3-amino-3-methylbutan-2-yl)-2-[(2R)-1-methoxypropan-2-yl]oxy-6-[4-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]pyrimidine-4-carboxamide	KI	0.034 nM	US-9593097: Axl inhibitors
N-[(1R,2R)-2- hydroxy- cyclobutyl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]-2- [(2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.034 nM	US-9593097: Axl inhibitors
4-{[(1S,2R)-2- cyanocyclopropyl] methoxy}-N-[(2R)- 1-hydroxypropan- 2-yl]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.035 nM	US-9593097: Axl inhibitors
4-(benzyloxy)-N- [(2R)-1- hydroxypropan-2- yl]-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.037 nM	US-9593097: Axl inhibitors
N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 4-{[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.038 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-N-[(2R)- 3-hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.038 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N- (2,2,2- trifluoroethyl)- 1,3,5-triazine-2- carboxamide	KI	0.039 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-(3,3- difluorobutan-2- yl)-1,3,5-triazine- 2-carboxamide	KI	0.04 nM	US-9593097: Axl inhibitors
N-(3-amino-3- methylbutan-2-yl)- 2-[(1- cyanocyclopropyl) methoxy]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.04 nM	US-9593097: Axl inhibitors
N-(2-hydroxycyclobutyl)-2-[(2R)-1-methoxypropan-2-yl]oxy-6-[4-(4-methoxy-2H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl]pyrimidine-4-carboxamide	KI	0.041 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N- (propan-2-yl)- 1,3,5-triazine-2- carboxamide	KI	0.042 nM	US-9593097: Axl inhibitors
N-[(1R,2S)-2- hydroxycyclobutyl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin- 1-yl]-2-[(2R- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.042 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- N-(2,2,2- trifluoroethyl)- 1,3,5-triazine-2- carboxamide	KI	0.048 nM	US-9593097: Axl inhibitors
N-[(3R,4S)-4- hydroxytetrahydro- furan-3-yl]-2- {[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.048 nM	US-9593097: Axl inhibitors
2-[(1- cyanocyclopropyl) methoxy]-N-[(2R)- 1-hydroxypropan- 2-yl]-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.049 nM	US-9593097: Axl inhibitors
N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]-2- [(2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.05 nM	US-9593097: Axl inhibitors
N-(2- methoxyethyl)-4- [4-(4-methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-6- [(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.051 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6- {[(1S,2R)-2- cyanocyclopropyl] methoxy}-N- cyclobutyl-1,3,5- triazine-2- carboxamide	KI	0.053 nM	US-9593097: Axl inhibitors
4- (cyclo- propylmethoxy)- N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.053 nM	US-9593097: Axl inhibitors
6-[4-(4-ethoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- N-[(2R)-1- hydroxypropan-2- yl]-2-{[(2R)-1- methoxypropan-2- yl]oxy}pyrimidine- 4-carboxamide	KI	0.054 nM	US-9593097: Axl inhibitors

ChEMBL bioactivities

3511 potent at pChembl≥5 of 3609 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL5758853
10.92	Ki	0.012	nM	CHEMBL5935453
10.92	Ki	0.012	nM	CHEMBL5932919
10.85	Ki	0.014	nM	CHEMBL5792035
10.82	Ki	0.015	nM	CHEMBL5923596
10.82	Ki	0.015	nM	CHEMBL5930737
10.80	Ki	0.016	nM	CHEMBL5906788
10.80	Ki	0.016	nM	CHEMBL6041852
10.80	Ki	0.016	nM	CHEMBL5931969
10.74	Ki	0.018	nM	CHEMBL5819606
10.72	Ki	0.019	nM	CHEMBL5912055
10.70	Ki	0.02	nM	CHEMBL5964033
10.70	Ki	0.02	nM	CHEMBL5880806
10.70	Ki	0.02	nM	CHEMBL5972896
10.68	Ki	0.021	nM	CHEMBL5851400
10.68	Ki	0.021	nM	CHEMBL5820622
10.68	Ki	0.021	nM	CHEMBL5804857
10.60	Ki	0.025	nM	CHEMBL5813796
10.59	Ki	0.026	nM	CHEMBL5911851
10.55	Ki	0.028	nM	CHEMBL5990089
10.55	Ki	0.028	nM	CHEMBL5934471
10.55	Ki	0.028	nM	CHEMBL5952989
10.54	Ki	0.029	nM	CHEMBL6019578
10.52	Ki	0.03	nM	CHEMBL5952495
10.52	Ki	0.03	nM	CHEMBL5913877
10.52	Ki	0.03	nM	CHEMBL6028906
10.49	Ki	0.032	nM	CHEMBL5929819
10.49	Ki	0.032	nM	CHEMBL6039322
10.48	Ki	0.033	nM	CHEMBL5851291
10.47	Ki	0.034	nM	CHEMBL5855090
10.47	Ki	0.034	nM	CHEMBL5866479
10.47	Ki	0.034	nM	CHEMBL5907610
10.46	Ki	0.035	nM	CHEMBL5914736
10.43	Ki	0.037	nM	CHEMBL5814025
10.42	Ki	0.038	nM	CHEMBL5844227
10.42	Ki	0.038	nM	CHEMBL5865745
10.41	Ki	0.039	nM	CHEMBL5809410
10.40	Ki	0.04	nM	CHEMBL5886143
10.40	Ki	0.04	nM	CHEMBL5831618
10.39	Ki	0.041	nM	CHEMBL5803601
10.38	Ki	0.042	nM	CHEMBL5900027
10.38	Ki	0.042	nM	CHEMBL5941635
10.32	Ki	0.048	nM	CHEMBL6019416
10.32	Ki	0.048	nM	CHEMBL5822798
10.31	Ki	0.049	nM	CHEMBL5781623
10.31	Ki	0.049	nM	CHEMBL5803601
10.30	Ki	0.05	nM	CHEMBL5783301
10.29	Ki	0.051	nM	CHEMBL5966426
10.28	Ki	0.053	nM	CHEMBL5987998
10.28	Ki	0.053	nM	CHEMBL5993500

PubChem BioAssay actives

1115 with measured affinity, of 2525 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0001	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	624840: Binding constant for AXL kinase domain	kd	0.0001	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-[4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-chlorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-[4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,5-difluorophenyl]-5-(4-fluorophenyl)-4-oxo-1-propan-2-ylpyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-cyclohexyl-3-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyanilino]-1-methylpyrazole-4-carboxamide	1849343: Binding affinity to AXL (unknown origin) assessed as dissociation constant by competition binding assay	kd	0.0003	uM
3-[(3-cyclopentyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)amino]-6-ethyl-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.0003	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-1-(oxan-4-ylmethyl)-4-oxo-5-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,5-difluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-4-oxo-1-propan-2-ylpyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-1-[2-(dimethylamino)-2-oxoethyl]-5-(4-fluorophenyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0005	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,5-difluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0005	uM
N-[2-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]-1,3-dihydroisoindol-4-yl]-N-methylmethanesulfonamide	1529866: Inhibition of N-terminal His-tagged recombinant human AXL (473 to end amino acids) expressed by baculovirus in Sf9 cells using axltide substrate and ATP by ADP-Glo luminescence assay	ic50	0.0005	uM
2-(2,3,4-trihydroxyphenyl)-2,3-dihydrochromen-4-one	1915844: Inhibition of AXL (unknown origin) by biochemical assay	ic50	0.0005	uM
3-(4-fluorophenyl)-N-[4-[[2-[[2-(1-methylpiperidin-4-yl)acetyl]amino]-4-pyridinyl]oxy]phenyl]-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0006	uM
6-ethyl-3-[[3-(3-ethylcyclopentyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]amino]-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624309: Inhibition of AXL (unknown origin) using poly (Glu, Tyr) as substrate after 60 mins by ELISA	ic50	0.0007	uM
1-(3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl)-3-N-[(7S)-7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-1,2,4-triazole-3,5-diamine	1374805: Inhibition of wild-type human partial length AXL (R497 to Y821 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP	ic50	0.0007	uM
Gilteritinib	1562831: Inhibition of N-terminal GST-tagged human AXL (464 to 885 residues) cytoplasmic domain expressed in baculovirus expression system by ELISA	ic50	0.0007	uM
N-[5-(6,7-dimethoxyquinolin-4-yl)oxy-2-pyridinyl]-2,5-dioxo-1-phenyl-7,8-dihydro-6H-quinoline-3-carboxamide	2064258: Inhibition of AXL (unknown origin) by HTRF kinase assay	ic50	0.0007	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(2,4-difluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0008	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-3-fluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0008	uM
N-[3-fluoro-4-(1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	1418401: Inhibition of recombinant His-tagged human Axl (473 to end residues) cytoplasmic domain expressed in insect system using poly (Glu-Ala-Tyr) peptide as substrate after 5 mins in presence of ADP by fluorescence analysis	ic50	0.0008	uM
N-[3-fluoro-4-[[2-(1-methylpyrazol-4-yl)-4-pyridinyl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1764488: Inhibition of AXL (unknown origin) using poly [Glu, Tyr] 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA	ic50	0.0008	uM
N-[4-[6-(cyclopropanecarbonylamino)pyrimidin-4-yl]oxyphenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0008	uM
N-[2,5-difluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0008	uM
N-[2-fluoro-4-[[2-[[2-(1-methylpiperidin-4-yl)acetyl]amino]-4-pyridinyl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0008	uM
N-methyl-N-[2-[2-(4-morpholin-4-ylanilino)-5-(trifluoromethyl)pyrimidin-4-yl]-1,3-dihydroisoindol-4-yl]methanesulfonamide	1529866: Inhibition of N-terminal His-tagged recombinant human AXL (473 to end amino acids) expressed by baculovirus in Sf9 cells using axltide substrate and ATP by ADP-Glo luminescence assay	ic50	0.0009	uM
N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridinyl]oxy]-3-fluorophenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1764488: Inhibition of AXL (unknown origin) using poly [Glu, Tyr] 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA	ic50	0.0009	uM
Crizotinib	617240: Inhibition of AXL	ic50	0.0010	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-1-(oxan-4-ylmethyl)-4-oxo-5-phenylpyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0010	uM
N-[2-[4-[(3S)-1-methylsulfonylpiperidin-3-yl]-1,3-thiazol-2-yl]-4-piperazin-1-ylphenyl]-1H-imidazole-2-carboxamide	1434708: Inhibition of Axl (unknown origin)	ic50	0.0010	uM
N-[3-fluoro-4-[7-(2-hydroxy-2-methylpropoxy)quinolin-4-yl]oxyphenyl]-1,5-dimethyl-3-oxo-2-phenylpyrazole-4-carboxamide	2100797: Inhibition of AXL (unknown origin)	ic50	0.0010	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-1-(oxan-4-yl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0011	uM
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-1-(4-fluorophenyl)-4-methoxy-2-oxopyridine-3-carboxamide	1691581: Inhibition of Axl (unknown origin)	ic50	0.0011	uM
1-cyclopentyl-N-[3-fluoro-4-[[2-[[2-(1-methylpiperidin-4-yl)acetyl]amino]-4-pyridinyl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxopyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0011	uM
5-[4-(6,7-dimethoxyquinazolin-4-yl)oxy-3-fluoroanilino]-1-methyl-3-(3-methylphenyl)-1,6-naphthyridin-4-one	2100798: Inhibition of recombinant AXL (unknown origin) by FRET based Z’-LYTE assay	ic50	0.0011	uM
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	2151501: Inhibition of Axl (unknown origin) by kinase profiling assay	ic50	0.0011	uM
6-ethyl-N-[3-fluoro-4-[(5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]phenyl]-1,2-dimethyl-4-oxoquinoline-3-carboxamide	1626951: Binding affinity to human AXL by active site dependent completion binding assay	kd	0.0012	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-4-oxo-1-(oxolan-2-ylmethyl)pyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0012	uM
1-(2,5-difluorophenyl)-N-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-2-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxamide	2064247: Inhibition of AXL (unknown origin)	ic50	0.0012	uM
N-[4-[2-amino-5-[4-[[(2R)-1,4-dioxan-2-yl]methoxy]-3-methoxyphenyl]-3-pyridinyl]-3-fluorophenyl]-5-(5-methyl-2-pyridinyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	2064251: Inhibition of AXL (unknown origin) by kinase profiling assay	ic50	0.0013	uM
N-[2,5-difluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-2,5-dioxo-1-phenyl-7,8-dihydro-6H-quinoline-3-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0013	uM
5-[4-(6,7-dimethoxyquinazolin-4-yl)oxy-3-fluoroanilino]-1-ethyl-3-(4-methylphenyl)-1,6-naphthyridin-4-one	2100798: Inhibition of recombinant AXL (unknown origin) by FRET based Z’-LYTE assay	ic50	0.0013	uM
5-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-3-fluoroanilino]-3-(4-fluorophenyl)-1-propan-2-yl-1,6-naphthyridin-4-one	2078792: Inhibition of AXL (unknown origin) by ELISA analysis	ic50	0.0014	uM
5-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-3-fluoroanilino]-3-(4-fluorophenyl)-1-(2-methoxyethyl)-1,6-naphthyridin-4-one	2078792: Inhibition of AXL (unknown origin) by ELISA analysis	ic50	0.0014	uM
1-[(4-aminocyclohexyl)methyl]-N-(3-phenylpropyl)-3-(4-piperazin-1-ylphenyl)pyrazolo[3,4-d]pyrimidin-6-amine	663571: Inhibition of Axl using KKKKEEIYFFF-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0014	uM
1-cyclopentyl-3-(4-fluorophenyl)-N-[4-[6-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]pyrimidin-4-yl]oxyphenyl]-2,4-dioxopyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0015	uM
1-N’-[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]-2-pyridinyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	1533345: Inhibition of AXL (unknown origin)	ic50	0.0015	uM
6-ethyl-5-(oxan-4-ylamino)-3-[(7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl)amino]pyrazine-2-carboxamide	1624309: Inhibition of AXL (unknown origin) using poly (Glu, Tyr) as substrate after 60 mins by ELISA	ic50	0.0016	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	6
Valproic Acid	decreases expression, affects cotreatment	5
Cisplatin	affects expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	increases expression, increases methylation	3
bisphenol A	decreases expression	2
sodium arsenite	increases expression	2
cobaltous chloride	decreases expression, increases expression	2
Decitabine	affects expression, decreases methylation, increases expression	2
Zoledronic Acid	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Doxorubicin	increases expression, affects response to substance	2
Lipopolysaccharides	affects expression, affects response to substance, increases expression	2
Methyl Methanesulfonate	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
napabucasin	decreases expression	1
chloroacetaldehyde	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
sodium arsenate	increases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
3,4-dichloroaniline	decreases expression	1
arsenite	decreases reaction, affects binding	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
doxifluridine	decreases response to substance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1

ChEMBL screening assays

701 unique, capped per target: 698 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4424133	Binding	Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	Discovery of a potent tyrosine kinase AXL inhibitor bearing the 3-((2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)pyrazine core. — Bioorg Med Chem Lett
CHEMBL1964114	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: AXL	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 factor-dependent cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1KS	Abcam HeLa AXL KO 1	Cancer cell line	Female
CVCL_B1KT	Abcam HeLa AXL KO 2	Cancer cell line	Female
CVCL_D8HT	Ubigene HCT 116 AXL KO	Cancer cell line	Male
CVCL_D9YC	Ubigene HeLa AXL KO	Cancer cell line	Female
CVCL_HG04	HCT 116 AXL KO Tet-inducible	Cancer cell line	Male
CVCL_SE39	HAP1 AXL (-)	Cancer cell line	Male
CVCL_UE62	Ba/F3 AXL	Factor-dependent cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT01103518	PHASE4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	PHASE4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	PHASE4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00827151	PHASE3	WITHDRAWN	Bone Mass Accrual in Adolescent Athletes
NCT00064987	PHASE2	TERMINATED	Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
NCT00130117	PHASE2	COMPLETED	Study of Leptin for the Treatment of Hypothalamic Amenorrhea
NCT00152282	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of Asoprisnil and Estrogen Administration to Postmenopausal Women
NCT00196391	PHASE2	COMPLETED	A Trial to Evaluate DR-2021 in Women With Secondary Amenorrhea
NCT00383656	PHASE2	UNKNOWN	Pulsatile GnRH in Anovulatory Infertility
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT00392756	PHASE1	COMPLETED	Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
NCT00493961	PHASE1	COMPLETED	Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism
NCT00914823	PHASE1	COMPLETED	Kisspeptin Administration in the Adult
NCT01438034	PHASE1	COMPLETED	Kisspeptin in the Evaluation of Delayed Puberty
NCT03118479	PHASE1	TERMINATED	Effect of Varying Testosterone Levels on Insulin Sensitivity in Men With Idiopathic Hypogonadotropic Hypogonadism (IHH)
NCT00881608	PHASE1	TERMINATED	Study to Evaluate Menses Induction in Women Administered Proellex
NCT07152730	PHASE1	WITHDRAWN	A Study to Measure Pharmacokinetic (PK) Concentrations of Gonadotropin-Releasing Hormone Delivered by the OmniPod Pump
NCT00392457	Not specified	COMPLETED	Investigating the Regulation of Reproductive Hormones in Adult Men
NCT00494169	Not specified	COMPLETED	Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders
NCT00623116	Not specified	UNKNOWN	A Study to Characterize Epidemiology, Clinical and Genetic Features of Kallmann Syndrome in Finland
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01914172	Not specified	COMPLETED	Health Needs of Patients With Kallmann Syndrome
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04733274	Not specified	ACTIVE_NOT_RECRUITING	Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing
NCT05971836	Not specified	ACTIVE_NOT_RECRUITING	The Molecular Basis of Inherited Reproductive Disorders
NCT03916978	PHASE2/PHASE3	RECRUITING	Autologous PRP Intra Ovarian Infusion to Restore Ovarian Function in Menopausal Women
NCT00556400	PHASE1/PHASE2	TERMINATED	Treatment of Menorrhagia in Women With Thrombocytopenia Using Platelets or Platelets and Hormones
NCT01187043	PHASE1/PHASE2	COMPLETED	Determination of the Lowest, Safe and Effective Dose of Proellex
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00011388	Not specified	COMPLETED	Reproductive Effects of Pesticide, PCB and Mercury Exposure in Laotian Immigrants
NCT00243607	Not specified	COMPLETED	Hydrotherapy Against Menopausal Symptoms in Breast Cancer Survivors
NCT00260286	Not specified	COMPLETED	Effects of Gynecological Age on LH Sensitivity to Energy Availability
NCT00456274	Not specified	UNKNOWN	Baselines in Reproductive Disorders
NCT00589654	Not specified	ACTIVE_NOT_RECRUITING	Menstrual Cycle Maintenance and Quality of Life: A Prospective Study
NCT01423487	Not specified	WITHDRAWN	Efficacy and Safety of Metformin in Preventing Patients With Risperidone From Weight Gain and Amenorrhea
NCT01500447	Not specified	RECRUITING	Inherited Reproductive Disorders
NCT01511588	Not specified	COMPLETED	Hormonal Regulation of Puberty and Fertility