ALK

Summary

ALK (ALK receptor tyrosine kinase, HGNC:427) is a protein-coding gene on chromosome 2p23.2-p23.1, encoding ALK tyrosine kinase receptor (Q9UM73). Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. In precision oncology, ALK Mutation confers sensitivity to Lorlatinib in Lung Non-small Cell Carcinoma (CIViC Level A); 98 further curated variant–drug associations are listed below.

This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).

Source: NCBI Gene 238 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuroblastoma, susceptibility to, 3 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 6,574 total — 19 pathogenic, 8 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 15 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 68
• Drug target: yes — 11 curated mechanism-of-action drugs; 61 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 7 — Alectinib Hydrochloride, Brigatinib, Ceritinib, +4 more
• Precision-oncology evidence (CIViC): 99 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 6 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_004304
• Interaction hub: 2,740 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:427
Approved symbol	ALK
Name	ALK receptor tyrosine kinase
Location	2p23.2-p23.1
Locus type	gene with protein product
Status	Approved
Aliases	CD246, ALK1
Ensembl gene	ENSG00000171094
Ensembl biotype	protein_coding
OMIM	105590
Entrez	238

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000389048

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 4: 1, TSL 5: 2

ENST00000389048, ENST00000431873, ENST00000453137, ENST00000498037, ENST00000618119, ENST00000638605, ENST00000642122, ENST00001144644

RefSeq mRNA: 2 — MANE Select: NM_004304 NM_001353765, NM_004304

CCDS: CCDS33172, CCDS86828

Canonical transcript exons

ENST00000389048 — 29 exons

Exon	Start	End
ENSE00001140354	29192774	29193922
ENSE00001154361	29196770	29196860
ENSE00001154367	29197542	29197676
ENSE00001154381	29209786	29209878
ENSE00001154390	29213984	29214081
ENSE00001154395	29220706	29220835
ENSE00001154399	29222344	29222408
ENSE00001154403	29222517	29222607
ENSE00001154407	29223342	29223528
ENSE00001154411	29225461	29225565
ENSE00001154417	29226922	29227074
ENSE00001154420	29227574	29227672
ENSE00001154426	29232304	29232448
ENSE00001154428	29233565	29233696
ENSE00001154433	29239680	29239830
ENSE00001255591	29228884	29229066
ENSE00001255625	29275099	29275227
ENSE00001255635	29275402	29275496
ENSE00001255668	29320751	29320882
ENSE00001255673	29328350	29328481
ENSE00001255693	29383732	29383859
ENSE00001290865	29694850	29695014
ENSE00001313023	29717578	29717697
ENSE00001313033	29531915	29532116
ENSE00001329399	29251105	29251267
ENSE00001682043	29207171	29207272
ENSE00001794937	29919993	29921586
ENSE00003584441	29318304	29318404
ENSE00003638382	29296888	29297057

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 85.61.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3489 / max 2521.9109, expressed in 256 samples.

Highest expression (Bgee): sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis, type B pancreatic cell, olfactory bulb.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ALK is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	2.8e-45	-0.82	2:29319257:T:C
Nerve Tibial	eqtl	3.5e-13	+0.37	2:29884636:G:C
Lung	eqtl	2.9e-05	-0.27	2:29198339:T:TCTC
Brain Frontal Cortex BA9	eqtl	1.5e-04	+1.22	2:29377977:G:A
Adipose Visceral Omentum	eqtl	4.3e-04	+0.26	2:29196725:G:T
Brain Cortex	eqtl	4.5e-04	+1.25	2:29413691:C:T
Skin Sun Exposed Lower leg	eqtl	6.5e-04	-0.28	2:29414922:GT:G
Adipose Subcutaneous	eqtl	1.7e-03	+0.20	2:29196725:G:T
Small Intestine Terminal Ileum	eqtl	2.2e-03	-0.96	2:29533644:C:A
Colon Sigmoid	eqtl	3.2e-03	+0.15	2:29919355:T:C
Esophagus Gastroesophageal Junction	eqtl	5.3e-03	+0.20	2:29874613:T:C
Esophagus Muscularis	eqtl	6.5e-03	+0.19	2:29885608:G:C
Brain Anterior cingulate cortex BA24	eqtl	1.5e-02	+0.87	2:30754078:A:G
Esophagus Mucosa	eqtl	3.4e-02	+0.21	2:29889681:TATAG:T
Brain Substantia nigra	eqtl	4.1e-02	-0.53	2:29292568:T:C

FANTOM5 promoters

showing 10 of 24 alternative TSS:

Promoter ID	TPM avg	Samples expressed
27658	1.4789	177
27595	0.3449	50
27659	0.3409	45
27649	0.0288	5
27647	0.0156	4
27646	0.0134	2
27648	0.0122	2
27599	0.0117	3
27657	0.0115	2
27655	0.0108	3

Top tissues by expression

showing 100 of 267 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	85.61	gold quality
male germ cell	CL:0000015	85.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.22	gold quality
type B pancreatic cell	CL:0000169	83.34	gold quality
olfactory bulb	UBERON:0002264	83.23	gold quality
ventral tegmental area	UBERON:0002691	78.37	gold quality
cervix squamous epithelium	UBERON:0006922	77.67	gold quality
diaphragm	UBERON:0001103	77.39	gold quality
superior vestibular nucleus	UBERON:0007227	77.39	gold quality
medial globus pallidus	UBERON:0002477	77.03	silver quality
subthalamic nucleus	UBERON:0001906	76.80	silver quality
buccal mucosa cell	CL:0002336	76.70	silver quality
dorsal plus ventral thalamus	UBERON:0001897	76.44	silver quality
globus pallidus	UBERON:0001875	76.35	silver quality
thymus	UBERON:0002370	76.19	gold quality
Brodmann (1909) area 23	UBERON:0013554	75.67	gold quality
inferior vagus X ganglion	UBERON:0005363	75.22	silver quality
cerebellar vermis	UBERON:0004720	74.78	silver quality
middle temporal gyrus	UBERON:0002771	74.13	gold quality
vena cava	UBERON:0004087	74.02	gold quality
trachea	UBERON:0003126	73.82	gold quality
pharyngeal mucosa	UBERON:0000355	73.76	gold quality
cardia of stomach	UBERON:0001162	73.68	gold quality
trigeminal ganglion	UBERON:0001675	73.35	silver quality
nipple	UBERON:0002030	73.25	gold quality
body of tongue	UBERON:0011876	73.15	gold quality
dorsal root ganglion	UBERON:0000044	73.10	silver quality
superior surface of tongue	UBERON:0007371	73.06	gold quality
tongue	UBERON:0001723	73.04	gold quality
pericardium	UBERON:0002407	72.88	gold quality
substantia nigra pars reticulata	UBERON:0001966	72.87	gold quality
medulla oblongata	UBERON:0001896	72.77	gold quality
lateral globus pallidus	UBERON:0002476	72.74	gold quality
substantia nigra pars compacta	UBERON:0001965	72.63	silver quality
lateral nuclear group of thalamus	UBERON:0002736	72.61	gold quality
pylorus	UBERON:0001166	72.59	gold quality
pons	UBERON:0000988	72.58	silver quality
secondary oocyte	CL:0000655	71.83	gold quality
oocyte	CL:0000023	71.55	gold quality
CA1 field of hippocampus	UBERON:0003881	71.52	silver quality
endothelial cell	CL:0000115	71.33	gold quality
penis	UBERON:0000989	71.29	gold quality
occipital lobe	UBERON:0002021	71.15	gold quality
mammary duct	UBERON:0001765	70.14	gold quality
tongue squamous epithelium	UBERON:0006919	70.05	gold quality
orbitofrontal cortex	UBERON:0004167	69.83	silver quality
primary visual cortex	UBERON:0002436	69.38	gold quality
pituitary gland	UBERON:0000007	69.00	gold quality
hypothalamus	UBERON:0001898	68.86	gold quality
urethra	UBERON:0000057	68.85	gold quality
pancreatic ductal cell	CL:0002079	68.34	silver quality
Brodmann (1909) area 46	UBERON:0006483	68.31	silver quality
prefrontal cortex	UBERON:0000451	67.81	gold quality
cingulate cortex	UBERON:0003027	67.56	gold quality
anterior cingulate cortex	UBERON:0009835	67.50	gold quality
sural nerve	UBERON:0015488	67.17	gold quality
midbrain	UBERON:0001891	67.12	gold quality
temporal lobe	UBERON:0001871	66.94	gold quality
superior frontal gyrus	UBERON:0002661	66.85	gold quality
epithelial cell of pancreas	CL:0000083	66.78	gold quality
amygdala	UBERON:0001876	66.76	gold quality
cervix epithelium	UBERON:0004801	66.36	gold quality
parietal lobe	UBERON:0001872	66.28	gold quality
adenohypophysis	UBERON:0002196	66.25	gold quality
neocortex	UBERON:0001950	66.07	gold quality
frontal cortex	UBERON:0001870	66.02	gold quality
substantia nigra	UBERON:0002038	65.97	gold quality
entorhinal cortex	UBERON:0002728	65.65	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.61	gold quality
forebrain	UBERON:0001890	65.58	gold quality
cerebral cortex	UBERON:0000956	65.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.18	gold quality
deltoid	UBERON:0001476	65.14	gold quality
gingival epithelium	UBERON:0001949	65.06	gold quality
telencephalon	UBERON:0001893	64.91	gold quality
left testis	UBERON:0004533	64.76	gold quality
hair follicle	UBERON:0002073	64.46	gold quality
postcentral gyrus	UBERON:0002581	64.39	gold quality
right testis	UBERON:0004534	64.32	gold quality
testis	UBERON:0000473	64.24	gold quality
upper arm skin	UBERON:0004263	64.11	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.11	gold quality
nucleus accumbens	UBERON:0001882	64.08	gold quality
oviduct epithelium	UBERON:0004804	63.85	gold quality
mucosa of urinary bladder	UBERON:0001259	63.76	gold quality
triceps brachii	UBERON:0001509	63.76	gold quality
gluteal muscle	UBERON:0002000	63.67	gold quality
putamen	UBERON:0001874	63.53	gold quality
brain	UBERON:0000955	63.38	gold quality
right frontal lobe	UBERON:0002810	63.10	gold quality
Ammon’s horn	UBERON:0001954	62.87	gold quality
mammalian vulva	UBERON:0000997	62.79	gold quality
cranial nerve II	UBERON:0000941	62.64	silver quality
quadriceps femoris	UBERON:0001377	62.57	gold quality
jejunum	UBERON:0002115	62.54	gold quality
biceps brachii	UBERON:0001507	62.14	gold quality
gingiva	UBERON:0001828	61.84	gold quality
squamous epithelium	UBERON:0006914	61.71	gold quality
muscle tissue	UBERON:0002385	61.60	gold quality
vastus lateralis	UBERON:0001379	61.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.16

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 70 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	26.1
Postcentral gyrus	tissue	5.9
Nucleus accumbens	tissue	5.6
Hippocampus	tissue	5.1	high
Choroid plexus	tissue	4.4
Ventral forebrain	tissue	2.5
Pituitary gland	tissue	2.4
Septum	tissue	2.4
Periaqueductal gray	tissue	2.2
Caudate putamen	tissue	2.2
Cerebral cortex	tissue	2.1	high
Somatosensory cortex	tissue	2.1
Prefrontal cortex	tissue	2.0
Motor cortex	tissue	2.0
Hypothalamus	tissue	2.0
Insular cortex	tissue	2.0
Amygdala	tissue	1.9
Retrosplenial and cingulate cortex	tissue	1.9
Retrosplenial cortex	tissue	1.9
Temporal cortex	tissue	1.9
Superior colliculi	tissue	1.8
Hippocampal formation	tissue	1.8
Entorhinal cortex	tissue	1.8
Occipital cortex	tissue	1.8
Thalamus	tissue	1.6
Frontal cortex	tissue	1.5
Basal ganglia	tissue	1.5	medium
Medulla oblongata	tissue	1.5
Pons	tissue	1.4
Putamen	tissue	1.4
Olfactory bulb	tissue	1.4
Substantia nigra	tissue	1.3
Spinal cord	tissue	1.3
Midbrain	tissue	1.2
Cerebellum	tissue	1.2	high
Testis	tissue	1.1	low
Corpus callosum	tissue	0.9
Retina	tissue	0.6
Adrenal gland	tissue	0.6	low
Adipose tissue	tissue	0.3	not detected
Thyroid gland	tissue	0.3	low
Rectum	tissue	0.2	low
Colon	tissue	0.2	low
Small intestine	tissue	0.2	not detected
Gallbladder	tissue	0.2	low
Appendix	tissue	0.2	not detected
Skin 1	tissue	0.1	low
Breast	tissue	0.1	not detected
Stomach 1	tissue	0.1	not detected
Vagina	tissue	0.1	low
Seminal vesicle	tissue	0.1	low
Salivary gland	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected
Lung	tissue	0.1	low
Duodenum	tissue	0.1	not detected
Cervix	tissue	0.0	low
Lymph node	tissue	0.0	low
Heart muscle	tissue	0.0	low
Ovary	tissue	0.0	low
Parathyroid gland	tissue	0.0	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Inferior colliculus (16.8), Nucleus tractus solitarii (12.2), Lateral hypothalamic area (10.9), Dorsal motor vagal complex (10.8), Motor hypoglossal nucleus (10.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, ESR1, JUNB, PHOX2B, STAT5A, TCF23, TXK

miRNA regulators (miRDB)

Targeting ALK by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 60 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-378G	99.71	64.90	1106

Functional genomics

gnomAD constraint: pLI 3.82e-06, LOEUF 0.562, missense Z 0.957 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000389048 splits into 5 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:29,193,227–29,197,620	403 / 366.2	1.10	no
2:29,197,621–29,214,059	83 / 139.7	0.59	no
2:29,214,060–29,239,792	575 / 626.6	0.92	no
2:29,239,793–29,251,140	15 / 33.5	0.45	no
2:29,251,141–29,920,659	987 / 939.5	1.05	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth (PMID:11809760)
• ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1-restricted CD8+ T-cell epitopes. (PMID:11877285)
• ALK-positive anaplastic large cell lymphoma had significantly higher levels of caspase 3, while high expression of the antiapoptotic proteins Bcl-2 and PI9 was almost completely restricted to ALK-negative cases. (PMID:12036886)
• Novel fusion partners CARS and KIAA1618 (ALO17) have been detected with variant rearrangements of ALK in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor cases. (PMID:12112524)
• results do not support any involvement of ALK in the stimulation of tumorigenic cell growth or differentiation (PMID:12115586)
• midkine binds to ALK and has a role in signal transduction for cell growth and survival (PMID:12122009)
• ALK-ShcC signal activation, possibly caused by co-amplification with the N-myc gene, might give additional effects on malignant tumor progression of neuroblastoma.ShcC is a potent substrate of the activated ALK kinase. (PMID:12185581)
• co-expression of c-Myc and ALK was seen in tumor cells of ALK-positive anaplastic large cell lymphomas; C-Myc may be a downstream target of ALK signaling (PMID:12213716)
• novel fusion created by the ALK gene on chromosome 2p23 and NPM on 5q35 or other variant translocation partners in a rare variant of diffuse large B-cell lymphoma (PMID:12763927)
• In a case of anaplastic large cell lymphoma, ALK is fused to a portion of non-muscle myosin heavy chain gene, MYH9, localized 6 bp downstream of MSN-ALK in the same exonic sequence, resulting in an in-frame fusion of the two partner proteins. (PMID:12800156)
• Src-kinases, particularly pp60(c-src), associate with and are activated by NPM-ALK expression in various cells, and in cell lines established from patients with large cell lymphoma (PMID:14563642)
• results show a pivotal role for Bcl-XL in ALK-mediated oncogenicity (PMID:14656879)
• FOXO3a is a barrier to hematopoietic transformation that is overcome by phosphorylation and cytoplasmic relocalization induced by the expression of NPM-ALK (PMID:14962911)
• High dose therapy and stem cell transplantation does not produce long-term disease free survival in patients with recurrent chemotherapy-sensitive ALK-negative large cell lymphoma. (PMID:15004538)
• STAT3 directly contributes to the high level of TIMP1 expression in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. (PMID:15161657)
• ALK receptor tyrosine kinase has roles promoting cell growth and neurite outgrowth (PMID:15226403)
• ALK has roles in oncogenesis of haematopoietic and non-haematopoietic tumors [review] (PMID:15583856)
• Although 9 of 36 patients with cutaneous CD30(+) lymphoproliferative diseases had progression of their disease, neither mutations of the p53 gene nor ALK immunoreactivity were found in any of these biopsies. (PMID:15713979)
• analysis of differentiation of PC12 cells and human embryonic kidney 293 cells transfected with ALK shows absence of agonist activity of pleiotrophin (PMID:15886198)
• ALK-mediated alphaDGK activation is dependent on p60src tyrosine kinase, with which alphaDGK forms a complex; alphaDGK activation is involved in the control of ALK-mediated mitogenic properties. (PMID:15928040)
• CONCLUSIONS: ALK-ALCL arising in the skin represents a single disease with a broad spectrum of morphology; clinicians and pathologists should be aware of this neutrophil-rich (NR) variant with aggressive clinical presentation. (PMID:15933425)
• We conclude that Jak3 activation is predominantly restricted to ALK-positive ALCL tumors. (PMID:16153455)
• Genomic PCR and subsequent sequencing showed that the breakpoints were located in intron 23 of SEC31-like 1 protein-transport protein and intron 20 of ALK (PMID:16161041)
• Potent and selective ALK inhibitors may have therapeutic application for anaplastic lymphoma kinase. (PMID:16254137)
• Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract may show ALK immunopositivity but do not show consistent ALK rearrangement by fluorescent in situ hybridization. (PMID:16623783)
• can be adapted for the identification of known and unknown translocation partners of chimeric ALK fusion proteins involved in oncogenesis (PMID:16651537)
• constitutive expression of C/EBPbeta in ALK-positive anaplastic large cell lymphoma and its relationship to NPM-ALK (PMID:16709933)
• NPM/ALK-carrying T cell lymphoma (ALK+TCL) cells secrete IL-10 and TGF-beta and express FoxP3, indicating their T regulatory (Treg) cell phenotype. (PMID:16766651)
• Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma. (PMID:16825495)
• AUF1 was phosphorylated by ALK in vitro and was hyperphosphorylated in NPM-ALK-expressing cells. (PMID:16835382)
• recruitment of insulin receptor substrate-1 to activated ALK and the activation of NF-kappaB are essential for the autocrine growth and survival signaling of midkine (PMID:16878150)
• ALK has a proapoptotic activity in the absence of ligand, whereas it is antiapoptotic in the presence of its ligand and when the kinase is intrinsically activated. (PMID:16880530)
• CD26 and cell surface adenosine deaminase are selectively expressed on ALK-positive, but not on ALK-negative, anaplastic large cell lymphoma and Hodgkin’s lymphoma (PMID:17071493)
• molecular signature of ALK- anaplastic large-cell lymphoma included overexpression of CCR7, CNTFR, IL22, and IL21 genes (PMID:17077326)
• A functional role for Shc and likely FRS2 in ALK-dependant MAP-kinase activation and neuronal differentiation of PC12 cells. (PMID:17274988)
• This study thus supports the possibility that activated ALK may be important in human breast cancers and potentially activated either through the PTN/RPTPbeta/zeta signaling pathway. (PMID:17490616)
• identify splicing factor as a novel nucleophosmin 1/anaplastic lymphoma kinase-binding protein and substrate (PMID:17537995)
• phosphorylation of ALK in PTN-stimulated cells is mediated through the PTN/RPTPbeta/zeta signaling pathway (PMID:17681947)
• JunB is a critical target of mTOR and is translationally regulated in NPM-ALK-positive lymphomas. (PMID:17690253)
• Pleiotrophin failed to activate anaplastic lymphoma kinase (ALK) in neuroblastoma/glioblastoma cells expressing this receptor. ALK is still an orphan receptor in vertebrates. (PMID:17904822)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	alk	ENSDARG00000095833
mus_musculus	Alk	ENSMUSG00000055471
rattus_norvegicus	Alk	ENSRNOG00000008683

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), LMTK2 (ENSG00000164715), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:103305) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 37 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	2
delayed hair appearance	1
abnormal sympathetic ganglion morphology	1
abnormal superior cervical ganglion morphology	1
enlarged superior cervical ganglion	1
abnormal stellate ganglion morphology	1
small testis	1
decreased body size	1
increased anxiety-related response	1
decreased locomotor activity	1
abnormal hypothalamus secretion	1
delayed sexual maturation	1
apnea	1
abnormal eye morphology	1
abnormal seminiferous tubule morphology	1
abnormal sperm number	1
decreased vertical activity	1
decreased circulating testosterone level	1
increased circulating alkaline phosphatase level	1
increased circulating chloride level	1
increased alcohol consumption	1
abnormal long bone diaphysis morphology	1
decreased testis weight	1
abnormal behavior	1
decreased Sertoli cell number	1

+12 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca fascicularis	Q5IFJ9	99.4%	Diamond
Pan troglodytes	Q5IS37	99.4%	Diamond
Saimiri boliviensis boliviensis	Q5IS82	99.0%	Diamond
Gallus gallus	P08941	98.7%	Diamond
Felis catus	P14238	98.7%	Diamond
Bos taurus	Q05688	97.7%	Diamond
Sus scrofa	P24786	95.8%	Diamond
Xenopus tropicalis	A0JM20	95.5%	Diamond
Xenopus laevis	Q8QFP9	95.5%	Diamond
Cavia porcellus	P14617	89.8%	Diamond
Canis lupus familiaris	P0DV84	89.1%	Diamond
Caenorhabditis briggsae	Q61G93	84.2%	Diamond
Caenorhabditis elegans	Q8I7I5	84.2%	Diamond
Takifugu rubripes	Q8AXC6	71.9%	Diamond
Drosophila melanogaster	P13368	62.3%	Diamond
Drosophila virilis	P20806	62.3%	Diamond
Lymnaea stagnalis	O76997	54.2%	Diamond
Hydra vulgaris	Q25197	50.8%	Diamond
Branchiostoma lanceolatum	O02466	50.0%	Diamond
Aedes aegypti	Q93105	49.8%	Diamond
Geodia cydonium	P42159	48.4%	Diamond
Dictyostelium discoideum	Q54XQ2	42.8%	Diamond
Gardner-Arnstein feline sarcoma virus	P00542	99.1%	Diamond
Snyder-Theilen feline sarcoma virus	P00543	99.1%	Diamond
UR2 sarcoma virus	P00529	98.7%	Diamond
Avian sarcoma virus PRCII	P00541	78.4%	Diamond
Fujinami sarcoma virus	P00530	72.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CLIP4	protein-coding	79745
TOGARAM2	protein-coding	165186
PCARE	protein-coding	388939
SNORA10B	snoRNA	109616960
YPEL5	protein-coding	51646
LBH	protein-coding	81606

Protein

Protein identifiers

ALK tyrosine kinase receptor — Q9UM73 (reviewed: Q9UM73)

Alternative names: Anaplastic lymphoma kinase

All UniProt accessions (5): Q9UM73, A0A087WZL3, A0A0K2YUJ3, E7EPW7, H7BZ33

UniProt curated annotations — full annotation on UniProt →

Function. Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis. Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response. In contrast, ALKAL1 is not a potent physiological ligand for ALK. Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK. May function as regulator of gastric epithelial differentiation.

Subunit / interactions. Homodimer; homodimerizes following heparin- and ligand-binding. Interacts with CBL, IRS1, PIK3R1 and PLCG1. Interacts with FRS2 and SHC1. Interacts with PTN and MDK.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells.

Post-translational modifications. Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity. In cells not stimulated by a ligand, receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) dephosphorylates ALK at the sites in ALK that are undergoing autophosphorylation through autoactivation. Phosphorylation at Tyr-1507 is critical for SHC1 association. N-glycosylated.

Disease relevance. A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. Neuroblastoma 3 (NBLST3) [MIM:613014] A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. Disease susceptibility is associated with variants affecting the gene represented in this entry. The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth. A chromosomal aberration involving ALK is found in one subject with colorectal cancer. Translocation t(2;2)(p23.1;p23.3). A 5 million base pair tandem duplication generates an in-frame WDCP-ALK gene fusion. A chromosomal aberration involving ALK has been identified in a subset of patients with non-small-cell lung carcinoma. This aberration leads to the production of a fusion protein between the N-terminus of EML4 et the C-terminus of ALK. It is unclear whether the fusion protein is caused by a simple inversion within 2p (inv(2)(p21p23)) or whether the chromosome translocation involving 2p is more complex. When tested in a heterologous system, the fusion protein EML4-ALK possesses transforming activity that is dependent on ALK catalytic activity, possibly due to spontaneous dimerization mediated by the EML4 moiety, leading to ALK kinase activation.

Activity regulation. Activated upon ALKAL2 ligand-binding. ALKAL2-driven activation is coupled with heparin-binding. Following ligand-binding, homodimerizes and autophosphorylates, activating its kinase activity. Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand. Staurosporine, crizotinib and CH5424802 act as inhibitors of ALK kinase activity.

Domain organisation. The EGF-like region drives the cytokine specificity for ALKAL2. The heparin-binding region binds heparin glycosaminoglycan. Heparin-binding is required for ALKAL2-driven activation.

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

RefSeq proteins (2): NP_001340694, NP_004295* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000998	MAM_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR002011	Tyr_kinase_rcpt_2_CS	Conserved_site
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR050122	RTK	Family
IPR055163	ALK/LTK-like_GRD	Domain

Pfam: PF00629, PF07714, PF12810

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)

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

UniProt features (187 total): strand 45, helix 42, sequence variant 38, glycosylation site 16, modified residue 7, disulfide bond 6, mutagenesis site 6, region of interest 5, binding site 4, domain 4, turn 3, compositionally biased region 2, topological domain 2, site 2, signal peptide 1, chain 1, active site 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 79 structures by resolution:

PDB	Title	Method	Resolution (Å)
7MZY	Anaplastic lymphoma kinase (ALK) extracellular fragment of ligand binding region 673-986	X-RAY DIFFRACTION	1.5
4Z55	Anaplastic lymphoma kinase catalytic domain complexed with pyrazolopyrimidine derivative …	X-RAY DIFFRACTION	1.55
9GBE	Structure of Human Anaplastic Lymphoma Kinase (ALK) harboring the G1202R/L1196M Compound …	X-RAY DIFFRACTION	1.58
5A9U	Structure of C1156Y Mutant Human Anaplastic Lymphoma Kinase in Complex with PF-06463922 …	X-RAY DIFFRACTION	1.6
8ARJ	Anaplastic Lymphoma Kinase with a novel carboline inhibitor	X-RAY DIFFRACTION	1.65
4CLJ	Structure of L1196M Mutant Human Anaplastic Lymphoma Kinase in Complex with PF-06463922 …	X-RAY DIFFRACTION	1.66
2YFX	Structure of L1196M Mutant Anaplastic Lymphoma Kinase in Complex with Crizotinib	X-RAY DIFFRACTION	1.7
4ANL	Structure of G1269A Mutant Anaplastic Lymphoma Kinase	X-RAY DIFFRACTION	1.7
4FNX	Crystal structure of the apo R1275Q anaplastic lymphoma kinase catalytic domain	X-RAY DIFFRACTION	1.7
4FOC	Crystal structure of human anaplastic lymphoma kinase in complex with …	X-RAY DIFFRACTION	1.7
5AAC	Structure of C1156Y Mutant Human Anaplastic Lymphoma Kinase in Complex with Crizotinib	X-RAY DIFFRACTION	1.7
5FTQ	Crystal structure of the ALK kinase domain in complex with Cmpd 17	X-RAY DIFFRACTION	1.7
4CMT	Structure of the Human Anaplastic Lymphoma Kinase in Complex with the inhibitor …	X-RAY DIFFRACTION	1.73
5AAA	Structure of L1198F Mutant Human Anaplastic Lymphoma Kinase in Complex with Crizotinib	X-RAY DIFFRACTION	1.73
3AOX	X-ray crystal structure of human anaplastic lymphoma kinase in complex with CH5424802	X-RAY DIFFRACTION	1.75
4FNW	Crystal structure of the apo F1174L anaplastic lymphoma kinase catalytic domain	X-RAY DIFFRACTION	1.75
4ANQ	Structure of G1269A Mutant Anaplastic Lymphoma Kinase in Complex with Crizotinib	X-RAY DIFFRACTION	1.76
4CTB	Structure of the Human Anaplastic Lymphoma Kinase in Complex with the inhibitor …	X-RAY DIFFRACTION	1.79
3L9P	Crystal Structure of the Anaplastic Lymphoma Kinase Catalytic Domain	X-RAY DIFFRACTION	1.8
4CMU	Structure of the Human Anaplastic Lymphoma Kinase in Complex with the inhibitor …	X-RAY DIFFRACTION	1.8
6CDT	Structure of Human Anaplastic Lymphoma Kinase Domain	X-RAY DIFFRACTION	1.8
7R7K	Structure of Human Anaplastic Lymphoma Kinase Domain in complex with …	X-RAY DIFFRACTION	1.83
4ANS	Structure of L1196M,G1269A Double Mutant Anaplastic Lymphoma Kinase in Complex with …	X-RAY DIFFRACTION	1.85
5AA8	Structure of C1156Y,L1198F Mutant Human Anaplastic Lymphoma Kinase in Complex with …	X-RAY DIFFRACTION	1.86
7BTT	A X-ray cocrystal structure of XMU-MP-5 bound to the ALK kinase domain	X-RAY DIFFRACTION	1.86
5IUI	Crystal Structure of Anaplastic Lyphoma Kinase (ALK) in complex with 4	X-RAY DIFFRACTION	1.88
2XP2	Structure of the Human Anaplastic Lymphoma Kinase in Complex with Crizotinib (PF-02341066)	X-RAY DIFFRACTION	1.9
2YHV	Structure of L1196M Mutant Anaplastic Lymphoma Kinase	X-RAY DIFFRACTION	1.9
2YJR	Structure of F1174L Mutant Anaplastic Lymphoma Kinase	X-RAY DIFFRACTION	1.9
2YJS	Structure of C1156Y Mutant Anaplastic Lymphoma Kinase	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UM73-F1	68.26	0.20

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 7NX3

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, CD markers, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutated cancer genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH approved · IF supported

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 (3)

Position	Role
1249	proton acceptor
1057–1058	breakpoint for translocation to form the eml4-alk fusion protein (variant 1)
1058–1059	breakpoint for translocation to form the eml4-alk fusion protein (variant 2)

Ligand- & substrate-binding residues (4)

Position	Role
1124	ATP
1150	ATP
1197–1199	ATP
1270	ATP

Post-translational modifications (7)

Type	Positions
Phosphotyrosine	1078, 1092, 1096, 1131, 1278, 1507, 1604

Disulfide bonds (6)

Type	Positions
Disulfide bond	688–701, 783–794, 906–928, 987–995, 990–1006, 1008–1021

Glycosylation sites (16)

Type	Positions
N-linked (glcnac…) asparagine	169, 244, 285, 324, 411, 424, 445, 563, 571, 627, 709, 808, 863, 864, 886, 986

Mutagenesis-validated functional residues (6)

Position	Phenotype
48–52	abolished heparin-binding, leading to decreased alk activation.
859	slightly decreased autophosphorylation. decreased autophosphorylation and subsequent activation; when associated with a-974.
966	slightly decreased autophosphorylation. strongly reduced autophosphorylation and subsequent activation; when associated with a-994.
974	slightly decreased autophosphorylation. decreased autophosphorylation and subsequent activation; when associated with a-859.
994	slstrongly reduced autophosphorylation and subsequent activation; when associated with a-966.
1507	impairs interaction with shc1.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 17; 13 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-9700645	ALK mutants bind TKIs ⚕	curated
R-HSA-9717264	ASP-3026-resistant ALK mutants ⚕	curated
R-HSA-9717301	NVP-TAE684-resistant ALK mutants ⚕	curated
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-9717316	alectinib-resistant ALK mutants ⚕	curated
R-HSA-9717319	brigatinib-resistant ALK mutants ⚕	curated
R-HSA-9717323	ceritinib-resistant ALK mutants ⚕	curated
R-HSA-9717326	crizotinib-resistant ALK mutants ⚕	curated
R-HSA-9717329	lorlatinib-resistant ALK mutants ⚕	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9700649	Drug resistance of ALK mutants ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-9851151	MDK and PTN in ALK signaling	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-201556	Signaling by ALK	electronic
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—

MSigDB gene sets: 361 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_DENDRITE_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GCANCTGNY_MYOD_Q6, GOBP_ADULT_BEHAVIOR, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT, GOMF_KINASE_ACTIVATOR_ACTIVITY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (15): signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), phosphorylation (GO:0016310), peptidyl-tyrosine autophosphorylation (GO:0038083), regulation of cell population proliferation (GO:0042127), regulation of apoptotic process (GO:0042981), regulation of neuron differentiation (GO:0045664), protein autophosphorylation (GO:0046777), neuron development (GO:0048666), negative regulation of lipid catabolic process (GO:0050995), energy homeostasis (GO:0097009), positive regulation of dendrite development (GO:1900006), protein phosphorylation (GO:0006468), nervous system development (GO:0007399), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (11): protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), heparin binding (GO:0008201), receptor signaling protein tyrosine kinase activator activity (GO:0030298), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): plasma membrane (GO:0005886), protein-containing complex (GO:0032991), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Drug resistance of ALK mutants	7
Signaling by ALK in cancer	3
Signaling by Receptor Tyrosine Kinases	1
Signaling by ALK	1
Disease	1
Signal Transduction	1
Diseases of signal transduction by growth factor receptors and second messengers	1

GO top-level categories

55 GO namespaces:

Category	Terms
regulation of cellular process	2
neuron differentiation	2
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
phosphate-containing compound metabolic process	1
peptidyl-tyrosine phosphorylation	1
protein autophosphorylation	1
cell population proliferation	1
apoptotic process	1
regulation of programmed cell death	1
regulation of cell differentiation	1
protein phosphorylation	1
cell development	1
negative regulation of catabolic process	1
lipid catabolic process	1
negative regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
multicellular organismal-level homeostasis	1
positive regulation of neuron projection development	1
dendrite development	1
regulation of dendrite development	1
positive regulation of developmental process	1
phosphorylation	1
protein modification process	1
system development	1
animal gross anatomical part developmental process	1
regulation of metabolic process	1
primary metabolic process	1
protein kinase activity	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
protein tyrosine kinase activator activity	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
membrane	1
cell periphery	1
cellular_component	1
protein-containing complex	1
extracellular vesicle	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
cell surface receptor protein tyrosine kinase signaling pathway	BP	direct assay
peptidyl-tyrosine autophosphorylation	BP	direct assay
phosphorylation	BP	direct assay
protein autophosphorylation	BP	direct assay
extracellular exosome	CC	high-throughput assay
plasma membrane	CC	direct assay
protein-containing complex	CC	direct assay
heparin binding	MF	direct assay
identical protein binding	MF	physical interaction
protein tyrosine kinase activity	MF	direct assay
receptor signaling protein tyrosine kinase activator activity	MF	direct assay
transmembrane receptor protein tyrosine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,740 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALK	EML4	Q9HC35	974
ALK	KRAS	P01116	882
ALK	NPM1	P06748	866
ALK	CD274	Q9NZQ7	857
ALK	ACVR1B	P36896	835
ALK	TNFRSF8	P28908	800
ALK	PIK3CA	P42336	763
ALK	TP53	P04637	759
ALK	NRAS	P01111	752
ALK	STAT3	P40763	737
ALK	MYCN	P04198	731
ALK	KIF5B	P33176	731
ALK	EML1	O00423	725
ALK	STK11	Q15831	717
ALK	NAPSA	O96009	701

IntAct

Human interaction partners of ALK in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 65 partners by confidence:

Partner	Interaction type	MIscore	Records
SHC1	physical association	0.690	2
ALKAL1	direct interaction	0.660	7
PIK3R1	physical association	0.590	3
ALKAL2	physical association	0.560	5
PTPRZ1	physical association	0.540	2
HSP90AB1	physical association	0.520	2
CRKL	physical association	0.520	1
RACK1	physical association	0.520	1
NCK2	physical association	0.510	3
RET	physical association	0.500	1
PKM	phosphorylation reaction	0.440	1
PIK3R2	association	0.420	1
PTPN11	proximity	0.410	1
H1-4	physical association	0.400	1
H1-5	physical association	0.400	1
CBLC	physical association	0.370	2
CRK	physical association	0.370	2
SLA2	physical association	0.370	2
SRMS	physical association	0.370	2
ABL1	physical association	0.370	1
BLK	physical association	0.370	1
DUSP19	physical association	0.370	1
FGR	physical association	0.370	1
FRK	physical association	0.370	1
GRAP2	physical association	0.370	1
GRB10	physical association	0.370	1
GRB14	physical association	0.370	1
HCK	physical association	0.370	1
HSH2D	physical association	0.370	1
KARS1	physical association	0.370	1

BioGRID (743 interactions; top human partners by supporting records in a sample of 600 records): SHC1 (Affinity Capture-Western; 6 records), APBB1 (Proximity Label-MS; 4 records), GRB2 (Affinity Capture-Western; 4 records), PDIA4 (Affinity Capture-Western; 4 records), ANKLE2 (Proximity Label-MS; 3 records), BCAR1 (Affinity Capture-MS; 3 records), CANX (Affinity Capture-Western; 3 records), CLCC1 (Proximity Label-MS; 3 records), CRKL (Proximity Label-MS; 3 records), DNAJB11 (Affinity Capture-Western; 3 records), GAB1 (Proximity Label-MS; 3 records), GNB2L1 (Affinity Capture-MS; 3 records), HYOU1 (Proximity Label-MS; 3 records), LEMD3 (Affinity Capture-MS; 3 records), NUMB (Proximity Label-MS; 3 records)

SIGNOR signaling

showing 24 of 25 signaling interactions:

A	Effect	B	Mechanism
PTN	up-regulates	ALK	binding
ALK	up-regulates	PLCG1	binding
ALK	up-regulates	STAT3	binding
ALK	down-regulates	SFPQ	phosphorylation
PTPRB	down-regulates	ALK	dephosphorylation
PTPRZ1	down-regulates	ALK	dephosphorylation
alectinib	down-regulates	ALK	“chemical inhibition”
crizotinib	down-regulates	ALK	“chemical inhibition”
5-chloro-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	down-regulates	ALK	“chemical inhibition”
ALK	unknown	GRB2	phosphorylation
ALK	“up-regulates activity”	PIK3R3	phosphorylation
ceritinib	“down-regulates activity”	ALK	“chemical inhibition”
ALK	“up-regulates activity”	ATIC	phosphorylation
ALK	“up-regulates quantity”	MAPT	phosphorylation
ALK	“up-regulates activity”	STAT3	phosphorylation
ALK	“up-regulates activity”	GSK3B	phosphorylation
ALK	“up-regulates activity”	HES1	phosphorylation
ALK	up-regulates	SHC1	phosphorylation
ALK	up-regulates	SHC3	phosphorylation
ALK	“up-regulates activity”	ALK	phosphorylation
crizotinib	“down-regulates activity”	ALK	“chemical inhibition”
2-[[2-[[1-[2-(dimethylamino)-1-oxoethyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	“down-regulates activity”	ALK	“chemical inhibition”
5-chloro-N2-[2-methoxy-4-[4-(4-methyl-1-piperazinyl)-1-piperidinyl]phenyl]-N4-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	“down-regulates activity”	ALK	“chemical inhibition”
ALK	“up-regulates activity”	CDK9	phosphorylation

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ ALK-GRB2-TNK2 complex	3	ALK, GRB2, TNK2
★ ALK-ERRFI1-GRB2 complex	3	ALK, ERRFI1, GRB2
★ ALK-BTK complex	2	ALK, BTK
★ ALK-IGF1R complex	2	ALK, IGF1R

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
MDK	receptor	Signaling by Midkine
PTN	receptor	Signaling by Pleiotrophin

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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 ALK	6	61.2×	4e-08
Signaling by CSF3 (G-CSF)	6	61.2×	4e-08
Downstream signal transduction	8	54.4×	7e-10
Tie2 Signaling	5	53.7×	1e-06
Regulation of signaling by CBL	6	53.2×	9e-08
FLT3 Signaling	8	49.4×	8e-10
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	46.4×	2e-06
Signaling by CSF1 (M-CSF) in myeloid cells	7	43.3×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	6	68.0×	6e-08
peptidyl-tyrosine phosphorylation	7	47.6×	5e-08
cell surface receptor protein tyrosine kinase signaling pathway	13	36.4×	2e-14
ephrin receptor signaling pathway	6	33.3×	4e-06
epidermal growth factor receptor signaling pathway	8	32.0×	5e-08
ERK1 and ERK2 cascade	5	25.6×	1e-04
cellular response to transforming growth factor beta stimulus	5	22.3×	2e-04
insulin receptor signaling pathway	6	21.5×	4e-05

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

ALK amplifications, fusions and mutations have been shown to be driving events in non-small cell lung cancer. While crizontinib has demonstrated efficacy in treating the amplification, mutations in ALK have been shown to confer resistance to current tyrosine kinase inhibitors. Second-generation TKI’s have seen varied success in treating these resistant cases, and the HSP90 inhibitor 17-AAG has been shown to be cytostatic in ALK-altered cell lines.

From intOGen — cancer-driver classification: activating (oncogene-like) across 6 cancer types — BRCA, HCC, NBL, NSCLC, PROSTATE, SCLC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for ALK: 6,574 ClinVar records (27 pathogenic / likely pathogenic); 22 CIViC cancer variants; 15 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

6,574 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	8
Uncertain significance	3694
Likely benign	2192
Benign	139

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 27 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
18083	NM_004304.5(ALK):c.3824G>A (p.Arg1275Gln)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
18085	NM_004304.5(ALK):c.3575G>C (p.Arg1192Pro)	Pathogenic	criteria provided, single submitter	3
65671	NM_004304.5(ALK):c.3733T>G (p.Phe1245Val)	Likely pathogenic	criteria provided, single submitter	3
375887	NM_004304.5(ALK):c.3521T>G (p.Phe1174Cys)	Likely pathogenic	criteria provided, single submitter	2
2445401	NM_004304.5(ALK):c.402G>C (p.Lys134Asn)	Likely pathogenic	criteria provided, single submitter	1
1527803	GRCh37/hg19 2p23.2-21(chr2:29899368-42441440)x1	Pathogenic	criteria provided, single submitter	1
3247472	NC_000002.11:g.(?29287735)(29430158_?)del	Pathogenic	criteria provided, single submitter	1
65670	NM_004304.5(ALK):c.3520T>G (p.Phe1174Val)	Pathogenic	no assertion criteria provided	2
217849	NM_004304.5(ALK):c.3520T>C (p.Phe1174Leu)	Pathogenic	no assertion criteria provided	2
217850	NM_004304.5(ALK):c.3520T>A (p.Phe1174Ile)	Pathogenic	no assertion criteria provided	2
217852	NM_004304.5(ALK):c.3522C>G (p.Phe1174Leu)	Pathogenic	no assertion criteria provided	2
217855	NM_004304.5(ALK):c.3733T>A (p.Phe1245Ile)	Pathogenic	no assertion criteria provided	2
217856	NM_004304.5(ALK):c.3734T>G (p.Phe1245Cys)	Pathogenic	no assertion criteria provided	2
217851	NM_004304.5(ALK):c.3522C>A (p.Phe1174Leu)	Pathogenic	no assertion criteria provided	1
217857	NM_004304.5(ALK):c.3735C>A (p.Phe1245Leu)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ALK’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 3,616):

Position(s)	Effect	Δscore	Sites
2:29193928	acceptor_gain	1.0000
2:29196768–29196769	donor_loss	1.0000	5
2:29196861–29196862	acceptor_loss	1.0000	4
2:29220704–29220705	donor_loss	1.0000	5
2:29222342–29222343	donor_loss	1.0000	5
2:29222515–29222516	donor_loss	1.0000	5
2:29222608–29222609	acceptor_loss	1.0000	6
2:29222610	acceptor_gain	1.0000
2:29222614	acceptor_gain	1.0000
2:29223340–29223341	donor_loss	1.0000	2

AlphaMissense

3,676 missense substitutions predicted likely pathogenic (of 10,546 scored), across 832 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1296	9	0.995	1.000
M1273	9	0.992	1.000
M1362	9	0.974	0.999
M1166	9	0.968	0.999
M1328	9	0.947	0.995
M1348	9	0.937	0.999
M1290	9	0.921	0.999
M1199	9	0.905	0.998
M1089	9	0.849	0.982
D1249	8	1.000	1.000
N1254	8	1.000	1.000
D1270	8	1.000	1.000
F1127	8	0.999	1.000
D1163	8	0.999	1.000
D1311	8	0.999	1.000
F1164	8	0.998	1.000
H1247	8	0.998	1.000
F1271	8	0.998	1.000
D1276	8	0.998	1.000
F1306	8	0.998	1.000

HPA cancer prognostics

RNA cancer specificity: Group enriched (Glioblastoma Multiforme, Ovary Serous Cystadenocarcinoma, Skin Cutaneous Melanoma, Thyroid Carcinoma)

Disease associations

OMIM: gene MIM:105590 | disease phenotypes: MIM:211980, MIM:613014, MIM:167000, MIM:182280

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
neuroblastoma, susceptibility to, 3	Definitive	Autosomal dominant	5
spastic diplegia	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
neuroblastoma, susceptibility to, 3	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Childhood solid tumours	green
Childhood solid tumours cancer susceptibility	green
Embryonal tumour of possible germline origin	green
Hereditary spastic paraplegia, childhood onset	amber

Mondo (10): lung cancer (MONDO:0008903), neuroblastoma, susceptibility to, 3 (MONDO:0013083), hereditary neoplastic syndrome (MONDO:0015356), ovarian cancer (MONDO:0008170), small cell lung carcinoma (MONDO:0008433), neuroblastoma (MONDO:0005072), endometrial carcinoma (MONDO:0002447), lung carcinoma (MONDO:0005138), rhabdomyosarcoma (MONDO:0005212), spastic diplegia (MONDO:0001167)

Orphanet (5): Inherited cancer-predisposing syndrome (Orphanet:140162), Neuroblastoma (Orphanet:635), Rare ovarian cancer (Orphanet:213500), Small cell lung cancer (Orphanet:70573), Rhabdomyosarcoma (Orphanet:780)

HPO phenotypes

showing 60 of 68 phenotypes (HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000238	Hydrocephalus
HP:0000315	Abnormality of the orbital region
HP:0000520	Proptosis
HP:0000708	Atypical behavior
HP:0000737	Irritability
HP:0000822	Hypertension
HP:0000834	Abnormality of the adrenal glands
HP:0000958	Dry skin
HP:0000970	Anhidrosis
HP:0000989	Pruritus
HP:0000998	Hypertrichosis
HP:0001000	Abnormal skin pigmentation
HP:0001017	Anemic pallor
HP:0001053	Hypopigmented skin patches
HP:0001058	Poor wound healing
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001336	Myoclonus
HP:0001482	Subcutaneous nodule
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001928	Abnormality of coagulation
HP:0001945	Fever
HP:0002028	Chronic diarrhea
HP:0002034	Abnormal rectum morphology
HP:0002098	Respiratory distress
HP:0002176	Spinal cord compression
HP:0002239	Gastrointestinal hemorrhage
HP:0002277	Horner syndrome
HP:0002315	Headache
HP:0002516	Increased intracranial pressure
HP:0002574	Episodic abdominal pain
HP:0002653	Bone pain
HP:0002716	Lymphadenopathy
HP:0002756	Pathologic fracture
HP:0003005	Ganglioneuroma
HP:0003006	Neuroblastoma
HP:0003270	Abdominal distention
HP:0003281	Increased circulating ferritin concentration
HP:0003330	Abnormal bone structure
HP:0003334	Elevated circulating catecholamine level
HP:0003764	Nevus
HP:0004375	Neoplasm of the nervous system
HP:0004390	Hamartomatous polyposis
HP:0004912	Hypophosphatemic rickets
HP:0005220	Multiple intestinal neurofibromatosis
HP:0005249	Functional intestinal obstruction
HP:0005600	Congenital giant melanocytic nevus
HP:0007110	Central hypoventilation
HP:0008775	Abnormal prostate morphology
HP:0010314	Premature thelarche
HP:0010543	Opsoclonus
HP:0011976	Elevated urinary catecholamine level
HP:0011977	Elevated urinary homovanillic acid
HP:0011978	Elevated urinary vanillylmandelic acid
HP:0012056	Cutaneous melanoma
HP:0012378	Fatigue

GWAS associations

15 associations:

Study	Trait	p-value
GCST008758_14	Pre-treatment viral load in HIV-1 infection	7e-18
GCST008295_44	Number of decayed, missing and filled tooth surfaces or use of dentures	2e-9
GCST011346_36	Total cholesterol levels	4e-9
GCST010989_181	Body size at age 10	3e-8
GCST011347_56	Low density lipoprotein cholesterol levels	4e-8
GCST008386_3	Carbamazepine-induced serious cutaneous adverse reaction	5e-8
GCST008306_9	Dentures	6e-8
GCST003670_7	Systolic blood pressure	1e-6
GCST008384_3	Carbamazepine-induced reaction with eosinophilia and systemic symptoms	1e-6
GCST002726_14	Glucose homeostasis traits	3e-6
GCST008176_7	Gestational age at birth (child effect)	4e-6
GCST008551_22	Simvastatin-induced myopathy	5e-6
GCST003095_3	Adiponectin levels (BMI-adjusted)	7e-6
GCST002783_359	Body mass index	8e-6
GCST90000582_8	Spontaneous coronary artery dissection	8e-6

EFO canonical traits (from GWAS)

11 canonical traits:

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:0004340	body mass index
EFO:0007737	BMI-adjusted adiponectin measurement
EFO:0006335	systolic blood pressure
EFO:0005112	gestational age
EFO:0010078	dentures
EFO:1002004	drug hypersensitivity syndrome
EFO:0010125	viral load
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors

6 disease descriptors:

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D009447	Neuroblastoma	C04.557.465.625.600.590.650.550; C04.557.470.670.590.650.550; C04.557.580.625.600.590.650.550
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
D055752	Small Cell Lung Carcinoma	C04.588.894.797.520.109.220.624; C08.381.540.140.750; C08.785.520.100.220.750
C537945	Cerebral palsy, spastic, diplegic *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (19): CHEMBL2111387 (CHIMERIC PROTEIN), CHEMBL3883330 (CHIMERIC PROTEIN), CHEMBL4247 (SINGLE PROTEIN), CHEMBL4296165 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296166 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523743 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748220 (PROTEIN-PROTEIN INTERACTION), CHEMBL4748232 (PROTEIN-PROTEIN INTERACTION), CHEMBL4879537 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465388 (CHIMERIC PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ALK protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

11 curated-mechanism drugs:

Drug	Modality	Max phase
ALECTINIB HYDROCHLORIDE	Small molecule	4
BRIGATINIB	Small molecule	4
CERITINIB	Small molecule	4
CRIZOTINIB	Small molecule	4
ENSARTINIB	Small molecule	4
ENTRECTINIB	Small molecule	4
LORLATINIB	Small molecule	4
ASP-3026	Small molecule	1
CEP-37440	Small molecule	1
CONTELTINIB	Small molecule	1
PLB1003	Unknown	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 326,070 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 61 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1738797	ALECTINIB	4	7,111
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL3286830	LORLATINIB	4	3,833
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL1852688	INFIGRATINIB	4	2,298
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	330
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL3353410	OSIMERTINIB	4	9,448
CHEMBL189963	PALBOCICLIB	4	13,796
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL4298138	REPOTRECTINIB	4	1,100
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL535	SUNITINIB	4	80,232
CHEMBL3622821	UPADACITINIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL428690	ALVOCIDIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL1879463	DACTOLISIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL50	QUERCETIN	3
CHEMBL3545308	ROCILETINIB	3
CHEMBL276711	SEMAXANIB	3
CHEMBL3809489	BEMCENTINIB	2
CHEMBL513909	BI-2536	2
CHEMBL575448	BMS-754807	2
CHEMBL1967878	CENISERTIB	2
CHEMBL2010872	CEP-11981	2
CHEMBL5095063	ENVONALKIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL5095068	IRUPLINALKIB	2
CHEMBL253969	OSI-632	2
CHEMBL607707	PELITINIB	2
CHEMBL475251	R-406	2
CHEMBL14762	SELICICLIB	2
CHEMBL4297627	SELITRECTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL363648	TAK-715	2
CHEMBL572878	TOZASERTIB	2
CHEMBL1090090	VX-702	2
CHEMBL5314412	ZOTIZALKIB	2
CHEMBL3545360	ASP-3026	1
CHEMBL3951811	CEP-37440	1
CHEMBL3899477	CONTELTINIB	1
CHEMBL5095166	APG-2449	1
CHEMBL574738	AST-487	1
CHEMBL1908397	KW-2449	1
CHEMBL49120	PD-0166285	1
CHEMBL1084546	PF-00562271	1
CHEMBL1980391	RG-1530	1

Clinical evidence (CIViC)

Drug × variant × indication, from 130 curated evidence items; also 1 diagnostic, 1 prognostic, 1 predisposing. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 99 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
ALK Mutation	Lorlatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC A	EID11286
ALK R1275Q	Crizotinib	Neuroblastoma	Sensitivity/Response	CIViC B	EID2342 +3
ALK G1269A AND v::ALK Fusion	Ensartinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID8861
ALK Mutation	Ceritinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID1237
EML4::ALK Fusion AND ALK C1156Y	Ensartinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID8860
EML4::ALK Fusion AND ALK L1196M	Ensartinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID7865
ALK F1174L	Crizotinib	Neuroblastoma	Resistance	CIViC B	EID2345 +1
ALK I1171	Ceritinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID1284 +2
ALK F1174L	Crizotinib	Neuroblastoma	Sensitivity/Response	CIViC C	EID1271 +1
ALK Alternative Transcript (ATI)	Crizotinib	Skin Melanoma	Sensitivity/Response	CIViC C	EID1936
ALK Alternative Transcript (ATI)	Entrectinib	Mucosal Melanoma	Sensitivity/Response	CIViC C	EID7421
ALK F1245V	Entrectinib	Neuroblastoma	Sensitivity/Response	CIViC C	EID2987
ALK I1171T	Ceritinib	Neuroblastoma	Sensitivity/Response	CIViC C	EID9404
EML4::ALK Fusion AND ALK C1156Y	Lorlatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID842
EML4::ALK Fusion AND ALK F1245C	Ceritinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID1338
EML4::ALK Fusion AND ALK I1171N AND ALK L1196M	Lorlatinib	Malignant Pleural Mesothelioma	Sensitivity/Response	CIViC C	EID11113
EML4::ALK Fusion AND ALK L1198F AND ALK C1156Y	Crizotinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID844
FUS::TFCP2 Fusion AND ALK Exon 2-18 Deletion	Alectinib	Spindle Cell Rhabdomyosarcoma	Sensitivity/Response	CIViC C	EID12406
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID4034 +4
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID4042 +3
ALK I1171	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID4610 +2
EML4::ALK Fusion AND ALK Amplification	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID766 +2
EML4::ALK Fusion AND ALK G1269A	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID4619 +2
EML4::ALK Fusion AND ALK L1196M	Crizotinib	Lung Adenocarcinoma	Resistance	CIViC C	EID237 +2
ALK G1269A AND v::ALK Fusion	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID4617 +1
ALK I1171	Alectinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID1283 +1
EML4::ALK Fusion AND ALK C1156Y	Crizotinib	Lung Adenocarcinoma	Resistance	CIViC C	EID236 +1
EML4::ALK Fusion AND ALK T1151dup	Crizotinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID444 +1
ALK F1174L AND RANBP2::ALK Fusion	Crizotinib	Inflammatory Myofibroblastic Tumor	Resistance	CIViC C	EID32
ALK F1245C	Crizotinib	Neuroblastoma	Resistance	CIViC C	EID1333

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

CIViC curated variants (22)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

L1198F (missense variant), F1245V (missense variant), G1202R (missense variant), S1206Y (missense variant), L1152R (missense variant), G1269A (missense variant), I1171T (missense variant), Amplification, L1196M (missense variant), C1156Y (missense variant), T1151dup (inframe insertion), Mutation (gene variant,gain of function variant), Exon 2-18 Deletion, I1171 (missense variant), V1180L (missense variant), F1245C (missense variant), Exon 4-11 Deletion (inframe deletion), I1171N (missense variant), I1171S (missense variant), F1174L (missense variant), Alternative Transcript (ATI), R1275Q (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs187926838	carbamazepine	Toxicity	Allele G is associated with increased risk of severe cutaneous adverse reactions when treated with carbamazepine as compared to allele A.	PMID:31066027

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type XIX RTKs: Leukocyte tyrosine kinase (LTK) receptor family

Most potent curated ligand interactions (29 total), top 25:

Ligand	Action	Affinity	Parameter
brigatinib	Inhibition	10.05	pKi
ceritinib	Inhibition	9.7	pIC50
belizatinib	Inhibition	9.44	pKd
ensartinib	Inhibition	9.4	pIC50
GSK-1838705A	Inhibition	9.3	pIC50
gilteritinib	Inhibition	9.3	pIC50
TL13-112	Inhibition	9.22	pIC50
lorlatinib	Inhibition	9.15	pKi
compound 8e [PMID: 24432909]	Inhibition	9.1	pIC50
iruplinalkib	Inhibition	9.0	pIC50
ficonalkib	Inhibition	9.0	pIC50
neladalkib	Inhibition	9.0	pIC50
crizotinib	Inhibition	9.0	pIC50
repotrectinib	Inhibition	8.98	pIC50
NVP-TAE684	Inhibition	8.96	pKd
zotizalkib	Inhibition	8.85	pIC50
dirozalkib	Inhibition	8.77	pIC50
alectinib	Inhibition	8.72	pIC50
compound 25b [PMID: 22564207]	Inhibition	8.72	pIC50
envonalkib	Inhibition	8.71	pIC50
CEP-37440	Inhibition	8.51	pIC50
AZD3463	Inhibition	8.0	pIC50
compound 5m [PMID: 20483621]	Inhibition	8.0	pIC50
compound 5n [PMID: 20483621]	Inhibition	8.0	pIC50
compound 5g [PMID: 20483621]	Inhibition	7.96	pIC50

Binding affinities (BindingDB)

2443 measured of 2915 human assays (2959 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
AP26113	IC50	0.07 nM
CHEMBL5593687	IC50	0.1 nM
CHEMBL3286826	IC50	0.11 nM
CHEMBL3824308	IC50	0.12 nM
8-(4-aminopiperidin-1-yl)-9-bromo-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.168 nM	US-9126931: Tetracyclic compound
CHEMBL3286825	IC50	0.18 nM
CHEMBL3823235	IC50	0.18 nM
CHEMBL3822611	IC50	0.18 nM
CHEMBL3128069	IC50	0.2 nM
CHEMBL3286823	IC50	0.21 nM
CHEMBL3823549	IC50	0.22 nM
CHEMBL3823416	IC50	0.24 nM
CHEMBL5598386	IC50	0.24 nM
CHEMBL4522012	IC50	0.27 nM
CHEMBL3824327	IC50	0.28 nM
CHEMBL4286522	KI	0.29 nM
9-bromo-8-[(3S,5R)-4-cyclobutyl-3,5-dimethylpiperazin-1-yl]-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.3 nM	US-9126931: Tetracyclic compound
8-[4-(azetidin-1-yl)piperidin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.3 nM	US-9126931: Tetracyclic compound
9-ethyl-8-[4-(4-hydroxypiperidin-1-yl)piperidin-1-yl]-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.3 nM	US-9126931: Tetracyclic compound
5-chloro-N4-2-(isopropylsulfonyl)phenyl)-N2-(7-methoxy-1-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)pyrimidine-2,4-diamine	IC50	0.3 nM	US-10053458: Pyrimidine-2,4-diamine derivative and anticancer pharmaceutical composition comprising same as effective ingredient
CHEMBL3824304	IC50	0.31 nM
8-(4-cyclobutylpiperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.32 nM	US-9126931: Tetracyclic compound
9-bromo-8-(4-tert-butylpiperazin-1-yl)-11-oxospiro[5H-benzo[b]carbazole-6,4’-oxane]-3-carbonitrile	IC50	0.32 nM	US-9126931: Tetracyclic compound
CHEMBL3823107	IC50	0.33 nM
CHEMBL3823603	IC50	0.33 nM
CHEMBL3823256	IC50	0.33 nM
CHEMBL4101954	IC50	0.33 nM
CHEMBL5590922	IC50	0.33 nM
CHEMBL3286828	IC50	0.34 nM
CHEMBL3823017	IC50	0.36 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
CHEMBL3823190	IC50	0.38 nM
CHEMBL3823296	IC50	0.39 nM
9-chloro-6,6-dimethyl-8-(4-morpholin-4-ylpiperidin-1-yl)-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.391 nM	US-9126931: Tetracyclic compound
6,6-dimethyl-8-[4-(oxetan-3-yl)piperazin-1-yl]-11-oxo-9-(3-propan-2-yloxyprop-1-ynyl)-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.4 nM	US-9126931: Tetracyclic compound
8-[4-[2-(dimethylamino)acetyl]piperazin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.4 nM	US-9126931: Tetracyclic compound
3-(2-(1-(2-(dimethylamino)acetyl)-5-methoxyindolin-6-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)thiophene-2-carboxamide	IC50	0.4 nM
CHEMBL4855319	IC50	0.4 nM
CHEMBL3823577	IC50	0.42 nM
US9126931, 601	IC50	0.456 nM	US-9126931: Tetracyclic compound
CHEMBL3824290	IC50	0.49 nM
CHEMBL3822557	IC50	0.49 nM
CHEMBL4790570	IC50	0.49 nM
5,5-dimethyl-11-oxo-3-(4-piperidin-1-ylpiperidin-1-yl)-6H-pyrido[4,3-b]carbazole-8-carbonitrile	IC50	0.494 nM	US-9126931: Tetracyclic compound
2-[4-(1-methylpiperidin-4-yl)-2-propan-2-yloxyanilino]-7-[2-(trifluoromethoxy)phenyl]thieno[3,2-d]pyrimidine-6-carboxamide	IC50	0.5 nM	US-9115140: Thienopyrimidine derivatives, processes for the preparation thereof and therapeutic uses thereof
CHEMBL3785774	IC50	0.5 nM
CHEMBL4753933	IC50	0.5 nM
CHEMBL1946804	IC50	0.51 nM
9-acetyl-8-[2-(diethylamino)ethoxy]-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	IC50	0.53 nM	US-9126931: Tetracyclic compound

ChEMBL bioactivities

4638 potent at pChembl≥5 of 4762 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.15	IC50	0.07	nM	CHEMBL3397300
10.00	Ki	0.1	nM	CHEMBL3286823
10.00	Ki	0.1	nM	CHEMBL3286825
10.00	IC50	0.1	nM	CHEMBL5593687
9.96	IC50	0.11	nM	CHEMBL3286826
9.92	Ki	0.12	nM	CHEMBL3286828
9.92	IC50	0.12	nM	CHEMBL3824308
9.82	IC50	0.15	nM	TAE-684
9.78	IC50	0.168	nM	CHEMBL3892880
9.77	IC50	0.17	nM	CHEMBL3687205
9.74	IC50	0.18	nM	CHEMBL3286825
9.74	IC50	0.18	nM	CHEMBL3823235
9.74	IC50	0.18	nM	CHEMBL3822611
9.70	IC50	0.2	nM	CERITINIB
9.70	IC50	0.2	nM	CHEMBL3128069
9.70	Ki	0.2	nM	CHEMBL3128069
9.70	IC50	0.2	nM	LORLATINIB
9.68	IC50	0.21	nM	CHEMBL3286823
9.68	IC50	0.21	nM	CHEMBL3687207
9.68	IC50	0.21	nM	CHEMBL4758611
9.66	Ki	0.22	nM	CHEMBL3286815
9.66	IC50	0.22	nM	CHEMBL3823549
9.66	IC50	0.22	nM	CHEMBL3687206
9.64	IC50	0.23	nM	CHEMBL3889838
9.62	Kd	0.24	nM	CHEMBL2172315
9.62	IC50	0.24	nM	CHEMBL3823416
9.62	IC50	0.24	nM	CHEMBL3687201
9.62	IC50	0.24	nM	CHEMBL4743579
9.62	IC50	0.24	nM	CHEMBL5598386
9.62	IC50	0.24	nM	CHEMBL5844539
9.60	IC50	0.25	nM	CERITINIB
9.59	IC50	0.26	nM	CHEMBL3687202
9.59	IC50	0.26	nM	CHEMBL3687204
9.59	IC50	0.26	nM	CHEMBL3687211
9.57	IC50	0.27	nM	CHEMBL4522012
9.55	IC50	0.28	nM	CHEMBL3824327
9.54	Ki	0.29	nM	CHEMBL3286820
9.54	Ki	0.29	nM	CHEMBL4286522
9.52	Ki	0.3	nM	CHEMBL3128066
9.52	IC50	0.3	nM	CHEMBL3917178
9.52	IC50	0.3	nM	CHEMBL3953815
9.52	IC50	0.3	nM	CHEMBL3929615
9.52	IC50	0.3	nM	CHEMBL5928907
9.51	IC50	0.31	nM	CHEMBL3218856
9.51	IC50	0.31	nM	CHEMBL3824304
9.49	IC50	0.32	nM	CHEMBL3946496
9.49	IC50	0.32	nM	CHEMBL3915577
9.48	IC50	0.33	nM	CHEMBL3823107
9.48	IC50	0.33	nM	CHEMBL3823603
9.48	IC50	0.33	nM	CHEMBL3823256

PubChem BioAssay actives

2665 with measured affinity, of 6100 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
(17R)-20-amino-14-fluoro-5,9,17-trimethyl-10-oxo-18-oxa-5,6,9,21-tetrazatetracyclo[17.3.1.03,7.011,16]tricosa-1(23),3,6,11(16),12,14,19,21-octaene-4-carbonitrile	1579876: Inhibition of ALK (unknown origin)	ki	<0.0001	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0001	uM
(17S)-20-amino-14-fluoro-5,17-dimethyl-10,18-dioxa-4,5,21-triazatetracyclo[17.3.1.02,6.011,16]tricosa-1(23),2(6),3,11(16),12,14,19,21-octaene-3-carbonitrile	2026363: Binding affinity to ALK (unknown origin) assessed as inhibition of constant	ki	0.0001	uM
(16R)-19-amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,11,13,18,20-heptaene-3-carbonitrile	2187695: Binding affinity to recombinant ALK (unknown origin) assessed as inhibition constant in presence of ATP by microfluidic mobility shift assay	ki	0.0001	uM
8-[1-[3-(dimethylamino)propyl]pyrazol-3-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	2091128: Inhibition of wild type ALK (unknown origin) by enzymatic assay	ic50	0.0001	uM
5-chloro-2-N-[4-[4-(dimethylamino)piperidin-1-yl]-2-methoxyphenyl]-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0001	uM
5-chloro-4-N-(2-diethylphosphorylphenyl)-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0001	uM
5-chloro-2-N-(6-methoxy-1,2,3,4-tetrahydroisoquinolin-7-yl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1710806: Inhibition of crizotinib-resistant ALK G1269A mutant (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay	ic50	0.0002	uM
(16R)-19-amino-13-fluoro-3,5,8,16-tetramethyl-17-oxa-4,8,20-triaza-5-azoniatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,10(15),11,13,18,20-octaen-9-one	1419634: Inhibition of ALK (unknown origin)	ki	0.0002	uM
4-[(2,6-dichloro-3-fluorophenyl)methoxymethyl]-12-(1-piperidin-4-ylpyrazol-4-yl)-8,9,11-triazatricyclo[6.4.0.02,6]dodeca-1,6,9,11-tetraene	2119175: Inhibition of ALK (unknown origin)	ic50	0.0002	uM
2-[4-[4-[[5-chloro-4-(2-dimethylphosphorylanilino)pyrimidin-2-yl]amino]-3-methoxyphenyl]piperazin-1-yl]ethanol	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0002	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0002	uM
3,5-difluoro-N-[6-[[4-(2-hydroxypropan-2-yl)piperidin-1-yl]methyl]-1-[4-(propan-2-ylcarbamoyl)cyclohexyl]benzimidazol-2-yl]benzamide	702988: Binding affinity to human ALK by Ambit titration assay	kd	0.0002	uM
Ceritinib	1882662: Inhibition of ALK (unknown origin)	ic50	0.0002	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-(2-methoxy-4-morpholin-4-ylphenyl)pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0002	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0002	uM
5-chloro-2-N-(9-methoxy-2,3,5,6-tetrahydro-1H-[1,2,4]triazino[4,3-a]quinolin-8-yl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1449869: Inhibition of wild type ALK (unknown origin) using TK as substrate after 30 mins by HTRF assay	ic50	0.0003	uM
4-(furan-2-ylmethoxymethyl)-12-(1-piperidin-4-ylpyrazol-4-yl)-8,9,11-triazatricyclo[6.4.0.02,6]dodeca-1,6,9,11-tetraene	2119175: Inhibition of ALK (unknown origin)	ic50	0.0003	uM
(3S)-1-[6-[2-methyl-4-[(1-methylpiperidin-4-yl)amino]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-N-[[4-(trifluoromethoxy)phenyl]methyl]piperidine-3-carboxamide	1579904: Inhibition of ALK (unknown origin) by TR-FRET assay	ic50	0.0003	uM
5-chloro-2-N-(4-dimethylphosphoryl-2-methoxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0003	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0003	uM
5-chloro-2-N-[4-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-2-methoxyphenyl]-4-N-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0003	uM
5-chloro-2-N-(4-dimethylphosphoryl-2-methoxyphenyl)-4-N-(2-methylsulfonylphenyl)pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0003	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-(1-methylpyrrolidin-3-yl)oxyphenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0003	uM
5-chloro-2-N-[4-[2-(dimethylamino)ethyl]-2-methoxy-5-methylphenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1426181: Inhibition of ALK G1269A mutant (unknown origin) using peptide as substrate measured after 30 mins by fluorescence assay	ic50	0.0004	uM
N-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]-N’-hydroxyoctanediamide	1769653: Inhibition of ALK G1202R mutant (unknown origin)	ic50	0.0004	uM
3-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]thiophene-2-carboxamide	392353: Inhibition of ALK	ic50	0.0004	uM
2-[5-[6-amino-5-[(1R)-1-[5-fluoro-2-(triazol-2-yl)phenyl]ethoxy]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]propan-2-ol	1074745: Inhibition of human recombinant ALK L1196M mutant kinase domain (amino acids 1093 to 1141) expressed in baculovirus using 5’FAM-KKSRGDYMTMQIG-CONH2 as substrate incubated for 15 mins prior to Km levels of ATP addition measured after 1 hr by microfluidic mobility shift assay	ki	0.0004	uM
6-amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-N-[4-[(3R,5S)-3,5-dimethylpiperazine-1-carbonyl]phenyl]pyridazine-3-carboxamide	1579874: Inhibition of ALK (unknown origin) by kinome scan-based assay	ic50	0.0004	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-(1-methylpiperidin-4-yl)phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0004	uM
4-fluoro-N-[6-[[4-(2-hydroxypropan-2-yl)piperidin-1-yl]methyl]-1-[4-(propan-2-ylcarbamoyl)cyclohexyl]benzimidazol-2-yl]benzamide	702988: Binding affinity to human ALK by Ambit titration assay	kd	0.0004	uM
Brigatinib	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0004	uM
4-N-(2-dimethylphosphorylphenyl)-5-fluoro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0004	uM
1-[4-[[5-chloro-4-(2-dimethylphosphorylanilino)pyrimidin-2-yl]amino]-3-methoxyphenyl]piperidin-4-ol	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0004	uM
4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-5-methylpyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0004	uM
5-chloro-2-N-(7-propan-2-yloxy-1,2,3,4-tetrahydroisoquinolin-6-yl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1710803: Inhibition of ALK (unknown origin) using peptide substrate incubated for 30 mins in presence of ATP by fluorescence assay	ic50	0.0005	uM
Crizotinib	1416643: Inhibition of recombinant ALK (unknown origin) after 1 hr by fluorescence assay	ec50	0.0005	uM
4-fluoro-2-methoxy-3-(1-methylpiperidin-4-yl)-11-oxo-5-propan-2-yl-6H-indolo[2,3-b]quinoline-8-carbonitrile	1700647: Inhibition of N-terminal GST tagged wild-type human ALK cytoplasmic domain (1058-1620 amino acids) expressed Sf9 cells pre-incubated for 30 mins before addition of Ulight-CKKSRGDYMTMQIG substrate and measured after 90 mins by fluorescence based assay	ic50	0.0005	uM
5-chloro-2-N-[(6E)-3-methoxy-5,5-dimethyl-6-(4-methylpiperazin-1-yl)imino-7,8-dihydronaphthalen-2-yl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	1290623: Inhibition of wild type ALK (unknown origin) after 30 mins by HTRF assay	ic50	0.0005	uM
3-[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-methyl-5-propan-2-yloxyphenyl]piperidin-1-yl]-N-[2-[2-(prop-2-enoylamino)ethoxy]ethyl]propanamide	1708461: Inhibition of N-terminal GST tagged human ALK cytoplasmic domain (1058 to 1620 residues) expressed in Sf21 cells by mobility shift assay	ic50	0.0005	uM
2-fluoro-6-[[2-[2-methoxy-4-(4-propan-2-ylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	392239: Inhibition of ALK	ic50	0.0005	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	1579876: Inhibition of ALK (unknown origin)	ic50	0.0005	uM
6-[6-amino-5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-pyridinyl]-1’-methylspiro[1H-indole-3,4’-piperidine]-2-one	1056226: Inhibition of human ALK (unknown origin) using poly[Glu:Tyr] as substrate by nanoliter kinase assay	ic50	0.0005	uM
N-[6-chloro-19-methoxy-17-(4-methylpiperazin-1-yl)-2,4,8,22-tetrazatetracyclo[14.3.1.13,7.19,13]docosa-1(19),3,5,7(22),9,11,13(21),16(20),17-nonaen-10-yl]-N-methylmethanesulfonamide	643167: Inhibition of baculovirus expressed GST-tagged human ALK cytoplasmic domain using PLCgamma as substrate after 15 mins by time-resolved fluorescence analysis	ic50	0.0005	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-[4-(4-methyl-1,4-diazepan-1-yl)piperidin-1-yl]phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0005	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-(1-methylpiperidin-4-yl)oxyphenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0005	uM
5-chloro-4-N-(2-dimethylphosphorylphenyl)-2-N-[2-methoxy-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0005	uM
4-fluoro-3-[1-(2-hydroxyethyl)piperidin-4-yl]-2-methoxy-11-oxo-5-propan-2-yl-6H-indolo[2,3-b]quinoline-8-carbonitrile	1700647: Inhibition of N-terminal GST tagged wild-type human ALK cytoplasmic domain (1058-1620 amino acids) expressed Sf9 cells pre-incubated for 30 mins before addition of Ulight-CKKSRGDYMTMQIG substrate and measured after 90 mins by fluorescence based assay	ic50	0.0006	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-methylsulfonylphenyl)pyrimidine-2,4-diamine	1310801: Inhibition of human ALK using poly[Glu:Tyr] (4:1) as substrate and [gamma-33P]ATP measured after 1 hr	ic50	0.0006	uM
N-[5-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-4-methoxy-2-(4-methyl-1,4-diazepan-1-yl)phenyl]prop-2-enamide	1350809: Inhibition of recombinant human N-terminal GST/His6-fused ALK L1196M mutant expressed in Sf9 insect cells using Tyr 1 peptide as substrate after 1 hr by Z-LYTE assay	ic50	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Crizotinib	decreases response to substance, decreases reaction, affects response to substance, decreases activity, increases expression (+7 more)	21
NVP-TAE684	increases response to substance, decreases phosphorylation, decreases reaction, decreases response to substance, increases mutagenesis (+2 more)	11
ceritinib	affects response to substance, decreases phosphorylation, decreases activity	3
tanespimycin	decreases activity, decreases expression	2
alectinib	decreases activity, affects response to substance	2
Aldrin	affects cotreatment, increases expression, decreases expression	2
Dichlorodiphenyldichloroethane	affects cotreatment, increases expression, decreases expression	2
Dichlorodiphenyl Dichloroethylene	affects cotreatment, increases expression, decreases expression	2
Dieldrin	decreases expression, affects cotreatment, increases expression	2
Ethylnitrosourea	increases mutagenesis, decreases phosphorylation, decreases reaction, decreases response to substance	2
Tretinoin	decreases expression, increases expression, affects cotreatment, increases cleavage	2
lorlatinib	decreases activity, decreases phosphorylation	1
WY-135	decreases expression, decreases phosphorylation	1
bisphenol A	affects cotreatment, affects methylation	1
terbufos	increases methylation	1
2,4-diaminopyrimidine	decreases response to substance, decreases phosphorylation, decreases reaction	1
benzo(e)pyrene	decreases methylation	1
2,4-diaminopyridine	affects binding, decreases activity	1
aflatoxin B2	decreases methylation	1
2,2-(2-chlorophenyl-4’-chlorophenyl)-1,1-dichloroethene	affects cotreatment, increases expression	1
N-(3-phenoxycinnamyl)acetohydroxamic acid	decreases activity	1
17-(dimethylaminoethylamino)-17-demethoxygeldanamycin	decreases stability	1
9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo(h)(1,6)naphthyridin-2(1H)-one	decreases response to substance	1
N-(2-(2-(4-(4-(2-hydroxypropyl)piperazin-1-yl)-2-methoxyphenylamino)pyrrolo(2,1-f)(1,2,4)triazin-7-yl)phenyl)-N-methylmethanesulfonamide	increases response to substance, increases activity	1
Pemetrexed	affects response to substance	1
Fulvestrant	affects cotreatment, affects methylation	1
Acetylcysteine	affects phosphorylation, affects activity	1
Adenosine Triphosphate	affects binding, increases reaction, decreases response to substance	1
Amiodarone	increases expression	1
Amphotericin B	increases expression	1

ChEMBL screening assays

1815 unique, capped per target: 1801 binding, 13 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005525	Binding	Inhibition of NPM-ALK in human Karpas299 cells at 50 nM	Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. — *Proc Natl Acad Sci U S A*
CHEMBL861020	Functional	Antiproliferative activity against SUDHL1 expressing NPM-ALK by MTT assay	Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application. — *J Med Chem*
CHEMBL4313077	ADMET	Inhibition of human ALK 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

196 cell lines: 185 cancer cell line, 9 factor-dependent cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0019	SH-SY5Y	Cancer cell line	Female
CVCL_0389	LA-N-5	Cancer cell line	Male
CVCL_0522	SH-EP007	Cancer cell line	Female
CVCL_0523	SH-SY5Y-SPA4CT	Cancer cell line	Female
CVCL_0524	SH-EP	Cancer cell line	Female
CVCL_0531	SK-N-SH	Cancer cell line	Female
CVCL_0538	SU-DHL-1	Cancer cell line	Male
CVCL_0575	WAC2	Cancer cell line	Female
CVCL_0F47	SH-EP1	Cancer cell line	Female
CVCL_1170	DEL	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 322 trials:

NCT	Phase	Status	Title
NCT00190697	Phase 4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	Phase 4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	Phase 4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	Phase 4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	Phase 4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	Phase 4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	Phase 4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	Phase 4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	Phase 4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	Phase 4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	Phase 4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	Phase 4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	Phase 4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	Phase 4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	Phase 4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	Phase 4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	Phase 4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	Phase 4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	Phase 4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	Phase 4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	Phase 4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	Phase 4	UNKNOWN	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	Phase 4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	Phase 4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	Phase 4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	Phase 4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00632528	Phase 3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00001806	Phase 3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	Phase 3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	Phase 3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	Phase 3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	Phase 3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	Phase 3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	Phase 3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	Phase 3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	Phase 3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	Phase 3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	Phase 3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	Phase 3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	Phase 3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer
NCT00003695	Phase 3	COMPLETED	Chemotherapy With or Without Surgery in Treating Patients With Stage II or Stage III Ovarian Cancer
NCT00003998	Phase 3	COMPLETED	Carboplatin Plus Paclitaxel or Docetaxel in Treating Patients With Ovarian Epithelial Cancer
NCT00004115	Phase 3	UNKNOWN	Monoclonal Antibody Therapy in Treating Patients With Ovarian Cancer or Primary Peritoneal Cancer in Remission Following Surgery and Chemotherapy
NCT00004166	Phase 3	COMPLETED	Amifostine in Treating Patients With Ovarian Epithelial Cancer Who Are Receiving Chemotherapy
NCT00004921	Phase 3	COMPLETED	High-Dose Chemotherapy Compared With Standard Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer That Has Been Removed During Surgery
NCT00004934	Phase 3	COMPLETED	Paclitaxel and Carboplatin With or Without Epirubicin in Treating Patients With Stage IIB, Stage III, or Stage IV Invasive Ovarian Epithelial, Fallopian Tube, or Peritoneal Cancer
NCT00005590	Phase 3	COMPLETED	Levofloxacin to Prevent Infection Following Chemotherapy in Treating Patients With Solid Tumors or Lymphoma
NCT00006356	Phase 3	TERMINATED	Chemotherapy With or Without Surgery in Treating Patients With Recurrent Ovarian Cancer
NCT00006453	Phase 3	COMPLETED	Carboplatin With or Without Gemcitabine in Treating Patients With Advanced Ovarian Epithelial Cancer That Has Not Responded to Previous Chemotherapy
NCT00006454	Phase 3	COMPLETED	Paclitaxel Plus Carboplatin With or Without Topotecan in Treating Patients With Stage IIB, Stage III, or Stage IV Ovarian Epithelial Cancer
NCT00011986	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer
NCT00028743	Phase 3	COMPLETED	Combination Chemotherapy Regimens in Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
NCT00033605	Phase 3	COMPLETED	Octreotide in Preventing Diarrhea in Patients Who Are Undergoing Radiation Therapy to the Pelvis
NCT00043082	Phase 3	COMPLETED	S0200 Carboplatin With or Without Doxil in Patients With Recurrent Ovarian Cancer
NCT00050375	Phase 3	TERMINATED	Clinical Trial for Ovarian Cancer (OvaRex®)
NCT00052468	Phase 3	COMPLETED	Carboplatin/Paclitaxel +/-Gemcitabine in Treating Patients With Ovarian Epithelial or Fallopian Tube Cancer
NCT00057720	Phase 3	COMPLETED	TLK286 (Telcyta) vs. Doxil/Caelyx or Hycamtin in Platinum Refractory or Resistant Ovarian Cancer
NCT00098878	Phase 3	COMPLETED	Carboplatin in Treating Patients With Stage IC-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
NCT00102375	Phase 3	COMPLETED	Paclitaxel, Carboplatin, and Topotecan in Patients With Ovarian Cancer

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ALK across ~30M SureChEMBL compounds — explore on Sugi Predict.