MAP3K19

Summary

MAP3K19 (mitogen-activated protein kinase kinase kinase 19, HGNC:26249) is a protein-coding gene on chromosome 2q21.3, encoding Mitogen-activated protein kinase kinase kinase 19 (Q56UN5).

Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in MAPK cascade.

Source: NCBI Gene 80122 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 159 total
• Druggable target: yes — 41 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_025052

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26249
Approved symbol	MAP3K19
Name	mitogen-activated protein kinase kinase kinase 19
Location	2q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23074, RCK
Ensembl gene	ENSG00000176601
Ensembl biotype	protein_coding
Entrez	80122

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 10 protein_coding, 6 protein_coding_CDS_not_defined, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000358371, ENST00000375844, ENST00000375845, ENST00000392915, ENST00000392917, ENST00000392918, ENST00000414343, ENST00000425952, ENST00000437365, ENST00000468155, ENST00000478805, ENST00000486077, ENST00000637841, ENST00000638025, ENST00000656750, ENST00000658678, ENST00000661220, ENST00000661533, ENST00000662522, ENST00000668969, ENST00000669521, ENST00000669737

RefSeq mRNA: 7 — MANE Select: NM_025052 NM_001018044, NM_001018046, NM_001018047, NM_001282883, NM_001321177, NM_001400438, NM_025052

CCDS: CCDS2176, CCDS33293, CCDS63020, CCDS63021, CCDS63022

Canonical transcript exons

ENST00000392915 — 13 exons

Exon	Start	End
ENSE00001685316	134980821	134981518
ENSE00001765030	135040363	135040502
ENSE00001853615	134964491	134964916
ENSE00001868191	135030312	135030500
ENSE00003495525	135005435	135005531
ENSE00003503709	134983676	134983825
ENSE00003609392	135021715	135021830
ENSE00003619845	134998738	134998997
ENSE00003625939	134991537	134991580
ENSE00003634971	134985800	134988253
ENSE00003653269	134999937	135000015
ENSE00003793397	135024626	135024741
ENSE00003795436	135047185	135047447

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 96.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1904 / max 43.3976, expressed in 56 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30758	0.1379	44
30759	0.0525	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	96.54	gold quality
right uterine tube	UBERON:0001302	94.45	gold quality
sperm	CL:0000019	93.62	gold quality
epithelium of bronchus	UBERON:0002031	93.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.21	gold quality
male germ cell	CL:0000015	93.08	gold quality
bronchus	UBERON:0002185	92.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.72	gold quality
olfactory bulb	UBERON:0002264	90.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.96	gold quality
type B pancreatic cell	CL:0000169	85.86	gold quality
superficial temporal artery	UBERON:0001614	85.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.87	gold quality
hair follicle	UBERON:0002073	84.41	gold quality
diaphragm	UBERON:0001103	84.23	gold quality
tongue squamous epithelium	UBERON:0006919	81.58	gold quality
epithelium of nasopharynx	UBERON:0001951	81.07	gold quality
CA1 field of hippocampus	UBERON:0003881	78.95	gold quality
right testis	UBERON:0004534	78.64	gold quality
left testis	UBERON:0004533	78.43	gold quality
oviduct epithelium	UBERON:0004804	77.55	gold quality
fallopian tube	UBERON:0003889	77.54	gold quality
mucosa of urinary bladder	UBERON:0001259	77.41	gold quality
cervix epithelium	UBERON:0004801	77.24	gold quality
testis	UBERON:0000473	76.79	gold quality
gingival epithelium	UBERON:0001949	76.77	gold quality
cervix squamous epithelium	UBERON:0006922	76.48	gold quality
thymus	UBERON:0002370	76.19	gold quality
caput epididymis	UBERON:0004358	76.11	gold quality
left ventricle myocardium	UBERON:0006566	75.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting MAP3K19, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-1972	97.67	67.38	1172

Literature-anchored findings (GeneRIF, showing 2)

• Mitogen-activated protein kinase kinase kinase 19 (MAP3K19) is overexpressed in the lungs of chronic obstructive pulmonary disease (COPD) patients. (PMID:27935962)
• The protein kinase MAP3K19 phosphorylates MAP2Ks and thereby activates ERK and JNK kinases and increases viability of KRAS-mutant lung cancer cells. (PMID:32358059)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	map3k19	ENSDARG00000094272
mus_musculus	Map3k19	ENSMUSG00000051590
rattus_norvegicus	Map3k19	ENSRNOG00000003952
caenorhabditis_elegans		WBGENE00017578

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), STRADB (ENSG00000082146), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Protein

Protein identifiers

Mitogen-activated protein kinase kinase kinase 19 — Q56UN5 (reviewed: Q56UN5)

Alternative names: Regulated in COPD, protein kinase, SPS1/STE20-related protein kinase YSK4

All UniProt accessions (6): Q56UN5, A0A1B0GTF4, A0A590UJK1, A0A590UJV9, C9JGQ2, H7C041

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q56UN5-1	1	yes
Q56UN5-3	3
Q56UN5-4	4
Q56UN5-5	5
Q56UN5-7	7

RefSeq proteins (7): NP_001018054, NP_001018056, NP_001018057, NP_001269812, NP_001308106, NP_001387367, NP_079328* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (23 total): splice variant 4, sequence variant 4, region of interest 4, compositionally biased region 4, binding site 2, sequence conflict 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q56UN5-F1	44.13	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 1186 (proton acceptor)

Ligand- & substrate-binding residues (2): 1067–1075; 1089

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SHEN_SMARCA2_TARGETS_DN, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, TGFB_UP.V1_DN, SIRNA_EIF4GI_DN, MIR196A_1_3P, MIR141_3P, MIR200A_3P, MIR4251, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_2

GO Biological Process (3): MAPK cascade (GO:0000165), protein phosphorylation (GO:0006468), intracellular signal transduction (GO:0035556)

GO Molecular Function (7): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
intracellular signaling cassette	1
phosphorylation	1
protein modification process	1
intracellular anatomical structure	1
signal transduction	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1

Protein interactions and networks

STRING

2040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAP3K19	KRABD2	Q6ZNG9	492
MAP3K19	ANKRD66	B4E2M5	446
MAP3K19	THSD7B	Q9C0I4	442
MAP3K19	STRADA	Q7RTN6	428
MAP3K19	ANKUB1	A6NFN9	419
MAP3K19	ARL15	Q9NXU5	399
MAP3K19	DYRK1B	Q9Y463	396
MAP3K19	HOATZ	Q6PI97	395
MAP3K19	POLM	Q9NP87	391
MAP3K19	LRRC71	Q8N4P6	382
MAP3K19	BLTP3A	Q6BDS2	366
MAP3K19	RAB3GAP1	Q15042	365
MAP3K19	FAM216B	Q8N7L0	355
MAP3K19	GRB14	Q14449	346
MAP3K19	HASPIN	Q8TF76	325

IntAct

2 interactions, top by confidence:

A	B	Type	Score
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): MAP3K19 (Two-hybrid), MAP3K19 (Reconstituted Complex), MAP3K19 (PCA), MAP3K19 (Affinity Capture-MS), TKT (Cross-Linking-MS (XL-MS)), MAP3K19 (Cross-Linking-MS (XL-MS)), SKIL (Cross-Linking-MS (XL-MS)), MAP3K19 (Affinity Capture-RNA)

ESM2 similar proteins: A0A140LI88, A4D1E1, D3Z987, D3ZUC6, E5FYH0, E5FYH1, E9Q3S4, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, O35923, O54952, O88491, O95405, P38398, P48754, P51587, P97929, Q0VBV7, Q0VGT4, Q2M3C7, Q3V089, Q56UN5, Q5DTT3, Q5F2C3, Q5VWN6, Q61493, Q68DQ2, Q6J6I8, Q6J6I9, Q6J6J0, Q6NSW3, Q6ZP01, Q7TSY8, Q7Z570, Q80U44, Q864S8, Q864U1

Diamond homologs: A0A078CGE6, A0A194W8T8, A2AQW0, A2QHV0, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A7A1P0, A8XJW8, A9RVK2, A9SY39, B0LT89, B0XXN8, B5VNQ3, C4YRB7, E9Q3S4, F4HRJ4, G4N7X0, G4NDR3, H2L099, O00506, O14047, O14305, O22040, O22042, O24527, O54748, O61122, O61125, O81472, O95382, P0CY23, P0CY24, P23561, P27636, P28829

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	139
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1796 predictions. Top by Δscore:

Variant	Effect	Δscore
2:134983674:A:AC	donor_gain	1.0000
2:134983675:C:CC	donor_gain	1.0000
2:134999935:A:AC	donor_gain	1.0000
2:134999936:C:CC	donor_gain	1.0000
2:134999936:CTT:C	donor_gain	1.0000
2:135005429:CAGTA:C	donor_loss	1.0000
2:135005430:AGTAC:A	donor_loss	1.0000
2:135005431:GTAC:G	donor_loss	1.0000
2:135005432:TA:T	donor_loss	1.0000
2:135005433:A:AG	donor_loss	1.0000
2:135005434:C:CT	donor_loss	1.0000
2:135005434:CCTT:C	donor_gain	1.0000
2:135005528:ACTC:A	acceptor_gain	1.0000
2:135005528:ACTCC:A	acceptor_loss	1.0000
2:135005529:CTC:C	acceptor_gain	1.0000
2:135005529:CTCC:C	acceptor_gain	1.0000
2:135005529:CTCCT:C	acceptor_loss	1.0000
2:135005530:TC:T	acceptor_gain	1.0000
2:135005530:TCC:T	acceptor_loss	1.0000
2:135005530:TCCT:T	acceptor_gain	1.0000
2:135005531:CC:C	acceptor_gain	1.0000
2:135005532:C:CC	acceptor_gain	1.0000
2:135005533:T:G	acceptor_loss	1.0000
2:135005541:C:CT	acceptor_gain	1.0000
2:135005542:A:C	acceptor_gain	1.0000
2:135021827:CTTT:C	acceptor_gain	1.0000
2:135021831:C:CC	acceptor_gain	1.0000
2:134964915:CC:C	acceptor_gain	0.9900
2:134964916:CC:C	acceptor_gain	0.9900
2:134964917:C:CC	acceptor_gain	0.9900

AlphaMissense

8891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:134980990:A:G	W1251R	0.999
2:134980990:A:T	W1251R	0.999
2:134981044:A:G	W1233R	0.999
2:134981044:A:T	W1233R	0.999
2:134981130:T:A	D1204V	0.999
2:134981184:T:A	D1186V	0.999
2:134981184:T:G	D1186A	0.999
2:134980962:A:C	M1260R	0.998
2:134980988:C:A	W1251C	0.998
2:134980988:C:G	W1251C	0.998
2:134981129:G:C	D1204E	0.998
2:134981129:G:T	D1204E	0.998
2:134981130:T:G	D1204A	0.998
2:134981131:C:G	D1204H	0.998
2:134981166:A:T	V1192D	0.998
2:134981178:T:A	K1188I	0.998
2:134981187:C:G	R1185P	0.998
2:134981313:A:T	V1143D	0.998
2:134981474:T:A	K1089N	0.998
2:134981474:T:G	K1089N	0.998
2:134981481:G:T	A1087D	0.998
2:134980960:C:G	A1261P	0.997
2:134980962:A:G	M1260T	0.997
2:134980962:A:T	M1260K	0.997
2:134980976:A:C	C1255W	0.997
2:134980978:A:G	C1255R	0.997
2:134980985:G:C	S1252R	0.997
2:134980985:G:T	S1252R	0.997
2:134980987:T:G	S1252R	0.997
2:134981130:T:C	D1204G	0.997

dbSNP variants (sampled 300 via entrez): RS1000008647 (2:135047288 A>G), RS1000065951 (2:134994519 G>T), RS1000079510 (2:135039402 C>G), RS1000102849 (2:135049151 G>T), RS1000143820 (2:135041143 G>A), RS1000149216 (2:135019933 G>A,C), RS1000180391 (2:135037733 A>G), RS1000182078 (2:134974226 C>T), RS1000182895 (2:134996065 G>A), RS1000197460 (2:134974557 A>C,G), RS1000202540 (2:134995982 C>T), RS1000289109 (2:135017323 C>T), RS1000314162 (2:134966121 A>G), RS1000357479 (2:135013767 C>G,T), RS1000379282 (2:135000182 T>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_43	Body mass index	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6191 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

41 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 563,286 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL180022	NERATINIB	4	9,404
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4	117,814
CHEMBL101253	VATALANIB	3	11,319
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL377300	BRIVANIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230609	FORETINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL215152	DEFOSBARASERTIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — STE20 subfamily

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
BIIB068	Inhibition	6.89	pKd

ChEMBL bioactivities

82 potent at pChembl≥5 of 82 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.28	Kd	0.52	nM	LESTAURTINIB
9.07	Kd	0.86	nM	STAUROSPORINE
8.92	Kd	1.2	nM	CHEMBL4290597
8.73	IC50	1.85	nM	STAUROSPORINE
8.29	Kd	5.1	nM	CHEMBL1241674
8.28	Kd	5.2	nM	NINTEDANIB
8.28	Kd	5.2	nM	KW-2449
8.26	Kd	5.5	nM	FORETINIB
8.06	IC50	8.67	nM	STAUROSPORINE
8.02	Kd	9.6	nM	BAY-985
7.92	Kd	12	nM	SU-014813
7.92	Kd	12	nM	DOVITINIB
7.82	Kd	15	nM	MIDOSTAURIN
7.81	IC50	15.6	nM	STAUROSPORINE
7.80	Kd	16	nM	NERATINIB
7.80	Kd	16	nM	BOSUTINIB
7.77	Kd	17	nM	SUNITINIB
7.72	Kd	19	nM	FEDRATINIB
7.60	Kd	25	nM	ERLOTINIB
7.48	Kd	33	nM	GSK-690693
7.41	Kd	39	nM	CHEMBL1908395
7.32	Kd	48	nM	RUBOXISTAURIN
7.29	Kd	51	nM	TOZASERTIB
7.27	Kd	54	nM	RAF-265
7.24	IC50	57	nM	CHEMBL4782804
7.23	IC50	59	nM	CHEMBL4871593
7.17	Kd	67	nM	R-406
7.11	Kd	78	nM	PHA-665752
7.10	Kd	79	nM	DASATINIB
7.01	Kd	97	nM	CHEMBL4066819
7.00	Kd	100	nM	CHEMBL1349996
7.00	Kd	99	nM	SORAFENIB
6.92	Kd	120	nM	AST-487
6.89	Kd	130	nM	CHEMBL4744041
6.89	Kd	130	nM	CGP-52421
6.80	Kd	160	nM	CHEMBL4755663
6.72	Kd	190	nM	CHEMBL1474834
6.72	Kd	190	nM	CHEMBL464552
6.70	Kd	200	nM	CHEMBL4799297
6.70	Kd	200	nM	MOTESANIB
6.66	Kd	220	nM	CHEMBL2153264
6.64	Kd	230	nM	CHEMBL379218
6.62	Kd	240	nM	CHEMBL386051
6.62	Kd	240	nM	GEFITINIB
6.60	Kd	250	nM	CEDIRANIB
6.60	Kd	250	nM	LINIFANIB
6.58	Kd	260	nM	BMS-345541
6.57	Kd	270	nM	RUXOLITINIB
6.57	Kd	270	nM	AXITINIB
6.54	Kd	290	nM	CHEMBL408982

PubChem BioAssay actives

75 with measured affinity, of 185 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
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508136: Binding affinity to YSK4	kd	0.0005	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	625136: Binding constant for YSK4 kinase domain	kd	0.0009	uM
3-[(3R)-3-(4,5-dimethoxy-8-oxo-9,14,16-triazatetracyclo[8.7.0.02,7.011,15]heptadeca-1(17),2,4,6,10,12,15-heptaen-9-yl)piperidin-1-yl]-3-oxopropanenitrile	1415055: Binding affinity to DNA-tagged recombinant human YSK4 (1019 to 1328 residues) expressed in mammalian expression system by KINOMEscan assay	kd	0.0012	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625136: Binding constant for YSK4 kinase domain	kd	0.0051	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625136: Binding constant for YSK4 kinase domain	kd	0.0052	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625136: Binding constant for YSK4 kinase domain	kd	0.0052	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625136: Binding constant for YSK4 kinase domain	kd	0.0055	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	625136: Binding constant for YSK4 kinase domain	kd	0.0120	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	625136: Binding constant for YSK4 kinase domain	kd	0.0120	uM
Midostaurin	508136: Binding affinity to YSK4	kd	0.0150	uM
Bosutinib	625136: Binding constant for YSK4 kinase domain	kd	0.0160	uM
Neratinib	625136: Binding constant for YSK4 kinase domain	kd	0.0160	uM
Sunitinib	508136: Binding affinity to YSK4	kd	0.0170	uM
Fedratinib	625136: Binding constant for YSK4 kinase domain	kd	0.0190	uM
Erlotinib	625136: Binding constant for YSK4 kinase domain	kd	0.0250	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	625136: Binding constant for YSK4 kinase domain	kd	0.0330	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625136: Binding constant for YSK4 kinase domain	kd	0.0390	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	625136: Binding constant for YSK4 kinase domain	kd	0.0480	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	625136: Binding constant for YSK4 kinase domain	kd	0.0510	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	625136: Binding constant for YSK4 kinase domain	kd	0.0540	uM
N-[4-[[3-(prop-2-enoylamino)benzoyl]amino]phenyl]-6-(1H-pyrazol-5-yl)pyridine-2-carboxamide	1725919: Inhibition of wild-type human partial length YSK4 (T1019 to H1328 residues) expressed in mammalian expression system by Kinomescan method	ic50	0.0570	uM
1-(7-ethyl-7-hydroxy-5,6-dihydrocyclopenta[b]pyridin-2-yl)-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one	1784563: Inhibition of YSK4 (unknown origin)	ic50	0.0590	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625136: Binding constant for YSK4 kinase domain	kd	0.0670	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625136: Binding constant for YSK4 kinase domain	kd	0.0780	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	625136: Binding constant for YSK4 kinase domain	kd	0.0790	uM
8-[[6-(2-methoxyethylcarbamoyl)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474317: Binding affinity to partial length wild-type human YSK4 (T1019 to H1328 residues) expressed in bacterial expression system by kinome scan assay	kd	0.0970	uM
Sorafenib	508136: Binding affinity to YSK4	kd	0.0990	uM
(1E)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one	1722618: Binding affinity to MAP3K19 (unknown origin)	kd	0.1000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	625136: Binding constant for YSK4 kinase domain	kd	0.1200	uM
N-[[2-methyl-4-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]phenyl]methyl]-3-propan-2-yloxyazetidine-1-carboxamide	1696254: Binding affinity to wild-type human partial length YSK4 (T1019 to H1328 residues) expressed in mammalian expression system by Kinomescan method	kd	0.1300	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide	508136: Binding affinity to YSK4	kd	0.1300	uM
4-tert-butyl-N-[[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl]benzamide	1696254: Binding affinity to wild-type human partial length YSK4 (T1019 to H1328 residues) expressed in mammalian expression system by Kinomescan method	kd	0.1600	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	625136: Binding constant for YSK4 kinase domain	kd	0.1900	uM
6-(1,3-benzodioxol-5-yl)-N-methyl-N-[(2-methyl-1,3-thiazol-4-yl)methyl]quinazolin-4-amine	594093: Binding affinity to human Ysk4	kd	0.1900	uM
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	625136: Binding constant for YSK4 kinase domain	kd	0.2000	uM
4-pyridin-2-yl-1H-imidazo[4,5-c]pyridin-2-amine	693128: Binding affinity to YSK4	kd	0.2200	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625136: Binding constant for YSK4 kinase domain	kd	0.2300	uM
Gefitinib	625136: Binding constant for YSK4 kinase domain	kd	0.2400	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625136: Binding constant for YSK4 kinase domain	kd	0.2400	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	625136: Binding constant for YSK4 kinase domain	kd	0.2500	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	625136: Binding constant for YSK4 kinase domain	kd	0.2500	uM
N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine	625136: Binding constant for YSK4 kinase domain	kd	0.2600	uM
Ruxolitinib	625136: Binding constant for YSK4 kinase domain	kd	0.2700	uM
Axitinib	625136: Binding constant for YSK4 kinase domain	kd	0.2700	uM
(1Z)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one	445579: Binding affinity to Ysk4 assessed as dissociation constant	kd	0.2900	uM
4-aminocinnoline-3-carboxamide	1948885: Inhibition of YSK4 (unknown origin) assessed as dissociation constant	kd	0.3000	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625136: Binding constant for YSK4 kinase domain	kd	0.4800	uM
(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-ol	625136: Binding constant for YSK4 kinase domain	kd	0.5000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	625136: Binding constant for YSK4 kinase domain	kd	0.7000	uM
2-[4-[(1E)-1-hydroxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanol	625136: Binding constant for YSK4 kinase domain	kd	0.9100	uM

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	increases methylation	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

130 unique, capped per target: 130 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1039045	Binding	Binding affinity to Ysk4 assessed as dissociation constant	Evaluation of substituted 6-arylquinazolin-4-amines as potent and selective inhibitors of cdc2-like kinases (Clk). — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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