CDK15

Summary

CDK15 (cyclin dependent kinase 15, HGNC:14434) is a protein-coding gene on chromosome 2q33.1, encoding Cyclin-dependent kinase 15 (Q96Q40). Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at ‘Thr-34’.

Enables protein serine/threonine kinase activity. Predicted to be involved in regulation of cell cycle phase transition. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 65061 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 66 total
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001366386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14434
Approved symbol	CDK15
Name	cyclin dependent kinase 15
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	PFTAIRE2
Ensembl gene	ENSG00000138395
Ensembl biotype	protein_coding
OMIM	616147
Entrez	65061

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000260967, ENST00000410091, ENST00000434439, ENST00000450471, ENST00000451080, ENST00000460149, ENST00000466337, ENST00000488419, ENST00000493754, ENST00000652192

RefSeq mRNA: 4 — MANE Select: NM_001366386 NM_001261435, NM_001261436, NM_001366386, NM_139158

CCDS: CCDS2350, CCDS58746, CCDS58747, CCDS92927

Canonical transcript exons

ENST00000652192 — 14 exons

Exon	Start	End
ENSE00000000297	201806537	201806787
ENSE00003474063	201847381	201847474
ENSE00003476429	201812483	201812562
ENSE00003523928	201833848	201833971
ENSE00003580487	201872278	201872326
ENSE00003589424	201880028	201880167
ENSE00003611693	201807494	201807643
ENSE00003617898	201890785	201890927
ENSE00003632123	201854874	201854937
ENSE00003632778	201807858	201807952
ENSE00003640314	201823665	201823727
ENSE00003659051	201822809	201822903
ENSE00003689329	201835643	201835763
ENSE00003899886	201893301	201895550

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 92.19.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4219 / max 161.6394, expressed in 341 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24688	0.9696	311
24685	0.3935	26
24689	0.0375	13
24684	0.0121	6
24686	0.0092	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	92.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.55	gold quality
epithelial cell of pancreas	CL:0000083	85.61	gold quality
kidney epithelium	UBERON:0004819	84.66	gold quality
sperm	CL:0000019	84.58	gold quality
germinal epithelium of ovary	UBERON:0001304	83.30	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.14	gold quality
secondary oocyte	CL:0000655	82.39	gold quality
buccal mucosa cell	CL:0002336	81.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.33	gold quality
lower lobe of lung	UBERON:0008949	79.11	silver quality
upper arm skin	UBERON:0004263	79.01	gold quality
cauda epididymis	UBERON:0004360	78.25	gold quality
left ventricle myocardium	UBERON:0006566	78.11	gold quality
superficial temporal artery	UBERON:0001614	77.52	gold quality
left ovary	UBERON:0002119	72.39	gold quality
oocyte	CL:0000023	72.15	gold quality
right ovary	UBERON:0002118	72.09	gold quality
ovary	UBERON:0000992	70.80	gold quality
caput epididymis	UBERON:0004358	69.90	silver quality
myocardium	UBERON:0002349	69.81	gold quality
nasal cavity epithelium	UBERON:0005384	69.70	gold quality
stromal cell of endometrium	CL:0002255	69.53	gold quality
gall bladder	UBERON:0002110	69.31	gold quality
epithelium of nasopharynx	UBERON:0001951	68.36	gold quality
parietal pleura	UBERON:0002400	67.74	silver quality
endothelial cell	CL:0000115	65.48	gold quality
deltoid	UBERON:0001476	65.30	gold quality
muscle tissue	UBERON:0002385	64.35	gold quality
layer of synovial tissue	UBERON:0007616	63.17	silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	11.61
E-CURD-112	yes	10.38
E-MTAB-9801	yes	7.17
E-ANND-3	yes	5.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting CDK15, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-885-5P	99.59	68.59	879

Literature-anchored findings (GeneRIF, showing 3)

• In summary, our results suggest that ALS2CR7 confers TRAIL resistance to cancer cells via phosphorylation of survivin. (PMID:24866247)
• Cyclin-dependent kinase 15 upregulation is correlated with poor prognosis for patients with breast cancer. (PMID:34162268)
• CDK15 promotes colorectal cancer progression via phosphorylating PAK4 and regulating beta-catenin/ MEK-ERK signaling pathway. (PMID:34262144)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk15	ENSDARG00000006093
mus_musculus	Cdk15	ENSMUSG00000026023
rattus_norvegicus	Cdk15	ENSRNOG00000022899

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 15 — Q96Q40 (reviewed: Q96Q40)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein, Cell division protein kinase 15, Serine/threonine-protein kinase ALS2CR7, Serine/threonine-protein kinase PFTAIRE-2

All UniProt accessions (2): Q96Q40, F8WDP7

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at ‘Thr-34’.

Miscellaneous. May be due to competing acceptor splice site.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96Q40-1	1	yes
Q96Q40-3	3
Q96Q40-4	4
Q96Q40-5	5
Q96Q40-6	6

RefSeq proteins (4): NP_001248364, NP_001248365, NP_001353315, NP_631897 (=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
IPR042761	CDK15_STKc	Domain
IPR050108	CDK	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.22 — cyclin-dependent kinase (BRENDA: 49 organisms, 441 substrates, 555 inhibitors, 8 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ADAQHATPPKKKRKVEDPKDF	0.046–0.521	2
ATP	0.0052–0.017	2
FIN1	0.003	1
PKTPKKAKKL	0.0029	1

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 (16 total): splice variant 6, sequence variant 5, binding site 2, chain 1, domain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q40-F1	72.75	0.43

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): 224 (proton acceptor)

Ligand- & substrate-binding residues (2): 109–117; 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, TGACCTY_ERR1_Q2, TGCTGAY_UNKNOWN, GOBP_REGULATION_OF_CELL_CYCLE, AACTTT_UNKNOWN, P300_01, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, CTGYNNCTYTAA_UNKNOWN, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GOCC_TRANSFERASE_COMPLEX, GOCC_PROTEIN_KINASE_COMPLEX, GOBP_CELL_CYCLE_PROCESS, GOCC_CYCLIN_DEPENDENT_PROTEIN_KINASE_HOLOENZYME_COMPLEX, GOMF_CYCLIN_BINDING

GO Biological Process (2): regulation of cell cycle phase transition (GO:1901987), protein phosphorylation (GO:0006468)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), cyclin binding (GO:0030332), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
cellular anatomical structure	2
regulation of cell cycle process	1
cell cycle phase transition	1
phosphorylation	1
protein modification process	1
protein serine/threonine kinase activity	1
cyclin-dependent protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
cation 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
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2793 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK15	CCNY	Q8ND76	743
CDK15	TEKT3	Q9BXF9	403
CDK15	HEATR6	Q6AI08	399
CDK15	FSIP2	Q5CZC0	389
CDK15	DDX6	P26196	387
CDK15	CLMP	Q9H6B4	365
CDK15	PLPPR5	Q32ZL2	354
CDK15	CCNC	P24863	339
CDK15	CCNK	O75909	336
CDK15	NDUFS6	O75380	294
CDK15	LNPEP	Q9UIQ6	290
CDK15	TERT	O14746	289
CDK15	CDC37L1	Q7L3B6	284
CDK15	CCNA2	P20248	283
CDK15	TSPYL6	Q8N831	276

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CDK9	AIP	psi-mi:“MI:0914”(association)	0.730
CDK15	FKBP5	psi-mi:“MI:0915”(physical association)	0.670
CDK15	HSP90AA1	psi-mi:“MI:0914”(association)	0.560
HSP90AA1	CDK15	psi-mi:“MI:0915”(physical association)	0.560
CDK15	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.520
CDK15	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
DNMT3B	CDK15	psi-mi:“MI:0915”(physical association)	0.400
CDC37	CDK15	psi-mi:“MI:0915”(physical association)	0.400
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK18	MTA2	psi-mi:“MI:0914”(association)	0.350
CDK14	FGR	psi-mi:“MI:0914”(association)	0.350
CDK15	TUSC2	psi-mi:“MI:0914”(association)	0.350
CDK18	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
CDK15	NDUFA4	psi-mi:“MI:0914”(association)	0.350
CDK2	CDK15	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (199): HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), HSP90AB3P (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT2 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), CDC37 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), PDCL (Affinity Capture-MS), MARK2 (Affinity Capture-MS), CDK15 (Affinity Capture-MS), ANXA8L1 (Affinity Capture-MS)

ESM2 similar proteins: A1D624, A2Y4B6, A4IIW7, A8X5H5, B0VXE8, B0VXL7, B6A7Q3, C0RW22, G5EBT1, O23145, O35495, O35831, O35832, O44514, O61847, O94921, P21965, P29620, P43289, P51137, P51138, P51139, Q00536, Q00537, Q04735, Q04899, Q07002, Q0TWJ7, Q11179, Q1RLU9, Q39012, Q39019, Q3V3A1, Q40518, Q5RD01, Q5XIT0, Q63686, Q6CCB0, Q6DJM7, Q84M93

Diamond homologs: A4IIW7, A8XA58, B0VXE8, B0VXL7, B6A7Q3, C0RW22, G5ECH7, O35495, O35831, O35832, O55076, O61847, O74456, O94921, O96821, P00546, P04551, P06493, P11440, P13863, P17157, P23111, P23437, P23572, P23573, P24033, P24100, P24923, P24941, P25859, P29618, P29619, P34112, P34117, P35567, P38973, P39951, P43063, P43450, P48609

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2736 predictions. Top by Δscore:

Variant	Effect	Δscore
2:201807614:G:GT	donor_gain	1.0000
2:201812481:A:AG	acceptor_gain	1.0000
2:201812482:G:GG	acceptor_gain	1.0000
2:201812559:GAAG:G	donor_gain	1.0000
2:201812560:AAGGT:A	donor_loss	1.0000
2:201812561:AGGT:A	donor_loss	1.0000
2:201812562:GGT:G	donor_loss	1.0000
2:201812563:G:T	donor_loss	1.0000
2:201812564:T:A	donor_loss	1.0000
2:201822807:A:AG	acceptor_gain	1.0000
2:201822808:G:GA	acceptor_gain	1.0000
2:201822808:GC:G	acceptor_gain	1.0000
2:201822808:GCTT:G	acceptor_gain	1.0000
2:201822808:GCTTC:G	acceptor_gain	1.0000
2:201822902:TGGTG:T	donor_loss	1.0000
2:201822903:GGTGA:G	donor_loss	1.0000
2:201822904:GTGAG:G	donor_loss	1.0000
2:201822905:TGAGT:T	donor_loss	1.0000
2:201822906:G:GT	donor_loss	1.0000
2:201833846:A:AG	acceptor_gain	1.0000
2:201833847:G:GG	acceptor_gain	1.0000
2:201833968:TTTGG:T	donor_loss	1.0000
2:201833970:TGGTA:T	donor_loss	1.0000
2:201833971:GGT:G	donor_loss	1.0000
2:201833972:GT:G	donor_loss	1.0000
2:201833973:TAA:T	donor_loss	1.0000
2:201790576:G:GT	donor_gain	0.9900
2:201790660:GGTAA:G	donor_loss	0.9900
2:201790662:T:A	donor_loss	0.9900
2:201807492:A:AG	acceptor_gain	0.9900

AlphaMissense

2845 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:201812509:A:T	K132I	0.999
2:201812510:A:C	K132N	0.999
2:201812510:A:T	K132N	0.999
2:201822890:T:A	V177D	0.999
2:201833909:G:T	R223M	0.999
2:201833912:A:C	D224A	0.999
2:201833912:A:T	D224V	0.999
2:201833864:T:C	L208P	0.998
2:201833909:G:C	R223T	0.998
2:201833912:A:G	D224G	0.998
2:201833913:C:A	D224E	0.998
2:201833913:C:G	D224E	0.998
2:201833919:A:C	K226N	0.998
2:201833919:A:T	K226N	0.998
2:201833954:T:A	L238H	0.998
2:201833958:A:C	K239N	0.998
2:201833958:A:T	K239N	0.998
2:201833966:A:T	D242V	0.998
2:201835649:C:A	A246D	0.998
2:201812503:C:A	A130D	0.997
2:201812561:A:C	E149D	0.997
2:201812561:A:T	E149D	0.997
2:201822818:T:C	L153P	0.997
2:201823675:T:C	L185P	0.997
2:201833905:C:G	H222D	0.997
2:201833910:G:C	R223S	0.997
2:201833910:G:T	R223S	0.997
2:201833911:G:C	D224H	0.997
2:201833917:A:G	K226E	0.997
2:201833918:A:T	K226I	0.997

dbSNP variants (sampled 300 via entrez): RS1000000505 (2:201841933 G>T), RS1000001450 (2:201809182 A>C,G), RS1000018268 (2:201886582 C>T), RS1000038113 (2:201892859 G>A), RS1000074776 (2:201823372 A>T), RS1000109816 (2:201893288 C>A,G), RS1000134343 (2:201867158 T>A,C,G), RS1000142668 (2:201808839 T>C), RS1000152833 (2:201872128 A>G), RS1000184358 (2:201858595 C>T), RS1000345682 (2:201828262 G>A), RS1000362081 (2:201851346 G>A,C), RS1000373942 (2:201874144 C>A,T), RS1000396986 (2:201851674 T>C), RS1000420809 (2:201827965 T>C,G)

Disease associations

OMIM: gene MIM:616147 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006288_239	Heel bone mineral density	2.000000e-09
GCST006288_502	Heel bone mineral density	4.000000e-13
GCST006979_80	Heel bone mineral density	2.000000e-21
GCST006979_81	Heel bone mineral density	6.000000e-16
GCST90020026_372	Hip index	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559691 (PROTEIN FAMILY), CHEMBL5483184 (PROTEIN COMPLEX), CHEMBL5856 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 141,991 (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
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL384304	RG-547	2	93
CHEMBL445813	AT-7519	2	2,614
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
CHEMBL574738	AST-487	1	451

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — TAIRE subfamily

ChEMBL bioactivities

20 potent at pChembl≥5 of 20 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.14	Kd	7.2	nM	RG-547
7.50	Kd	32	nM	FORETINIB
7.21	Kd	62	nM	AT-7519
7.08	Kd	84	nM	AST-487
6.58	Kd	260	nM	STAUROSPORINE
6.48	Kd	330	nM	ALVOCIDIB
6.29	Kd	510	nM	PHA-665752
6.13	Kd	740	nM	BMS-387032
5.89	Kd	1300	nM	LESTAURTINIB
5.80	Kd	1600	nM	BOSUTINIB
5.68	Kd	2100	nM	TAE-684
5.68	Kd	2100	nM	CHEMBL379218
5.66	IC50	2200	nM	INDIRUBIN
5.58	Kd	2600	nM	KW-2449
5.54	Kd	2900	nM	SORAFENIB
5.52	IC50	3024	nM	CHEMBL4160662
5.31	Kd	4900	nM	ENZASTAURIN
5.07	Kd	8600	nM	FEDRATINIB

PubChem BioAssay actives

19 with measured affinity, of 206 total; 17 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
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0072	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	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0320	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0620	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.0840	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	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.2600	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.3300	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	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.5100	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	624718: Binding constant for PFTAIRE2 kinase domain	kd	0.7400	uM
(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	507668: Binding affinity to PFTAIRE2	kd	1.3000	uM
Bosutinib	624718: Binding constant for PFTAIRE2 kinase domain	kd	1.6000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624718: Binding constant for PFTAIRE2 kinase domain	kd	2.1000	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	624718: Binding constant for PFTAIRE2 kinase domain	kd	2.1000	uM
2-(2-hydroxy-1H-indol-3-yl)indol-3-one	1378312: Inhibition of recombinant human CDK expressed in baculovirus infected sf9 cells after 10 mins by SDS-PAGE based autoradiography	ic50	2.2000	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624718: Binding constant for PFTAIRE2 kinase domain	kd	2.6000	uM
Sorafenib	507668: Binding affinity to PFTAIRE2	kd	2.9000	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	624718: Binding constant for PFTAIRE2 kinase domain	kd	4.9000	uM
Fedratinib	624718: Binding constant for PFTAIRE2 kinase domain	kd	8.6000	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation	2
Nickel	decreases expression	2
Smoke	increases expression	2
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
CGP 52608	increases reaction, affects binding	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Malathion	increases expression	1
Methapyrilene	increases methylation	1
Niclosamide	decreases expression	1
Valproic Acid	decreases methylation	1
Vanadates	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
p-Chloromercuribenzoic Acid	decreases expression	1

ChEMBL screening assays

95 unique, capped per target: 95 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1064257	Binding	Inhibition of CDK in human A2780 cells assessed as reduction of RNAP2 phosphorylation at Ser2 site at 5 uM after 6 hrs by Western bloting	Design, synthesis, and evaluation of 2-methyl- and 2-amino-N-aryl-4,5-dihydrothiazolo[4,5-h]quinazolin-8-amines as ring-constrained 2-anilino-4-(thiazol-5-yl)pyrimidine cyclin-dependent kinase inhibitors. — J Med Chem

Clinical trials (associated diseases)

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