CDK19

Summary

CDK19 (cyclin dependent kinase 19, HGNC:19338) is a protein-coding gene on chromosome 6q21, encoding Cyclin-dependent kinase 19 (Q9BWU1).

This gene encodes a protein that is one of the components of the Mediator co-activator complex. The Mediator complex is a multi-protein complex required for transcriptional activation by DNA binding transcription factors of genes transcribed by RNA polymerase II. The protein encoded by this gene is similar to cyclin-dependent kinase 8 which can also be a component of the Mediator complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 23097 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 87 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 99 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 65
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015076

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19338
Approved symbol	CDK19
Name	cyclin dependent kinase 19
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1028, bA346C16.3
Ensembl gene	ENSG00000155111
Ensembl biotype	protein_coding
OMIM	614720
Entrez	23097

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000323817, ENST00000368911, ENST00000413605, ENST00000457688, ENST00000460913, ENST00000463016, ENST00000468997, ENST00000497709, ENST00000886111, ENST00000927994, ENST00000955607

RefSeq mRNA: 4 — MANE Select: NM_015076 NM_001300960, NM_001300963, NM_001300964, NM_015076

CCDS: CCDS5085, CCDS75503

Canonical transcript exons

ENST00000368911 — 13 exons

Exon	Start	End
ENSE00001019260	110622815	110622912
ENSE00001019264	110626776	110626845
ENSE00001019265	110622088	110622166
ENSE00001019268	110621104	110621370
ENSE00001346850	110609978	110614666
ENSE00001726803	110638649	110638706
ENSE00001816360	110815009	110815469
ENSE00003462615	110627002	110627145
ENSE00003627159	110670431	110670541
ENSE00003638116	110632030	110632161
ENSE00003644821	110746126	110746201
ENSE00003675822	110667434	110667574
ENSE00003789597	110623290	110623362

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 96.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4842 / max 178.4977, expressed in 1595 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75066	2.4256	1016
75065	1.3547	723
75067	0.9010	488
75060	0.6057	191
75061	0.5127	242
75062	0.3072	147
75064	0.2133	69
75063	0.1586	58
75054	0.0055	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	96.38	gold quality
medial globus pallidus	UBERON:0002477	96.01	gold quality
corpus callosum	UBERON:0002336	95.86	gold quality
globus pallidus	UBERON:0001875	95.82	gold quality
cortical plate	UBERON:0005343	95.63	gold quality
cranial nerve II	UBERON:0000941	95.07	gold quality
lateral globus pallidus	UBERON:0002476	94.33	gold quality
inferior olivary complex	UBERON:0002127	94.06	gold quality
middle frontal gyrus	UBERON:0002702	93.80	gold quality
inferior vagus X ganglion	UBERON:0005363	93.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.65	gold quality
tongue squamous epithelium	UBERON:0006919	93.32	gold quality
ganglionic eminence	UBERON:0004023	93.31	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.20	gold quality
spinal cord	UBERON:0002240	92.96	gold quality
subthalamic nucleus	UBERON:0001906	92.46	gold quality
putamen	UBERON:0001874	92.41	gold quality
middle temporal gyrus	UBERON:0002771	91.98	gold quality
primary visual cortex	UBERON:0002436	91.94	gold quality
Ammon’s horn	UBERON:0001954	91.64	gold quality
ventricular zone	UBERON:0003053	91.49	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.34	gold quality
medulla oblongata	UBERON:0001896	91.28	gold quality
occipital lobe	UBERON:0002021	91.23	gold quality
CA1 field of hippocampus	UBERON:0003881	91.18	gold quality
amygdala	UBERON:0001876	90.90	gold quality
esophagus squamous epithelium	UBERON:0006920	90.56	gold quality
sperm	CL:0000019	90.47	gold quality
postcentral gyrus	UBERON:0002581	90.41	gold quality
parietal lobe	UBERON:0001872	90.38	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	71.01
E-ANND-3	yes	5.32
E-HCAD-13	no	2.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

303 targeting CDK19, 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-3163	100.00	77.23	8605
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 26)

• plays a role in mechanisms of transcriptional regulation upon protein phosphorylation. (review) (PMID:20408451)
• Microarrays identified target genes for each CDK, and we selected six genes: two target genes of CDK8, two target genes of CDK19 and two genes that were targets for both. (PMID:22117896)
• CDK8 and CDK19, individually interact with PRMT5 and WDR77, and their interactions with PRMT5 cause transcriptional repression of C/EBPbeta target genes. (PMID:23749998)
• Data suggest that, during neurogenesis, Mediator complex cyclin-dependent kinases (CDK8, CDK19) interact directly with PRC2 (polycomb repressive complex 2) subunit EZH2 (enhancer of zeste homolog 2), as well as SUZ12 (suppressor of zeste 12 homolog). (PMID:26002960)
• Mediator-associated kinases CDK8 and CDK19 restrain increased activation of key super-enhancer-associated genes in acute myeloid leukaemia (AML) cells (PMID:26416749)
• Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. (PMID:27678455)
• On stimulation of TLR9, CDK8/19 positively regulates inflammatory gene transcription in cooperation with NF-kappaB and C/EBPbeta. (PMID:28151579)
• High CDK19 expression is associated with osteosarcoma. (PMID:28416637)
• Genes coregulated by CDK8/19 and NFkappaB include IL8, CXCL1, and CXCL2. (PMID:28855340)
• These findings confirm that UF-linked mutations in MED12 disrupt composite Mediator-associated kinase activity and identify CDK8/19 as prospective therapeutic targets in uterine fibroids. (PMID:29440396)
• The CDK19 may enable metabolic and transcriptional reprogramming through enhancers and chromatin looping. (PMID:30585107)
• siRNA knockdown of CDK8 or CDK19 had no effect on HIV transcription. This result was confirmed using CDK8 or CDK19 inhibitors, Cortistatin A and Senexin A. these results indicate that CDK8 or CDK19 are not required for HIV transcription. (PMID:31044597)
• Study highlights CDK19 as a prognostic biomarker for prostate cancer (PCa) predicting disease recurrence independently from established prognostic markers. Furthermore, the results support the recently identified highly relevant role of CDK19 and CDK8 for PCa progression. (PMID:31271443)
• lncRNA CASC2 activated paclitaxel resistance in breast cancer through regulation of miR-18a-5p/CDK19 (PMID:31352515)
• findings demonstrate that human CDK19 fully replaces the function of Cdk8 in the fly, the human disease-associated CDK19 variants behave as strong loss-of-function variants, and deleterious CDK19 variants underlie a syndromic neurodevelopmental disorder (PMID:32330417)
• Cyclin-Dependent Kinases 8 and 19 Regulate Host Cell Metabolism during Dengue Virus Serotype 2 Infection. (PMID:32560467)
• CDK19 as a Potential HPV-Independent Biomarker for Recurrent Disease in HNSCC. (PMID:32752128)
• ISOC1 promotes the proliferation of gastric cancer cells by positively regulating CDK19. (PMID:33275227)
• CDK19-related disorder results from both loss-of-function and gain-of-function de novo missense variants. (PMID:33495529)
• A novel variant of CDK19 causes a severe neurodevelopmental disorder with infantile spasms. (PMID:33568421)
• Cyclin-dependent kinase 19 upregulation correlates with an unfavorable prognosis in hepatocellular carcinoma. (PMID:34649520)
• CDK19 regulates the proliferation of hematopoietic stem cells and acute myeloid leukemia cells by suppressing p53-mediated transcription of p21. (PMID:35110726)
• Inhibition of Cyclin-Dependent Kinase 8/Cyclin-Dependent Kinase 19 Suppresses Its Pro-Oncogenic Effects in Prostate Cancer. (PMID:35181333)
• Hotair promotes the migration and proliferation in ovarian cancer by miR-222-3p/CDK19 axis. (PMID:35451651)
• CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF. (PMID:36006697)
• CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins. (PMID:37378433)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk19	ENSDARG00000043858
mus_musculus	Cdk19	ENSMUSG00000038481
rattus_norvegicus	Cdk19	ENSRNOG00000000583
drosophila_melanogaster	Cdk8	FBGN0015618

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), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 19 — Q9BWU1 (reviewed: Q9BWU1)

Alternative names: CDC2-related protein kinase 6, Cell division cycle 2-like protein kinase 6, Cell division protein kinase 19, Cyclin-dependent kinase 11, Death-preventing kinase

All UniProt accessions (4): Q9BWU1, F6QTA4, H0YDW9, Q5JQZ9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Perinuclear region. Nucleus.

Disease relevance. Developmental and epileptic encephalopathy 87 (DEE87) [MIM:618916] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE87 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BWU1-1	1	yes
Q9BWU1-2	2

RefSeq proteins (4): NP_001287889, NP_001287892, NP_001287893, NP_055891* (*=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
IPR050108	CDK	Family

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 (22 total): sequence variant 8, compositionally biased region 5, binding site 2, modified residue 2, chain 1, domain 1, splice variant 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWU1-F1	77.97	0.59

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): 151 (proton acceptor)

Ligand- & substrate-binding residues (2): 52; 27–35

Post-translational modifications (2): 1, 449

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9833110	RSV-host interactions
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-5663205	Infectious disease
R-HSA-9820952	Respiratory Syncytial Virus Infection Pathway
R-HSA-9824446	Viral Infection Pathways
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 426 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GCACCTT_MIR18A_MIR18B, KOBAYASHI_EGFR_SIGNALING_24HR_UP, TAATAAT_MIR126, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MENSE_HYPOXIA_UP, TAL1ALPHAE47_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, EFC_Q6, ATGTTAA_MIR302C, CDP_01, ONKEN_UVEAL_MELANOMA_UP, MCAATNNNNNGCG_UNKNOWN, BILD_E2F3_ONCOGENIC_SIGNATURE

GO Biological Process (4): positive regulation of apoptotic process (GO:0043065), cellular response to lipopolysaccharide (GO:0071222), protein phosphorylation (GO:0006468), regulation of cell cycle (GO:0051726)

GO Molecular Function (8): protein serine/threonine kinase activity (GO:0004674), cyclin-dependent protein serine/threonine kinase activity (GO:0004693), 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 (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), CKM complex (GO:1990508), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Adipogenesis	1
Respiratory Syncytial Virus Infection Pathway	1
Metabolism of lipids	1
Metabolism	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein kinase activity	2
cytoplasm	2
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
phosphorylation	1
protein modification process	1
cell cycle	1
regulation of cellular process	1
protein serine/threonine kinase activity	1
cyclin-dependent protein kinase activity	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
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK19	CCNC	P24863	997
CDK19	MED13	Q9UHV7	995
CDK19	MED12	Q93074	990
CDK19	CCNL1	Q9UK58	980
CDK19	MED12L	Q86YW9	953
CDK19	MED13L	Q71F56	922
CDK19	CDK8	P49336	838
CDK19	EIF3F	O00303	734
CDK19	MED7	O43513	703
CDK19	CCNL2	Q96S94	656
CDK19	MED31	Q9Y3C7	650
CDK19	MED19	A0JLT2	646
CDK19	MED14	O60244	614
CDK19	TCEA1	P23193	589
CDK19	TCEA2	Q15560	581

IntAct

74 interactions, top by confidence:

A	B	Type	Score
CCNC	CDK8	psi-mi:“MI:0914”(association)	0.980
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CDK8	MED14	psi-mi:“MI:0914”(association)	0.900
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
MED31	MED19	psi-mi:“MI:0914”(association)	0.840
MED7	MED19	psi-mi:“MI:0914”(association)	0.840
MED11	MED19	psi-mi:“MI:0914”(association)	0.840
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
MED10	MED14	psi-mi:“MI:0914”(association)	0.830
MED12	CCNC	psi-mi:“MI:0914”(association)	0.800
CDK19	MED14	psi-mi:“MI:0914”(association)	0.800
CDK19	MED7	psi-mi:“MI:0914”(association)	0.800
MED30	MED19	psi-mi:“MI:0914”(association)	0.790
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
MED14	MED19	psi-mi:“MI:0914”(association)	0.790
MED19	MED14	psi-mi:“MI:0914”(association)	0.790
CDK19	MED19	psi-mi:“MI:0914”(association)	0.770
CDK19	MED19	psi-mi:“MI:0915”(physical association)	0.770

BioGRID (288): CDK19 (Affinity Capture-MS), CDK19 (Affinity Capture-MS), CDK19 (Affinity Capture-MS), CDK19 (Affinity Capture-MS), CDK19 (Affinity Capture-MS), CDK19 (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED27 (Affinity Capture-MS), MED31 (Affinity Capture-MS), MED16 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED12 (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED13L (Affinity Capture-MS), MED1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZNK2, B1H3E1, D3ZSZ3, E1BMN8, E2QWQ2, O42099, O54949, O55047, O88506, O95747, P19139, P21868, P33674, P49137, P68399, P68400, Q01887, Q01973, Q03351, Q08CW1, Q15139, Q17IE8, Q1ECX4, Q58A45, Q5R495, Q5XIS9, Q60737, Q62101, Q640Q5, Q66KH9, Q6P9R2, Q6ZWH5, Q7XKA8, Q863I2, Q86UE8, Q8BZ03, Q8C0V0, Q8NEV1, Q8QGV6, Q90327

Diamond homologs: A1CL96, A1D624, A2QU77, A2X6X1, A2XUW1, A3LUB9, A4QXX4, A8XA58, O13958, O55076, O61847, O96821, P00546, P06493, P0C661, P0CS76, P0CS77, P11440, P21127, P23111, P23437, P23572, P24033, P24100, P24788, P24923, P24941, P29618, P29619, P34112, P34117, P34556, P35567, P39073, P39951, P43063, P43450, P46892, P48734, P48963

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDK19	unknown	PAK1	phosphorylation
CDK19	“form complex”	CyclinC/CDK19	binding
CDK19	“down-regulates quantity by destabilization”	NOTCH1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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
Respiratory Syncytial Virus Infection Pathway	21	100.8×	8e-37
RSV-host interactions	21	80.1×	9e-35
Adipogenesis	21	80.1×	9e-35
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	14	73.6×	4e-22
Regulation of lipid metabolism by PPARalpha	21	72.2×	8e-34
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	14	67.2×	1e-21
Transcriptional regulation of white adipocyte differentiation	21	66.5×	5e-33
Epigenetic regulation by WDR5-containing histone modifying complexes	14	52.7×	5e-20

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	18	110.5×	2e-31
positive regulation of transcription initiation by RNA polymerase II	19	105.4×	1e-32
RNA polymerase II preinitiation complex assembly	18	99.8×	9e-31
somatic stem cell population maintenance	9	45.5×	2e-11
transcription initiation at RNA polymerase II promoter	5	38.2×	9e-06
protein ubiquitination	10	8.4×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	62
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3899506	NM_015076.5(CDK19):c.599G>A (p.Arg200Gln)	Pathogenic
929848	NM_015076.5(CDK19):c.94T>C (p.Tyr32His)	Pathogenic
975815	NM_015076.5(CDK19):c.82G>A (p.Gly28Arg)	Pathogenic
4849505	NM_015076.5:c.128+28397_204+4425del	Likely pathogenic
973820	NM_015076.5(CDK19):c.598C>T (p.Arg200Trp)	Likely pathogenic
975817	NM_015076.5(CDK19):c.589T>C (p.Phe197Leu)	Likely pathogenic

SpliceAI

4123 predictions. Top by Δscore:

Variant	Effect	Δscore
6:110622162:ATACA:A	acceptor_gain	1.0000
6:110622163:TACA:T	acceptor_gain	1.0000
6:110622165:CA:C	acceptor_gain	1.0000
6:110622167:C:CC	acceptor_gain	1.0000
6:110622175:C:CT	acceptor_gain	1.0000
6:110622811:ATACT:A	donor_loss	1.0000
6:110622812:TA:T	donor_loss	1.0000
6:110622813:A:AC	donor_gain	1.0000
6:110622814:C:CA	donor_gain	1.0000
6:110622814:CT:C	donor_gain	1.0000
6:110622814:CTCTA:C	donor_gain	1.0000
6:110622836:T:TA	donor_gain	1.0000
6:110622908:TGAAG:T	acceptor_gain	1.0000
6:110622909:GAAG:G	acceptor_gain	1.0000
6:110622910:AAG:A	acceptor_gain	1.0000
6:110622911:AG:A	acceptor_gain	1.0000
6:110622913:C:CC	acceptor_gain	1.0000
6:110622914:T:C	acceptor_loss	1.0000
6:110626847:T:C	acceptor_gain	1.0000
6:110626847:T:TC	acceptor_gain	1.0000
6:110632162:C:CC	acceptor_gain	1.0000
6:110667571:TATG:T	acceptor_gain	1.0000
6:110667572:ATGC:A	acceptor_loss	1.0000
6:110667573:TG:T	acceptor_gain	1.0000
6:110667574:GCTAA:G	acceptor_loss	1.0000
6:110667575:C:CC	acceptor_gain	1.0000
6:110667576:T:G	acceptor_loss	1.0000
6:110670426:CTTA:C	donor_loss	1.0000
6:110670427:TTA:T	donor_loss	1.0000
6:110670429:A:AC	donor_gain	1.0000

AlphaMissense

3324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:110622141:A:C	Y353D	1.000
6:110622161:A:G	F346S	1.000
6:110622842:A:G	F335S	1.000
6:110622860:G:T	A329D	1.000
6:110622861:C:G	A329P	1.000
6:110622877:T:A	R323S	1.000
6:110622877:T:G	R323S	1.000
6:110622878:C:A	R323I	1.000
6:110622878:C:G	R323T	1.000
6:110622879:T:C	R323G	1.000
6:110622887:G:T	P320Q	1.000
6:110622899:A:G	L316P	1.000
6:110622899:A:T	L316Q	1.000
6:110622902:A:G	L315P	1.000
6:110622911:A:G	L312P	1.000
6:110626800:A:G	L279P	1.000
6:110626818:A:C	M273R	1.000
6:110626835:C:A	W267C	1.000
6:110626835:C:G	W267C	1.000
6:110626836:C:G	W267S	1.000
6:110626837:A:G	W267R	1.000
6:110626837:A:T	W267R	1.000
6:110627013:C:T	G260E	1.000
6:110627014:C:A	G260W	1.000
6:110627014:C:G	G260R	1.000
6:110627014:C:T	G260R	1.000
6:110627019:A:T	V258D	1.000
6:110627028:A:C	I255R	1.000
6:110627028:A:T	I255K	1.000
6:110627031:C:G	R254P	1.000

dbSNP variants (sampled 300 via entrez): RS1000004179 (6:110774076 A>G), RS1000055241 (6:110715591 G>A,T), RS1000059428 (6:110645635 T>A), RS1000062440 (6:110728944 G>A), RS1000068426 (6:110665460 T>C,G), RS1000068626 (6:110813041 G>A), RS1000075959 (6:110630005 A>C), RS1000081896 (6:110740421 G>A,C), RS1000100209 (6:110733771 C>T), RS1000103203 (6:110808837 T>C), RS1000113402 (6:110721464 G>A,T), RS1000123301 (6:110721725 G>A), RS1000124023 (6:110727358 T>C), RS1000147039 (6:110612499 C>A), RS1000154976 (6:110796167 T>C)

Disease associations

OMIM: gene MIM:614720 | disease phenotypes: MIM:618916, MIM:618977

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 87	Strong	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (5): neurodevelopmental disorder (MONDO:0700092), developmental and epileptic encephalopathy, 87 (MONDO:0030059), optic atrophy 12 (MONDO:0033549), microcephaly (MONDO:0001149), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (0):

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000414	Bulbous nose
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000601	Hypotelorism
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000687	Widely spaced teeth
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000750	Delayed speech and language development
HP:0000954	Single transverse palmar crease
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001276	Hypertonia

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002934_7	Zinc levels	1.000000e-06
GCST006879_15	Blood metabolite levels	6.000000e-25
GCST006879_16	Blood metabolite levels	5.000000e-08
GCST006879_17	Blood metabolite levels	2.000000e-26
GCST006879_23	Blood metabolite levels	7.000000e-31
GCST006879_24	Blood metabolite levels	3.000000e-25
GCST006879_3	Blood metabolite levels	8.000000e-29
GCST006879_4	Blood metabolite levels	7.000000e-37
GCST007325_224	General risk tolerance (MTAG)	4.000000e-09
GCST90013658_6	Myeloperoxidase-DNA complexes	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0011039	myeloperoxidase (MPO)-DNA complex measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL3559691 (PROTEIN FAMILY), CHEMBL3883323 (PROTEIN COMPLEX), CHEMBL3885556 (PROTEIN FAMILY), CHEMBL4296126 (PROTEIN-PROTEIN INTERACTION), CHEMBL6002 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 269,243 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL941	IMATINIB	4	111,611
CHEMBL101253	VATALANIB	3	11,319
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL5199065	ISTISOCICLIB	2	21
CHEMBL103667	DORAMAPIMOD	2	1,681
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL445813	AT-7519	2	2,614
CHEMBL483321	CP-724714	2	872
CHEMBL558752	RAF-265	2	2,721
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL4076837	SENEXIN B	1	104
CHEMBL4225966	SEL-120 FREE BASE	1	91
CHEMBL296468	BMS-387032	1	2,075
CHEMBL4578881	SEL-120	1	66
CHEMBL482767	SNS-314	1	336
CHEMBL574738	AST-487	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CDK8 subfamily

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
CCT251545	Inhibition	8.6	pKd
compound 51 [Mallinger et al., 2016]	Inhibition	8.25	pIC50
JH-VIII-49	Inhibition	8.1	pIC50
cortistatin A	Inhibition	8.0	pKd
romaciclib	Inhibition	7.98	pIC50
linifanib	Inhibition	7.92	pKd
ponatinib	Inhibition	7.92	pKd
sorafenib	Inhibition	6.99	pKd
pexidartinib	Inhibition	6.85	pIC50

Binding affinities (BindingDB)

71 measured of 71 human assays (71 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
5-cyclopropyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	0.48 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	0.77 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	0.827 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.09 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3,7,7-trimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
13-chloro-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(13),2(6),4,9,11-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7-cyclohexyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclobutane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7S)-7-cyclohexyl-3-ethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7R)-7-cyclohexyl-3-ethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	1.41 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
Staurosporine	KD	1.7 nM
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxylic acid	IC50	3.01 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-1’-(2,2,2-trifluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	3.14 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
4-[2-[6-[4-(3-hydroxypropyl)piperazine-1-carbonyl]naphthalen-2-yl]ethylamino]quinoline-6-carbonitrile	IC50	4.1 nM	US-12281080: Quinoline-based compounds and methods of inhibiting CDK8/19
(7S)-7-(oxan-4-yl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	4.46 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	4.58 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
4-[2-[6-(1-oxo-1,4-thiazinane-4-carbonyl)naphthalen-2-yl]ethylamino]quinoline-6-carbonitrile	IC50	5.8 nM	US-12281080: Quinoline-based compounds and methods of inhibiting CDK8/19
3-methylspiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	6.1 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	8.22 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7S)-7-cyclohexyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	8.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-methoxyethyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	11.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	11.9 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7-methyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	14.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-5-(2-methoxyphenyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	16.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-chloro-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	16.6 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-ethyl-7,7-dimethyl-5-[2-(trifluoromethyl)phenyl]-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	16.7 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(7R)-7-cyclohexyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	19.3 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-3-(2,2,2-trifluoroethyl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	19.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-5-(4-sulfamoylphenyl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxylic acid	IC50	20.7 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-methoxyethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-oxane]-4-carboxamide	IC50	20.9 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-ethenyl-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	29.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7-methyl-7-propan-2-yl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	31.1 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
13-chloro-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(13),2(6),4,9,11-pentaene-4-carboxylic acid	IC50	31.4 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
1’-(2,2,2-trifluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,4’-piperidine]-4-carboxamide	IC50	40.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-(3,6-dihydro-2H-pyran-4-yl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	70.5 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-5-(4-sulfamoylphenyl)-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	81.3 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
5-(3,6-dihydro-2H-pyran-4-yl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxylic acid	IC50	86.6 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)-5-(2-methoxyphenyl)-7,7-dimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	97.3 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
7,7-dimethyl-5-phenyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-4-carboxamide	IC50	107 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
3-(2-fluoroethyl)spiro[8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(9),2(6),4,10,12-pentaene-7,1’-cyclohexane]-4-carboxamide	IC50	148 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors
(3S,5S,8R,9S,10S,13S,14S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-amine	IC50	150 nM	US-12325725: Cyclin-dependent kinase degraders and methods of use
(3S,8R,9S,10R,13S,14S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-amine	IC50	150 nM	US-12325725: Cyclin-dependent kinase degraders and methods of use
3-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]-N-[(3S,5S,10S,13S,14S,17S)-17-isoquinolin-7-yl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]-N-methylpropanamide	IC50	150 nM	US-12325725: Cyclin-dependent kinase degraders and methods of use
3-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]-N-[(3S,5S,10S,13S,14S,17S)-17-isoquinolin-7-yl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl]-N-methylpropanamide	IC50	150 nM	US-12325725: Cyclin-dependent kinase degraders and methods of use
13-chloro-3,7,7-trimethyl-8-oxa-3,11-diazatricyclo[7.4.0.02,6]trideca-1(13),2(6),4,9,11-pentaene-4-carboxamide	IC50	158 nM	US-10208056: Condensed tricyclic compounds as protein kinase inhibitors

ChEMBL bioactivities

333 potent at pChembl≥5 of 346 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	IC50	0.08	nM	CHEMBL3799396
9.44	IC50	0.36	nM	CHEMBL4061525
9.32	IC50	0.48	nM	CHEMBL4792305
9.26	IC50	0.55	nM	CHEMBL4083552
9.24	IC50	0.57	nM	CHEMBL4086487
9.22	IC50	0.6	nM	CHEMBL3798726
9.15	IC50	0.7	nM	CHEMBL3798611
9.11	IC50	0.77	nM	CHEMBL4070408
9.11	IC50	0.77	nM	CHEMBL4777356
9.10	Kd	0.7943	nM	CHEMBL6163999
9.08	IC50	0.827	nM	CHEMBL4789603
9.01	IC50	0.97	nM	CHEMBL4060856
9.00	IC50	1	nM	CHEMBL3797571
9.00	IC50	1	nM	CHEMBL3799396
9.00	IC50	1	nM	CHEMBL4076395
9.00	IC50	0.99	nM	CHEMBL4066819
8.96	IC50	1.1	nM	CHEMBL3799212
8.96	IC50	1.1	nM	CHEMBL4074204
8.96	IC50	1.09	nM	CHEMBL4791276
8.89	IC50	1.3	nM	CHEMBL4062244
8.89	IC50	1.3	nM	CHEMBL4071040
8.89	IC50	1.3	nM	CHEMBL4082469
8.85	IC50	1.4	nM	CHEMBL3798944
8.85	IC50	1.4	nM	CHEMBL3799307
8.85	IC50	1.41	nM	CHEMBL4785713
8.85	IC50	1.41	nM	CHEMBL4797707
8.85	IC50	1.41	nM	CHEMBL4789863
8.85	IC50	1.41	nM	CHEMBL4779550
8.85	IC50	1.41	nM	CHEMBL4789125
8.85	IC50	1.41	nM	CHEMBL4780792
8.85	IC50	1.41	nM	CHEMBL4776812
8.85	IC50	1.41	nM	CHEMBL5752178
8.85	IC50	1.41	nM	CHEMBL5817322
8.82	Kd	1.5	nM	AST-487
8.74	IC50	1.8	nM	CHEMBL3797571
8.74	IC50	1.8	nM	CHEMBL3799307
8.74	IC50	1.8	nM	CHEMBL3799592
8.72	IC50	1.9	nM	CHEMBL3798726
8.72	IC50	1.9	nM	CHEMBL4077627
8.72	IC50	1.9	nM	CHEMBL4552616
8.70	IC50	2	nM	CHEMBL4877883
8.70	IC50	2	nM	CHEMBL4850566
8.70	IC50	2	nM	CHEMBL5396725
8.68	IC50	2.1	nM	CHEMBL3798853
8.68	IC50	2.1	nM	CHEMBL3800105
8.62	IC50	2.4	nM	CHEMBL3800080
8.62	IC50	2.4	nM	CHEMBL4090775
8.60	IC50	2.5	nM	CHEMBL3798663
8.60	IC50	2.5	nM	CHEMBL3800311
8.60	IC50	2.49	nM	CHEMBL5561973

PubChem BioAssay actives

210 with measured affinity, of 742 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
8-[3-chloro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-1-methyl-2,3,8-triazaspiro[4.5]dec-1-en-4-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0001	uM
8-[[6-(methylamino)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0004	uM
8-phenoxy-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0006	uM
8-[(6-acetamido-3-pyridinyl)oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0006	uM
8-[3-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-5-(trifluoromethyl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0006	uM
8-[3-chloro-5-[4-(1-methylpyrazol-4-yl)phenyl]-4-pyridinyl]-1-methyl-1,3,8-triazaspiro[4.5]decane-2,4-dione	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0007	uM
8-[(2-methyl-3-pyridinyl)oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0008	uM
8-[[6-(2-methoxyethylcarbamoyl)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0010	uM
8-[[6-(methylcarbamoyl)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0010	uM
8-[(6-carbamoyl-3-pyridinyl)oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0010	uM
8-[3-chloro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0010	uM
8-[(6-amino-3-pyridinyl)oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0011	uM
8-[2-amino-3-chloro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0011	uM
8-methylsulfanyl-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0013	uM
8-[[6-(2-methoxyethylcarbamoyl)-2-methyl-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0013	uM
8-[(6-methyl-3-pyridinyl)oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0013	uM
8-[3-chloro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0014	uM
8-[3-chloro-5-[4-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]phenyl]-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0014	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435522: Binding constant for CDK11 kinase domain	kd	0.0015	uM
8-[3-(3-amino-1-methylindazol-6-yl)-5-chloro-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0018	uM
8-[[6-(2-ethoxyethylcarbamoyl)-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0019	uM
1-methyl-8-[(2-methyl-3-pyridinyl)oxy]-4,5-dihydrothieno[3,4-g]indazole-6-carboxamide	1613763: Displacement of Kinase tracer 236 from GST-fused CDK19/cyclin C (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0019	uM
8-[5-(1-methylindazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	1769450: Inhibition of tracer 236 binding to recombinant human GST/His-tagged CDK11 (1 to 502 residues)/Cyclin C( 1 to 283 residues) expressed in insect cells by Lanthascreen assay	ic50	0.0020	uM
8-[3-chloro-5-(1-methylindazol-5-yl)-2H-pyrazolo[3,4-b]pyridin-4-yl]-2,8-diazaspiro[4.5]decan-1-one	1769450: Inhibition of tracer 236 binding to recombinant human GST/His-tagged CDK11 (1 to 502 residues)/Cyclin C( 1 to 283 residues) expressed in insect cells by Lanthascreen assay	ic50	0.0020	uM
3-methyl-5-[5-methyl-4-[[4-(trifluoromethyl)phenyl]methyl]-1,2,4-triazol-3-yl]-2H-indazole	2030656: Inhibition of CDK19 (unknown origin)	ic50	0.0020	uM
8-[2-amino-3-chloro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0021	uM
8-[2-amino-5-[4-(1-methylpyrazol-4-yl)phenyl]-3-(trifluoromethyl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0021	uM
8-[[6-[(2-hydroxy-2-methylpropyl)carbamoyl]-3-pyridinyl]oxy]-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0024	uM
8-[3-chloro-5-[4-(1-methylpyrazol-4-yl)phenyl]-4-pyridinyl]-1-methyl-1,3,8-triazaspiro[4.5]decan-4-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0024	uM
8-[3-chloro-5-[4-[1-(2-hydroxyethyl)pyrazol-4-yl]phenyl]-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0025	uM
8-[3-chloro-5-(2,2-dioxo-1,3-dihydro-2,1-benzothiazol-5-yl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0025	uM
5,6-dibromo-4-(difluoromethyl)-1-(oxan-4-yl)-2-piperazin-1-ylbenzimidazole	2070944: Inhibition of CDK19 (unknown origin) by HTRF assay	ic50	0.0025	uM
8-[2-amino-3-chloro-5-(1-methylindazol-5-yl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0026	uM
8-pyridin-3-yloxy-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0027	uM
N-(4-propan-2-ylphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1921467: Inhibition of CDK19/Cyclin C (unknown origin) by LanthaScreen binding assay	ic50	0.0027	uM
8-[2-amino-3-fluoro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0027	uM
8-methoxy-4,5-dihydrothieno[3,4-g][1,2]benzothiazole-6-carboxamide	1474369: Inhibition of kinase tracer-236 binding to GST-tagged CDK19/CyclinC (unknown origin) after 60 mins by TR-FRET assay	ic50	0.0028	uM
8-[3-chloro-5-[3-(methylamino)-1H-indazol-6-yl]-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0029	uM
4-[2-[6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl]ethylamino]quinoline-6-carbonitrile	1825674: Binding affinity to recombinant human CDK19/cyclinC assessed as dissociation constant by TR FRET based assay	kd	0.0029	uM
4-[2-[6-(4-methylpiperazine-1-carbonyl)naphthalen-2-yl]ethylamino]quinazoline-6-carbonitrile	1825674: Binding affinity to recombinant human CDK19/cyclinC assessed as dissociation constant by TR FRET based assay	kd	0.0029	uM
8-[3-fluoro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0030	uM
9-[5-(1-methylindazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-2,9-diazaspiro[5.5]undecan-1-one	1769450: Inhibition of tracer 236 binding to recombinant human GST/His-tagged CDK11 (1 to 502 residues)/Cyclin C( 1 to 283 residues) expressed in insect cells by Lanthascreen assay	ic50	0.0030	uM
8-[3-(3-amino-1H-indazol-6-yl)-5-chloro-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0033	uM
8-[2-amino-3-chloro-5-[4-(1-methylpyrazol-4-yl)phenyl]-4-pyridinyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0033	uM
8-[3-[4-(1-methylpyrazol-4-yl)phenyl]-5-(trifluoromethyl)-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0035	uM
8-[2-amino-3-chloro-5-[4-(1-methylpyrazol-4-yl)phenyl]-4-pyridinyl]-2,8-diazaspiro[4.5]decan-1-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0035	uM
8-[3-chloro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-1-(trifluoromethyl)-2,3,8-triazaspiro[4.5]dec-1-en-4-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0037	uM
[(3R)-3-hydroxypyrrolidin-1-yl]-[3-[[4-(1-methylpyrazol-4-yl)phenyl]methyl]-2H-indazol-5-yl]methanone	1283632: Binding affinity to CDK19/Cyclin C (unknown origin) by reporter displacement assay	ic50	0.0040	uM
8-[3-chloro-5-[4-(1-methylpyrazol-4-yl)phenyl]-4-pyridinyl]-1-(2,2,2-trifluoroethyl)-1,3,8-triazaspiro[4.5]decan-4-one	1295749: Binding affinity to CDK8/CDK19 in human 7dF3 cells preincubated for 2 hrs followed by addition 10 uM of beta-oestradiol measured after 24 hrs by luciferase reporter gene assay	ic50	0.0040	uM
8-[3-chloro-5-(1-methyl-2,2-dioxo-3H-2,1-benzothiazol-5-yl)-4-pyridinyl]-2-methyl-1,3,8-triazaspiro[4.5]dec-1-en-4-one	1295765: Binding affinity to human CDK19 (1 to 502 amino acid residues)/Cyclin C (1 to 283 amino acid residues) by reporter displacement assay	ic50	0.0048	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
trichostatin A	decreases expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
afuresertib	increases expression	1
triphenyl phosphate	affects expression	1
afimoxifene	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
lei gong teng	increases expression	1
epigallocatechin gallate	increases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
motexafin gadolinium	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
NSC 689534	affects binding, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Panobinostat	decreases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Aspirin	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1

ChEMBL screening assays

210 unique, capped per target: 209 binding, 1 functional

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
CHEMBL1963813	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CDC2L6	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1N1	Abcam HeLa CDK19 KO	Cancer cell line	Female
CVCL_SI31	HAP1 CDK19 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice