CCNK

Summary

CCNK (cyclin K, HGNC:1596) is a protein-coding gene on chromosome 14q32.2, encoding Cyclin-K (O75909). Regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases. It is a common-essential gene (DepMap: required in 98.9% of cancer cell lines).

The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities.

Source: NCBI Gene 8812 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with hypertelorism and distinctive facies (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 25 total — 1 pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001099402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1596
Approved symbol	CCNK
Name	cyclin K
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	CPR4
Ensembl gene	ENSG00000090061
Ensembl biotype	protein_coding
OMIM	603544
Entrez	8812

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000389879, ENST00000553636, ENST00000553865, ENST00000555049, ENST00000555842, ENST00000555942, ENST00000556641, ENST00000557165, ENST00000557441, ENST00000887098, ENST00000887099, ENST00000887100, ENST00000940763

RefSeq mRNA: 1 — MANE Select: NM_001099402 NM_001099402

CCDS: CCDS45160

Canonical transcript exons

ENST00000389879 — 11 exons

Exon	Start	End
ENSE00000660284	99501356	99501413
ENSE00001383836	99502719	99502984
ENSE00001484271	99503611	99503644
ENSE00002518659	99481409	99481479
ENSE00002528733	99510157	99512440
ENSE00003553163	99492626	99492874
ENSE00003579666	99495498	99495629
ENSE00003584025	99502207	99502376
ENSE00003656376	99493514	99493595
ENSE00003680020	99500766	99500871
ENSE00003689557	99507076	99507147

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.3461 / max 2172.1082, expressed in 1825 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141380	73.5867	1824
141384	1.2648	806
141381	0.9331	558
141383	0.4668	221
141379	0.0692	7
141377	0.0182	4
141378	0.0073	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.43	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.95	gold quality
left ventricle myocardium	UBERON:0006566	95.68	gold quality
ileal mucosa	UBERON:0000331	95.56	gold quality
amniotic fluid	UBERON:0000173	94.74	gold quality
monocyte	CL:0000576	94.43	gold quality
tibialis anterior	UBERON:0001385	94.34	gold quality
leukocyte	CL:0000738	94.28	gold quality
parotid gland	UBERON:0001831	94.18	gold quality
oviduct epithelium	UBERON:0004804	94.13	gold quality
pancreatic ductal cell	CL:0002079	93.85	gold quality
bone marrow cell	CL:0002092	93.65	gold quality
tendon of biceps brachii	UBERON:0008188	93.19	gold quality
secondary oocyte	CL:0000655	93.09	gold quality
colonic epithelium	UBERON:0000397	93.04	gold quality
trachea	UBERON:0003126	92.95	gold quality
rectum	UBERON:0001052	92.65	gold quality
epithelial cell of pancreas	CL:0000083	92.21	gold quality
penis	UBERON:0000989	92.21	gold quality
trabecular bone tissue	UBERON:0002483	92.17	gold quality
adult organism	UBERON:0007023	92.13	gold quality
blood	UBERON:0000178	91.93	gold quality
sperm	CL:0000019	91.79	gold quality
islet of Langerhans	UBERON:0000006	91.79	gold quality
stromal cell of endometrium	CL:0002255	91.72	gold quality
myocardium	UBERON:0002349	91.71	gold quality
medial globus pallidus	UBERON:0002477	91.67	gold quality
gastrocnemius	UBERON:0001388	91.65	gold quality
muscle of leg	UBERON:0001383	91.42	gold quality
thymus	UBERON:0002370	91.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

73 targeting CCNK, 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-3646	100.00	73.56	5283
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-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-518A-5P	99.70	69.01	2209

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 21)

• P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. (PMID:11884399)
• cyclin K may play a role in regulating the cell cycle or apoptosis (PMID:11988847)
• The cyclin K fold comprises two typical cyclin boxes with two short helices preceding the N-terminal box. A prominent feature of cyclin K is an additional helix (H4a) in the first cyclin box that obstructs the binding pocket for the p27. (PMID:17169370)
• Cyclin K-expressing multiple myeloma LP-1 cells have lost their migration properties and display enhanced clonogenic capacities (PMID:20459741)
• These results reveal an unexpectedly direct role for CDK9-cyclin K in checkpoint pathways that maintain genome integrity in response to replication stress. (PMID:20930849)
• Cyclin K inhibits HIV-1 gene expression and replication by interfering with cyclin-dependent kinase 9 (CDK9)-cyclin T1 interaction in Nef-dependent manner. (PMID:21555514)
• Cyclin K interacts with CDK12 and CDK13 but not CDK9 in cells, and is required to maintain self-renewal in ES cells. (PMID:22547058)
• Cyclin K1 is the primary cyclin partner for CDK12/CrkRS and it is required for activation of CDK12/CrkRS to phosphorylate the C-terminal domain of RNA Pol II. (PMID:22988298)
• Cyclin K is highly expressed in mammalian testes in a developmentally regulated manner. (PMID:25004108)
• that cyclin K may be a novel molecular link between germ cell development, cancer development and embryonic stem cell maintenance. (PMID:25004108)
• Data show that most mutations prevent formation of the cyclin-dependent kinase 12 (Cdk12)/cyclin K (CycK) complex, rendering the kinase inactive. (PMID:25712099)
• Structures of CDK12/CycK complexes solved in the presence of AMP-PNP. (PMID:26597175)
• SETD1A and cyclin K complexes may represent a therapeutic opportunity for acute myeloid leukemia and, potentially, for other cancers. (PMID:29474905)
• Cyclin K expression positively correlates with cell proliferation; knockdown of cyclin K or its cognate kinase CDK12 prevents the assembly of prereplicative complex in the G1 cell cycle phase. (PMID:29760377)
• Cyclin K regulates prereplicative complex assembly to promote mammalian cell proliferation (PMID:29760377)
• Facial characteristics caused by CCNK variations, possibly through a mechanism of haploinsufficiency. (PMID:30122539)
• Cyclin K interacts with beta-catenin to induce Cyclin D1 expression and facilitates tumorigenesis and radioresistance in lung cancer. (PMID:33042275)
• Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer. (PMID:34289372)
• HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity. (PMID:34380030)
• CYCLIN K down-regulation induces androgen receptor gene intronic polyadenylation, variant expression and PARP inhibitor vulnerability in castration-resistant prostate cancer. (PMID:36129942)
• CCNK Gene Deficiency Influences Neural Progenitor Cells Via Wnt5a Signaling in CCNK-Related Syndrome. (PMID:37597256)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccnk	ENSMUSG00000021258
rattus_norvegicus	Ccnk	ENSRNOG00000006985
drosophila_melanogaster	CycK	FBGN0025674
caenorhabditis_elegans		WBGENE00009650

Paralogs (6): CCNT2 (ENSG00000082258), CCNT1 (ENSG00000129315), CCNH (ENSG00000134480), CCNL1 (ENSG00000163660), CCNL2 (ENSG00000221978), CCNQ (ENSG00000262919)

Protein

Protein identifiers

Cyclin-K — O75909 (reviewed: O75909)

All UniProt accessions (4): O75909, G3V235, G3V2Q3, G3V5E1

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases. Plays a role in transcriptional regulation via its role in regulating the phosphorylation of the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A).

Subunit / interactions. Regulatory subunit of cyclin-dependent kinases. Identified in a complex with a kinase and the RNA polymerase II holoenzyme. Interacts with POLR2A. Interacts with CDK12 and CDK13. Interacts with CDK9 according to PubMed:10574912; does not interact with CDK9 according to PubMed:22012619. (Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Highest levels in testis.

Disease relevance. Intellectual developmental disorder with hypertelorism and distinctive facies (IDDHDF) [MIM:618147] An autosomal dominant neurodevelopmental disorder characterized by developmental delay and intellectual disability, language defects, and distinctive facial dysmorphism including high hairline, hypertelorism, thin eyebrows, dysmorphic ears, broad nasal bridge and tip, and narrow jaw. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the cyclin family. Cyclin C subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O75909-3	1	yes
O75909-2	2
O75909-1	3
O75909-4	4

RefSeq proteins (1): NP_001092872* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004367	Cyclin_C-dom	Domain
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR043198	Cyclin/Ssn8	Family

Pfam: PF00134, PF21797

UniProt features (44 total): helix 16, compositionally biased region 6, splice variant 5, turn 5, modified residue 4, strand 4, chain 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2I53	X-RAY DIFFRACTION	1.5
5EFQ	X-RAY DIFFRACTION	2
4NST	X-RAY DIFFRACTION	2.2
7NXJ	X-RAY DIFFRACTION	2.36
8P81	X-RAY DIFFRACTION	2.68
5ACB	X-RAY DIFFRACTION	2.7
9JK1	X-RAY DIFFRACTION	2.72
6CKX	X-RAY DIFFRACTION	2.8
8BU1	X-RAY DIFFRACTION	2.98
7NXK	X-RAY DIFFRACTION	3
6B3E	X-RAY DIFFRACTION	3.06
8BUN	X-RAY DIFFRACTION	3.08
8BU4	X-RAY DIFFRACTION	3.09
8BU2	X-RAY DIFFRACTION	3.13
8BU5	X-RAY DIFFRACTION	3.13
4CXA	X-RAY DIFFRACTION	3.15
4UN0	X-RAY DIFFRACTION	3.15
8BUA	X-RAY DIFFRACTION	3.19
8BUD	X-RAY DIFFRACTION	3.2
8BUQ	X-RAY DIFFRACTION	3.2
8BU7	X-RAY DIFFRACTION	3.25
8BUE	X-RAY DIFFRACTION	3.25
8BUT	X-RAY DIFFRACTION	3.25
8BUS	X-RAY DIFFRACTION	3.26
8BUF	X-RAY DIFFRACTION	3.3
8BUM	X-RAY DIFFRACTION	3.36
8BUL	X-RAY DIFFRACTION	3.4
8BUK	X-RAY DIFFRACTION	3.41
8BUP	X-RAY DIFFRACTION	3.41
8BU3	X-RAY DIFFRACTION	3.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75909-F1	66.43	0.42

Functional residue map

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

Post-translational modifications (4): 329, 340, 324, 328

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-162582	Signal Transduction
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-167172	Transcription of the HIV genome
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 251 (showing top): REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_REGULATION_OF_PHOSPHORYLATION, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, YY1_Q6, GOMF_KINASE_ACTIVATOR_ACTIVITY, CAGCAGG_MIR370, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, REACTOME_HIV_INFECTION, YY1_02, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_VIRAL_GENOME_REPLICATION, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (11): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), transcription by RNA polymerase II (GO:0006366), DNA damage response (GO:0006974), regulation of signal transduction (GO:0009966), positive regulation of DNA-templated transcription, elongation (GO:0032786), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), host-mediated suppression of viral genome replication (GO:0044828), positive regulation of transcription by RNA polymerase II (GO:0045944), cell division (GO:0051301), regulation of transcription by RNA polymerase II (GO:0006357), regulation of cell cycle (GO:0051726)

GO Molecular Function (6): cyclin-dependent protein serine/threonine kinase activity (GO:0004693), RNA polymerase II CTD heptapeptide repeat kinase activity (GO:0008353), protein kinase binding (GO:0019901), cyclin-dependent protein serine/threonine kinase activator activity (GO:0061575), protein binding (GO:0005515), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538)

GO Cellular Component (6): cyclin K-CDK12 complex (GO:0002944), cyclin K-CDK13 complex (GO:0002945), nucleus (GO:0005634), nucleoplasm (GO:0005654), cyclin/CDK positive transcription elongation factor complex (GO:0008024), cyclin-dependent protein kinase holoenzyme complex (GO:0000307)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
RNA Polymerase II Transcription	4
Transcription of the HIV genome	3
Generic Transcription Pathway	2
RNA Polymerase II Transcription Elongation	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Transcriptional Regulation by TP53	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Late Phase of HIV Life Cycle	1
Signaling by TGFB family members	1
Signaling by TGF-beta Receptor Complex	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cyclin-dependent protein serine/threonine kinase activity	3
positive regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
protein serine/threonine kinase activity	2
cyclin-dependent protein kinase holoenzyme complex	2
regulation of protein serine/threonine kinase activity	1
DNA-templated transcription	1
cellular response to stress	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
DNA-templated transcription elongation	1
regulation of DNA-templated transcription elongation	1
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
viral genome replication	1
host-mediated perturbation of viral process	1
regulation of transcription by RNA polymerase II	1
cellular process	1
regulation of DNA-templated transcription	1
cell cycle	1
regulation of cellular process	1
cyclin-dependent protein kinase activity	1
RNA polymerase II CTD heptapeptide repeat modifying activity	1
kinase binding	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase activator activity	1
binding	1
cyclin-dependent protein kinase regulator activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
transcription elongation factor complex	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1
carboxy-terminal domain protein kinase complex	1
serine/threonine protein kinase complex	1

Protein interactions and networks

STRING

1650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNK	CDK9	P50750	998
CCNK	CDK13	Q14004	997
CCNK	CDK12	Q9NYV4	997
CCNK	POLR2A	P24928	825
CCNK	CDK7	P50613	821
CCNK	RFX6	Q8HWS3	808
CCNK	DDB1	Q16531	794
CCNK	CCNT2	O60583	747
CCNK	CCNH	P51946	729
CCNK	DTX2	Q86UW9	720
CCNK	CTDP1	Q9Y5B0	720
CCNK	SS18L1	O75177	704
CCNK	RFX3	P48380	661
CCNK	SETD1A	O15047	632
CCNK	HEXIM1	O94992	625

IntAct

66 interactions, top by confidence:

A	B	Type	Score
CCNK	CDK13	psi-mi:“MI:0407”(direct interaction)	0.830
CDK13	CCNK	psi-mi:“MI:0914”(association)	0.830
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
CDK12	CCNK	psi-mi:“MI:0914”(association)	0.690
RBPMS	CCNK	psi-mi:“MI:0915”(physical association)	0.670
CCNK	RBPMS	psi-mi:“MI:0915”(physical association)	0.670
BHLHE40	CCNK	psi-mi:“MI:0915”(physical association)	0.560
NDC80	CCNK	psi-mi:“MI:0915”(physical association)	0.560
CCNK	TLE5	psi-mi:“MI:0915”(physical association)	0.560
LZTS2	CCNK	psi-mi:“MI:0915”(physical association)	0.560
TLE5	CCNK	psi-mi:“MI:0915”(physical association)	0.560
CCNK	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
CCNK	BHLHE40	psi-mi:“MI:0915”(physical association)	0.560
CCNK	NDC80	psi-mi:“MI:0915”(physical association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
ATXN1	CCNK	psi-mi:“MI:0915”(physical association)	0.510
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
CCNK	CDC73	psi-mi:“MI:0914”(association)	0.460
CCNK	POLR2A	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (163): CCNK (Two-hybrid), CCNK (Two-hybrid), NDC80 (Two-hybrid), RBPMS (Two-hybrid), LZTS2 (Two-hybrid), CCNK (Two-hybrid), TSC22D4 (Two-hybrid), CCDC85B (Two-hybrid), NECAB2 (Two-hybrid), CCNK (Affinity Capture-MS), USHBP1 (Two-hybrid), EFEMP2 (Two-hybrid), KCNRG (Two-hybrid), CCNK (Two-hybrid), CCNK (Two-hybrid)

ESM2 similar proteins: F1N2W9, F1QDI9, F1QMB9, O00763, O75909, O88874, O94776, P10276, P11416, P13631, P18514, P18911, P22605, P22681, P22682, P23798, P25500, P25916, P35227, P51003, Q13191, Q14123, Q3TTA7, Q5FBR4, Q5SDR3, Q61183, Q63421, Q640D5, Q64338, Q66JB6, Q69ZT9, Q6NRE7, Q7T3E6, Q7ZTI3, Q80TJ7, Q86UE8, Q8CFK2, Q8IU60, Q8JIR0, Q8K4S7

Diamond homologs: A1C7R6, A3LPX1, A4RD79, F1QMB9, O75909, O88874, O94503, P24863, P25008, P39947, P47821, P55168, P93411, Q0CV29, Q16JA2, Q1EAW8, Q28F72, Q29AI1, Q2GVK1, Q2UDB2, Q3ZCK5, Q4KLA0, Q4WZT9, Q56YF8, Q5A4H9, Q5BBA8, Q62447, Q6BYF8, Q6CAC7, Q6CP20, Q6FJE8, Q75AX7, Q7QB13, Q86KE7, Q9C1M4, Q9FJK6, Q9FJK7, Q9HE63, O60563, O60583

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CCNK	“form complex”	CyclinK/CDK12	binding
CCNK	“form complex”	CyclinK/CDK13	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	5	32.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	17
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
585310	NM_001099402.2(CCNK):c.331A>G (p.Lys111Glu)	Pathogenic

SpliceAI

2966 predictions. Top by Δscore:

Variant	Effect	Δscore
14:99492906:A:G	donor_gain	1.0000
14:99495493:TTTA:T	acceptor_loss	1.0000
14:99495496:A:AG	acceptor_gain	1.0000
14:99495496:AGGT:A	acceptor_gain	1.0000
14:99495497:G:A	acceptor_loss	1.0000
14:99495497:G:GA	acceptor_gain	1.0000
14:99495497:GGT:G	acceptor_gain	1.0000
14:99495497:GGTG:G	acceptor_gain	1.0000
14:99495626:AAAGG:A	donor_loss	1.0000
14:99495627:AAGGT:A	donor_loss	1.0000
14:99495628:AGGTA:A	donor_loss	1.0000
14:99495630:G:GG	donor_gain	1.0000
14:99495630:GT:G	donor_loss	1.0000
14:99495631:T:G	donor_loss	1.0000
14:99498664:T:G	donor_gain	1.0000
14:99500760:TTTTA:T	acceptor_loss	1.0000
14:99500761:TTTAG:T	acceptor_loss	1.0000
14:99500763:TAG:T	acceptor_loss	1.0000
14:99500764:A:AT	acceptor_loss	1.0000
14:99502205:A:AG	acceptor_gain	1.0000
14:99502206:G:GT	acceptor_gain	1.0000
14:99502374:A:T	donor_gain	1.0000
14:99503609:A:AG	acceptor_gain	1.0000
14:99503610:G:GG	acceptor_gain	1.0000
14:99503642:CAG:C	donor_loss	1.0000
14:99503645:GT:G	donor_loss	1.0000
14:99503646:T:A	donor_loss	1.0000
14:99507070:TTGTA:T	acceptor_loss	1.0000
14:99507071:TGTAG:T	acceptor_loss	1.0000
14:99507072:GTAG:G	acceptor_loss	1.0000

AlphaMissense

3749 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:99492747:T:A	W24R	1.000
14:99492747:T:C	W24R	1.000
14:99492748:G:C	W24S	1.000
14:99492749:G:C	W24C	1.000
14:99492749:G:T	W24C	1.000
14:99492750:T:G	Y25D	1.000
14:99492753:T:A	W26R	1.000
14:99492753:T:C	W26R	1.000
14:99492755:G:C	W26C	1.000
14:99492755:G:T	W26C	1.000
14:99492813:G:A	E46K	1.000
14:99492815:G:C	E46D	1.000
14:99492815:G:T	E46D	1.000
14:99492825:C:A	R50S	1.000
14:99492825:C:G	R50G	1.000
14:99492826:G:C	R50P	1.000
14:99492829:G:C	R51P	1.000
14:99492834:G:C	G53R	1.000
14:99492834:G:T	G53C	1.000
14:99492835:G:A	G53D	1.000
14:99492835:G:T	G53V	1.000
14:99492838:C:A	A54D	1.000
14:99492841:G:C	R55P	1.000
14:99492844:T:C	F56S	1.000
14:99492847:T:A	I57N	1.000
14:99492858:G:C	G61R	1.000
14:99492858:G:T	G61C	1.000
14:99492859:G:A	G61D	1.000
14:99492859:G:T	G61V	1.000
14:99492868:T:G	L64W	1.000

dbSNP variants (sampled 300 via entrez): RS1000002771 (14:99508730 G>C), RS1000051674 (14:99508549 A>G), RS1000090247 (14:99498027 T>C), RS1000318344 (14:99504745 C>T), RS1000363308 (14:99496187 T>C,G), RS1000374237 (14:99491506 T>A,C), RS1000541714 (14:99503367 A>G), RS1000597616 (14:99509605 C>T), RS1000614667 (14:99490013 A>C), RS1000659773 (14:99509138 G>A), RS1000825070 (14:99482923 A>T), RS1000907875 (14:99501056 G>C), RS1000948595 (14:99480158 G>A), RS1000952223 (14:99507708 C>G), RS1001059377 (14:99503243 G>T)

Disease associations

OMIM: gene MIM:603544 | disease phenotypes: MIM:618147

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with hypertelorism and distinctive facies	Limited	Autosomal dominant

Mondo (1): intellectual developmental disorder with hypertelorism and distinctive facies (MONDO:0029143)

Orphanet (0):

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000637	Long palpebral fissure
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001182	Tapered finger
HP:0001263	Global developmental delay
HP:0001763	Pes planus
HP:0002194	Delayed gross motor development
HP:0002342	Moderate intellectual disability
HP:0004209	Clinodactyly of the 5th finger
HP:0009890	High anterior hairline
HP:0009928	Thick nasal alae
HP:0010862	Delayed fine motor development
HP:0010864	Severe intellectual disability
HP:0012434	Delayed early-childhood social milestone development
HP:0012801	Narrow jaw
HP:0045074	Thin eyebrow
HP:0100023	Recurrent hand flapping

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003474_8	Scalp hair shape	1.000000e-07
GCST006192_48	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-08
GCST006195_91	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2346490 (SINGLE PROTEIN), CHEMBL3038475 (PROTEIN COMPLEX), CHEMBL4106169 (PROTEIN COMPLEX), CHEMBL4296067 (PROTEIN COMPLEX), CHEMBL6066049 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193761 (PROTEIN-PROTEIN INTERACTION), CHEMBL6196201 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 57,585 (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
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL4291684	TAMBICICLIB	2	1
CHEMBL5095102	INIXACICLIB	2	9
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL4462530	ZEMIRCICLIB	2	429
CHEMBL5199065	ISTISOCICLIB	2	21
CHEMBL4439321	ATUVECICLIB	1	129
CHEMBL4756595	ENITOCICLIB	1	55
CHEMBL5090754	SY-5609	1	54

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs77769901	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

Binding affinities (BindingDB)

97 measured of 100 human assays (100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(6-amino-3-pyridinyl)-9-ethyl-N-[[6-(2-methyl-4-pyridinyl)-3-pyridinyl]methyl]purin-6-amine	IC50	12 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
9-ethyl-2-pyridin-3-yl-N-[(6-pyridin-3-yl-3-pyridinyl)methyl]purin-6-amine	IC50	16 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[3-cyclopropyl-7-[(7-phenylimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	18 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
2-(2-aminopyrimidin-5-yl)-9-ethyl-N-[[6-(2-methyl-4-pyridinyl)-3-pyridinyl]methyl]purin-6-amine	IC50	19 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[7-[(3-methylimidazo[2,1-b][1,3]thiazol-6-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	20 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(5,7-dimethylimidazo[1,2-a]pyrimidin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	21 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-ethyl-7-[(5-methylimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	24 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(6-chloroimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	26 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(1-methylbenzimidazol-5-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	26.9 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[(5-methoxyimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	28 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
2-(6-amino-3-pyridinyl)-9-ethyl-N-[(6-pyridin-2-yl-3-pyridinyl)methyl]purin-6-amine	IC50	30 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[3-ethyl-7-[(8-methylimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	31 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(6-fluoroimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	33 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[(5-methylimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	36 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[(6-cyclopropylimidazo[1,2-b]pyridazin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	37 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(5-methylimidazo[1,2-a]pyridin-3-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	38 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(7-methylimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	38 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(6-methylimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	40 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(5-methylimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	40 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(7-cyclopropyl-[1,2,4]triazolo[1,5-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	40 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[[7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	44 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[(5,7-dimethylimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	45 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[(5-propan-2-yloxyimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	46 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[[5-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	48 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[[6-methyl-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	48 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-(imidazo[1,2-a]pyridin-2-ylmethylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	50.2 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
9-propan-2-yl-N-[(6-pyridin-3-yl-3-pyridinyl)methyl]-2-pyrimidin-5-ylpurin-6-amine	IC50	51 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[7-[(8-methylimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	51.7 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
2-[[5-[9-propan-2-yl-6-[(6-pyridin-3-yl-3-pyridinyl)methylamino]purin-2-yl]-2-pyridinyl]amino]ethanol	IC50	53 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
9-ethyl-N-[[6-(2-methyl-4-pyridinyl)-3-pyridinyl]methyl]-2-pyrimidin-5-ylpurin-6-amine	IC50	56 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[7-[[8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methylamino]-3-cyclopropylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	62 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(3-methylimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	63 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
2-(6-amino-3-pyridinyl)-9-propan-2-yl-N-[(6-pyridin-3-yl-3-pyridinyl)methyl]purin-6-amine	IC50	65 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[7-(1H-benzimidazol-2-ylmethylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	65 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
US12473303, Compound H-APPAMP-018	IC50	65 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclobutyl-7-[(8-methylimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	65 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[(8-cyclopropylimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	70 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-(imidazo[1,2-a]pyrimidin-2-ylmethylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	71.5 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-propan-2-yl-7-(quinolin-2-ylmethylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	75 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[(5-cyclopropylimidazo[1,2-a]pyridin-2-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	75 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
2-(2-aminopyrimidin-5-yl)-9-ethyl-N-[(6-pyridin-2-yl-3-pyridinyl)methyl]purin-6-amine	IC50	77 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
2-[[4-[9-propan-2-yl-6-[(6-pyridin-3-yl-3-pyridinyl)methylamino]purin-2-yl]-2-pyridinyl]amino]ethanol	IC50	86 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
2-(2-aminopyrimidin-5-yl)-9-propan-2-yl-N-[(6-pyridin-3-yl-3-pyridinyl)methyl]purin-6-amine	IC50	87 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
2-(6-methyl-3-pyridinyl)-9-propan-2-yl-N-[(6-pyridin-3-yl-3-pyridinyl)methyl]purin-6-amine	IC50	90 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[7-[(3-cyclopropylimidazo[1,2-a]pyridin-2-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	93 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
CHEMBL4288923	IC50	94 nM
2-(2-amino-4-pyridinyl)-9-propan-2-yl-N-[(6-pyridin-3-yl-3-pyridinyl)methyl]purin-6-amine	IC50	94 nM	US-20250101023: HETEROARYL DERIVATIVE AND USES THEREOF
(3R,4R)-4-[[[7-(imidazo[1,2-a]pyridin-3-ylmethylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	96 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[7-[[6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methylamino]-3-ethylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	100 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use
(3R,4R)-4-[[[3-cyclopropyl-7-[[6-cyclopropyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	IC50	100 nM	US-12473303: 4-[[(7-aminopyrazolo[1,5-a]pyrimidin-5-yl)amino methyl]piperidin-3-ol compounds and their therapeutic use

ChEMBL bioactivities

932 potent at pChembl≥5 of 969 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL5573550
9.00	IC50	1	nM	CHEMBL5567321
8.96	IC50	1.1	nM	CHEMBL6165957
8.92	IC50	1.2	nM	CHEMBL6150992
8.92	IC50	1.2	nM	CHEMBL6163025
8.92	IC50	1.2	nM	CHEMBL6170783
8.89	IC50	1.3	nM	CHEMBL6151419
8.77	IC50	1.7	nM	CHEMBL6145574
8.70	IC50	2	nM	CHEMBL4287416
8.70	IC50	2	nM	CHEMBL4293213
8.70	IC50	2	nM	CHEMBL3656841
8.70	IC50	2	nM	CHEMBL5575019
8.70	IC50	2	nM	CHEMBL5955040
8.70	IC50	2	nM	CHEMBL5760232
8.52	IC50	3	nM	ZOTIRACICLIB
8.52	IC50	3	nM	CHEMBL5573404
8.52	IC50	3	nM	CHEMBL5572601
8.52	IC50	3	nM	CHEMBL5571201
8.52	IC50	3	nM	DINACICLIB
8.41	IC50	3.9	nM	CHEMBL6133414
8.40	IC50	4	nM	CHEMBL5961536
8.40	IC50	4	nM	CHEMBL6043217
8.37	IC50	4.3	nM	CHEMBL6145090
8.30	IC50	5	nM	CHEMBL6058548
8.22	IC50	6	nM	CHEMBL4281048
8.21	IC50	6.2	nM	CHEMBL6167432
8.21	IC50	6.1	nM	CHEMBL6161777
8.21	IC50	6.2	nM	CHEMBL6145796
8.20	IC50	6.3	nM	CHEMBL6146811
8.16	IC50	6.9	nM	CHEMBL5929886
8.15	IC50	7	nM	DINACICLIB
8.15	IC50	7	nM	CHEMBL6144121
8.10	IC50	8	nM	CHEMBL5573275
8.07	Kd	8.6	nM	CHEMBL4160662
8.05	IC50	9	nM	TAMBICICLIB
8.05	EC50	9	nM	CHEMBL5595312
8.05	IC50	8.9	nM	CHEMBL6163487
8.04	IC50	9.2	nM	CHEMBL6143494
8.04	IC50	9.22	nM	CHEMBL5929886
8.00	IC50	10	nM	CHEMBL4160662
8.00	IC50	10	nM	CHEMBL4277623
8.00	IC50	10	nM	CHEMBL5571531
7.96	IC50	11	nM	CHEMBL6173831
7.92	IC50	12	nM	CHEMBL4286005
7.92	IC50	12	nM	CHEMBL5169449
7.92	EC50	12	nM	CHEMBL258721
7.89	IC50	13	nM	STAUROSPORINE
7.89	IC50	13	nM	CHEMBL2377825
7.89	IC50	13	nM	CHEMBL4159417
7.89	IC50	12.8	nM	CHEMBL6173333

PubChem BioAssay actives

280 with measured affinity, of 519 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
2-[(3R)-4-[9-ethyl-6-[(6-pyrazol-1-yl-3-pyridinyl)methylamino]purin-2-yl]morpholin-3-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0010	uM
2-[(2S)-1-[6-[[6-(5-amino-3-methylpyrazol-1-yl)-3-pyridinyl]methylamino]-9-ethylpurin-2-yl]piperidin-2-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0010	uM
4-N-[5-chloro-4-[2-(oxan-4-ylmethylamino)-1,3-thiazol-4-yl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0020	uM
4-N-[5-chloro-4-[2-[(4-fluorophenyl)methylamino]-1,3-thiazol-4-yl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0020	uM
2-[(2S)-1-[9-ethyl-6-[[6-(furan-3-yl)-3-pyridinyl]methylamino]purin-2-yl]piperidin-2-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0020	uM
4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	1648273: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay	ic50	0.0020	uM
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene	1549276: Inhibition of human recombinant full length His-tagged CDK9/cyclin K expressed in baculovirus expression system	ic50	0.0030	uM
2-[(3R)-4-[9-ethyl-6-[[6-(furan-3-yl)-3-pyridinyl]methylamino]purin-2-yl]morpholin-3-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0030	uM
2-[(3R)-4-[9-ethyl-6-[[6-(1,3-oxazol-2-yl)-3-pyridinyl]methylamino]purin-2-yl]morpholin-3-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0030	uM
2-[(2S)-1-[9-ethyl-6-[(6-pyrazol-1-yl-3-pyridinyl)methylamino]purin-2-yl]piperidin-2-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0030	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0030	uM
4-[[[4-[5-chloro-2-[[4-(2-methoxyethylamino)cyclohexyl]amino]-4-pyridinyl]-1,3-thiazol-2-yl]amino]methyl]oxane-4-carbonitrile	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0060	uM
2-[(2S)-1-[6-[[6-(3,5-dimethylpyrazol-1-yl)-3-pyridinyl]methylamino]-9-ethylpurin-2-yl]piperidin-2-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0080	uM
3-benzyl-1-[4-[(5-cyano-2-pyridinyl)amino]cyclohexyl]-1-[4-(1-methyl-6-oxo-3-pyridinyl)phenyl]urea	1870804: Binding affinity to human CDK13 (694 to 1039 residues)/CyclinK (1 to 267 residues) expressed in baculovirus infected in Sf9 cells by Biolayer interferometry	kd	0.0086	uM
4-[[[4-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-1,3-thiazol-2-yl]amino]methyl]oxane-4-carbonitrile	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0090	uM
N-[(5,6-dichloro-1H-benzimidazol-2-yl)methyl]-2-morpholin-4-yl-9-propan-2-ylpurin-6-amine	2116058: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incuabted for 60 mins by TR-FRET assay	ec50	0.0090	uM
4-[[[4-[5-chloro-2-[[4-[[(2S)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-1,3-thiazol-2-yl]amino]methyl]oxane-4-carbonitrile	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0100	uM
2-[(3R)-4-[6-[[6-(3,5-dimethylpyrazol-1-yl)-3-pyridinyl]methylamino]-9-ethylpurin-2-yl]morpholin-3-yl]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0100	uM
1-(2,6-dichlorophenyl)-6-[[4-(2-hydroxyethoxy)phenyl]methyl]-3-propan-2-yl-5H-pyrazolo[5,4-d]pyrimidin-4-one	2116058: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incuabted for 60 mins by TR-FRET assay	ec50	0.0120	uM
4-N-[5-chloro-4-[2-(oxan-4-ylmethylamino)-1,3-thiazol-4-yl]-2-pyridinyl]-1-N-(3-methoxypropyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0120	uM
5-(2-aminoethylsulfanyl)-3-cyclobutyl-N-[(4-pyridin-2-ylphenyl)methyl]-2H-pyrazolo[4,3-d]pyrimidin-7-amine	1880980: Inhibition of GST-tagged human CDK13/Cyclin K expressed in Sf9 cells using RBER-IRStide peptide as substrate in presence of ATP and [gamma33-P] ATP by radioisotope filter binding assay	ic50	0.0120	uM
N-[4-(1-methylpyrazol-4-yl)phenyl]-N-[4-(quinazolin-2-ylamino)cyclohexyl]acetamide	1356598: Inhibition of N-terminal FLAG-tagged human full-length CDK12 (1 to 1490 residues)/N-terminal His-tagged CycK (1 to 580 residues) expressed in Sf9 cells assessed as reduction in ATP-dependent ULight-4E-BP1 (Thr37/Thr46) substrate peptide phosphorylation pre-incubated for 60 mins by LANCE Ultra assay	ic50	0.0130	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	745521: Inhibition of CDK9/Cyclin K (unknown origin)-mediated phosphorylation of peptide substrate incubated for 15 mins prior to substrate addition measured after 90 mins by P33-radiolabeled assay	ic50	0.0130	uM
4-[[4-amino-5-(2-nitrobenzoyl)-1,3-thiazol-2-yl]amino]benzenesulfonamide	745521: Inhibition of CDK9/Cyclin K (unknown origin)-mediated phosphorylation of peptide substrate incubated for 15 mins prior to substrate addition measured after 90 mins by P33-radiolabeled assay	ic50	0.0130	uM
4-N-[5-chloro-4-[2-(oxan-4-ylmethylsulfanyl)-1,3-thiazol-4-yl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0140	uM
4-N-[4-[2-(benzylamino)-1,3-thiazol-4-yl]-5-chloro-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0140	uM
4-(7-methylsulfonyl-1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine	1820463: Inhibition of CDK12/cyclin K (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay	ic50	0.0150	uM
(2R)-2-[[6-[[4-(5-methylthiophen-2-yl)phenyl]methylamino]-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	2107658: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incubated for 1 hr by TR-FRET assay	ec50	0.0150	uM
(2R)-2-[[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]amino]butan-1-ol	2107658: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incubated for 1 hr by TR-FRET assay	ec50	0.0160	uM
(2S)-2-[[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]amino]butan-1-ol	2116057: Inhibition of CDK12/cyclin K (unknown origin) in HEK293T cells incubated for 1 hr by TR-FRET assay	ec50	0.0160	uM
(2R)-2-[[6-[(4-phenylphenyl)methylamino]-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	2107658: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incubated for 1 hr by TR-FRET assay	ec50	0.0170	uM
4-N-[5-chloro-4-[2-(2,2,2-trifluoroethylamino)-1,3-thiazol-4-yl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0170	uM
3-benzyl-1-[4-[(5-cyano-2-pyridinyl)amino]cyclohexyl]-1-(4-piperazin-1-ylphenyl)urea	1870804: Binding affinity to human CDK13 (694 to 1039 residues)/CyclinK (1 to 267 residues) expressed in baculovirus infected in Sf9 cells by Biolayer interferometry	kd	0.0170	uM
(2R)-2-[[6-[3-(3,4-dimethylphenyl)propylamino]-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	2107658: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incubated for 1 hr by TR-FRET assay	ec50	0.0180	uM
2-[[6-[[6-(5-amino-3-methylpyrazol-1-yl)-3-pyridinyl]methylamino]-9-ethylpurin-2-yl]-(2-hydroxyethyl)amino]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0180	uM
N-[(1S,3R)-3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]-1-methylcyclohexyl]-5-[[(E)-4-(dimethylamino)but-2-enoyl]amino]pyridine-2-carboxamide	1609469: Competitive irreversible inhibition of CDK12/cyclinK (unknown origin) in presence of Km ATP	ic50	0.0200	uM
N-(4-propan-2-ylphenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	1921465: Inhibition of CDK9/Cyclin K (unknown origin) by LanthaScreen binding assay	ic50	0.0200	uM
6-[[[2-[[(2R)-1-hydroxybutan-2-yl]amino]-9-propan-2-ylpurin-6-yl]amino]methyl]-3-pyridin-2-yl-1H-pyridin-2-one	2107658: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incubated for 1 hr by TR-FRET assay	ec50	0.0210	uM
(2R)-2-[[6-[3-(3,4-dichlorophenyl)propylamino]-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	2107658: Inhibition of 6His-tagged wild type CDK12/cyclin K (unknown origin) infected in insect cells incubated for 1 hr by TR-FRET assay	ec50	0.0210	uM
4-N-[4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]-5-fluoropyrimidin-2-yl]cyclohexane-1,4-diamine	1983417: Inhibition of CDK13/Cyclin K (unknown origin) preincubated for 10 mins followed by substrate and ATP addition measured after 200 mins by ADP-Glo luminescence assay	ic50	0.0215	uM
4-N-[5-chloro-4-[2-(oxan-4-ylmethylamino)-1,3-thiazol-4-yl]-2-pyridinyl]cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0220	uM
5-(2-aminoethylsulfanyl)-3-cyclobutyl-N-[(4-pyrazol-1-ylphenyl)methyl]-2H-pyrazolo[4,3-d]pyrimidin-7-amine	1880980: Inhibition of GST-tagged human CDK13/Cyclin K expressed in Sf9 cells using RBER-IRStide peptide as substrate in presence of ATP and [gamma33-P] ATP by radioisotope filter binding assay	ic50	0.0220	uM
5-(2-aminoethylsulfanyl)-3-propan-2-yl-N-[(4-pyrazin-2-ylphenyl)methyl]-2H-pyrazolo[4,3-d]pyrimidin-7-amine	1880980: Inhibition of GST-tagged human CDK13/Cyclin K expressed in Sf9 cells using RBER-IRStide peptide as substrate in presence of ATP and [gamma33-P] ATP by radioisotope filter binding assay	ic50	0.0220	uM
9-ethyl-N-[(6-pyrazol-1-yl-3-pyridinyl)methyl]-2-pyridin-3-ylpurin-6-amine	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0220	uM
2-[[6-[[6-(5-amino-3-methylpyrazol-1-yl)-3-pyridinyl]methylamino]-9-ethylpurin-2-yl]amino]ethanol	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0220	uM
4-(1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine	1820463: Inhibition of CDK12/cyclin K (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay	ic50	0.0240	uM
N-[4-[(3R)-3-[[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]amino]piperidine-1-carbonyl]phenyl]prop-2-enamide	1652530: Inhibition of human CDK12/cyclin K using Pol2-CTD as substrate by [gamma-33P]ATP-based radioisotope filter binding assay	ic50	0.0250	uM
4-N-[5-chloro-4-[2-(cyclohexylmethylamino)-1,3-thiazol-4-yl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0270	uM
2-(6-amino-3-pyridinyl)-9-ethyl-N-[[6-(1,3-oxazol-2-yl)-3-pyridinyl]methyl]purin-6-amine	2096918: Inhibition of recombinant human CDK12/Cyclin K using RNA Pol II-CTD as substrate preincubated for ~20 mins followed by 33P-ATP addition measured after 120 mins by HotSpot kinase assay	ic50	0.0270	uM
4-N-[5-chloro-4-[2-(oxan-4-ylmethoxy)-1,3-thiazol-4-yl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	1417613: Inhibition of CDK9/Cyclin K (unknown origin) using PDKtide as substrate incubated at 37 degreeC for 1 hr followed by incubation at room temperature for 5 mins by ADP-Glo reagent based luminescence assay	ic50	0.0280	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	increases expression, decreases methylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
diethyl maleate	decreases expression	1
sodium bichromate	decreases expression	1
nickel subsulfide	decreases expression	1
butyraldehyde	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
polyhexamethyleneguanidine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases 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	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

243 unique, capped per target: 243 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4612767	Binding	Binding affinity to Cyclin K (unknown origin) assessed as change in molecular weight at 10 fold excess of protein measured after 1 hr by LC-MS/MS analysis	Discovery of MFH290: A Potent and Highly Selective Covalent Inhibitor for Cyclin-Dependent Kinase 12/13. — J Med Chem

Clinical trials (associated diseases)

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