CCNT1

Summary

CCNT1 (cyclin T1, HGNC:1599) is a protein-coding gene on chromosome 12q13.11-q13.12, encoding Cyclin-T1 (O60563). Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large s….

This gene encodes a member of the highly conserved cyclin C subfamily. The encoded protein tightly associates with cyclin-dependent kinase 9, and is a major subunit of positive transcription elongation factor b (p-TEFb). In humans, there are multiple forms of positive transcription elongation factor b, which may include one of several different cyclins along with cyclin-dependent kinase 9. The complex containing the encoded cyclin and cyclin-dependent kinase 9 acts as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and is both necessary and sufficient for full activation of viral transcription. This cyclin and its kinase partner are also involved in triggering transcript elongation through phosphorylation of the carboxy-terminal domain of the largest RNA polymerase II subunit. Overexpression of this gene is implicated in tumor growth. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 904 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 92 total — 1 pathogenic
• Druggable target: yes — 34 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): ambiguous (mixed evidence) across 1 cancer types
• MANE Select transcript: NM_001240

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1599
Approved symbol	CCNT1
Name	cyclin T1
Location	12q13.11-q13.12
Locus type	gene with protein product
Status	Approved
Aliases	CCNT, CYCT1
Ensembl gene	ENSG00000129315
Ensembl biotype	protein_coding
OMIM	143055
Entrez	904

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000261900, ENST00000417344, ENST00000550457, ENST00000551989, ENST00000618666, ENST00000898548, ENST00000898549, ENST00000898550, ENST00000898551, ENST00000898552

RefSeq mRNA: 5 — MANE Select: NM_001240 NM_001240, NM_001277842, NM_001413198, NM_001413199, NM_001413200

CCDS: CCDS61109, CCDS8766

Canonical transcript exons

ENST00000261900 — 9 exons

Exon	Start	End
ENSE00000914192	48714443	48714524
ENSE00000938798	48705768	48705896
ENSE00000938799	48701013	48701073
ENSE00000938800	48699778	48699840
ENSE00000938801	48698138	48698183
ENSE00000938802	48695999	48696162
ENSE00001164708	48688458	48694436
ENSE00001164718	48716515	48716707
ENSE00003460781	48695759	48695829

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 92.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.6508 / max 318.8178, expressed in 1806 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130736	28.6301	1804
130738	1.0578	587
130735	0.6109	236
130737	0.3206	154
130739	0.0242	4
130740	0.0071	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	92.97	gold quality
superior surface of tongue	UBERON:0007371	91.89	gold quality
renal medulla	UBERON:0000362	91.70	gold quality
pylorus	UBERON:0001166	91.64	gold quality
cauda epididymis	UBERON:0004360	91.33	gold quality
mammary duct	UBERON:0001765	91.27	gold quality
caput epididymis	UBERON:0004358	90.80	gold quality
adrenal tissue	UBERON:0018303	90.78	gold quality
nipple	UBERON:0002030	90.68	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.65	gold quality
pericardium	UBERON:0002407	90.63	gold quality
lower lobe of lung	UBERON:0008949	90.49	gold quality
corpus epididymis	UBERON:0004359	90.45	gold quality
calcaneal tendon	UBERON:0003701	90.21	gold quality
trigeminal ganglion	UBERON:0001675	90.06	gold quality
male germ cell	CL:0000015	89.97	gold quality
saphenous vein	UBERON:0007318	89.75	gold quality
biceps brachii	UBERON:0001507	89.50	gold quality
superficial temporal artery	UBERON:0001614	89.34	gold quality
seminal vesicle	UBERON:0000998	89.05	gold quality
skin of hip	UBERON:0001554	88.90	gold quality
epithelium of nasopharynx	UBERON:0001951	88.76	gold quality
nasopharynx	UBERON:0001728	88.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.68	gold quality
urethra	UBERON:0000057	88.61	gold quality
epithelium of mammary gland	UBERON:0003244	88.55	gold quality
cardia of stomach	UBERON:0001162	88.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.37	gold quality
jejunum	UBERON:0002115	88.15	gold quality
cartilage tissue	UBERON:0002418	88.11	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.78
E-MTAB-4850	no	443.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
HES1	Activation

Upstream regulators (CollecTRI, top): PML, TBXT

miRNA regulators (miRDB)

165 targeting CCNT1, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
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-520D-5P	99.98	73.34	4883
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 40)

• Activity inhibited by 7SK small nuclear RNA. (PMID:11713533)
• P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA. (PMID:11884399)
• CDK9 has the intrinsic property to shuttle between nucleus and cytoplasm, and enhanced expression of cyclin T1 promotes its nuclear localization. (PMID:12115727)
• P-TEFb is a key mediator of Myc activated transcription by stimulating elongation (PMID:12177005)
• fluctuation in CycT1 levels during human macrophage differentiation may be involved in the regulation of HIV-1 replication (PMID:12368300)
• chimeras between kinase-inactive mutant Cdk9 and truncated cyclin T1 proteins efficiently inhibit Tat transactivation and human immunodeficiency virus gene expression (PMID:12368330)
• Tat and trans-activation-responsive (TAR) RNA-independent induction of HIV-1 long terminal repeat by this protein requires Sp1 (PMID:12458222)
• Cyclin T1 binding to HIV-1 tat is regulated by the differential acetylation of tat (PMID:12486002)
• cyclin T1 binds with granulin to inhibit transcription (PMID:12588988)
• the transcriptional repressor PIE-1 from Caenorhabditis elegans binds Cyclin T1 via an alanine-containing heptapeptide repeat and inhibits transcriptional elongation {cyclin T1) (PMID:12651893)
• recruitment to nuclear bodies via direct interaction with PML protein (PMID:12727882)
• Since Tat also binds to this cyclin T1 domain and the association between 7SK RNA/MAQ1 and P-TEFb competes with the binding of Tat to cyclin T1, we speculate that the TAR RNA/Tat lentivirus system has evolved to subvert the cellular 7SK RNA/MAQ1 system (PMID:12832472)
• major portion of nuclear P-TEFb is sequestered and inactivated by the coordinated actions of the 7SK snRNA (PMID:14627702)
• RNAi-mediated gene silencing of P-TEFb in HeLa cells was not lethal and inhibited Tat transactivation and HIV-1 replication in host cells (PMID:14963154)
• review of work indicating under some circumstances TAK/P-TEFb is likely to be limiting for HIV replication in CD4+ T cells and macrophages; review of mechanisms of regulation of the TAK/P-TEFb subunits in these cell types (PMID:15049426)
• NUFIP and P-TEFb with BRCA1 activate transcription by RNA polymerase II (PMID:15107825)
• a histidine-rich stretch in CycT1 was found to direct the transcriptional activity of this P-TEFb complex when tethered artificially to DNA. (PMID:15563843)
• HEXIM1 and HEXIM2 maintain the balance between active and inactive forms of P-TEFb, a heterodimeric complex composed of cyclin-dependent kinase 9 and cyclin T. (PMID:15713661)
• downregulation of hCycT1 did not cause apoptotic cell death (PMID:15913611)
• increased estrogen down regulated gene 1 expression results in inhibition of cyclin T1 recruitment and estrogen receptor 1 DNA binding (PMID:15940264)
• analysis of positive transcription elongation factor - HEXIM1 - 7SK RNA complex (PMID:15994294)
• Role of P-TEFb as an activator of transcription elongation can be separated from its role in RNA processing; neither function is universally required for expression of mammalian pol II-dependent genes. (PMID:16308568)
• the interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct its binding to P-TEFb and subcellular localization that culminates in the inhibition of transcription (PMID:16362050)
• human cyclin T1 expression is sufficient to support Tat-mediated transactivation in primary mouse CD4 T lymphocytes and monocytes/macrophages and increases in vitro and in vivo HIV-1 production by these stimulated cells. (PMID:16439541)
• Finally, two inhibitors of cyclin-dependent kinase 9 (a dominant negative CDK9 and flavopiridol) repressed activity from the MR and BMPR2 promoters (PMID:16615932)
• Using DNA microarray technology, we found that more than 20% of genes induced by PMA require cyclin T1 for their normal level of induction, and approximately 15% of genes repressed by PMA require cyclin T1 for their normal level of repression. (PMID:16764723)
• These data link the P-TEFb equilibrium to the intracellular transcriptional demand and proliferative/differentiated states of cells. (PMID:16980611)
• Prostratin induces Cyclin T1 expression and P-TEFb function and this is likely to be involved in prostratin reactivation of latent HIV-1 proviruses (PMID:17014716)
• WRN is a novel cellular cofactor for HIV-1 replication, and the WRN helicase participates in the recruitment of PCAF/P-TEFb-containing transcription complexes (PMID:17317667)
• Cdk9/Cyclin T1 complex may be important in the activation/differentiation program of lymphoid cells and that its upregulation may contribute to malignant transformation. (PMID:17352406)
• These results suggest that acetylation of CDK9 is an important posttranslational modification that is involved in regulating P-TEFb transcriptional elongation function. (PMID:17452463)
• Upon induction of NF-kappaB, a subset of target genes is regulated differentially by either P-TEFb or DSIF.[P-TEFb, DSIF] (PMID:17502349)
• Regions important for the interactions with partners as the TRM give insights into the spatial arrangment of critical residues that build up the interface for its regulatory factors. (PMID:17540406)
• Tax may compete and functionally substitute for Brd4 in P-TEFb regulation.Tax and Brd4 compete for binding to P-TEFb through direct interaction with cyclin T1 (PMID:17686863)
• Overexpression of the BRD4 P-TEFb-interacting domain disrupts the interaction between the HIV transactivator Tat and P-TEFb and suppresses the ability of Tat to transactivate the HIV promoter (PMID:17690245)
• provide structural insights how Hexim1 recognizes the Cyclin T1 subunit of positive transcription elongation factor b (PMID:17724342)
• Identification of ENL-associated proteins by mass spectrometry revealed enzymes with a known role in transcriptional elongation: pTEFb and DOT1L. (PMID:17855633)
• while the P-TEFb level remains constant, the Brd4-P-TEFb interaction increases dramatically in cells progressing from late mitosis to early G(1). (PMID:18039861)
• This data suggests an active role for the Cdk9/Cyclin T1 complex during lymphoid differentiation through germinal center reaction. (PMID:18205180)
• HIV infection increases the sensitivity of microglia and astrocytes to inflammatory stimulation and support the use of these mice as a model to investigate various aspects of the in vivo mechanism of HIV-induced neuronal dysfunction (PMID:18353948)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccnt1	ENSDARG00000017525
mus_musculus	Ccnt1	ENSMUSG00000011960
rattus_norvegicus	Ccnt1	ENSRNOG00000053054
drosophila_melanogaster	CycH	FBGN0022936
drosophila_melanogaster	CycT	FBGN0025455
caenorhabditis_elegans		WBGENE00000507
caenorhabditis_elegans		WBGENE00000508
caenorhabditis_elegans		WBGENE00021714

Paralogs (6): CCNT2 (ENSG00000082258), CCNK (ENSG00000090061), CCNH (ENSG00000134480), CCNL1 (ENSG00000163660), CCNL2 (ENSG00000221978), CCNQ (ENSG00000262919)

Protein

Protein identifiers

Cyclin-T1 — O60563 (reviewed: O60563)

All UniProt accessions (1): O60563

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II. (Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat’s affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.

Subunit / interactions. Cyclin-T1 is the predominant cyclin that associates with CDK9 to form a heterodimer called P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31. Component of a complex which is at least composed of HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H, and NCL/nucleolin. Component of the 7SK snRNP complex at least composed of P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, BCDIN3, SART3 proteins and 7SK and U6 snRNAs. Interacts (via central region) with ZMYND8 (via N-terminus); the interaction is direct and the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex. Interacts with BRD4, targets chromatin binding. Interacts with JMJD6. Interacts with MDFIC. Interacts with HSF1. Interacts with HTATSF1. Interacts with TBX21. (Microbial infection) Interacts with the transactivation region of HIV-1, HIV-2 and SIV Tat. (Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. ADP-ribosylation on serine residues by PARP1 in response to DNA damage disrupts the phase separation activity of CCNT1, thereby preventing activation of CDK9.

Domain organisation. The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance binding of the P-TEFb complex to the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II).

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

Isoforms (2)

UniProt ID	Names	Canonical?
O60563-1	1	yes
O60563-2	2

RefSeq proteins (5): NP_001231, NP_001264771, NP_001400127, NP_001400128, NP_001400129 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR043198	Cyclin/Ssn8	Family
IPR047320	CYCLIN_CCNT1_rpt2	Domain

Pfam: PF00134, PF21797

UniProt features (68 total): modified residue 20, helix 15, compositionally biased region 7, region of interest 5, turn 5, cross-link 3, splice variant 2, sequence variant 2, mutagenesis site 2, strand 2, chain 1, site 1, sequence conflict 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
3MI9	X-RAY DIFFRACTION	2.1
3BLH	X-RAY DIFFRACTION	2.48
2PK2	X-RAY DIFFRACTION	2.67
3BLR	X-RAY DIFFRACTION	2.8
3MY1	X-RAY DIFFRACTION	2.8
7NWK	X-RAY DIFFRACTION	2.81
3BLQ	X-RAY DIFFRACTION	2.9
4OR5	X-RAY DIFFRACTION	2.9
4IMY	X-RAY DIFFRACTION	2.94
3TN8	X-RAY DIFFRACTION	2.95
4BCH	X-RAY DIFFRACTION	2.96
3LQ5	X-RAY DIFFRACTION	3
3MIA	X-RAY DIFFRACTION	3
4OGR	X-RAY DIFFRACTION	3
4BCF	X-RAY DIFFRACTION	3.01
4BCG	X-RAY DIFFRACTION	3.08
4BCI	X-RAY DIFFRACTION	3.1
6W9E	X-RAY DIFFRACTION	3.1
4BCJ	X-RAY DIFFRACTION	3.16
6GZH	X-RAY DIFFRACTION	3.17
3TNH	X-RAY DIFFRACTION	3.2
4EC9	X-RAY DIFFRACTION	3.21
3TNI	X-RAY DIFFRACTION	3.23
6Z45	X-RAY DIFFRACTION	3.37
6CYT	X-RAY DIFFRACTION	3.5
4EC8	X-RAY DIFFRACTION	3.6
8I0L	X-RAY DIFFRACTION	3.6
8K5R	X-RAY DIFFRACTION	3.75
5L1Z	X-RAY DIFFRACTION	5.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60563-F1	60.32	0.30

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): 261 (essential for interacting with hiv-1 tat)

Post-translational modifications (23): 117, 340, 388, 390, 416, 474, 475, 485, 487, 495, 499, 530, 531, 549, 552, 556, 563, 564, 577, 637 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
261	loss of hiv-1 tat transactivation.
517–527	in mutant 9a; impaired formation of phase-separated liquid droplets, leading to decreased ability to activate cdk9.

Function

Pathways and Gene Ontology

Reactome pathways

34 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-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-176034	Interactions of Tat with host cellular proteins
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-9018519	Estrogen-dependent gene expression
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-162909	Host Interactions of HIV factors
R-HSA-1643685	Disease
R-HSA-167169	HIV Transcription Elongation
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)

MSigDB gene sets: 270 (showing top): E2F_Q4, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, E2F4DP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOMF_KINASE_ACTIVATOR_ACTIVITY, E2F1DP1_01, REACTOME_HIV_INFECTION, E2F1DP2_01, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_PROCESS, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (9): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), transcription by RNA polymerase II (GO:0006366), response to xenobiotic stimulus (GO:0009410), positive regulation of DNA-templated transcription, elongation (GO:0032786), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), host-mediated activation of viral transcription (GO:0043923), positive regulation of transcription by RNA polymerase II (GO:0045944), cell division (GO:0051301), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (12): transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), chromatin binding (GO:0003682), protein kinase binding (GO:0019901), cyclin-dependent protein serine/threonine kinase activator activity (GO:0061575), RNA polymerase binding (GO:0070063), 7SK snRNA binding (GO:0097322), DNA-binding transcription factor binding (GO:0140297), molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), snRNA binding (GO:0017069)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cyclin/CDK positive transcription elongation factor complex (GO:0008024), P-TEFb complex (GO:0070691)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Transcription of the HIV genome	5
RNA Polymerase II Transcription	3
HIV Infection	2
RNA Polymerase II Transcription Elongation	1
Tat-mediated elongation of the HIV-1 transcript	1
HIV Transcription Elongation	1
Host Interactions of HIV factors	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Transcriptional Regulation by TP53	1
ESR-mediated signaling	1
HIV Life Cycle	1
Viral Infection Pathways	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
binding	2
cellular anatomical structure	2
regulation of protein serine/threonine kinase activity	1
DNA-templated transcription	1
response to chemical	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
host-mediated perturbation of viral transcription	1
host-mediated activation of viral process	1
regulation of transcription by RNA polymerase II	1
cellular process	1
regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
kinase binding	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase activator activity	1
enzyme binding	1
snRNA binding	1
transcription factor binding	1
protein-macromolecule adaptor activity	1
cyclin-dependent protein kinase regulator activity	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
transcription elongation factor complex	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1
carboxy-terminal domain protein kinase complex	1
cyclin/CDK positive transcription elongation factor complex	1

Protein interactions and networks

STRING

2556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNT1	BRD4	O60885	999
CCNT1	HEXIM1	O94992	999
CCNT1	CDK9	P50750	999
CCNT1	RBM8A	Q9Y5S9	995
CCNT1	AFF4	Q9UHB7	994
CCNT1	MLLT1	Q03111	984
CCNT1	AFF1	P51825	984
CCNT1	ELL	P55199	977
CCNT1	LARP7	Q4G0J3	974
CCNT1	MEPCE	Q7L2J0	962
CCNT1	ELL2	O00472	933
CCNT1	CDK7	P50613	930
CCNT1	MLLT3	P42568	929
CCNT1	MYC	P01106	894
CCNT1	CCNH	P51946	891

IntAct

205 interactions, top by confidence:

A	B	Type	Score
CDK9	CCNT1	psi-mi:“MI:0914”(association)	0.980
CCNT1	CDK9	psi-mi:“MI:0915”(physical association)	0.980
CDK9	CCNT1	psi-mi:“MI:0407”(direct interaction)	0.980
CCNT1	CDK9	psi-mi:“MI:0914”(association)	0.980
CCNT1	CDK9	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
CDK9	CCNT1	psi-mi:“MI:0915”(physical association)	0.980
HEXIM1	CCNT1	psi-mi:“MI:0407”(direct interaction)	0.930
HEXIM1	CCNT1	psi-mi:“MI:0915”(physical association)	0.930
CCNT1	HEXIM1	psi-mi:“MI:0407”(direct interaction)	0.930
HEXIM1	CCNT1	psi-mi:“MI:0914”(association)	0.930
CCNT1	HEXIM1	psi-mi:“MI:0914”(association)	0.930

BioGRID (474): KAT2B (Reconstituted Complex), tat (Reconstituted Complex), CCNT1 (Reconstituted Complex), CCNT1 (Affinity Capture-Western), CCNT1 (Affinity Capture-Western), TP73 (Affinity Capture-Western), CCNT1 (Reconstituted Complex), CCNT1 (Affinity Capture-Western), tat (Reconstituted Complex), CCNT1 (Affinity Capture-MS), CCNT1 (Affinity Capture-MS), CCNT1 (Affinity Capture-MS), CCNT1 (Affinity Capture-MS), CCNT1 (Affinity Capture-MS), CCNT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R6X6S3, A2AM29, A2BIL7, A6QP06, B5DE93, D2H526, E1BB50, F1QW93, O60293, O60563, O60583, O93383, P25992, P42568, Q03111, Q0VBM2, Q10728, Q14693, Q14AX6, Q1L8U8, Q1LVC2, Q24595, Q3MJK5, Q5ZK36, Q62901, Q640I9, Q69ZW3, Q6DD45, Q6P1G2, Q6P2L6, Q7YZA2, Q7ZX31, Q7ZXG4, Q80TZ9, Q8BRB7, Q8HXN7, Q8NDI1, Q8WYB5, Q90YL3, Q91ZP3

Diamond homologs: A3LPX1, F1QMB9, O60563, O60583, O74627, O75909, O88874, O96433, P24863, P47821, P55168, Q0E474, Q28F72, Q2QQS5, Q2RAC5, Q3ZCK5, Q4KLA0, Q52KE7, Q56YF8, Q5I0H5, Q5RD50, Q5ZJP9, Q62447, Q6GN15, Q6T8E9, Q6Z7H3, Q7TQK0, Q7ZVX0, Q8GYM6, Q8HXN7, Q8RWV3, Q96S94, Q9AS36, Q9C8P7, Q9FKE6, Q9JJA7, Q9QWV9, Q9R1Q2, Q9UK58, Q9XT26

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CCNT1	“up-regulates quantity by expression”	HES1	“transcriptional regulation”
MAML1	up-regulates	CCNT1	relocalization
PLK1	“down-regulates activity”	CCNT1	phosphorylation
CCNT1	“form complex”	P-TEFb	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
Formation of RNA Pol II elongation complex	9	18.7×	1e-07
RNA Polymerase II Transcription Elongation	9	18.7×	1e-07
SARS-CoV-1 modulates host translation machinery	5	16.6×	6e-04
RNA Polymerase II Pre-transcription Events	11	16.3×	2e-08
SARS-CoV-1-host interactions	8	15.1×	4e-06
Influenza Viral RNA Transcription and Replication	5	11.6×	2e-03
Influenza Infection	6	11.3×	6e-04
Transcription of the HIV genome	6	11.2×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
transcription elongation by RNA polymerase II	7	25.4×	4e-06
positive regulation of transcription elongation by RNA polymerase II	9	22.2×	2e-07
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	5	20.3×	9e-04
RNA polymerase II preinitiation complex assembly	6	13.4×	9e-04
positive regulation of transcription initiation by RNA polymerase II	5	11.1×	7e-03
cytoplasmic translation	6	9.1×	5e-03
mRNA splicing, via spliceosome	10	7.5×	3e-04
RNA splicing	8	5.8×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: ambiguous (mixed evidence) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	66
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
633775	GRCh37/hg19 12q13.11-13.12(chr12:49034325-49468966)x1	Pathogenic

SpliceAI

1382 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48694434:TGCCT:T	acceptor_loss	1.0000
12:48694438:T:A	acceptor_loss	1.0000
12:48695757:AC:A	donor_gain	1.0000
12:48695758:CC:C	donor_gain	1.0000
12:48695825:CAGTT:C	acceptor_gain	1.0000
12:48695830:C:CC	acceptor_gain	1.0000
12:48696159:CAGG:C	acceptor_gain	1.0000
12:48696170:C:CT	acceptor_gain	1.0000
12:48696171:A:T	acceptor_gain	1.0000
12:48699842:T:C	acceptor_gain	1.0000
12:48701006:AACTT:A	donor_loss	1.0000
12:48701007:ACTT:A	donor_loss	1.0000
12:48701008:CTTA:C	donor_loss	1.0000
12:48701009:TTA:T	donor_loss	1.0000
12:48701010:T:TG	donor_loss	1.0000
12:48701011:A:AC	donor_gain	1.0000
12:48701011:A:AT	donor_loss	1.0000
12:48701012:C:CC	donor_gain	1.0000
12:48701069:TAAGC:T	acceptor_gain	1.0000
12:48701074:C:CC	acceptor_gain	1.0000
12:48701074:CTA:C	acceptor_loss	1.0000
12:48701075:T:A	acceptor_loss	1.0000
12:48705762:TCCTA:T	donor_loss	1.0000
12:48705763:CCTA:C	donor_loss	1.0000
12:48705764:CTAC:C	donor_loss	1.0000
12:48705765:TA:T	donor_loss	1.0000
12:48705766:ACCTC:A	donor_loss	1.0000
12:48705767:CCTCA:C	donor_gain	1.0000
12:48705892:ACAGA:A	acceptor_gain	1.0000
12:48705893:CAGA:C	acceptor_gain	1.0000

AlphaMissense

4779 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48699836:A:C	F146L	1.000
12:48699836:A:T	F146L	1.000
12:48699838:A:G	F146L	1.000
12:48696041:A:G	W222R	0.999
12:48696041:A:T	W222R	0.999
12:48696042:C:A	W221C	0.999
12:48696042:C:G	W221C	0.999
12:48696044:A:G	W221R	0.999
12:48696044:A:T	W221R	0.999
12:48696070:A:G	I212T	0.999
12:48701036:T:A	E137V	0.999
12:48701048:A:G	L133P	0.999
12:48705861:T:A	K93N	0.999
12:48705861:T:G	K93N	0.999
12:48705866:C:G	A92P	0.999
12:48705868:G:T	A91E	0.999
12:48696039:C:A	W222C	0.998
12:48696039:C:G	W222C	0.998
12:48696070:A:C	I212S	0.998
12:48696094:G:T	A204D	0.998
12:48698171:A:G	L170S	0.998
12:48699783:A:T	V164D	0.998
12:48699786:A:G	L163P	0.998
12:48701024:A:G	L141S	0.998
12:48705862:T:A	K93I	0.998
12:48705865:G:T	A92D	0.998
12:48705873:A:C	F89L	0.998
12:48705873:A:T	F89L	0.998
12:48705874:A:G	F89S	0.998
12:48705875:A:G	F89L	0.998

dbSNP variants (sampled 300 via entrez): RS1000108153 (12:48704586 A>G), RS1000211999 (12:48705992 T>A,C,G), RS1000265176 (12:48700547 C>A,G,T), RS1000311266 (12:48711573 T>C), RS1000317904 (12:48700253 A>G), RS1000320883 (12:48711355 G>C), RS1000354872 (12:48698972 T>C), RS1000360570 (12:48716317 C>A), RS1000373487 (12:48716129 A>G), RS1000536759 (12:48716954 T>G), RS1000563973 (12:48706146 T>C), RS1000874448 (12:48688502 A>C,T), RS1000925417 (12:48688228 G>A,C,T), RS1001111509 (12:48705656 T>C), RS1001115020 (12:48695119 C>A,G,T)

Disease associations

OMIM: gene MIM:143055 | disease phenotypes: MIM:147920

GenCC curated gene-disease

Mondo (1): Kabuki syndrome 1 (MONDO:0007843)

Orphanet (1): Kabuki syndrome (Orphanet:2322)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002595_10	Clozapine-induced agranulocytosis	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2108 (SINGLE PROTEIN), CHEMBL2111389 (PROTEIN COMPLEX), CHEMBL3885549 (PROTEIN COMPLEX), CHEMBL5291961 (PROTEIN COMPLEX GROUP), CHEMBL6195585 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

34 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 73,287 (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
CHEMBL3545110	RIBOCICLIB	4	8,018
CHEMBL3894860	TRILACICLIB	4	2,086
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL3904602	LEROCICLIB	3	1,012
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL2347597	ASNUCICLIB	2	100
CHEMBL3115681	NARAZACICLIB	2	287
CHEMBL3545283	RIVICICLIB	2	968
CHEMBL3655762	CYC-065	2	388
CHEMBL3905910	VORUCICLIB	2	856
CHEMBL4067549	ULECACICLIB	2	41
CHEMBL4442620	RONICICLIB	2	367
CHEMBL4446357	EBVACICLIB	2	599
CHEMBL445813	AT-7519	2	2,614
CHEMBL4462530	ZEMIRCICLIB	2	429
CHEMBL5095094	CULMERCICLIB	2	12
CHEMBL5199065	ISTISOCICLIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL488436	AZD-5438	1
CHEMBL1230607	PHA-793887	1
CHEMBL258805	SU-9516	1
CHEMBL269538	HARMINE	1
CHEMBL296468	BMS-387032	1
CHEMBL3545083	RGB-286638	1
CHEMBL4439321	ATUVECICLIB	1
CHEMBL4754493	BTX-A51	1

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

Binding affinities (BindingDB)

2028 measured of 2194 human assays (2196 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[[6-[2-[(4-aminocyclohexyl)amino]-5-chloro-4-pyridinyl]-3-fluoro-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00015 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-(2-methoxyethylamino)cyclohexyl]amino]-4-pyridinyl]-3-fluoro-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00017 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-3-fluoro-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00023 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-(propylamino)cyclohexyl]amino]-4-pyridinyl]-3-fluoro-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00017 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[(4-hydroxycyclohexyl)amino]-4-pyridinyl]-3-fluoro-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00016 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00017 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[(4-hydroxycyclohexyl)amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00024 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.0003 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[5-fluoro-6-[(4-methyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]cyclohexane-1,4-diamine	IC50	0.0003 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[3,5-difluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]cyclohexane-1,4-diamine	IC50	0.00026 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-[(2-methyl-1,3-dioxolan-2-yl)amino]cyclohexyl]amino]-4-pyridinyl]-3-fluoro-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00027 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-(dipropylamino)cyclohexyl]amino]-4-pyridinyl]-3-fluoro-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00031 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-(ethylamino)cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00028 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-(dimethylamino)cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.0003 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-[2-(trifluoromethoxy)ethylamino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00036 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-(oxan-4-ylamino)cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.00043 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[5-fluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-1-N-(2-methylsulfonylethyl)cyclohexane-1,4-diamine	IC50	0.00049 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[6-[(4-fluorooxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	IC50	0.00063 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[6-[(4-methyl-1,1-dioxothian-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.0007 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[3-fluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[6-[[(2R,6S)-2,6-dimethyloxan-4-yl]methylamino]-2-pyridinyl]-2-pyridinyl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[4-[3-bromo-6-(oxan-4-ylmethylamino)-2-pyridinyl]-5-chloro-2-pyridinyl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[3-chloro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[3-fluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[5-fluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-[[5-chloro-4-[3-chloro-6-[(2,2-dimethyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]amino]cyclohexan-1-ol	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
(2S)-3-[[4-[[5-chloro-4-[3-chloro-6-[(2,2-dimethyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]amino]cyclohexyl]amino]-1,1,1-trifluoropropan-2-ol	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
(2R)-3-[[4-[[5-chloro-4-[3-chloro-6-[(2,2-dimethyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]amino]cyclohexyl]amino]-1,1,1-trifluoropropan-2-ol	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[3-chloro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-1-N-[2-(trifluoromethoxy)ethyl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[6-[(4-methoxyoxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[6-(oxan-4-ylmethylamino)-5-(trifluoromethyl)-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[6-[(4-methyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[6-[(4-fluorooxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[5-fluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[3-chloro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-1-N-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[3-chloro-6-[[(3S)-oxan-3-yl]methylamino]-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[3-chloro-6-[[(3R)-oxan-3-yl]methylamino]-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[6-[[(4S)-2,2-dimethyloxan-4-yl]methylamino]-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[6-[(2,2-dimethyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-4-N-[(2R)-1-methoxypropan-2-yl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[5-fluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]-1-N-[(1,1-dioxothian-4-yl)methyl]cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[5-fluoro-6-[(4-methyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-1-N-(1,1-dioxothiolan-3-yl)cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
1-N-[5-chloro-4-[5-fluoro-6-[(4-methyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-4-N-(2-methyl-1,3-dioxolan-2-yl)cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[5-fluoro-6-[(4-methyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-1-N-(1,1-dioxothian-4-yl)cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[5-fluoro-6-[(4-methyloxan-4-yl)methylamino]-2-pyridinyl]-2-pyridinyl]-1-N-(1,1-dioxothietan-3-yl)cyclohexane-1,4-diamine	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
[4-[[[6-[5-chloro-2-[[4-[[(2R)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxan-4-yl]methanol	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
[4-[[[6-[5-chloro-2-[[4-(2-methoxyethylamino)cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxan-4-yl]methanol	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-[[[6-[5-chloro-2-[[4-(diethylamino)cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	IC50	0.001 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[5-chloro-4-[6-[[(2R,6S)-2,6-dimethyloxan-4-yl]methylamino]-2-pyridinyl]-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	IC50	0.002 nM	US-8778951: Heteroaryl compounds and their uses
(2S)-3-[[4-[[5-chloro-4-[3-chloro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]amino]cyclohexyl]amino]-1,1,1-trifluoropropan-2-ol	IC50	0.002 nM	US-8778951: Heteroaryl compounds and their uses
4-N-[4-[3-bromo-6-(oxan-4-ylmethylamino)-2-pyridinyl]-5-chloro-2-pyridinyl]-1-N-(2-methoxyethyl)cyclohexane-1,4-diamine	IC50	0.002 nM	US-8778951: Heteroaryl compounds and their uses

ChEMBL bioactivities

3177 potent at pChembl≥5 of 3201 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL3656855
10.98	IC50	0.01052	nM	CHEMBL3653003
10.98	IC50	0.01058	nM	CHEMBL3656781
10.96	IC50	0.01108	nM	CHEMBL3652946
10.96	IC50	0.011	nM	CHEMBL3652958
10.96	IC50	0.011	nM	CHEMBL3653025
10.96	IC50	0.011	nM	CHEMBL3656851
10.95	IC50	0.01124	nM	CHEMBL3652915
10.95	IC50	0.01113	nM	CHEMBL3652923
10.94	IC50	0.01154	nM	CHEMBL3656779
10.93	IC50	0.01162	nM	CHEMBL3652953
10.92	IC50	0.01213	nM	CHEMBL3653046
10.91	IC50	0.01242	nM	CHEMBL3652896
10.90	IC50	0.01255	nM	CHEMBL3653007
10.89	IC50	0.01288	nM	CHEMBL3652912
10.89	IC50	0.013	nM	CHEMBL3653030
10.89	IC50	0.013	nM	CHEMBL3653043
10.88	IC50	0.0131	nM	CHEMBL3656812
10.87	IC50	0.01353	nM	CHEMBL3652945
10.87	IC50	0.01363	nM	CHEMBL3656771
10.85	IC50	0.01412	nM	CHEMBL3652954
10.85	IC50	0.014	nM	CHEMBL3653029
10.85	IC50	0.0142	nM	CHEMBL3653078
10.84	IC50	0.01443	nM	CHEMBL3652919
10.84	IC50	0.01443	nM	CHEMBL3653001
10.83	IC50	0.01485	nM	CHEMBL3656764
10.82	IC50	0.015	nM	CHEMBL3652903
10.82	IC50	0.015	nM	CHEMBL3653038
10.81	IC50	0.01532	nM	CHEMBL3652976
10.81	IC50	0.01541	nM	CHEMBL3656775
10.80	IC50	0.01582	nM	CHEMBL3652978
10.80	IC50	0.01581	nM	CHEMBL3653011
10.79	IC50	0.01626	nM	CHEMBL3652898
10.79	IC50	0.0161	nM	CHEMBL3656813
10.77	IC50	0.01713	nM	CHEMBL3652936
10.76	IC50	0.01737	nM	CHEMBL3652921
10.76	IC50	0.01747	nM	CHEMBL3653071
10.74	IC50	0.0181	nM	CHEMBL3652931
10.74	IC50	0.01809	nM	CHEMBL3652975
10.74	IC50	0.018	nM	CHEMBL3653033
10.74	IC50	0.018	nM	CHEMBL3656846
10.73	IC50	0.01857	nM	CHEMBL3652882
10.73	IC50	0.01842	nM	CHEMBL3656772
10.72	IC50	0.01922	nM	CHEMBL3652922
10.72	IC50	0.019	nM	CHEMBL3653027
10.72	IC50	0.01884	nM	CHEMBL3653068
10.71	IC50	0.01935	nM	CHEMBL3653014
10.70	IC50	0.02018	nM	CHEMBL3656780
10.68	IC50	0.021	nM	CHEMBL3653042
10.68	IC50	0.02111	nM	CHEMBL3653048

PubChem BioAssay actives

1275 with measured affinity, of 2787 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
cis-(1S,3R)-3-acetamido-N-[4-(5,5-dimethyl-4,6-dihydropyrrolo[2,1-e]pyrazol-3-yl)-5-fluoro-2-pyridinyl]cyclohexane-1-carboxamide	1684241: Binding affinity to human CDK9/CyclinT assessed as equilibrium dissociation constant by surface plasmon resonance analysis	kd	0.0001	uM
cis-(1S,3R)-3-acetamido-N-[5-chloro-4-(5,5-dimethyl-4,6-dihydropyrrolo[2,1-e]pyrazol-3-yl)-2-pyridinyl]cyclohexane-1-carboxamide	1684241: Binding affinity to human CDK9/CyclinT assessed as equilibrium dissociation constant by surface plasmon resonance analysis	kd	0.0001	uM
cis-(1S,3R)-3-acetamido-N-[5-chloro-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-2-pyridinyl]cyclohexane-1-carboxamide	1684241: Binding affinity to human CDK9/CyclinT assessed as equilibrium dissociation constant by surface plasmon resonance analysis	kd	0.0003	uM
3,4-dimethyl-5-[2-(4-piperazin-1-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-one	1317387: Inhibition of recombinant human His-tagged CDK9/cyclin T1 expressed in baculovirus infected sf9 cells using (biotinyl-Ahx-(Tyr-Ser-ProThr-Ser-Pro-Ser)4-NH2 as substrate after 45 mins by [gamma-32P]ATP based microbeta scintillation counting analysis	ki	0.0004	uM
4-[[4-(2,3-difluoro-6-methoxyphenyl)pyrimidin-2-yl]amino]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0004	uM
4-N-[5-chloro-4-[6-[(3-fluorophenyl)methylamino]-2-pyridinyl]-2-pyridinyl]cyclohexane-1,4-diamine	2142690: Inhibition of human CDK9/Cyclin T1 in presence of ATP by radiometric kinase assay	ic50	0.0004	uM
4-[[[6-[5-chloro-2-[[4-[[(2S)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]-4-pyridinyl]-2-pyridinyl]amino]methyl]oxane-4-carbonitrile	1696617: Displacement of Alexa Fluor 647 ADP Tracer from His-tagged human CDK9/Cyclin T1 expressed in baculovirus expression system incubated for 1 hr by adapta assay	ic50	0.0005	uM
2-[2-chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one	1921459: Inhibition of CDK9/cyclin T1 (unknown origin)	ki	0.0006	uM
7-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-4-morpholin-4-yl-3-propanoylchromen-2-one	1739162: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay	ic50	0.0007	uM
3,20-difluoro-N-(2-morpholin-4-ylethyl)-13,18-dioxa-5,7,25-triazatetracyclo[17.3.1.12,6.18,12]pentacosa-1(23),2(25),3,5,8(24),9,11,19,21-nonaene-11-carboxamide	2037436: Inhibition of CDK9/Cyclin-T1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based assay	ic50	0.0009	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1317393: Inhibition of CDK9/cyclin T1 (unknown origin)	ic50	0.0010	uM
5-fluoro-4-(4-fluoro-1-benzofuran-7-yl)-N-[3-methyl-5-(methylsulfonylmethyl)phenyl]pyrimidin-2-amine	1696593: Inhibition of His-tagged human CDK9/cyclin T1 expressed in insect cells using biotin Ttds-YISPLKSPYKISEG as substrate preincubated for 15 mins followed by ATP and substrate addition and measured after 25 mins by TR-FRET assay	ic50	0.0010	uM
4-[[[4-[5-chloro-2-[[4-(2-methoxyethylamino)cyclohexyl]amino]-4-pyridinyl]-1,3-thiazol-2-yl]amino]methyl]oxane-4-carbonitrile	1418190: Inhibition of recombinant full length His-tagged human CDK9/CyclinT1 expressed in baculovirus expression system	ic50	0.0010	uM
N-(3,4-dimethyl-1,2-oxazol-5-yl)-4-[[4-(2-fluoro-6-methoxyphenyl)pyrimidin-2-yl]amino]benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0010	uM
4-[[4-(2,3-difluoro-6-methoxyphenyl)pyrimidin-2-yl]amino]-N-(3,4-dimethyl-1,2-oxazol-5-yl)benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0010	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	2195218: Inhibition of CDK9/Cyclin T1 (unknown origin) using ULight MBP peptide as substrate in presence of ATP incubated for 1 hr by FRET based LANCE Ultra KinaSelect screen assay	ic50	0.0010	uM
4-[4-fluoro-2-[(2-fluoro-4-pyridinyl)methoxy]phenyl]-N-[3-(methylsulfonylmethyl)phenyl]-1,3,5-triazin-2-amine	1317375: Inhibition of human recombinant full length His-tagged CDK9/cyclin T1 expressed in insect cells using biotin-Ttds-YISPLKSPYKISEG as substrate preincubated for 15 mins measured after 25 mins by TR-FRET assay	ic50	0.0010	uM
(3R)-N-[5-chloro-4-[5-fluoro-6-(oxan-4-ylmethylamino)-2-pyridinyl]-2-pyridinyl]piperidine-3-carboxamide	1317371: Inhibition of CDK9/cyclin T1 (unknown origin) using cdk7tide peptide as substrate	ic50	0.0010	uM
4-ethyl-6-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-8-(morpholin-4-ylmethyl)-1,4-benzoxazin-3-one	1883436: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 10 mins followed by ATP and CTD3 addition and measured after 30 mins by mobility shift assay	ic50	0.0011	uM
N-[2-(dimethylamino)ethyl]-3,20-difluoro-13,18-dioxa-5,7,25-triazatetracyclo[17.3.1.12,6.18,12]pentacosa-1(23),2(25),3,5,8(24),9,11,19,21-nonaene-11-carboxamide	2037436: Inhibition of CDK9/Cyclin-T1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based assay	ic50	0.0011	uM
3,21-difluoro-N-(2-morpholin-4-ylethyl)-13,19-dioxa-5,7,26-triazatetracyclo[18.3.1.12,6.18,12]hexacosa-1(24),2(26),3,5,8(25),9,11,20,22-nonaene-11-carboxamide	2037436: Inhibition of CDK9/Cyclin-T1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based assay	ic50	0.0011	uM
3-acetyl-4-(4-ethylpiperazin-1-yl)-7-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]chromen-2-one	1739162: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay	ic50	0.0012	uM
4-N-[2-(dimethylamino)ethyl]-7-N-[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]quinazoline-4,7-diamine	1771099: Inhibition of human CDK9/cyclin-T1 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate incubated for 2 hrs by [gamma-33P]-ATP assay	ic50	0.0012	uM
[2-[[4-(3-propan-2-ylbenzotriazol-5-yl)-2-pyridinyl]amino]-4-pyridinyl]-pyrrolidin-1-ylmethanone	2081988: Inhibition of CDK9/Cyclin T1 (unknown origin) using PDKtide substrate incubated for 60 mins by ADP-Glo kinase assay	ic50	0.0013	uM
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide	1245692: Inhibition of recombinant human CDK9/cyclin-T1 using H-YSPTSPSYSPTSPSYSPTSPS-KKKK-OH as substrate after 90 mins by luminescence assay	ic50	0.0014	uM
3-acetyl-7-[[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]amino]-4-morpholin-4-ylchromen-2-one	1771099: Inhibition of human CDK9/cyclin-T1 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate incubated for 2 hrs by [gamma-33P]-ATP assay	ic50	0.0014	uM
3-acetyl-7-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-4-(4-methylpiperazin-1-yl)chromen-2-one	1739162: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay	ic50	0.0015	uM
7-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-4-morpholin-4-ylchromen-2-one	1739162: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay	ic50	0.0016	uM
3-acetyl-4-(1,4-diazepan-1-yl)-7-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]chromen-2-one	1739162: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay	ic50	0.0016	uM
4-ethyl-6-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-8-[[4-(oxetan-3-yl)piperazin-1-yl]methyl]-1,4-benzoxazin-3-one	1883436: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 10 mins followed by ATP and CTD3 addition and measured after 30 mins by mobility shift assay	ic50	0.0016	uM
[2-[2-chloro-4-(trifluoromethyl)phenyl]-5-hydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]-4-oxochromen-7-yl] dihydrogen phosphate	1696650: Inhibition of N-terminal His6-tagged thrombin cleavage site-fused human CDK9 (M1 to F372 residues)/cyclin-T1 (M1 to K726 residues) expressed in baculovirus infected Sf9 insect cells in presence of gamma-33P-ATP by filter binding assay	ki	0.0017	uM
3-acetyl-7-[[5-chloro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-4-(4-methylpiperazin-1-yl)chromen-2-one	1739162: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay	ic50	0.0017	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[4-(prop-2-enoylamino)benzoyl]piperidine-3-carboxamide	1652518: Inhibition of recombinant human full-length His-tagged CDK9/Cyclin T1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr in presence of Alexa Fluor 647 ADP Tracer-based Adapta assay	ic50	0.0018	uM
2-[(E)-2-(2,6-dichlorophenyl)ethenyl]-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	1479297: Inhibition of CDK9/cyclin T1 (unknown origin) using YSPTSPSYSPTSPSYSPTSPKKK as substrate after 30 mins in presence of [33P]-gamma-ATP by filter binding assay	ic50	0.0019	uM
4-(4-methylpiperazin-1-yl)-N-[4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]quinolin-7-amine	1771099: Inhibition of human CDK9/cyclin-T1 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate incubated for 2 hrs by [gamma-33P]-ATP assay	ic50	0.0019	uM
4-ethyl-6-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-8-[[(3R)-3-methylmorpholin-4-yl]methyl]-1,4-benzoxazin-3-one	1883436: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 10 mins followed by ATP and CTD3 addition and measured after 30 mins by mobility shift assay	ic50	0.0019	uM
N-[4-[11-[(3R)-3-aminopyrrolidin-1-yl]-7,8,9,10-tetrahydro-6H-cyclohepta[b]quinolin-2-yl]-2-pyridinyl]cyclopropanecarboxamide;hydrochloride	2000055: Inhibition of CDK9/CyclinT1 (unknown origin) by ADP-Glo kinase assay	ic50	0.0019	uM
N-[4-[12-[(3S)-3-aminopyrrolidin-1-yl]-6,7,8,9,10,11-hexahydrocycloocta[b]quinolin-2-yl]-2-pyridinyl]cyclopropanecarboxamide;hydrochloride	2000055: Inhibition of CDK9/CyclinT1 (unknown origin) by ADP-Glo kinase assay	ic50	0.0019	uM
4-[2-[[4-(3-propan-2-ylbenzotriazol-5-yl)-2-pyridinyl]amino]pyridine-4-carbonyl]piperazin-2-one	2081988: Inhibition of CDK9/Cyclin T1 (unknown origin) using PDKtide substrate incubated for 60 mins by ADP-Glo kinase assay	ic50	0.0019	uM
2-methyl-N-(3-nitrophenyl)-4,5-dihydro-[1,3]thiazolo[4,5-h]quinazolin-8-amine	461543: inhibition of CDK9/CyclinT1	ki	0.0020	uM
3-[[4-[4-methyl-2-(methylamino)-1,3-thiazol-5-yl]pyrimidin-2-yl]amino]benzenesulfonamide	741495: Inhibition of human recombinant His6 tagged CDK9/CyclinT1 expressed in Sf21 insect cells after 40 mins by scintillation counting analysis	ki	0.0020	uM
N-[3-(benzimidazol-1-ylmethyl)phenyl]-4-(2-fluoro-6-methoxyphenyl)pyrimidin-2-amine	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0020	uM
4-[[4-(2-fluoro-6-methoxyphenyl)pyrimidin-2-yl]amino]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0020	uM
4-[[4-(2-fluoro-6-methoxyphenyl)pyrimidin-2-yl]amino]-N-(1,3-thiazol-2-yl)benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0020	uM
N-(3,4-dimethyl-1,2-oxazol-5-yl)-4-[[4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0020	uM
4-[[4-(2-ethoxy-4-fluorophenyl)pyrimidin-2-yl]amino]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0020	uM
N-(3,4-dimethyl-1,2-oxazol-5-yl)-4-[[4-(2-ethoxy-6-fluorophenyl)pyrimidin-2-yl]amino]benzenesulfonamide	1373254: Inhibition of N-terminal GST-HIS6 fusion protein tagged human full length CDK9 (M1 to F372 residues)/N-terminal GST-HIS6 fusion protein tagged human Cyclin-T1 (M1 to K726 residues) expressed in Sf9 cells at 10 uM using TAMRA-Rbtide substrate and ATP incubated for 1 hr by fluorescent polarization assay	ic50	0.0020	uM
3-acetyl-7-[[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino]-4-morpholin-4-ylchromen-2-one	1739162: Inhibition of CDK9/Cyclin T1 (unknown origin) preincubated for 20 mins followed by ATP addition and measured after 120 mins in presence of [33P-gamma] ATP by hotspot kinase assay	ic50	0.0020	uM
3,22-difluoro-N-(4-morpholin-4-ylcyclohexyl)-13,20-dioxa-5,7,27-triazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8(26),9,11,21,23-nonaene-11-carboxamide	2037436: Inhibition of CDK9/Cyclin-T1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based assay	ic50	0.0020	uM
(3R)-N-[5-chloro-4-(5-fluoro-2-propan-2-yloxyphenyl)-2-pyridinyl]piperidine-3-carboxamide	1317371: Inhibition of CDK9/cyclin T1 (unknown origin) using cdk7tide peptide as substrate	ic50	0.0020	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
trichostatin A	decreases expression	1
beryllium sulfate	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
entinostat	decreases expression	1
2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone	affects binding, decreases reaction	1
ICG 001	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Deferasirox	decreases reaction, affects binding	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Hydrogen Peroxide	decreases expression	1
Mercuric Chloride	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

617 unique, capped per target: 614 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3705381	Binding	IMAP Assay: Cdk9/cyclinT1 is purchased from Millipore, cat #14-685. The final total protein concentration in the assay 4 nM. The 5TAMRA-cdk7tide peptide substrate, 5TAMRA-YSPTSPSYSPTSPSYSTPSPS–COOH, is purchased from Molecular Devices, cat	Heteroaryl compounds and their uses
CHEMBL4814491	ADMET	Inhibition of human recombinant CDK9/CyclinT expressed in baculovirus infected Sf9 cells using YSPTSPSYSPTSPSYSPTSPSKKK as substrate in presence of ATP measured after 30 mins by ADP-Glo assay	In vitro identification of imidazo[1,2-a]pyrazine-based antileishmanial agents and evaluation of L. major casein kinase 1 inhibition. — Eur J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SH48	HAP1 CCNT1 (-) 1	Cancer cell line	Male
CVCL_SH49	HAP1 CCNT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03855631	Not specified	COMPLETED	Exploiting Epigenome Editing in Kabuki Syndrome: a New Route Towards Gene Therapy for Rare Genetic Disorders