CDK4

Summary

CDK4 (cyclin dependent kinase 4, HGNC:1773) is a protein-coding gene on chromosome 12q14.1, encoding Cyclin-dependent kinase 4 (P11802). Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. In precision oncology, CDK4 Amplification confers sensitivity to Palbociclib in Liposarcoma (CIViC Level B); 4 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 58.0% of cell lines).

The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported.

Source: NCBI Gene 1019 — RefSeq curated summary.

At a glance

• Gene–disease (curated): melanoma, cutaneous malignant, susceptibility to, 3 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 1,127 total — 3 pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes — 56 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 5 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 58.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000075

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1773
Approved symbol	CDK4
Name	cyclin dependent kinase 4
Location	12q14.1
Locus type	gene with protein product
Status	Approved
Aliases	PSK-J3
Ensembl gene	ENSG00000135446
Ensembl biotype	protein_coding
OMIM	123829
Entrez	1019

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000257904, ENST00000546489, ENST00000547281, ENST00000547853, ENST00000549606, ENST00000550419, ENST00000551706, ENST00000551800, ENST00000551888, ENST00000552254, ENST00000552388, ENST00000552713, ENST00000552862, ENST00000553237, ENST00000918532, ENST00000918533, ENST00000918534, ENST00000918535

RefSeq mRNA: 1 — MANE Select: NM_000075 NM_000075

CCDS: CCDS8953

Canonical transcript exons

ENST00000257904 — 8 exons

Exon	Start	End
ENSE00001141069	57747727	57748617
ENSE00002374522	57752175	57752310
ENSE00003458939	57749182	57749317
ENSE00003465926	57750656	57750765
ENSE00003486099	57751207	57751342
ENSE00003497990	57750923	57751090
ENSE00003593565	57751500	57751736
ENSE00003676150	57749454	57749504

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 112.2027 / max 4011.7860, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131753	92.4356	1818
131754	18.7230	1782
131750	0.6972	324
131751	0.2111	84
131752	0.1358	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
embryo	UBERON:0000922	98.33	gold quality
ganglionic eminence	UBERON:0004023	98.33	gold quality
ventricular zone	UBERON:0003053	98.30	gold quality
stromal cell of endometrium	CL:0002255	97.91	gold quality
right adrenal gland	UBERON:0001233	97.21	gold quality
ovary	UBERON:0000992	97.13	gold quality
right ovary	UBERON:0002118	97.13	gold quality
smooth muscle tissue	UBERON:0001135	97.11	gold quality
right adrenal gland cortex	UBERON:0035827	97.06	gold quality
left ovary	UBERON:0002119	97.05	gold quality
left adrenal gland	UBERON:0001234	96.92	gold quality
left adrenal gland cortex	UBERON:0035825	96.76	gold quality
left uterine tube	UBERON:0001303	96.75	gold quality
endocervix	UBERON:0000458	96.70	gold quality
adrenal gland	UBERON:0002369	96.70	gold quality
ectocervix	UBERON:0012249	96.70	gold quality
body of uterus	UBERON:0009853	96.66	gold quality
myometrium	UBERON:0001296	96.43	gold quality
adenohypophysis	UBERON:0002196	96.38	gold quality
fallopian tube	UBERON:0003889	96.35	gold quality
pancreas	UBERON:0001264	96.34	gold quality
islet of Langerhans	UBERON:0000006	96.31	gold quality
gall bladder	UBERON:0002110	96.31	gold quality
body of pancreas	UBERON:0001150	96.29	gold quality
pituitary gland	UBERON:0000007	96.16	gold quality
vermiform appendix	UBERON:0001154	96.06	gold quality
adrenal tissue	UBERON:0018303	96.03	gold quality
right coronary artery	UBERON:0001625	95.95	gold quality
lymph node	UBERON:0000029	95.92	gold quality
uterine cervix	UBERON:0000002	95.91	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	2197.80
E-HCAD-4	yes	143.81
E-CURD-114	yes	61.29
E-HCAD-5	yes	42.44
E-MTAB-9067	yes	23.71
E-GEOD-125970	yes	22.02
E-CURD-122	yes	19.99
E-CURD-112	yes	9.12
E-MTAB-7303	no	352.50
E-MTAB-6524	no	319.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, CEBPA, E2F1, ESR1, ETS1, EZH2, FOS, GATA4, HDAC1, HR, IRF1, IRF3, JARID2, JUND, KLF4, KSR1, LRRC4, MAFA, MYC, NEUROG3, NFATC2, NFKB1, NFKB, NFKBID, NR3C1, PARP1, PAX3, PDGFB, POU4F2, PPARG, RELA, RUNX1, SATB1, SIN3B, SOX6, SOX9, SP1, STAT3, TFDP1, TGFB1

miRNA regulators (miRDB)

45 targeting CDK4, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4263	99.18	69.25	2236

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 58.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Rarity of CDK4 germline mutations in familial melanoma. (PMID:11828258)
• Reversal of growth suppression by p107 via direct phosphorylation by cyclin D1/cyclin-dependent kinase 4 (PMID:11884610)
• Results show that Tax directly interacts with CDK4. The Tax/CDK complex represents an active holoenzyme which capably phosphorylates the Rb protein in vitro and is resistant to repression by the inhibitor p21(CIP). (PMID:11971966)
• ultraviolet-B-induced cell cycle arrest in A431 cells is mediated by cyclin-dependent kinase 4 downregulation (PMID:11982759)
• Keratinocytes engineered to express cdk4(R24C) and hTERT but not p53DD did not exhibit an extended life span. (PMID:12077343)
• Sequential extension of proliferative lifespan in human fibroblasts is induced by over-expression of CDK4 or 6 and loss of p53 function. (PMID:12082615)
• data identify a new role for oncogenic Ras in CDK4 regulation and highlight the functional importance of CDK4 suppression in preventing uncontrolled growth (PMID:12357246)
• Cdk4 binds to p16INK4A and causes its phosphorylation (PMID:12529334)
• Interferon gamma reduces the activity of Cdk4 and Cdk2, inhibiting he G1 cell cycle in human hepatocellular carcinoma cells. (PMID:12531694)
• Cdk4-overexpressing cells divide in an apparently normal regulated fashion, are able to respond to changes in calcium levels, and fully differentiate . These results suggest that the differentiation pathways in Cdk4-overexpressing cells remain intact (PMID:12545164)
• Data provide evidence of a role for MDM2 and CDK4 in the pathogenesis of carcinosarcoma. (PMID:12565795)
• increases of cyclin D1, cyclin-dependent kinase 4, cyclin E, cyclin A, and Wee1 play an important role in the development of hepatocellular carcinoma from cirrhosis (PMID:12601350)
• Cells overexpressing cdk4 or cyclin D1 exhibited nuclear features characteristic of apoptosis. (PMID:12680219)
• DNA mutation analysis of the CDK4 gene in many types of neoplasms reveal it is very rare. Random mutagenisis the CDK4 gene showed that most of the mutations that disrupted interactions with p16(INK4) also knocked out the activity of CDK4. (PMID:12731669)
• significant difference in their biochemical properties between CDK4/cyclin D1 and CDK2/cyclin A affecting regulation of cellular RB function (PMID:14646596)
• susceptibility to skin tumor formation by forced expression of CDK4 (PMID:14647432)
• Data suggest that cyclin dependent kinase 4 is involved in the development of tobacco-mediated oral carcinogenesis, and that c-myc expression is absent in normal and high in later stages of oral cancer development. (PMID:14672406)
• cyclin-dependent kinase (CDK)2, -4, and -6 were down-regulated from the myelocytes/metamyelocytes stages and onward (PMID:14694185)
• CDK4 binding to cyclin D1 is stimulated by Cdc37 (PMID:14701845)
• cyclin D1/Cdk4 complexes are regulated by calcium/calmodulin-dependent protein kinase I (PMID:14754892)
• Cdk2 and Cdk4 phosphorylate human Cdt1 and induce its degradation (PMID:15004027)
• CDK4, MDM2, SAS and GLI genes are amplified in leiomyosarcoma, alveolar and embryonal rhabdomyosarcoma (PMID:15024701)
• A novel Cdk4 docking motif has been defined within a stretch of 19 amino acids from the C-terminal domain of the Rb protein that are essential for Cdk4 binding. (PMID:15169919)
• Transcriptional regulation of the CDK4 promotor is compared in normal breast cell lines vs breast cancer cell lines. (PMID:15208653)
• When expressed in transgenic mice, total CDK4 protein expression was increased by up to 5-fold, with a concomitant increase in CDK4 activity. (PMID:15480536)
• Expression levels of CDK4 predict the cellular effects ofmTOIR inhibitors in ovarian carcinoma. (PMID:15505422)
• This suggests that dysregulation of CCND2 and CDK4 plays a specific role in WT tumorigenesis. (PMID:15797629)
• CDK4 melanoma families known to date have a substitution of amino acid 24. (PMID:15880589)
• Breast cancer patients might benefit from inhibiting CDK4 kinase. (PMID:16413469)
• there is a novel function for CDK4-cyclin D3 activity in S and G(2) phase that is critical for G(2)/M progression and the fidelity of mitosis (PMID:16476733)
• the subtype 2 receptor-mediated antiproliferative effect of SRIH on TT cell proliferation may be exerted through a decrease in cyclin D1 and cdk4 levels (PMID:16601140)
• Mantle cell lymphoma should be very sensitive to targeted therapy aimed at functional inhibition of the cyclin D1/CDK4 complex. (PMID:16690963)
• There were no significant changes of CDK4 and E2F-1/4 expression in benzo(a)pyrene treated embryo lung fibroblasts. (PMID:16758952)
• cyclin D1/Cdk4 converts FOXM1c from an almost inactive form into a strong transactivator in G1-phase, i.e., just at the time point at which the transcriptional activity of FOXM1 is required for stimulation of the G1/S-transition (PMID:16913845)
• The data shows the expression and purification of an Hsp90-Cdc37-Cdk4 complex, defining its stoichiometry, and determining its 3D structure by single-particle electron microscopy. (PMID:16949366)
• significant cytoplasmic mislocalization of ordinarily nuclear RB in cells harboring Cdk4 mutations (PMID:17043357)
• Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleus might be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epithelia. (PMID:17072968)
• findings confirm CDK4 overexpression is a frequent phenomenon in laryngeal carcinoma, which occurs at transcriptional level but not related to gene amplification or mutation, & suggest cooperation with CCND1 may be involved in laryngeal tumor progression (PMID:17139501)
• Sensitization towards TRAIL was due to the transcriptional downregulation of survivin (PMID:17304504)
• The expression level of cyclin D1 and CDK4 protein increased in human embryonic lung fibroblasts treated with quartz. (PMID:17374178)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk4	ENSDARG00000087937
mus_musculus	Cdk4	ENSMUSG00000006728
rattus_norvegicus	Cdk4	ENSRNOG00000025602

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), PRP4K (ENSG00000112739), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Cyclin-dependent kinase 4 — P11802 (reviewed: P11802)

Alternative names: Cell division protein kinase 4, PSK-J3

All UniProt accessions (10): P11802, F8VTV8, F8VWX7, F8VXD2, F8VYH9, F8VYY1, F8VZ13, F8VZ51, F8VZZ0, F8W1L8

UniProt curated annotations — full annotation on UniProt →

Function. Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.

Subunit / interactions. Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with SEI1 and ZNF655. Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on ‘Tyr-88’ and ‘Tyr-89’); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex. The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23. Interacts with CEBPA (when phosphorylated). Interacts with FNIP1 and FNIP2.

Subcellular location. Cytoplasm. Nucleus. Nucleus membrane.

Post-translational modifications. Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B.

Disease relevance. Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048] A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequent activation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P11802-1	1	yes
P11802-2	2

RefSeq proteins (1): NP_000066* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR050108	CDK	Family

Pfam: PF00069

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (53 total): helix 16, strand 13, sequence variant 5, turn 5, mutagenesis site 3, binding site 2, modified residue 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, region of interest 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
9CSK	X-RAY DIFFRACTION	2.25
2W96	X-RAY DIFFRACTION	2.3
6P8E	X-RAY DIFFRACTION	2.3
2W9Z	X-RAY DIFFRACTION	2.45
7SJ3	X-RAY DIFFRACTION	2.51
2W99	X-RAY DIFFRACTION	2.8
6P8G	X-RAY DIFFRACTION	2.8
2W9F	X-RAY DIFFRACTION	2.85
6P8F	X-RAY DIFFRACTION	2.89
3G33	X-RAY DIFFRACTION	3
6P8H	X-RAY DIFFRACTION	3.19
5FWK	ELECTRON MICROSCOPY	3.9
5FWP	ELECTRON MICROSCOPY	7.2
5FWM	ELECTRON MICROSCOPY	8
5FWL	ELECTRON MICROSCOPY	9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11802-F1	87.56	0.68

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): 140 (proton acceptor)

Ligand- & substrate-binding residues (2): 12–20; 35

Post-translational modifications (2): 2, 172

Mutagenesis-validated functional residues (3):

Position	Phenotype
172	weak enzyme activity towards rb1, but no effect on binding of ccdn1 nor ccdn3.
172	retains moderate enzyme activity.
173	no effect on in vitro phosphorylation by cdk7. greatly reduced t-172 phosphorylation and enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

50 pathways

ID	Pathway
R-HSA-187577	SCF(Skp2)-mediated degradation of p27/p21
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585	Oncogene Induced Senescence
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-69231	Cyclin D associated events in G1
R-HSA-75815	Ubiquitin-dependent degradation of Cyclin D
R-HSA-8849470	PTK6 Regulates Cell Cycle
R-HSA-8878166	Transcriptional regulation by RUNX2
R-HSA-912446	Meiotic recombination
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-9630791	Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4
R-HSA-9630794	Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
R-HSA-9632697	Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4
R-HSA-9632700	Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6
R-HSA-9661069	Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)
R-HSA-9754119	Drug-mediated inhibition of CDK4/CDK6 activity
R-HSA-9929491	SPOP-mediated proteasomal degradation of PD-L1(CD274)
R-HSA-1266738	Developmental Biology
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-453279	Mitotic G1 phase and G1/S transition

MSigDB gene sets: 525 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, REACTOME_MEIOTIC_RECOMBINATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, MODULE_451, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, PAL_PRMT5_TARGETS_UP, HOFMANN_CELL_LYMPHOMA_UP, REACTOME_SCF_SKP2_MEDIATED_DEGRADATION_OF_P27_P21, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN

GO Biological Process (17): G1/S transition of mitotic cell cycle (GO:0000082), signal transduction (GO:0007165), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), regulation of G2/M transition of mitotic cell cycle (GO:0010389), regulation of gene expression (GO:0010468), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), positive regulation of fibroblast proliferation (GO:0048146), cell division (GO:0051301), regulation of cell cycle (GO:0051726), regulation of transcription initiation by RNA polymerase II (GO:0060260), regulation of type B pancreatic cell proliferation (GO:0061469), cellular response to lipopolysaccharide (GO:0071222), cellular response to interleukin-4 (GO:0071353), cellular response to phorbol 13-acetate 12-myristate (GO:1904628), cellular response to ionomycin (GO:1904637), protein phosphorylation (GO:0006468)

GO Molecular Function (11): cyclin-dependent protein serine/threonine kinase activity (GO:0004693), ATP binding (GO:0005524), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), cyclin binding (GO:0030332), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (14): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), bicellular tight junction (GO:0005923), nuclear membrane (GO:0031965), cyclin D1-CDK4 complex (GO:0097128), cyclin D2-CDK4 complex (GO:0097129), cyclin D3-CDK4 complex (GO:0097130), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Cellular Senescence	3
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	2
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	2
Cyclin E associated events during G1/S transition	1
Cyclin A:Cdk2-associated events at S phase entry	1
Chromatin modifying enzymes	1
Adipogenesis	1
G1 Phase	1
S Phase	1
Signaling by PTK6	1
Generic Transcription Pathway	1
Meiosis	1
Developmental Biology	1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1
Cyclin D associated events in G1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cyclin-dependent protein kinase holoenzyme complex	3
cellular process	2
regulation of cellular process	2
G2/M transition of mitotic cell cycle	2
cellular response to lipid	2
protein kinase activity	2
nuclear lumen	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cell communication	1
signaling	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to chemical	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
gene expression	1
regulation of macromolecule biosynthetic process	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
cell cycle	1
regulation of transcription by RNA polymerase II	1
transcription initiation at RNA polymerase II promoter	1
regulation of DNA-templated transcription initiation	1
type B pancreatic cell proliferation	1
regulation of epithelial cell proliferation	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to oxygen-containing compound	1
response to interleukin-4	1
cellular response to cytokine stimulus	1
cellular response to alcohol	1

Protein interactions and networks

STRING

7256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK4	CCND1	P24385	999
CDK4	CDKN2A	P42771	999
CDK4	CCNL2	Q96S94	999
CDK4	CDKN1A	P38936	998
CDK4	CDKN2B	P42772	998
CDK4	CCND2	P30279	997
CDK4	CCND3	P30281	997
CDK4	CDKN2C	P42773	997
CDK4	CDKN2D	P55273	997
CDK4	CDC37	Q16543	996
CDK4	CDKN1B	P46527	996
CDK4	CCNA2	P20248	996
CDK4	HSP90AB1	P08238	992
CDK4	HSP90AA1	P07900	990
CDK4	RB1	P06400	985

IntAct

438 interactions, top by confidence:

A	B	Type	Score
CDK4	CCND1	psi-mi:“MI:0915”(physical association)	0.990
CCND1	CDK4	psi-mi:“MI:0915”(physical association)	0.990
CCND1	CDK4	psi-mi:“MI:0407”(direct interaction)	0.990
CDK4	CCND1	psi-mi:“MI:0914”(association)	0.990
CCND3	CDK4	psi-mi:“MI:0915”(physical association)	0.980
CDK4	CCND3	psi-mi:“MI:0915”(physical association)	0.980
CDK4	CCND3	psi-mi:“MI:0914”(association)	0.980

BioGRID (718): CDK4 (Affinity Capture-Western), CDK4 (Affinity Capture-Western), CDK4 (Two-hybrid), CDK4 (Two-hybrid), CDKN2C (Two-hybrid), CDKN2D (Two-hybrid), HOOK1 (Two-hybrid), RB1 (Biochemical Activity), HIST1H1A (Biochemical Activity), RB1 (Biochemical Activity), CDK4 (Affinity Capture-MS), CDK4 (Affinity Capture-MS), CDK4 (Affinity Capture-MS), CDK4 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS)

ESM2 similar proteins: A8WIP6, B2MVY4, G5ECH7, O74456, P00546, P04551, P11802, P20911, P25859, P30285, P35426, P38973, P48609, P49615, P50613, P51166, P51952, P53778, P54119, P54664, P54665, P54666, P79432, Q00534, Q00535, Q00646, Q02399, Q03114, Q03147, Q06309, Q0J4I1, Q2PQN9, Q2QSL4, Q2V419, Q32KY4, Q38772, Q38774, Q38775, Q4KM34, Q5R7I7

Diamond homologs: B2MVY4, G5ECH7, O35832, O55076, O60145, O74456, O96821, P00546, P04551, P06493, P11440, P11802, P13863, P17157, P23111, P23437, P23572, P23573, P24033, P24100, P24923, P24941, P29618, P29619, P30285, P34112, P34117, P35426, P35567, P38973, P39951, P43063, P43450, P48609, P48734, P48963, P49615, P51166, P51958, P52389

SIGNOR signaling

73 interactions.

A	Effect	B	Mechanism
MYC	“up-regulates quantity by expression”	CDK4	“transcriptional regulation”
CDK4	down-regulates	RB1	phosphorylation
CDKN2A	down-regulates	CDK4	binding
CDK4	down-regulates	BRCA1	phosphorylation
CDK4	down-regulates	RASSF1	phosphorylation
CDK4	up-regulates	PELP1	phosphorylation
CDK4	down-regulates	MEF2A	binding
CDK4	down-regulates	MEF2C	binding
CDK4	down-regulates	MEF2C
CDK4	down-regulates	MEF2D	binding
CDK4	down-regulates	MYOD1	binding
CDK4	down-regulates	MYOG	binding
CDK4	up-regulates	FOXM1	phosphorylation
YES1	down-regulates	CDK4	phosphorylation
CDK4	“down-regulates activity”	SMAD3	phosphorylation
CDK4	down-regulates	SMAD3	phosphorylation
CDK4	down-regulates	RUNX3	phosphorylation
4-(2,6-dichlorobenzamido)-N-(piperidin-4-yl)-pyrazole-3-carboxamide	down-regulates	CDK4	“chemical inhibition”
alvocidib	down-regulates	CDK4	“chemical inhibition”
“alvocidib hydrochloride”	down-regulates	CDK4	“chemical inhibition”
CCND1	up-regulates	CDK4	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
G1 Phase	13	88.3×	8e-21
Cyclin D associated events in G1	15	60.3×	5e-21
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	5	54.7×	2e-06
Mitotic G1 phase and G1/S transition	14	44.5×	8e-18
Aberrant regulation of mitotic cell cycle due to RB1 defects	5	35.2×	1e-05
Diseases of mitotic cell cycle	5	34.0×	2e-05
G1/S Transition	7	28.1×	4e-07
Cyclin E associated events during G1/S transition	5	24.6×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of G1/S transition of mitotic cell cycle	6	33.9×	8e-06
G1/S transition of mitotic cell cycle	10	28.3×	2e-09
regulation of G1/S transition of mitotic cell cycle	6	25.9×	3e-05
negative regulation of cell growth	5	10.1×	6e-03
Wnt signaling pathway	6	8.4×	5e-03
regulation of cell cycle	8	8.4×	7e-04
cell division	11	7.2×	7e-05
protein stabilization	7	6.6×	5e-03

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

CDK4, along with its partner CDK6, are key players in cell cycle progression. The complex has been implicated in a number of cancer types, and is the focus of therapeutic research and development. One targeted therapy for CDK inhibition is palbociclib, which may slow the growth of advanced stage breast cancers. It has also been shown, in mouse, that CDK inhibition may sensitize mutant PIK3CA tumors to PI3K inhibitors.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MEL.

Clinical variants and AI predictions

ClinVar

1127 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	595
Likely benign	268
Benign	48

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
16928	NM_000075.4(CDK4):c.70C>T (p.Arg24Cys)	Pathogenic
16929	NM_000075.4(CDK4):c.71G>A (p.Arg24His)	Pathogenic
1801589	NM_000075.4(CDK4):c.279dup (p.Glu94Ter)	Pathogenic

SpliceAI

1146 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57749155:C:A	donor_gain	1.0000
12:57749452:A:AC	donor_gain	1.0000
12:57749453:C:CC	donor_gain	1.0000
12:57749453:CT:C	donor_gain	1.0000
12:57750654:A:AC	donor_gain	1.0000
12:57750655:C:CC	donor_gain	1.0000
12:57750657:TTCG:T	donor_gain	1.0000
12:57750921:A:AC	donor_gain	1.0000
12:57750922:C:CC	donor_gain	1.0000
12:57750922:CCA:C	donor_gain	1.0000
12:57750947:G:C	donor_gain	1.0000
12:57751202:CTCA:C	donor_loss	1.0000
12:57751203:TCACC:T	donor_loss	1.0000
12:57751204:CACC:C	donor_loss	1.0000
12:57751205:A:AT	donor_loss	1.0000
12:57751206:C:CG	donor_loss	1.0000
12:57748614:TTTC:T	acceptor_gain	0.9900
12:57748618:C:CC	acceptor_gain	0.9900
12:57748618:C:G	acceptor_loss	0.9900
12:57748619:T:C	acceptor_loss	0.9900
12:57749154:T:A	donor_gain	0.9900
12:57749176:CAGTA:C	donor_loss	0.9900
12:57749177:AGTAC:A	donor_loss	0.9900
12:57749178:GTACC:G	donor_loss	0.9900
12:57749179:TACC:T	donor_loss	0.9900
12:57749180:A:AT	donor_loss	0.9900
12:57749181:C:CA	donor_loss	0.9900
12:57749198:C:CA	donor_gain	0.9900
12:57749220:C:CT	donor_gain	0.9900
12:57749221:C:CT	donor_gain	0.9900

AlphaMissense

1940 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57750971:G:C	D158E	1.000
12:57750971:G:T	D158E	1.000
12:57750972:T:A	D158V	1.000
12:57750972:T:G	D158A	1.000
12:57750973:C:G	D158H	1.000
12:57751025:A:C	D140E	1.000
12:57751025:A:T	D140E	1.000
12:57751026:T:A	D140V	1.000
12:57751026:T:C	D140G	1.000
12:57751026:T:G	D140A	1.000
12:57751029:C:G	R139P	1.000
12:57751613:C:A	K35N	1.000
12:57751613:C:G	K35N	1.000
12:57749289:A:G	W238R	0.999
12:57749289:A:T	W238R	0.999
12:57750682:A:C	C202W	0.999
12:57750683:C:T	C202Y	0.999
12:57750686:C:T	G201D	0.999
12:57750694:C:A	W198C	0.999
12:57750694:C:G	W198C	0.999
12:57750696:A:G	W198R	0.999
12:57750696:A:T	W198R	0.999
12:57750702:C:G	D196H	0.999
12:57750740:G:T	P183H	0.999
12:57750750:A:G	Y180H	0.999
12:57750758:G:A	T177I	0.999
12:57750960:G:T	A162D	0.999
12:57750963:A:G	L161P	0.999
12:57750966:C:T	G160D	0.999
12:57750967:C:G	G160R	0.999

dbSNP variants (sampled 300 via entrez): RS1000052939 (12:57751699 C>A,G,T), RS1000416664 (12:57747962 G>A,C), RS1000870693 (12:57748322 C>G), RS1001155355 (12:57749593 T>C), RS1001309614 (12:57752223 G>A), RS1002207037 (12:57749098 C>A,T), RS1002814184 (12:57753200 C>A,G), RS1002943409 (12:57753214 T>G), RS1003172820 (12:57752727 T>G), RS1003208178 (12:57747486 G>A), RS1003386519 (12:57753451 G>A), RS1004281478 (12:57751102 G>A,C), RS1004656804 (12:57750297 G>A,T), RS1004724115 (12:57748846 C>T), RS1005006906 (12:57749964 T>C)

Disease associations

OMIM: gene MIM:123829 | disease phenotypes: MIM:609048, MIM:613659, MIM:621507

GenCC curated gene-disease

Disease	Classification	Inheritance
melanoma, cutaneous malignant, susceptibility to, 3	Definitive	Autosomal dominant
malignant pancreatic neoplasm	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
melanoma, cutaneous malignant, susceptibility to, 3	Definitive	AD

Mondo (7): familial melanoma (MONDO:0018961), hereditary neoplastic syndrome (MONDO:0015356), melanoma, cutaneous malignant, susceptibility to, 3 (MONDO:0012183), gastric cancer (MONDO:0001056), diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (MONDO:0858939), microcephaly 31, primary, autosomal recessive (MONDO:0980991), malignant pancreatic neoplasm (MONDO:0009831)

Orphanet (2): Familial melanoma (Orphanet:618), Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000488	Retinopathy
HP:0000958	Dry skin
HP:0001054	Numerous nevi
HP:0001062	Atypical nevus
HP:0001074	Atypical nevi in non-sun exposed areas
HP:0001480	Freckling
HP:0001482	Subcutaneous nodule
HP:0001595	Abnormal hair morphology
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002579	Gastrointestinal dysmotility
HP:0002861	Melanoma
HP:0002894	Neoplasm of the pancreas
HP:0003764	Nevus
HP:0006753	Neoplasm of the stomach
HP:0012056	Cutaneous melanoma
HP:0012211	Abnormal renal physiology
HP:0100013	Neoplasm of the breast
HP:0100763	Abnormality of the lymphatic system

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000987_14	Celiac disease or Rheumatoid arthritis	4.000000e-06
GCST002318_6	Rheumatoid arthritis	1.000000e-07
GCST002318_66	Rheumatoid arthritis	7.000000e-08
GCST006959_107	Rheumatoid arthritis	1.000000e-07
GCST006959_36	Rheumatoid arthritis	9.000000e-08
GCST010703_209	Brain morphology (MOSTest)	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (19): CHEMBL1907601 (PROTEIN COMPLEX), CHEMBL2095942 (PROTEIN COMPLEX GROUP), CHEMBL2111326 (SELECTIVITY GROUP), CHEMBL3038472 (PROTEIN COMPLEX), CHEMBL3038517 (PROTEIN FAMILY), CHEMBL3301385 (PROTEIN COMPLEX), CHEMBL331 (SINGLE PROTEIN), CHEMBL3559691 (PROTEIN FAMILY), CHEMBL3885548 (PROTEIN COMPLEX), CHEMBL3885553 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

56 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 260,604 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL3904602	LEROCICLIB	3	1,012
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL50	QUERCETIN	3	74,559
CHEMBL4802161	DALPICICLIB	3	423
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1276127	INDIRUBIN	2	181
CHEMBL14762	SELICICLIB	2
CHEMBL1738757	REBASTINIB	2
CHEMBL3115681	NARAZACICLIB	2
CHEMBL3545283	RIVICICLIB	2
CHEMBL384304	RG-547	2
CHEMBL3905910	VORUCICLIB	2
CHEMBL4067549	ULECACICLIB	2
CHEMBL4277900	CROZBACICLIB	2
CHEMBL4442620	RONICICLIB	2
CHEMBL4446357	EBVACICLIB	2

Clinical evidence (CIViC)

Drug × variant × indication: 5 predictive associations from 6 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
CDK4 Amplification	Palbociclib	Liposarcoma	Sensitivity/Response	CIViC B	EID1366 +1
CDK4 EXPRESSION	Alpelisib	Estrogen-receptor Positive Breast Cancer	Sensitivity/Response	CIViC D	EID264
CDK4 EXPRESSION	Palbociclib	Sarcoma	Sensitivity/Response	CIViC D	EID4872
CDK4 EXPRESSION	Ribociclib + Dexamethasone	Childhood B-cell Acute Lymphoblastic Leukemia	Sensitivity/Response	CIViC D	EID7798
CDK4 R24C	Palbociclib	Skin Melanoma	Sensitivity/Response	CIViC D	EID1376

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2069502	Other	3	somatropin recombinant	Turner Syndrome
rs2270777	Other	3	somatropin recombinant

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2069502	AGAP2, CDK4, MARCHF9, TSPAN31	3	2.00	1	somatropin recombinant
rs2270777	CDK4	3	2.00	1	somatropin recombinant

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CDK4 subfamily

Most potent curated ligand interactions (43 total), top 25:

Ligand	Action	Affinity	Parameter
trilaciclib	Inhibition	10.0	pKd
culmerciclib	Inhibition	9.46	pIC50
cimpuciclib	Inhibition	9.31	pIC50
atirmociclib	Inhibition	9.22	pKi
lerociclib	Inhibition	9.0	pIC50
R547	Inhibition	9.0	pKi
PF-06873600	Inhibition	8.86	pKi
tibremciclib	Inhibition	8.72	pIC50
inixaciclib	Inhibition	8.7	pIC50
abemaciclib	Inhibition	8.7	pIC50
crozbaciclib	Inhibition	8.52	pIC50
ulecaciclib	Inhibition	8.52	pKi
bireociclib	Inhibition	8.52	pIC50
narazaciclib	Inhibition	8.41	pIC50
RGB-286638	Inhibition	8.4	pIC50
Cdk4 inhibitor III	Inhibition	8.22	pIC50
vustanaciclib	Inhibition	8.0	pIC50
ribociclib	Inhibition	8.0	pIC50
dalpiciclib	Inhibition	7.96	pIC50
PRT3645	Inhibition	7.7	pIC50
Ro-0505124	Inhibition	7.7	pIC50
BSJ-03-204	Inhibition	7.57	pIC50
CP-10	Inhibition	7.52	pIC50
palbociclib	Inhibition	7.36	pIC50
BSJ-04-132	Inhibition	7.3	pIC50

Binding affinities (BindingDB)

1729 measured of 2813 human assays (2876 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[6-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.09 nM	US-10233188: CDK2/4/6 inhibitors
(3S,4S)-4-[[5-chloro-4-(5-fluoro-1,1-dimethyl-2,3-dihydropyrrolo[1,2-a]benzimidazol-7-yl)pyrimidin-2-yl]amino]-1-methylsulfonylpiperidin-3-ol	KI	0.1 nM	US-10766884: Cyclin dependent kinase inhibitors
6-(2-hydroxyethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	0.11 nM	US-10233188: CDK2/4/6 inhibitors
8-cyclopentyl-N-(2-piperazin-1-ylpyrimidin-5-yl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.13 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)-piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	KI	0.16 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.2 nM	US-10233188: CDK2/4/6 inhibitors
8-[(1R,3R)-3-hydroxycyclohexyl]-2-{[1-(methylsulfonyl)piperidin-4-yl]-amino}pyrido[2,3-d]pyrimidin-7(8H)-one	KI	0.26 nM	US-10233188: CDK2/4/6 inhibitors
8-phenyl-N-(4-piperazin-1-ylphenyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.32 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-(4-piperazin-1-ylphenyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.45 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
4-[[6-fluoro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]-N-methylpiperidine-1-sulfonamide	KI	0.48 nM	US-10233188: CDK2/4/6 inhibitors
8-Cyclopentyl-2-[4-(2-diethylaminoethoxy)phenylamino]-8H-pyrido[2,3-d]pyrimidin-7-one	IC50	0.7 nM
2-[[(3S,5R)-3,5-dimethylmorpholin-4-yl]methyl]-7-[5-fluoro-2-[[(3S,4R)-3-hydroxyoxan-4-yl]amino]pyrimidin-4-yl]-3-methyl-1-propan-2-ylquinolin-4-one	IC50	0.8 nM	US-20250136586: Substituted 7-(Pyrimidin-4-yl)Quinolin-4(1H)-One Compounds as Cyclin Dependent Kinase Inhibitors
8-cyclopentyl-N-(4-piperazin-1-ylphenyl)-4,6,8,10-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.83 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-(5-methyl-6-piperazin-1-yl-3-pyridinyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.91 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-(2-bicyclo[2.2.1]heptanyl)-N-(5-piperazin-1-yl-2-pyridinyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.94 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-[6-[4-(dimethylamino)piperidin-1-yl]-3-pyridinyl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	0.97 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-[6-[4-(dimethylamino)piperidin-1-yl]pyridazin-3-yl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
9-cyclohexyl-N-(4-piperazin-1-ylphenyl)pyrimido[4,5-b]indol-2-amine	IC50	1 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-[6-[4-(diethylamino)piperidin-1-yl]pyridazin-3-yl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
10-chloro-8-cyclopentyl-N-[5-[4-(dimethylamino)piperidin-1-yl]-2-pyridinyl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
2-[4-[[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]-3-pyridinyl]methyl]piperazin-1-yl]acetic acid	IC50	1 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
(3R,4R)-1-[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]pyridazin-3-yl]-3-(dimethylamino)piperidin-4-ol	IC50	1 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-N-(pyrimidin-4-yl)-1,3-thiazol-2-amine	IC50	1 nM
4-[(4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-yl)amino]benzonitrile	IC50	1 nM
N-(3,4-dichlorophenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	1 nM
N-(3,5-difluorophenyl)-4-{pyrazolo[1,5-a]pyridazin-3-yl}pyrimidin-2-amine	IC50	1 nM
2-[[(3S,5S)-3,5-dimethylmorpholin-4-yl]methyl]-7-[5-fluoro-2-[[(3S,4R)-3-hydroxyoxan-4-yl]amino]pyrimidin-4-yl]-3-methyl-1-propan-2-ylquinolin-4-one	IC50	1.1 nM	US-20250136586: Substituted 7-(Pyrimidin-4-yl)Quinolin-4(1H)-One Compounds as Cyclin Dependent Kinase Inhibitors
8-cyclopentyl-N-[5-(4-propan-2-ylpiperazin-1-yl)-2-pyridinyl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.2 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-(4-methylcyclohexyl)-N-(5-piperazin-1-yl-2-pyridinyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.2 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
9-cyclohexyl-N-(5-piperazin-1-yl-2-pyridinyl)pyrimido[4,5-b]indol-2-amine	IC50	1.3 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
N-[5-[3-(aminomethyl)piperidin-1-yl]-2-pyridinyl]-8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.3 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-[5-(1,2,3,6-tetrahydropyridin-4-yl)-2-pyridinyl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.3 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
(2R)-3-[[1-[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]pyridazin-3-yl]piperidin-4-yl]amino]propane-1,2-diol	IC50	1.3 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
2-[4-[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]pyridazin-3-yl]piperazin-1-yl]acetic acid	IC50	1.39 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-(6-piperazin-1-yl-3-pyridinyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.4 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-[5-[4-(methylamino)piperidin-1-yl]-2-pyridinyl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.4 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]-3-pyridinyl]-piperazin-1-ylmethanone	IC50	1.4 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
3-[[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]pyridazin-3-yl]amino]propan-1-ol	IC50	1.4 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
6-chloro-8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	KI	1.4 nM	US-10233188: CDK2/4/6 inhibitors
8-cyclopentyl-N-(6-piperazin-1-ylpyridazin-3-yl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.5 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
(2S)-2-[[1-[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]pyridazin-3-yl]piperidin-4-yl]amino]propan-1-ol	IC50	1.5 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
(3R)-1-[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]pyridazin-3-yl]pyrrolidin-3-ol	IC50	1.6 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-(1-adamantyl)-N-(5-piperazin-1-yl-2-pyridinyl)-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.6 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
8-cyclopentyl-N-[5-(1,4-diazepan-1-yl)-2-pyridinyl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.6 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
N-[6-(4-aminopiperidin-1-yl)pyridazin-3-yl]-8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.6 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
7-[5-fluoro-2-[[(3S,4R)-3-hydroxyoxan-4-yl]amino]pyrimidin-4-yl]-2-[[(3R)-3-hydroxypiperidin-1-yl]methyl]-3-methyl-1-propan-2-ylquinolin-4-one	IC50	1.6 nM	US-20250136586: Substituted 7-(Pyrimidin-4-yl)Quinolin-4(1H)-One Compounds as Cyclin Dependent Kinase Inhibitors
7-[5-fluoro-2-[[(3S,4R)-3-hydroxyoxan-4-yl]amino]pyrimidin-4-yl]-3-methyl-1-propan-2-yl-2-pyrrolidin-2-ylquinolin-4-one	IC50	1.6 nM	US-20250136586: Substituted 7-(Pyrimidin-4-yl)Quinolin-4(1H)-One Compounds as Cyclin Dependent Kinase Inhibitors
8-cyclopentyl-N-[5-[(3R)-3-methylpiperazin-1-yl]-2-pyridinyl]-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-amine	IC50	1.7 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors
(2R)-1-[[1-[6-[(8-cyclopentyl-4,6,8,11-tetrazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-5-yl)amino]pyridazin-3-yl]piperidin-4-yl]amino]propan-2-ol	IC50	1.7 nM	US-8841312: Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors

ChEMBL bioactivities

4187 potent at pChembl≥5 of 4533 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.59	IC50	0.026	nM	CHEMBL151546
10.33	Ki	0.047	nM	CHEMBL5272948
10.15	IC50	0.07	nM	CHEMBL5841163
10.10	IC50	0.08	nM	CHEMBL148580
10.10	IC50	0.08	nM	CHEMBL6064669
10.00	IC50	0.1	nM	CHEMBL5198209
10.00	Ki	0.1	nM	CHEMBL5266837
10.00	Ki	0.1	nM	CHEMBL5795283
10.00	Ki	0.1	nM	CHEMBL5799855
10.00	Ki	0.1	nM	CHEMBL5805872
10.00	Ki	0.1	nM	CHEMBL5876670
10.00	Ki	0.1	nM	CHEMBL6001085
10.00	Ki	0.1	nM	CHEMBL5882519
10.00	Ki	0.1	nM	CHEMBL6001033
10.00	Ki	0.1	nM	CHEMBL5749795
10.00	Ki	0.1	nM	CHEMBL6052225
10.00	Ki	0.1	nM	CHEMBL5907078
10.00	Ki	0.1	nM	CHEMBL5783305
10.00	Ki	0.1	nM	CHEMBL6026426
10.00	Ki	0.1	nM	CHEMBL5786491
10.00	IC50	0.1	nM	CHEMBL5765852
9.96	IC50	0.11	nM	CHEMBL5941236
9.96	IC50	0.11	nM	CHEMBL6043427
9.92	IC50	0.12	nM	CHEMBL5748748
9.89	IC50	0.13	nM	CHEMBL3698644
9.89	Ki	0.13	nM	EBVACICLIB
9.85	IC50	0.14	nM	CHEMBL4208172
9.80	Ki	0.16	nM	CHEMBL4750658
9.80	Ki	0.16	nM	CHEMBL5746772
9.80	Ki	0.16	nM	CHEMBL5281860
9.80	IC50	0.16	nM	CHEMBL5981421
9.77	IC50	0.17	nM	CHEMBL6064669
9.74	IC50	0.18	nM	CHEMBL5786556
9.72	Ki	0.19	nM	CHEMBL5281860
9.71	Ki	0.196	nM	CHEMBL5278015
9.70	IC50	0.2	nM	CHEMBL4453997
9.70	Ki	0.2	nM	CHEMBL5280928
9.70	Ki	0.2	nM	CHEMBL5921011
9.70	Ki	0.2	nM	CHEMBL6041338
9.70	Ki	0.2	nM	CHEMBL5982367
9.70	Ki	0.2	nM	CHEMBL5982735
9.70	Ki	0.2	nM	CHEMBL5851399
9.70	Ki	0.2	nM	CHEMBL5960728
9.70	Ki	0.2	nM	CHEMBL5782517
9.70	Ki	0.2	nM	CHEMBL5962008
9.70	Ki	0.2	nM	CHEMBL5801501
9.70	Ki	0.2	nM	CHEMBL5921680
9.70	Ki	0.2	nM	CHEMBL6001026
9.70	Ki	0.2	nM	CHEMBL5813123
9.70	IC50	0.2	nM	CHEMBL5751717

PubChem BioAssay actives

2877 with measured affinity, of 5471 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-cyclopentyl-6-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	<0.0001	uM
[3-(5-chlorothiophen-3-yl)-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]urea	1607703: Inhibition of CDK4 (unknown origin)	ic50	<0.0001	uM
1-morpholin-4-yl-3-[4-oxo-3-[5-(piperazine-1-carbonyl)thiophen-2-yl]-2H-indeno[1,2-c]pyrazol-5-yl]urea	1607703: Inhibition of CDK4 (unknown origin)	ic50	<0.0001	uM
6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1924112: Inhibition of CDK4 (unknown origin) assessed as inhibition constant	ki	0.0001	uM
2-(2-ethylphenyl)-5,7-dihydroxy-8-[(3R,4S)-3-hydroxy-1-methylpiperidin-4-yl]-2,3-dihydrochromen-4-one	1868057: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0001	uM
8-cyclopentyl-6-(cyclopropyloxymethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0001	uM
2-(4-carbamimidoylpiperazin-1-yl)-N-[3-(4-methoxyphenyl)-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]acetamide	1607703: Inhibition of CDK4 (unknown origin)	ic50	0.0001	uM
6-(2,2-difluoroethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
6-(2,2-difluoroethyl)-8-[(1S,2S)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1685179: Inhibition of non-phosphorylated CDK4/Cyclin D3 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0002	uM
8-cyclopentyl-6-(2-methoxyethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
3-(4-methoxyphenyl)-4-oxo-1H-indeno[2,1-d]pyrazole-5-carbaldehyde	1607703: Inhibition of CDK4 (unknown origin)	ic50	0.0002	uM
8-cyclopentyl-6-(ethoxymethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
6-acetyl-8-cyclopentyl-5-methyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0002	uM
N-(3-nitrophenyl)-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine	348894: Inhibition of CDK4 by radioactive glutathione plate-binding assay	ic50	0.0003	uM
5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)-N-(5-piperazin-1-yl-2-pyridinyl)pyrimidin-2-amine	2107973: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0003	uM
6-chloro-8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0003	uM
2-[8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	1685179: Inhibition of non-phosphorylated CDK4/Cyclin D3 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay	ki	0.0003	uM
N-[5-(6-ethyl-2,6-diazaspiro[3.3]heptan-2-yl)-2-pyridinyl]-5-fluoro-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0003	uM
5-fluoro-N-[5-(4-methylpiperazin-1-yl)-2-pyridinyl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0003	uM
5-fluoro-N-[5-[6-(3-fluoropropyl)-2,6-diazaspiro[3.3]heptan-2-yl]-2-pyridinyl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0003	uM
5-fluoro-N-[5-[6-(2-fluoroethyl)-2,6-diazaspiro[3.3]heptan-2-yl]-2-pyridinyl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0003	uM
5-fluoro-N-[5-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-2-pyridinyl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0003	uM
N-[5-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-pyridinyl]-5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-amine	2107973: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0003	uM
5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)-N-(5-piperidin-4-yl-2-pyridinyl)pyrimidin-2-amine	2107973: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0004	uM
6-chloro-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0004	uM
5-fluoro-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]-N-(5-morpholin-4-yl-2-pyridinyl)pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0004	uM
5-fluoro-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]-N-[5-[6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl]-2-pyridinyl]pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0004	uM
2-[8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]-7-oxopyrido[2,3-d]pyrimidin-6-yl]acetonitrile	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0005	uM
8-cyclohexyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0005	uM
8-cyclopentyl-6-(2-hydroxyethyl)-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0005	uM
Abemaciclib	2198994: Inhibition of human CDK4/cyclin D1 preincubated with compound for 20 mins followed by [33P]ATP addition and measured after 2 hrs by filter binding method	ic50	0.0005	uM
[4-[6-[[5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-yl]amino]-3-pyridinyl]piperazin-2-yl]methanol	2107973: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0006	uM
5-fluoro-4-(5-fluoro-1,1-dimethyl-2,3-dihydropyrrolo[1,2-a]benzimidazol-7-yl)-N-[5-(piperazin-1-ylmethyl)-2-pyridinyl]pyrimidin-2-amine	1374354: Inhibition of CDK4 (unknown origin) after 90 mins by ADP-Glo assay	ic50	0.0006	uM
5-fluoro-4-(5-fluoro-1-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazol-7-yl)-N-[5-[(4-propan-2-ylpiperazin-1-yl)methyl]-2-pyridinyl]pyrimidin-2-amine	1374354: Inhibition of CDK4 (unknown origin) after 90 mins by ADP-Glo assay	ic50	0.0006	uM
8-cycloheptyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0006	uM
N-[5-(3,8-diazabicyclo[3.2.1]octan-3-yl)-2-pyridinyl]-5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-amine	2107973: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0006	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148049: Binding affinity to human CDK4 incubated for 45 mins by Kinobead based pull down assay	kd	0.0006	uM
2-(4-chlorophenyl)-5,7-dihydroxy-8-[(3R,4S)-3-hydroxy-1-methylpiperidin-4-yl]-2,3-dihydrochromen-4-one	1868057: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0006	uM
2-(2-bromophenyl)-5,7-dihydroxy-8-[(3R,4S)-3-hydroxy-1-methylpiperidin-4-yl]-2,3-dihydrochromen-4-one	1868057: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0006	uM
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone	624780: Binding constant for CDK4-cyclinD1 kinase domain	kd	0.0006	uM
6-[2-(dimethylamino)ethyl]-N-[5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-yl]-7,8-dihydro-5H-1,6-naphthyridin-2-amine	1509614: Inhibition of recombinant human full length N-terminal GST-tagged CDK4 (1 to 303 residues)/cyclin D3 (1 to 292 residues) expressed in baculovirus expression system using eIF4E-binding protein 1 peptide and ATP as substrate incubated for 30 mins by LANCE ultra kinase assay	ic50	0.0007	uM
8-cyclopentyl-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0007	uM
8-cyclopentyl-2-[4-[2-(diethylamino)ethoxy]anilino]pyrido[2,3-d]pyrimidin-7-one	1795862: CDKs Assay from Article 10.1021/jm000271k: “Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases.”	ic50	0.0007	uM
N-[5-[(4-ethylpiperazin-1-yl)methyl]-2-pyridinyl]-5-fluoro-4-(2-methyl-3-propan-2-ylindazol-5-yl)pyrimidin-2-amine	2107973: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0008	uM
5-fluoro-4-(5-fluoro-1,1-dimethyl-2,3-dihydropyrrolo[1,2-a]benzimidazol-7-yl)-N-[5-[(4-methylpiperazin-1-yl)methyl]-2-pyridinyl]pyrimidin-2-amine	1374354: Inhibition of CDK4 (unknown origin) after 90 mins by ADP-Glo assay	ic50	0.0008	uM
8-[(1R,2S)-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1933532: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay	ki	0.0008	uM
5-fluoro-N-[5-(1-methylpiperidin-4-yl)-2-pyridinyl]-4-[(4R)-4-methyl-5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a]azepin-3-yl]pyrimidin-2-amine	1588588: Inhibition of human full length GST-tagged CDK4 (1 to 303(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay	ki	0.0008	uM
1-[8-methyl-12-(4-piperazin-1-ylanilino)-4-propan-2-yl-2,5,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),3,5,7,9,11-hexaen-7-yl]ethanone	1737183: Inhibition of recombinant human full-length N-terminal GST-fused CDK4 (1 to 303 residues)/GST-tagged CyclinD3 (1 to 292 residues) expressed in baculovirus expression system using ULight-elF4E-binding protein 1 peptide as substrate measured after 30 mins by LANCE assay	ic50	0.0008	uM
5,7-dihydroxy-8-[(3R,4S)-3-hydroxy-1-methylpiperidin-4-yl]-2-pyridin-4-yl-2,3-dihydrochromen-4-one	1868057: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0008	uM
5,7-dihydroxy-8-[(3R,4S)-3-hydroxy-1-methylpiperidin-4-yl]-2-(3-methylphenyl)-2,3-dihydrochromen-4-one	1868057: Inhibition of CDK4/Cyclin D1 (unknown origin)	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
palbociclib	decreases reaction, increases phosphorylation, increases reaction, decreases activity, increases expression (+3 more)	8
Resveratrol	decreases reaction, increases activity, increases expression, affects binding, decreases activity (+5 more)	8
sodium arsenite	affects cotreatment, affects binding, decreases activity, decreases expression, decreases reaction (+2 more)	6
(+)-JQ1 compound	decreases reaction, increases expression, decreases expression, increases reaction	5
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases reaction, affects reaction	5
Estradiol	affects binding, decreases reaction, increases activity, decreases phosphorylation, increases expression (+1 more)	5
abemaciclib	affects binding, decreases reaction, decreases activity	4
bisphenol A	increases expression, decreases reaction, affects cotreatment	4
methylselenic acid	increases reaction, decreases activity, decreases expression, affects binding	4
Arsenic Trioxide	decreases reaction, increases expression	4
Cisplatin	affects binding, decreases activity, decreases expression, decreases reaction, increases expression (+2 more)	4
Nanotubes, Carbon	decreases expression, affects cotreatment, increases expression	4
tanespimycin	decreases expression	3
Arsenic	affects methylation, increases expression, affects cotreatment, decreases expression	3
Cannabidiol	decreases expression, affects cotreatment	3
Curcumin	decreases expression	3
Quercetin	decreases expression, decreases reaction, increases activity, increases expression	3
Tetrachlorodibenzodioxin	increases phosphorylation, increases activity, increases reaction, decreases reaction, increases expression (+2 more)	3
Cadmium Chloride	decreases expression, increases expression	3
ribociclib	decreases activity, affects binding, decreases reaction	2
picrasidine I	increases expression, decreases expression	2
tubocapsenolide A	decreases reaction, increases degradation, decreases expression	2
geraniol	decreases expression	2
beta-ionone	decreases expression	2
trichostatin A	decreases expression	2
indole-3-carbinol	decreases activity, increases expression, decreases expression	2
2-oxindole	affects binding, decreases activity	2
perfluorooctanoic acid	increases expression	2
perfluorooctane sulfonic acid	increases expression	2
alvocidib	affects binding, decreases activity	2

ChEMBL screening assays

1142 unique, capped per target: 1086 binding, 53 functional, 2 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016197	Binding	Inhibition of CDK4/Cyclin D1 assessed as inhibition of retinoblastoma susceptibility gene product phosphorylation	Discovery of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-diones and 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4. — J Med Chem
CHEMBL666092	Functional	Inhibition of Rb21 phosphorylation by Cyclin D1-cyclin-dependent kinase 4	Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles. — Bioorg Med Chem Lett
CHEMBL4325186	ADMET	Inhibition of human CDK4/Cyclin D3 at 1 uM relative to control	Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis. — J Med Chem

Cellosaurus cell lines

131 cell lines: 69 telomerase immortalized cell line, 56 cancer cell line, 6 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0526	SK-MEL-28	Cancer cell line	Male
CVCL_0B76	WM3630	Cancer cell line	Sex unspecified
CVCL_0B78	WM3704	Cancer cell line	Sex unspecified
CVCL_1135	COLO 800	Cancer cell line	Male
CVCL_2240	WM39	Cancer cell line	Male
CVCL_3878	SK-MEL-37	Cancer cell line	Male
CVCL_5239	1205Lu	Cancer cell line	Male
CVCL_6031	SK-MEL-29	Cancer cell line	Male
CVCL_6036	SK-MEL-39	Cancer cell line	Male
CVCL_6793	WM1791C	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00578279	PHASE4	COMPLETED	Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN)With Alcohol in Unresectable Pancreatic Cancer: a Pilot Study
NCT00583479	PHASE4	COMPLETED	Prospective Study of Celiac Block Injection: 1 vs. 2
NCT00642733	PHASE4	TERMINATED	A Study of First Line Treatment With Tarceva (Erlotinib) in Combination With Gemcitabine in Patients With Locally Advanced Unresectable or Metastatic Pancreatic Cancer
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00920023	PHASE4	COMPLETED	Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI)
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT01041612	PHASE4	COMPLETED	Comparing Covered Self-expandable Metallic Stent (SEMS) Above/Across the Sphincter of Oddi
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT01768988	PHASE4	TERMINATED	Efficacy Of Pregabalin In The Treatment Of Pancreatic Cancer Pain. A Randomized Controlled Double-Blind, Parallel Group Study
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02044224	PHASE4	COMPLETED	Effects of Dexmedetomidine During IRE Procedures for Solid Tumours
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03891979	PHASE4	WITHDRAWN	Gut Microbiome Modulation to Enable Efficacy of Checkpoint-based Immunotherapy in Pancreatic Adenocarcinoma
NCT04025840	PHASE4	ACTIVE_NOT_RECRUITING	Perioperative Epidural Block and Dexamethasone in Pancreatic Cancer Surgery
NCT04058236	PHASE4	UNKNOWN	Glycocalyx Levels in Patients Undergoing Pancreatectomy
NCT04155008	PHASE4	TERMINATED	Nutrition and Pharmacological Algorithm for Oncology Patients Study
NCT04217096	PHASE4	UNKNOWN	Efficacy and Safety of Paclitaxel Liposome and S-1 as First-line Therapy in \ Advanced Pancreatic Cancer Patients
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04809935	PHASE4	UNKNOWN	EUS-Coeliac Plexus Block Versus Radiofrequency Ablation in Pain Relief of Patients With Malignancy
NCT05035147	PHASE4	RECRUITING	Albumin-bound Paclitaxel Combined With Gemcitabine First-line Inoperable Pancreatic Cancer
NCT05245877	PHASE4	RECRUITING	Pre- Vs. Postoperative Thromboprophylaxis in Pancreatic Surgery
NCT05784311	PHASE4	RECRUITING	Standard Versus Prolonged Antibiotic Prophylaxis After Pancreatoduodenectomy (SPARROW)
NCT06316908	PHASE4	COMPLETED	Permanent Celiac Plexus Block: Comparison of Pain Score in Unilateral and Bilateral Posterior Percutaneous Approach
NCT06779318	PHASE4	NOT_YET_RECRUITING	Maintenance Chemotherapy With S-1 vs. Observation After Adjuvant Therapy for Resected Pancreatic Cancer With High Risk of Recurrence/Metastasis
NCT07557394	PHASE4	NOT_YET_RECRUITING	A Prospective Non-randomized Controlled Interventional Study on the Effect of Shouhui Tongbian Capsules Combined With Pancreatin Enteric-coated Capsules on Pancreatic Exocrine Function in Patients After Curative Resection for Pancreatic Cancer
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia