CDC7
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Also known as Hsk1huCdc7HsCdc7
Summary
CDC7 (cell division cycle 7, HGNC:1745) is a protein-coding gene on chromosome 1p22.1, encoding Cell division cycle 7-related protein kinase (O00311). Kinase involved in initiation of DNA replication. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).
This gene encodes a cell division cycle protein with kinase activity that is critical for the G1/S transition. The yeast homolog is also essential for initiation of DNA replication as cell division occurs. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Multiple alternatively spliced transcript variants that encode the same protein have been detected.
Source: NCBI Gene 8317 — RefSeq curated summary.
At a glance
- GWAS associations: 24
- Clinical variants (ClinVar): 97 total
- Druggable target: yes — 7 molecules with ChEMBL bioactivity
- Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
- MANE Select transcript:
NM_003503
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:1745 |
| Approved symbol | CDC7 |
| Name | cell division cycle 7 |
| Location | 1p22.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | Hsk1, huCdc7, HsCdc7 |
| Ensembl gene | ENSG00000097046 |
| Ensembl biotype | protein_coding |
| OMIM | 603311 |
| Entrez | 8317 |
Gene structure
Transcript identifiers
Ensembl transcripts: 21 — 19 protein_coding, 2 protein_coding_CDS_not_defined
ENST00000234626, ENST00000426137, ENST00000428239, ENST00000486509, ENST00000497611, ENST00000897932, ENST00000897933, ENST00000897934, ENST00000897935, ENST00000897936, ENST00000897937, ENST00000913029, ENST00000913030, ENST00000913031, ENST00000913032, ENST00000913033, ENST00000913034, ENST00000913035, ENST00000913036, ENST00000913037, ENST00000913038
RefSeq mRNA: 3 — MANE Select: NM_003503
NM_001134419, NM_001134420, NM_003503
CCDS: CCDS734
Canonical transcript exons
ENST00000234626 — 12 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000776455 | 91520130 | 91520279 |
| ENSE00001296115 | 91524041 | 91525764 |
| ENSE00001647687 | 91511781 | 91511923 |
| ENSE00001670120 | 91513948 | 91514043 |
| ENSE00001697785 | 91513058 | 91513307 |
| ENSE00001773076 | 91511597 | 91511690 |
| ENSE00001800055 | 91508262 | 91508397 |
| ENSE00001918304 | 91500851 | 91500948 |
| ENSE00003483533 | 91501654 | 91501831 |
| ENSE00003483775 | 91507854 | 91507937 |
| ENSE00003518422 | 91515794 | 91515876 |
| ENSE00003587648 | 91514819 | 91514997 |
Expression profiles
Bgee: expression breadth ubiquitous, 218 present calls, max score 98.01.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5353 / max 380.6294, expressed in 1554 samples.
FANTOM5 promoters (5 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 4008 | 11.5161 | 1421 |
| 4009 | 2.0396 | 861 |
| 4007 | 0.6463 | 344 |
| 4010 | 0.2620 | 120 |
| 4011 | 0.0713 | 26 |
Top tissues by expression
278 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| secondary oocyte | CL:0000655 | 98.01 | gold quality |
| oocyte | CL:0000023 | 95.55 | gold quality |
| endothelial cell | CL:0000115 | 93.45 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 87.92 | gold quality |
| ventricular zone | UBERON:0003053 | 87.73 | gold quality |
| embryo | UBERON:0000922 | 86.82 | gold quality |
| ganglionic eminence | UBERON:0004023 | 86.05 | gold quality |
| buccal mucosa cell | CL:0002336 | 86.02 | gold quality |
| cortical plate | UBERON:0005343 | 86.00 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 84.63 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 83.61 | gold quality |
| cerebellar cortex | UBERON:0002129 | 83.54 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 83.39 | gold quality |
| cerebellum | UBERON:0002037 | 82.28 | gold quality |
| testis | UBERON:0000473 | 81.72 | gold quality |
| right testis | UBERON:0004534 | 81.16 | gold quality |
| left testis | UBERON:0004533 | 81.04 | gold quality |
| spleen | UBERON:0002106 | 79.71 | gold quality |
| bone marrow | UBERON:0002371 | 79.40 | gold quality |
| primary visual cortex | UBERON:0002436 | 77.75 | gold quality |
| adrenal tissue | UBERON:0018303 | 77.39 | gold quality |
| lymph node | UBERON:0000029 | 76.91 | gold quality |
| Brodmann (1909) area 23 | UBERON:0013554 | 76.73 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 76.37 | gold quality |
| vermiform appendix | UBERON:0001154 | 76.23 | gold quality |
| prefrontal cortex | UBERON:0000451 | 76.18 | gold quality |
| rectum | UBERON:0001052 | 76.16 | gold quality |
| middle temporal gyrus | UBERON:0002771 | 76.04 | gold quality |
| right frontal lobe | UBERON:0002810 | 75.78 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 75.76 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 3.47 |
| E-GEOD-99795 | no | 139.78 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): GLI2, STAT1
miRNA regulators (miRDB)
73 targeting CDC7, 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-LET-7A-3P | 100.00 | 74.03 | 3932 |
| HSA-LET-7B-3P | 100.00 | 74.08 | 3913 |
| HSA-LET-7F-1-3P | 100.00 | 74.02 | 3928 |
| HSA-MIR-98-3P | 100.00 | 74.08 | 3907 |
| HSA-MIR-30A-5P | 100.00 | 76.31 | 3233 |
| HSA-MIR-30B-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30C-5P | 100.00 | 76.29 | 3248 |
| HSA-MIR-30D-5P | 100.00 | 76.32 | 3233 |
| HSA-MIR-30E-5P | 100.00 | 76.32 | 3242 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-371B-5P | 99.99 | 75.34 | 4759 |
| HSA-MIR-373-5P | 99.98 | 75.36 | 4753 |
| HSA-MIR-616-5P | 99.98 | 75.58 | 4775 |
| HSA-MIR-4775 | 99.98 | 75.00 | 6394 |
| HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 |
| HSA-MIR-524-5P | 99.98 | 73.43 | 4882 |
| HSA-MIR-590-3P | 99.96 | 74.34 | 6478 |
| HSA-MIR-338-5P | 99.92 | 72.34 | 2951 |
| HSA-MIR-6508-5P | 99.92 | 70.67 | 2465 |
| HSA-MIR-8087 | 99.90 | 69.55 | 1351 |
| HSA-MIR-4697-3P | 99.89 | 67.09 | 1123 |
| HSA-MIR-9902 | 99.89 | 69.15 | 2250 |
| HSA-MIR-3065-3P | 99.87 | 70.25 | 1407 |
| HSA-MIR-8067 | 99.86 | 69.59 | 2260 |
| HSA-MIR-204-5P | 99.79 | 71.62 | 2439 |
| HSA-MIR-211-5P | 99.79 | 71.65 | 2440 |
| HSA-MIR-3617-5P | 99.75 | 69.41 | 1968 |
| HSA-MIR-641 | 99.75 | 69.35 | 1975 |
| HSA-MIR-4255 | 99.72 | 67.70 | 1541 |
| HSA-MIR-548M | 99.70 | 68.87 | 1749 |
Functional genomics
DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.
Literature-anchored findings (GeneRIF, showing 40)
- Drf1, a nuclear cell cycle-regulated protein binds to Cdc7 and activates the kinase (PMID:12065429)
- Down-regulation of Cdc7 by small interfering RNA in a variety of tumor cell lines causes an abortive S phase, leading to cell death by either p53-independent apoptosis or aberrant mitosis. (PMID:15466207)
- CR (periphilin) retards S-phase progression by modifying expression of Cdc7 and other genes involved in progression of DNA replication (PMID:15474462)
- ASKL1 in a complex with Cdc7 may play a role in normal progression of both S and M phases (PMID:15668232)
- CINP is part of the Cdc7-dependent mechanism of origin firing and a functional and physical link between Cdk2 and Cdc7 complexes at the origins (PMID:16082200)
- the majority of the Mcm2 isoforms phosphorylated by Cdc7 are not stably associated with chromatin (PMID:16446360)
- Cdc7-Dbf4 kinase efficiently phosphorylates p150. (PMID:16826239)
- Results describe the mapping of the sites in human Mcm2 protein that are phosphorylated by Cdc7. (PMID:16864800)
- Taken together, these results indicate that Cdc7/Dbf4 phosphorylation of MCM2 is essential for the initiation of DNA replication in mammalian cells. (PMID:16899510)
- MCM4 phosphorylation by Cdc7 kinase facilitates its interaction with Cdc45 on chromatin (PMID:17046832)
- Cdc7 kinase plays a role in maintaining cell viability during replication stress (PMID:17062569)
- CRM1 may down-regulate Cdc7 by masking its kinase domain (PMID:17711849)
- Cdc7/Dbf4 kinase activity inhibition affects specific phosphorylation sites on MCM2 in cancer cells (PMID:18286467)
- the ATR-dependent activation of the p38 MAP kinase is a major signaling pathway that induces apoptotic cell death after depletion of Cdc7 in cancer cells (PMID:18625709)
- increased Cdc7-Dbf4 abundance may be a common occurrence in human malignancies (PMID:18714392)
- chromatin-bound CDT1 is first stabilized and subsequently displaced by CDC7 activity, thereby ensuring the timely execution of DNA replication (PMID:19054765)
- These results indicate that Ddk functions as an upstream regulator to monitor S-phase checkpoint signaling. (PMID:19111665)
- differences in Cdc7 expression may account for some of the differences between malignant melanomas and benign melanocytic nevi. (PMID:19278428)
- Increased Cdc7 protein levels were significantly associated with arrested tumor differentiation, advanced clinical stage, genomic instability, and accelerated cell cycle progression. (PMID:19318489)
- Data show that CDC7L1 and CDC10 was up-regulated but the expression of CDK9, CDC20 and CLK3 was down- regulated in azoospermic testes. (PMID:19426592)
- Cdc7 phosphorylates Mcm2 promoting pre-replication complex assembly. (PMID:19647517)
- The interaction with LEDGF relieves autoinhibition of Cdc7-ASK kinase, imposed by the C terminus of ASK. (PMID:19864417)
- cell division cycle 7 is a replication associated protein with relationships to gene amplification and genomic instability in breast carcinomas. (PMID:19896697)
- Inhibition of Cdc7 kinase activity in cancer cells restricts DNA replication and induces apoptotic cell death by an unprecedented molecular mechanism of action. (PMID:20647475)
- Data syggest important implications for the continued development of promising Cdc7-targeted cancer therapies. (PMID:20707412)
- bipartite interaction between Cdc7 and Dbf4/ASK subunits facilitates ATP binding and substrate recognition by the Cdc7 kinase. (PMID:21536671)
- The results suggest that CDC7 expression level can be specific prognostic factors for Diffuse large B-cell lymphoma patients (PMID:22528513)
- cell death process induced by Cdc7 depletion (PMID:22574151)
- Significantly higher levels of apoptosis were detected in siCDC7-transfected cells. (PMID:22806309)
- Cdc7 phosphorylates and interacts with Tob to inhibit the Cul4-DDB1(Cdt2)-dependent Tob degradation. (PMID:23066029)
- The interaction between Claspin and Cdc7 is not dependent on Cdc7 kinase activity, but Claspin interaction with the DNA helicase subunit Mcm2 is lost upon Cdc7 inhibition. (PMID:23598722)
- Cdcy is universally up-regulated in oral squamous cell carcinoma is an independent prognostic marker, contributing to resistance to DNA damaging agents. (PMID:23684929)
- huCdc7 may play an important role in the development and progression of colorectal cancer. (PMID:23716994)
- MiR-630 promoted apoptosis by downregulation of CDC7. (PMID:25255219)
- The state of DUE-B phosphorylation is maintained by the equilibrium between Cdc7-dependent phosphorylation and PP2A-dependent dephosphorylation. (PMID:25258324)
- Our data show that Cdc7 is highly expressed in colorectal cancer (PMID:26208856)
- The presence of the index SNP rs1192415 (TGFBR3-CDC7) was associated with visual field progression in POAG (primary open-angle glaucoma) patients. (PMID:26383992)
- The data support a model where Cdc7 (de)phosphorylation is the molecular switch for the activation and inactivation of DNA replication in mitosis, directly connecting Cdc7 and PP1a/Cdk1 to the regulation of once-per-cell cycle DNA replication in mammalian cells. (PMID:27105124)
- Results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins. (PMID:27401717)
- we propose that phosphorylation of TOP2A by CDC7/DBF4 in early S-phase prevents its localization and/or activity at centromeres, and inhibition of TOP2A function could be relevant to prevent premature separation of centromeric DNA. (PMID:27407105)
Cross-species orthologs
6 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | cdc7 | ENSDARG00000023584 |
| mus_musculus | Cdc7 | ENSMUSG00000029283 |
| rattus_norvegicus | Cdc7 | ENSRNOG00000002105 |
| drosophila_melanogaster | Cdc7 | FBGN0028360 |
| drosophila_melanogaster | CG5790 | FBGN0032677 |
| caenorhabditis_elegans | cdc-7 | WBGENE00016421 |
Paralogs (12): VRK2 (ENSG00000028116), VRK1 (ENSG00000100749), VRK3 (ENSG00000105053), CSNK1A1 (ENSG00000113712), TTBK2 (ENSG00000128881), CSNK1G2 (ENSG00000133275), CSNK1D (ENSG00000141551), TTBK1 (ENSG00000146216), CSNK1G3 (ENSG00000151292), CSNK1G1 (ENSG00000169118), CSNK1A1L (ENSG00000180138), CSNK1E (ENSG00000213923)
Protein
Protein identifiers
Cell division cycle 7-related protein kinase — O00311 (reviewed: O00311)
All UniProt accessions (3): O00311, A0A384MTU6, B1AMW7
UniProt curated annotations — full annotation on UniProt →
Function. Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN.
Subunit / interactions. Forms a complex with either DBF4/DBF4A or DBF4B, leading to the activation of the kinase activity. Interacts with CLASPIN (via the acidic patch); the interaction is required for phosphorylation of MCM proteins and CLASPIN.
Subcellular location. Nucleus.
Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC7 subfamily.
Isoforms (1)
| UniProt ID | Names | Canonical? |
|---|---|---|
| O00311-1 | 1 | yes |
RefSeq proteins (3): NP_001127891, NP_001127892, NP_003494* (*=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 |
Pfam: PF00069
Enzyme classification (BRENDA):
- EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)
Substrate kinetics (BRENDA)
8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ATP | 0.0007–0.64 | 11 |
| KKRAARATSNVFA | 0.013–0.045 | 3 |
| PAH1 PHOSPHATIDATE PHOSPHATASE | 0.0002 | 2 |
| RRRLSSLRA | 0.0036–0.0037 | 2 |
| GTP | 0.46 | 1 |
| KKRAARASSNVFA | 0.02 | 1 |
| LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA | 0.0093 | 1 |
| MYELIN BASIC PROTEIN | 0.145 | 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 (51 total): helix 18, strand 11, sequence variant 9, turn 4, binding site 2, modified residue 2, chain 1, domain 1, sequence conflict 1, active site 1, cross-link 1
Structure
Experimental structures (PDB)
9 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 6YA6 | X-RAY DIFFRACTION | 1.44 |
| 6YA7 | X-RAY DIFFRACTION | 1.67 |
| 6YA8 | X-RAY DIFFRACTION | 1.79 |
| 4F9C | X-RAY DIFFRACTION | 2.08 |
| 4F9A | X-RAY DIFFRACTION | 2.17 |
| 5UWR | X-RAY DIFFRACTION | 2.24 |
| 5UWQ | X-RAY DIFFRACTION | 2.28 |
| 4F99 | X-RAY DIFFRACTION | 2.33 |
| 4F9B | X-RAY DIFFRACTION | 2.5 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-O00311-F1 | 72.49 | 0.57 |
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): 177 (proton acceptor)
Ligand- & substrate-binding residues (2): 64–72; 90
Post-translational modifications (3): 27, 503, 268
Function
Pathways and Gene Ontology
Reactome pathways
14 pathways
| ID | Pathway |
|---|---|
| R-HSA-176187 | Activation of ATR in response to replication stress |
| R-HSA-68962 | Activation of the pre-replicative complex |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 |
| R-HSA-1640170 | Cell Cycle |
| R-HSA-212436 | Generic Transcription Pathway |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition |
| R-HSA-69002 | DNA Replication Pre-Initiation |
| R-HSA-69206 | G1/S Transition |
| R-HSA-69278 | Cell Cycle, Mitotic |
| R-HSA-69306 | DNA Replication |
| R-HSA-69481 | G2/M Checkpoints |
| R-HSA-69620 | Cell Cycle Checkpoints |
| R-HSA-73857 | RNA Polymerase II Transcription |
| R-HSA-74160 | Gene expression (Transcription) |
MSigDB gene sets: 308 (showing top):
REACTOME_DNA_REPLICATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, WALLACE_PROSTATE_CANCER_RACE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_CELL_CYCLE_DNA_REPLICATION, FISCHER_G1_S_CELL_CYCLE, GOBP_CELL_CYCLE_PHASE_TRANSITION, GEORGES_CELL_CYCLE_MIR192_TARGETS, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, KONG_E2F3_TARGETS
GO Biological Process (9): G1/S transition of mitotic cell cycle (GO:0000082), double-strand break repair via break-induced replication (GO:0000727), signal transduction (GO:0007165), positive regulation of cell population proliferation (GO:0008284), positive regulation of nuclear cell cycle DNA replication (GO:0010571), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), cell cycle phase transition (GO:0044770), cell division (GO:0051301), protein phosphorylation (GO:0006468)
GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), kinase activity (GO:0016301), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), transferase activity (GO:0016740)
GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686)
Reactome top-level categories
Rollup of top-11 pathways:
| Category | Pathways |
|---|---|
| Cell Cycle | 2 |
| G2/M Checkpoints | 1 |
| DNA Replication Pre-Initiation | 1 |
| G1/S Transition | 1 |
| Generic Transcription Pathway | 1 |
| RNA Polymerase II Transcription | 1 |
| Cell Cycle, Mitotic | 1 |
| DNA Replication | 1 |
| Mitotic G1 phase and G1/S transition | 1 |
| Cell Cycle Checkpoints | 1 |
| Gene expression (Transcription) | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| cellular process | 2 |
| protein kinase activity | 2 |
| mitotic cell cycle | 1 |
| mitotic cell cycle phase transition | 1 |
| cell cycle G1/S phase transition | 1 |
| double-strand break repair via homologous recombination | 1 |
| cell communication | 1 |
| signaling | 1 |
| regulation of cellular process | 1 |
| cellular response to stimulus | 1 |
| cell population proliferation | 1 |
| regulation of cell population proliferation | 1 |
| positive regulation of cellular process | 1 |
| nuclear DNA replication | 1 |
| regulation of nuclear cell cycle DNA replication | 1 |
| positive regulation of cell cycle process | 1 |
| positive regulation of DNA-templated DNA replication | 1 |
| G2/M transition of mitotic cell cycle | 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 |
| cell cycle process | 1 |
| phosphorylation | 1 |
| protein modification process | 1 |
| kinase activity | 1 |
| phosphotransferase activity, alcohol group as acceptor | 1 |
| catalytic activity, acting on a protein | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| transferase activity, transferring phosphorus-containing groups | 1 |
| cation binding | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| binding | 1 |
| catalytic activity | 1 |
| intracellular membrane-bounded organelle | 1 |
| nuclear lumen | 1 |
| intracellular anatomical structure | 1 |
| spindle | 1 |
Protein interactions and networks
STRING
2634 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| CDC7 | DBF4 | Q9UBU7 | 999 |
| CDC7 | CDC45 | O75419 | 970 |
| CDC7 | MCM4 | P33991 | 968 |
| CDC7 | CDC6 | Q99741 | 943 |
| CDC7 | MCM3 | P25205 | 928 |
| CDC7 | TICRR | Q7Z2Z1 | 916 |
| CDC7 | MCM5 | P33992 | 904 |
| CDC7 | DBF4B | Q8NFT6 | 901 |
| CDC7 | CDT1 | Q9H211 | 880 |
| CDC7 | MCM10 | Q7L590 | 834 |
| CDC7 | TOPBP1 | Q92547 | 828 |
| CDC7 | CDC14A | Q9UNH5 | 824 |
| CDC7 | MCM6 | Q14566 | 822 |
| CDC7 | MCM7 | P33993 | 821 |
| CDC7 | CHEK2 | O96017 | 805 |
IntAct
134 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| DBF4 | CDC7 | psi-mi:“MI:0914”(association) | 0.890 |
| DBF4 | CDC7 | psi-mi:“MI:0915”(physical association) | 0.890 |
| CDC7 | DBF4 | psi-mi:“MI:0915”(physical association) | 0.890 |
| DBF4 | CDC7 | psi-mi:“MI:0915”(physical association) | 0.610 |
| DBF4 | CDC7 | psi-mi:“MI:0407”(direct interaction) | 0.610 |
| CDC7 | MCMBP | psi-mi:“MI:0915”(physical association) | 0.590 |
| CDC7 | IKZF1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | psi-mi:“MI:0915”(physical association) | 0.560 | |
| CDC7 | ZBTB8B | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | TSNAXIP1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | IKZF4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | FXR1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | BANP | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | TRIM37 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | IKZF3 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | ZBTB10 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | CALCOCO2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | ZBTB26 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | TRIM27 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | GOLGA2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | SERTAD2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | MTUS2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | STAM2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | GMEB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDC7 | LZTS1 | psi-mi:“MI:0915”(physical association) | 0.560 |
BioGRID (195): CDC7 (Affinity Capture-MS), CDC7 (Co-fractionation), CDC7 (Proximity Label-MS), CDC7 (Affinity Capture-MS), CDC7 (Affinity Capture-MS), CDC7 (Affinity Capture-MS), CDC7 (Affinity Capture-MS), IFT122 (Affinity Capture-MS), BRD4 (Synthetic Lethality), RPS11 (Synthetic Lethality), ING5 (Synthetic Lethality), CDC7 (Two-hybrid), CDC7 (Affinity Capture-MS), CDC7 (Affinity Capture-MS), CDC7 (Affinity Capture-MS)
ESM2 similar proteins: A2YMV6, A5D791, B2GUY1, C0SUT9, F4ICB6, F4JAA5, F4JBP3, O00311, O13889, O22042, P50526, Q0D598, Q0P4S5, Q16659, Q53WJ1, Q5F3W3, Q5R7U1, Q60DG4, Q63185, Q64702, Q6BDA0, Q6DDU8, Q6EU49, Q6L5D4, Q6NPP4, Q6YY75, Q6ZEZ5, Q7T0B0, Q7XIT1, Q8BI55, Q8GSA7, Q8GUI6, Q8L4H0, Q8L840, Q8RXY0, Q93VJ2, Q94C95, Q94CU5, Q9D9X6, Q9FT70
Diamond homologs: A0A194WDG1, A0A509AFG4, A2QU77, A2Y4B6, A4K2M3, A4K2P5, A4K2Q5, A4K2S1, A4K2T0, A4K2W5, A4K2Y1, A8WVU9, A8X6H4, A9S9Q8, B0Y4X4, B5X564, F4I114, F4JPX3, G4N374, G4NH08, G5ECH7, O00311, O13310, O13352, O23236, O35832, O54833, O64483, P06243, P18266, P18431, P19784, P20427, P21127, P21869, P24788, P29620, P33981, P34112, P34117
SIGNOR signaling
35 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| CDC7 | up-regulates | MCM2 | phosphorylation |
| CHEK1 | up-regulates | CDC7 | phosphorylation |
| CDC7 | up-regulates | MCM4 | phosphorylation |
| CDC7 | up-regulates | MCM7 | phosphorylation |
| CDC7 | unknown | RAD18 | phosphorylation |
| CDC7 | down-regulates | ESCO1 | phosphorylation |
| CDC7 | up-regulates | PSIP1 | phosphorylation |
| “Benzofuro(3,2-d)pyrimidin-4(3H)-one, 8-chloro-2-((2S)-2-pyrrolidinyl)-” | “down-regulates activity” | CDC7 | “chemical inhibition” |
| CDC7 | “up-regulates activity” | TARDBP | phosphorylation |
| CDC7 | “up-regulates activity” | CLSPN | phosphorylation |
| CDC7 | “down-regulates activity” | CDC5L | phosphorylation |
| CDK1 | up-regulates | CDC7 | phosphorylation |
| CyclinB/CDK1 | “up-regulates activity” | CDC7 | phosphorylation |
| CyclinA2/CDK2 | “up-regulates activity” | CDC7 | phosphorylation |
| CyclinE/CDK2 | “up-regulates activity” | CDC7 | phosphorylation |
| CDC7 | “up-regulates activity” | DTD1 | phosphorylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 70 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 |
|---|---|---|---|
| Activation of the pre-replicative complex | 5 | 48.0× | 1e-05 |
| Activation of ATR in response to replication stress | 5 | 44.2× | 1e-05 |
| Mitotic G1 phase and G1/S transition | 5 | 27.1× | 9e-05 |
| Cell Cycle, Mitotic | 5 | 7.1× | 9e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
97 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 79 |
| Likely benign | 3 |
| Benign | 1 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1537 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:91500949:G:GG | donor_gain | 1.0000 |
| 1:91507848:T:TA | acceptor_gain | 1.0000 |
| 1:91507852:A:AG | acceptor_gain | 1.0000 |
| 1:91507852:A:T | acceptor_loss | 1.0000 |
| 1:91507853:G:GG | acceptor_gain | 1.0000 |
| 1:91507853:GGT:G | acceptor_gain | 1.0000 |
| 1:91507935:AAG:A | donor_loss | 1.0000 |
| 1:91507936:AGGTA:A | donor_loss | 1.0000 |
| 1:91507937:GG:G | donor_loss | 1.0000 |
| 1:91507938:G:GC | donor_loss | 1.0000 |
| 1:91507939:T:A | donor_loss | 1.0000 |
| 1:91508395:TGGGT:T | donor_loss | 1.0000 |
| 1:91508396:GG:G | donor_gain | 1.0000 |
| 1:91508397:GG:G | donor_gain | 1.0000 |
| 1:91508397:GGTAG:G | donor_loss | 1.0000 |
| 1:91508398:G:C | donor_loss | 1.0000 |
| 1:91508398:G:GG | donor_gain | 1.0000 |
| 1:91508399:T:G | donor_loss | 1.0000 |
| 1:91511773:T:TA | acceptor_gain | 1.0000 |
| 1:91511779:A:AG | acceptor_gain | 1.0000 |
| 1:91511779:AG:A | acceptor_gain | 1.0000 |
| 1:91511780:G:GC | acceptor_gain | 1.0000 |
| 1:91511780:GG:G | acceptor_gain | 1.0000 |
| 1:91511780:GGA:G | acceptor_gain | 1.0000 |
| 1:91511780:GGAC:G | acceptor_gain | 1.0000 |
| 1:91511780:GGACA:G | acceptor_gain | 1.0000 |
| 1:91511807:A:G | acceptor_gain | 1.0000 |
| 1:91511919:AAAAA:A | donor_gain | 1.0000 |
| 1:91511920:AAAA:A | donor_gain | 1.0000 |
| 1:91511921:AAA:A | donor_gain | 1.0000 |
AlphaMissense
3805 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:91508267:T:C | F69L | 1.000 |
| 1:91508269:C:A | F69L | 1.000 |
| 1:91508269:C:G | F69L | 1.000 |
| 1:91508325:C:A | A88D | 1.000 |
| 1:91508328:T:C | L89P | 1.000 |
| 1:91508332:A:C | K90N | 1.000 |
| 1:91508332:A:T | K90N | 1.000 |
| 1:91511878:G:C | R176P | 1.000 |
| 1:91511881:A:C | D177A | 1.000 |
| 1:91511881:A:T | D177V | 1.000 |
| 1:91511897:T:A | N182K | 1.000 |
| 1:91511897:T:G | N182K | 1.000 |
| 1:91513072:A:C | D196A | 1.000 |
| 1:91513072:A:T | D196V | 1.000 |
| 1:91513073:C:A | D196E | 1.000 |
| 1:91513073:C:G | D196E | 1.000 |
| 1:91507937:G:C | G67R | 0.999 |
| 1:91507937:G:T | G67C | 0.999 |
| 1:91508268:T:G | F69C | 0.999 |
| 1:91508270:A:C | S70R | 0.999 |
| 1:91508272:C:A | S70R | 0.999 |
| 1:91508272:C:G | S70R | 0.999 |
| 1:91508277:T:A | V72D | 0.999 |
| 1:91508286:C:A | A75D | 0.999 |
| 1:91508330:A:C | K90Q | 0.999 |
| 1:91508330:A:G | K90E | 0.999 |
| 1:91508331:A:T | K90I | 0.999 |
| 1:91508376:T:C | L105P | 0.999 |
| 1:91508385:T:C | L108P | 0.999 |
| 1:91511611:T:A | V117D | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000114537 (1:91522883 ACAGT>A), RS1000187232 (1:91523172 A>C), RS1000326672 (1:91520929 T>C), RS1000468310 (1:91509946 A>G), RS1000563132 (1:91510240 A>G), RS1000593704 (1:91521196 A>G), RS1000616845 (1:91502815 A>C), RS1000655904 (1:91520700 A>G), RS1000973213 (1:91508761 A>G), RS1001028558 (1:91503071 G>C), RS1001044228 (1:91515404 G>C,T), RS1001062849 (1:91522484 T>C), RS1001284914 (1:91501043 T>C,G), RS1001616540 (1:91522323 G>T), RS1002069745 (1:91502443 CTG>C)
Disease associations
OMIM: gene MIM:603311 | disease phenotypes:
GenCC curated gene-disease
Mondo (1): premature menopause (MONDO:0001119)
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
24 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST000699_3 | Optic disc parameters | 3.000000e-28 |
| GCST000970_3 | Optic disc area | 8.000000e-17 |
| GCST002626_1 | Vertical cup-disc ratio | 1.000000e-15 |
| GCST002765_1 | Optic disc area | 8.000000e-56 |
| GCST002765_6 | Optic disc area | 4.000000e-38 |
| GCST003485_4 | Response to fenofibrate (HDL cholesterol levels) | 3.000000e-06 |
| GCST004047_1 | Optic nerve measurement (cup-to-disc ratio) | 1.000000e-07 |
| GCST004075_26 | Vertical cup-disc ratio | 3.000000e-20 |
| GCST004075_27 | Vertical cup-disc ratio | 2.000000e-23 |
| GCST004076_16 | Optic disc area | 6.000000e-81 |
| GCST004076_2 | Optic disc area | 2.000000e-60 |
| GCST004185_5 | Lung function (FEV1/FVC) | 6.000000e-20 |
| GCST004600_63 | Eosinophil percentage of white cells | 7.000000e-09 |
| GCST004899_6 | Gestational age at birth (maternal effect) | 9.000000e-07 |
| GCST008391_1 | Glaucoma (primary open-angle) | 2.000000e-08 |
| GCST008482_1 | Lung function (FVC) | 8.000000e-07 |
| GCST009411_10 | Optic disc area | 4.000000e-64 |
| GCST009412_8 | Vertical cup-disc ratio | 1.000000e-18 |
| GCST009462_20 | Optic disc size | 3.000000e-160 |
| GCST009724_86 | Vertical cup-disc ratio (multi-trait analysis) | 7.000000e-51 |
| GCST010320_94 | PR interval | 3.000000e-09 |
| GCST010321_176 | PR interval | 2.000000e-08 |
| GCST90002400_38 | Plateletcrit | 1.000000e-10 |
| GCST90011770_30 | Glaucoma (primary open-angle) | 1.000000e-29 |
EFO canonical traits (9, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0007805 | HDL cholesterol change measurement |
| EFO:0006939 | cup-to-disc ratio measurement |
| EFO:0004713 | FEV/FVC ratio |
| EFO:0007991 | eosinophil percentage of leukocytes |
| EFO:0005112 | gestational age |
| EFO:0005939 | parental genotype effect measurement |
| EFO:0004312 | vital capacity |
| EFO:0004462 | PR interval |
| EFO:0007985 | platelet crit |
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D008594 | Menopause, Premature | C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (3): CHEMBL2111377 (PROTEIN COMPLEX), CHEMBL4523630 (PROTEIN COMPLEX), CHEMBL5443 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,762 (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 |
|---|---|---|---|
| CHEMBL4297644 | SIMUROSERTIB | 2 | 63 |
| CHEMBL1232461 | MOLIBRESIB | 2 | 1,538 |
| CHEMBL1967878 | CENISERTIB | 2 | 358 |
| CHEMBL475251 | R-406 | 2 | 762 |
| CHEMBL4868568 | MONZOSERTIB | 2 | 14 |
| CHEMBL495727 | AT-9283 | 2 | 1,376 |
| CHEMBL482967 | CYC-116 | 1 | 651 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — CDC7 family
Most potent curated ligand interactions (8 total), top 8:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| compound 2 [PMID: 22560567] | Inhibition | 8.85 | pIC50 |
| compound 89S [PMID: 19115845] | Inhibition | 8.7 | pIC50 |
| monzosertib | Inhibition | 8.62 | pIC50 |
| XL413 | Inhibition | 8.47 | pIC50 |
| compound 74 [PMID: 24793884] | Inhibition | 8.42 | pIC50 |
| compound 77 [PMID: 24793884] | Inhibition | 8.17 | pIC50 |
| compound 18 [PMID: 20873740] | Inhibition | 7.66 | pIC50 |
| compound 1 [PMID: 24793884] | Inhibition | 6.49 | pIC50 |
Binding affinities (BindingDB)
187 measured of 340 human assays (340 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 5-[1-benzyl-5-[4-(dimethylamino)phenyl]triazol-4-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-amine | KI | 0.4 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| N-[5-(1-benzyltriazol-4-yl)-1H-indazol-3-yl]benzamide | KI | 0.4 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 5-[1-benzyl-5-(4-fluorophenyl)triazol-4-yl]-3-methyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazole | KI | 0.428 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| N-[5-(1-benzyltriazol-4-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]-3-fluorobenzamide | KI | 0.5 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 5-(1-benzyl-5-thiophen-2-yltriazol-4-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-amine | KI | 0.5 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 8-methyl-11-thia-9,14,16-triazatetracyclo[8.7.0.0^{2,7}.0^{12,17}]heptadeca-1,7,9,12(17),13,15-hexaen-13-amine | KI | 0.5 nM | |
| 5-(1-benzyl-5-phenyltriazol-4-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazole | KI | 0.601 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 5-[1-benzyl-5-(4-fluorophenyl)triazol-4-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-amine | KI | 0.8 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| N-[5-(1-benzyl-5-phenyltriazol-4-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]benzamide | KI | 0.8 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| N-[5-(1-benzyl-5-cyclopropyltriazol-4-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]-3-fluorobenzamide | KI | 0.9 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| (2Z)-5-(1H-indazol-5-ylimino)-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolan-3-one | IC50 | 1 nM | US-8742113: Furanone derivative |
| (2Z)-5-[(3-methylthiophen-2-yl)methylimino]-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolan-3-one | IC50 | 1 nM | US-8742113: Furanone derivative |
| 12-ethyl-11,13-dimethyl-8-thia-3,5,10-triazatricyclo[7.4.0.0^{2,7}]trideca-1(13),2(7),3,5,9,11-hexaen-6-amine | KI | 1 nM | |
| 5-[5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)triazol-4-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazole | KI | 1.05 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 5-(1,5-dibenzyltriazol-4-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-amine | KI | 1.1 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 5-(1-benzyl-5-phenyltriazol-4-yl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-amine | KI | 1.2 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 5-[1-benzyl-5-(1-methylpyrazol-4-yl)triazol-4-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-amine | KI | 1.9 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| ethyl (5Z)-2-(2-chlorophenyl)imino-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 2 nM | US-8742113: Furanone derivative |
| (2Z)-5-(4-fluoro-2-methylphenyl)imino-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolan-3-one | IC50 | 2 nM | US-8742113: Furanone derivative |
| 7-ethyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 2 nM | |
| 7-(2-fluoroethyl)-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 2 nM | |
| 2-(2-aminopyrimidin-4-yl)-7,7-dimethyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 2 nM | |
| (7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 2 nM | |
| 5,13,17-triazatetracyclo[8.7.0.0^{2,7}.0^{11,16}]heptadeca-1(10),2(7),3,5,8,11(16)-hexaen-12-one | IC50 | 2 nM | |
| 9-methyl-17-thia-2,12,14-triazatetracyclo[8.7.0.0^{3,8}.0^{11,16}]heptadeca-1,3(8),9,11(16),12,14-hexaen-15-amine | KI | 2 nM | |
| 11,13-dimethyl-12-(prop-2-en-1-yl)-8-thia-3,5,10-triazatricyclo[7.4.0.0^{2,7}]trideca-1(13),2(7),3,5,9,11-hexaen-6-amine | KI | 2 nM | |
| 5-[1-benzyl-5-(2-methylphenyl)triazol-4-yl]-3-methyl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazole | KI | 2.25 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| 3-hydroxypropyl (5Z)-2-(4-fluorophenyl)imino-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 3 nM | US-8742113: Furanone derivative |
| ethyl (5Z)-2-[4-(2-hydroxyethylamino)-2-methylphenyl]imino-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 3 nM | US-8742113: Furanone derivative |
| ethyl (2Z,5Z)-2-morpholin-4-ylimino-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 3 nM | US-8742113: Furanone derivative |
| propan-2-yl (5Z)-2-[4-(2-hydroxyethoxy)-2-methylphenyl]imino-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 3 nM | US-8742113: Furanone derivative |
| 2-methoxyethyl (5Z)-2-(2-chlorophenyl)imino-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 3 nM | US-8742113: Furanone derivative |
| 6-(2-methylpropyl)-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 3 nM | |
| 7-cyclobutyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 3 nM | |
| 7,7-dimethyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 3 nM | |
| 2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 3 nM | |
| 2-(2-aminopyrimidin-4-yl)-1-(2-fluoroethyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 3 nM | |
| 7-methyl-10-thia-8,13,15-triazatetracyclo[7.7.0.0^{2,6}.0^{11,16}]hexadeca-1,6,8,11(16),12,14-hexaen-12-amine | KI | 3 nM | |
| 5-[1-benzyl-5-(2-methylphenyl)triazol-4-yl]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-amine | KI | 3.4 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
| ethyl (5Z)-2-(1H-indazol-6-ylimino)-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 4 nM | US-8742113: Furanone derivative |
| 2-(dimethylamino)ethyl (5Z)-2-(2,4-difluorophenyl)imino-4-oxo-5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolane-3-carboxylate | IC50 | 4 nM | US-8742113: Furanone derivative |
| US8742113, 102 | IC50 | 4 nM | US-8742113: Furanone derivative |
| (2Z)-5-cycloheptylimino-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethylidene)oxolan-3-one | IC50 | 4 nM | US-8742113: Furanone derivative |
| US8742113, 244 | IC50 | 4 nM | US-8742113: Furanone derivative |
| 2-(2-aminopyrimidin-4-yl)-7-(propan-2-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 4 nM | |
| 2-(2-aminopyrimidin-4-yl)-7-(2-hydroxyethyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 4 nM | |
| 2-(2-amino-5-bromopyrimidin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 4 nM | |
| 2-(2-aminopyrimidin-4-yl)-1-(cyclopropylmethyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one | IC50 | 4 nM | |
| 11,12,13-trimethyl-8-thia-3,5,10-triazatricyclo[7.4.0.0^{2,7}]trideca-1(13),2(7),3,5,9,11-hexaen-6-amine | KI | 4 nM | |
| 5-(1-benzyltriazol-4-yl)-3-thiophen-2-yl-2,3,3a,4,5,6,7,7a-octahydro-1H-indazole | KI | 4.92 nM | US-9163007: 5-substituted indazoles as kinase inhibitors |
ChEMBL bioactivities
1040 potent at pChembl≥5 of 1063 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 10.05 | Ki | 0.09 | nM | CHEMBL1958411 |
| 9.96 | Ki | 0.11 | nM | CHEMBL1958417 |
| 9.92 | Ki | 0.12 | nM | CHEMBL1958412 |
| 9.90 | Ki | 0.1259 | nM | CHEMBL244793 |
| 9.90 | Ki | 0.1259 | nM | CHEMBL1964519 |
| 9.85 | Ki | 0.14 | nM | CHEMBL1958416 |
| 9.80 | Ki | 0.1585 | nM | CHEMBL2062936 |
| 9.80 | IC50 | 0.16 | nM | CHEMBL4436649 |
| 9.80 | IC50 | 0.16 | nM | CHEMBL4462898 |
| 9.80 | Ki | 0.1585 | nM | CHEMBL1986943 |
| 9.80 | Ki | 0.1585 | nM | CHEMBL2005509 |
| 9.74 | Ki | 0.18 | nM | CHEMBL1958414 |
| 9.74 | Ki | 0.18 | nM | CHEMBL1958415 |
| 9.70 | Ki | 0.2 | nM | CHEMBL1958419 |
| 9.70 | Ki | 0.2 | nM | CHEMBL1958420 |
| 9.70 | Ki | 0.1995 | nM | CHEMBL1965660 |
| 9.70 | Ki | 0.1995 | nM | CHEMBL1992220 |
| 9.60 | Ki | 0.25 | nM | CHEMBL1958418 |
| 9.60 | Ki | 0.2512 | nM | CHEMBL1980562 |
| 9.59 | IC50 | 0.26 | nM | SIMUROSERTIB |
| 9.55 | Ki | 0.28 | nM | CHEMBL1958408 |
| 9.52 | Ki | 0.3 | nM | CHEMBL1958406 |
| 9.50 | Ki | 0.3162 | nM | CHEMBL2062937 |
| 9.50 | Ki | 0.3162 | nM | CHEMBL1980253 |
| 9.50 | Ki | 0.3162 | nM | CHEMBL1996980 |
| 9.50 | Ki | 0.3162 | nM | CHEMBL1969151 |
| 9.50 | Ki | 0.3162 | nM | CHEMBL1973720 |
| 9.50 | Ki | 0.3162 | nM | CHEMBL1992363 |
| 9.50 | Ki | 0.3162 | nM | CHEMBL1982271 |
| 9.40 | Ki | 0.4 | nM | CHEMBL1969221 |
| 9.40 | Ki | 0.4 | nM | CHEMBL1999931 |
| 9.40 | Ki | 0.3981 | nM | CHEMBL1981079 |
| 9.40 | Ki | 0.3981 | nM | CHEMBL1972339 |
| 9.40 | Ki | 0.3981 | nM | CHEMBL1969221 |
| 9.40 | Ki | 0.3981 | nM | CHEMBL2002613 |
| 9.40 | Ki | 0.3981 | nM | CHEMBL1979933 |
| 9.40 | Ki | 0.3981 | nM | CHEMBL2005216 |
| 9.39 | IC50 | 0.41 | nM | CHEMBL4439133 |
| 9.37 | Ki | 0.428 | nM | CHEMBL1972339 |
| 9.37 | Kd | 0.424 | nM | SIMUROSERTIB |
| 9.37 | IC50 | 0.43 | nM | CHEMBL4570191 |
| 9.36 | IC50 | 0.44 | nM | CHEMBL4439133 |
| 9.36 | IC50 | 0.44 | nM | CHEMBL4471906 |
| 9.30 | Ki | 0.5012 | nM | CHEMBL1999931 |
| 9.30 | Ki | 0.5 | nM | CHEMBL2003638 |
| 9.30 | Ki | 0.5 | nM | CHEMBL3890525 |
| 9.30 | Ki | 0.5 | nM | CHEMBL505372 |
| 9.30 | Ki | 0.5 | nM | CHEMBL1958404 |
| 9.30 | Ki | 0.5 | nM | CHEMBL1958408 |
| 9.30 | Ki | 0.5012 | nM | CHEMBL2006450 |
PubChem BioAssay actives
758 with measured affinity, of 1861 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 2-(cyclohexylamino)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0001 | uM |
| 2-(benzylamino)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0001 | uM |
| 2-anilino-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0001 | uM |
| 2-(oxan-4-ylamino)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0001 | uM |
| 2-[cyclohexyl(methyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0001 | uM |
| 2-[(1-methylpiperidin-4-yl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0001 | uM |
| 2-(4-hydroxypiperidin-1-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0002 | uM |
| 2-[bis(2-methoxyethyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0002 | uM |
| 2-morpholin-4-yl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0002 | uM |
| 2-(4-methoxypiperidin-1-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0002 | uM |
| 2-(7-azabicyclo[2.2.1]heptan-1-yl)-6-(5-methyl-1H-pyrazol-4-yl)-3H-thieno[3,2-d]pyrimidin-4-one;hydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0002 | uM |
| 2-(2-azabicyclo[2.1.1]hexan-1-yl)-6-(5-methyl-1H-pyrazol-4-yl)-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0002 | uM |
| 4-[[4-chloro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]amino]cyclohexan-1-ol | 673702: Inhibition of CDC7 | ki | 0.0002 | uM |
| 2-[(2S)-1-azabicyclo[2.2.2]octan-2-yl]-6-(5-methyl-1H-pyrazol-4-yl)-3H-thieno[3,2-d]pyrimidin-4-one | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0003 | uM |
| 2-phenyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0003 | uM |
| 4-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-1,3,5-triazin-2-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0003 | uM |
| 1-N-[4-chloro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]-4-N,4-N-dimethylcyclohexane-1,4-diamine | 673702: Inhibition of CDC7 | ki | 0.0003 | uM |
| 6-(cyclohexylamino)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyridin-2-one | 727789: Inhibition of human Cdc7 using biotin-C6linker-TPSDSLIYDDGLS as substrate after 1 hr | ki | 0.0003 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-[(2S)-piperidin-2-yl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0004 | uM |
| 2-[(2S)-piperidin-2-yl]-6-[5-(trifluoromethyl)-1H-pyrazol-4-yl]-3H-thieno[3,2-d]pyrimidin-4-one;hydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0004 | uM |
| 8-methyl-11-thia-9,14,16-triazatetracyclo[8.7.0.02,7.012,17]heptadeca-1,7,9,12,14,16-hexaen-13-amine | 1798805: Radioactive Kinase Assay from Article 10.1016/j.bmcl.2008.11.093: “Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors.” | ki | 0.0005 | uM |
| 2-(cyclohexylamino)-4-(1H-indazol-5-yl)-1H-pyrimidin-6-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0005 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-(pyrrolidin-1-ylmethyl)-3H-thieno[3,2-d]pyrimidin-4-one | 1453928: Binding affinity to recombinant human full length Cdc7 (1 to 574 residues)/human N-terminal GST-tagged ASK (1 to 674 residues) expressed in baculovirus expression system by proteros reporter displacement assay | kd | 0.0005 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-[(2S)-1,2,3,6-tetrahydropyridin-2-yl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0005 | uM |
| N-[5-(1-benzyltriazol-4-yl)-1H-indazol-3-yl]benzamide | 673702: Inhibition of CDC7 | ki | 0.0005 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-[(2S,3S)-3-methylpyrrolidin-2-yl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0006 | uM |
| methyl 2-(2-chloroanilino)-4-hydroxy-5-[(Z)-pyrrolo[2,3-b]pyridin-3-ylidenemethyl]furan-3-carboxylate | 1444134: Inhibition of recombinant human Cdc7 (1 to 574 residues)/human N-terminal GST-tagged ASK (1 to 674 residues) expressed in baculovirus expression system using FITC-labeled MCM2 peptide as substrate measured after 5 hrs in presence of 5 uM ATP | ic50 | 0.0006 | uM |
| N-[(R)-cyclopropyl-(2-fluoro-3-pyridinyl)methyl]-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine | 1056819: Inhibition of Cdc7/Dbf4 (unknown origin)-mediated MCM2 phosphorylation at Ser53 by protein A amplified luminescent proximity homogeneous assay | ic50 | 0.0007 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-[(2S)-pyrrolidin-2-yl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0007 | uM |
| N-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine | 1056819: Inhibition of Cdc7/Dbf4 (unknown origin)-mediated MCM2 phosphorylation at Ser53 by protein A amplified luminescent proximity homogeneous assay | ic50 | 0.0008 | uM |
| N-[5-(1-benzyltriazol-4-yl)-1H-indazol-3-yl]-3-chlorobenzamide | 673702: Inhibition of CDC7 | ki | 0.0008 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-[(2R)-piperidin-2-yl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0009 | uM |
| 6-chloro-N-cyclohexyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-amine | 727789: Inhibition of human Cdc7 using biotin-C6linker-TPSDSLIYDDGLS as substrate after 1 hr | ki | 0.0009 | uM |
| 2-(2-aminopyrimidin-4-yl)-7-propan-2-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one | 411539: Inhibition of human Cdc7 assessed as inhibition of rate of phosphorylation of Mcm2 protein | ic50 | 0.0010 | uM |
| N-[(R)-cyclopropyl(phenyl)methyl]-5-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine | 1056819: Inhibition of Cdc7/Dbf4 (unknown origin)-mediated MCM2 phosphorylation at Ser53 by protein A amplified luminescent proximity homogeneous assay | ic50 | 0.0010 | uM |
| 2-[(2R)-1-azabicyclo[2.2.2]octan-2-yl]-6-(5-methyl-1H-pyrazol-4-yl)-3H-thieno[3,2-d]pyrimidin-4-one | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0010 | uM |
| 12-ethyl-11,13-dimethyl-8-thia-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-6-amine | 1798805: Radioactive Kinase Assay from Article 10.1016/j.bmcl.2008.11.093: “Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors.” | ki | 0.0010 | uM |
| 1,2-dimethyl-6-(5-methyl-1H-pyrazol-4-yl)-2-(2,2,2-trifluoroethyl)-3H-thieno[3,2-d]pyrimidin-4-one | 1364441: Inhibition of recombinant human Cdc7 (1 to 574 residues)/human N-terminal GST-tagged DBF4 (1 to 674 residues) expressed in baculovirus expression system using His-tagged MCM2 as substrate preincubated for 10 mins followed by ATP addition by HTRF assay | ic50 | 0.0010 | uM |
| 2-pyridin-4-ylspiro[5,6-dihydrothieno[3,2-c]pyridine-7,1’-cyclohexane]-4-one | 656449: Inhibition of CDC7/DBF4 using MCM-2 as substrate after 1 hr | ic50 | 0.0010 | uM |
| 2-(1H-pyrazol-4-yl)spiro[5,6-dihydrothieno[3,2-c]pyridine-7,1’-cyclohexane]-4-one | 656449: Inhibition of CDC7/DBF4 using MCM-2 as substrate after 1 hr | ic50 | 0.0010 | uM |
| 2-(1H-pyrazol-4-yl)spiro[5,6-dihydro-1-benzothiophene-7,1’-cyclohexane]-4-one | 656449: Inhibition of CDC7/DBF4 using MCM-2 as substrate after 1 hr | ic50 | 0.0010 | uM |
| 2-(7H-purin-6-yl)spiro[5,6-dihydrothieno[3,2-c]pyridine-7,1’-cyclohexane]-4-one | 656449: Inhibition of CDC7/DBF4 using MCM-2 as substrate after 1 hr | ic50 | 0.0010 | uM |
| N-[(R)-cyclopropyl-(2-fluoro-3-pyridinyl)methyl]-5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3,4-oxadiazol-2-amine | 1056819: Inhibition of Cdc7/Dbf4 (unknown origin)-mediated MCM2 phosphorylation at Ser53 by protein A amplified luminescent proximity homogeneous assay | ic50 | 0.0011 | uM |
| 2-[[(3S)-3-fluoropyrrolidin-1-yl]methyl]-6-(5-methyl-1H-pyrazol-4-yl)-3H-thieno[3,2-d]pyrimidin-4-one | 1453917: Inhibition of recombinant human full length Cdc7 (1 to 574 residues)/human N-terminal GST-tagged ASK (1 to 674 residues) expressed in baculovirus expression system using N-terminal His-tagged MCM2 as substrate pretreated for 10 mins followed by ATP addition by TR-FRET assay | ic50 | 0.0011 | uM |
| 4-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyridin-2-one | 651006: Inhibition of human CDC7/DBF4 expressed using baculovirus expression system assessed as [33P]gamma-ATP incorporation into substrate after 60 mins by gamma counting | ki | 0.0011 | uM |
| 2-[(2S)-azepan-2-yl]-6-(5-methyl-1H-pyrazol-4-yl)-3H-thieno[3,2-d]pyrimidin-4-one | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0012 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-[[(2S)-2-methylpyrrolidin-1-yl]methyl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1453917: Inhibition of recombinant human full length Cdc7 (1 to 574 residues)/human N-terminal GST-tagged ASK (1 to 674 residues) expressed in baculovirus expression system using N-terminal His-tagged MCM2 as substrate pretreated for 10 mins followed by ATP addition by TR-FRET assay | ic50 | 0.0012 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148040: Binding affinity to human CDC7 incubated for 45 mins by Kinobead based pull down assay | kd | 0.0012 | uM |
| 1’-(4-fluorophenyl)-1’-hydroxy-6-(5-methyl-1H-pyrazol-4-yl)spiro[1,3-dihydrothieno[3,2-d]pyrimidine-2,4’-cyclohexane]-4-one | 1364441: Inhibition of recombinant human Cdc7 (1 to 574 residues)/human N-terminal GST-tagged DBF4 (1 to 674 residues) expressed in baculovirus expression system using His-tagged MCM2 as substrate preincubated for 10 mins followed by ATP addition by HTRF assay | ic50 | 0.0012 | uM |
| 6-(5-methyl-1H-pyrazol-4-yl)-2-[(2S,4S)-4-methylpyrrolidin-2-yl]-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride | 1528722: Inhibition of N-terminal GST-fused full-length human CDC7 (1 to 574 end residues)/DBF4 (1 to 674 residues) expressed in baculovirus expression system using MCM2 as substrate preincubated with enzyme for 10 mins prior to 1 uM ATP addition by HTRF transcreener ADP assay | ic50 | 0.0013 | uM |
CTD chemical–gene interactions
71 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | decreases expression, decreases methylation, increases expression, affects expression | 4 |
| Cyclosporine | decreases expression | 4 |
| trichostatin A | affects cotreatment, decreases expression, affects expression | 3 |
| Benzo(a)pyrene | increases expression, affects methylation | 3 |
| Tetrachlorodibenzodioxin | affects expression, decreases expression | 3 |
| lasiocarpine | decreases expression, increases metabolic processing, increases expression | 2 |
| sodium arsenite | affects methylation, decreases expression | 2 |
| Carbamazepine | affects expression | 2 |
| Copper | increases expression, decreases expression, affects binding | 2 |
| Doxorubicin | affects response to substance, decreases expression | 2 |
| Phenylmercuric Acetate | affects cotreatment, decreases expression | 2 |
| Quercetin | decreases expression, affects expression | 2 |
| Tobacco Smoke Pollution | decreases expression | 2 |
| Tretinoin | decreases expression | 2 |
| Aflatoxin B1 | affects expression, decreases methylation | 2 |
| Cadmium Chloride | decreases expression | 2 |
| aristolochic acid I | increases expression | 1 |
| GSK-J4 | decreases expression | 1 |
| afuresertib | decreases expression | 1 |
| FR900359 | decreases phosphorylation | 1 |
| TAK-243 | increases sumoylation | 1 |
| triphenyl phosphate | affects expression | 1 |
| bisphenol A | decreases expression | 1 |
| geraniol | decreases expression | 1 |
| beta-lapachone | decreases expression | 1 |
| tris(1,3-dichloro-2-propyl)phosphate | decreases expression | 1 |
| ochratoxin A | decreases expression, affects cotreatment | 1 |
| 2,3-bis(3’-hydroxybenzyl)butyrolactone | affects cotreatment, increases expression | 1 |
| beta-methylcholine | affects expression | 1 |
| celastrol | decreases expression | 1 |
ChEMBL screening assays
222 unique, capped per target: 221 binding, 1 functional
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1035818 | Binding | Inhibition of human recombinant Cdc7/Dbf4 by IMAP assay | Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors. — Bioorg Med Chem Lett |
| CHEMBL1963731 | Functional | PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CDC7 | PubChem BioAssay data set |
Clinical trials (associated diseases)
82 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00417066 | PHASE4 | COMPLETED | Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders |
| NCT00732693 | PHASE4 | COMPLETED | Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure |
| NCT00837616 | PHASE4 | COMPLETED | Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism |
| NCT01853501 | PHASE4 | UNKNOWN | Effects of ADSC Therapy in Women With POF |
| NCT02783937 | PHASE4 | COMPLETED | Filgrastim for Premature Ovarian Insufficiency |
| NCT03535480 | PHASE4 | UNKNOWN | Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure |
| NCT00140998 | PHASE3 | COMPLETED | Estrogen Treatment (Oral vs. Patches) in Turner Syndrome |
| NCT00001951 | PHASE2 | COMPLETED | Hormone Replacement in Young Women With Premature Ovarian Failure |
| NCT00370019 | PHASE2 | WITHDRAWN | Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure |
| NCT00429494 | PHASE2 | COMPLETED | GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients |
| NCT03816852 | PHASE2 | SUSPENDED | The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency |
| NCT04536467 | PHASE2 | UNKNOWN | Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients |
| NCT06117982 | PHASE2 | COMPLETED | The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency |
| NCT02912104 | PHASE1 | COMPLETED | A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure |
| NCT03178695 | PHASE1 | COMPLETED | Inovium Ovarian Rejuvenation Trials |
| NCT04815213 | PHASE1 | ACTIVE_NOT_RECRUITING | The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans |
| NCT05138367 | PHASE1 | COMPLETED | Effects of UCA-PSCs in Women With POF |
| NCT06132542 | PHASE1 | UNKNOWN | Autologous ADMSC Transplantation in Patients With POI |
| NCT00948857 | PHASE2/PHASE3 | TERMINATED | Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF) |
| NCT04031456 | PHASE2/PHASE3 | RECRUITING | Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients |
| NCT02043743 | PHASE1/PHASE2 | UNKNOWN | Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure |
| NCT02062931 | PHASE1/PHASE2 | UNKNOWN | Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure |
| NCT02151890 | PHASE1/PHASE2 | COMPLETED | Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure |
| NCT02372474 | PHASE1/PHASE2 | COMPLETED | It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure |
| NCT02603744 | PHASE1/PHASE2 | UNKNOWN | Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF) |
| NCT02644447 | PHASE1/PHASE2 | COMPLETED | Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF |
| NCT03069209 | PHASE1/PHASE2 | UNKNOWN | Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF) |
| NCT03985462 | PHASE1/PHASE2 | WITHDRAWN | Very Small Embryonic-like Stem Cells for Ovary |
| NCT04009473 | PHASE1/PHASE2 | UNKNOWN | Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation |
| NCT04071574 | PHASE1/PHASE2 | COMPLETED | Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility |
| NCT04922398 | PHASE1/PHASE2 | UNKNOWN | Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency |
| NCT05462379 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment. |
| NCT06202547 | PHASE1/PHASE2 | UNKNOWN | Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure |
| NCT01129947 | EARLY_PHASE1 | WITHDRAWN | The Use of DHEA in Women With Premature Ovarian Failure |
| NCT05522634 | EARLY_PHASE1 | UNKNOWN | A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency |
| NCT07308327 | EARLY_PHASE1 | ACTIVE_NOT_RECRUITING | The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial |
| NCT00001275 | Not specified | COMPLETED | Ovarian Follicle Function in Patients With Primary Ovarian Failure |
| NCT00001306 | Not specified | COMPLETED | Steroid Therapy in Autoimmune Premature Ovarian Failure |
| NCT00006156 | Not specified | COMPLETED | Feasibility Study for Development of an Early Test for Ovarian Failure |
| NCT00119925 | Not specified | UNKNOWN | ‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists |
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): open-angle glaucoma, premature menopause