DBF4

Summary

DBF4 (DBF4-CDC7 kinase regulatory subunit, HGNC:17364) is a protein-coding gene on chromosome 7q21.12, encoding Protein DBF4 homolog A (Q9UBU7). Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. It is a selective cancer dependency (DepMap: 85.7% of cell lines).

Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in positive regulation of nuclear cell cycle DNA replication and regulation of cell cycle phase transition. Located in nuclear body.

Source: NCBI Gene 10926 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 91 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 85.7% of screened cell lines
• MANE Select transcript: NM_006716

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17364
Approved symbol	DBF4
Name	DBF4-CDC7 kinase regulatory subunit
Location	7q21.12
Locus type	gene with protein product
Status	Approved
Aliases	ASK, chif, ZDBF1, DBF4A
Ensembl gene	ENSG00000006634
Ensembl biotype	protein_coding
OMIM	604281
Entrez	10926

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000265728, ENST00000413643, ENST00000430279, ENST00000431138, ENST00000486925, ENST00000495067, ENST00000498144, ENST00000498726, ENST00000885651, ENST00000924359, ENST00000924360, ENST00000924361, ENST00000924362, ENST00000924363, ENST00000924364, ENST00000924365

RefSeq mRNA: 4 — MANE Select: NM_006716 NM_001318060, NM_001318061, NM_001318062, NM_006716

CCDS: CCDS5611

Canonical transcript exons

ENST00000265728 — 12 exons

Exon	Start	End
ENSE00000877195	87876493	87876778
ENSE00000877205	87907188	87909553
ENSE00003484091	87886844	87886894
ENSE00003494382	87887329	87887398
ENSE00003524237	87884979	87885158
ENSE00003524530	87887983	87888059
ENSE00003533337	87900764	87900878
ENSE00003555697	87904292	87904416
ENSE00003574111	87896474	87896510
ENSE00003603551	87878053	87878225
ENSE00003623689	87900221	87900349
ENSE00003623889	87897294	87897339

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 93.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7225 / max 688.3769, expressed in 1792 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79406	17.9599	1752
79407	9.3669	1584
79405	1.0633	516
79404	0.1905	44
79408	0.1418	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.23	gold quality
ventricular zone	UBERON:0003053	93.04	gold quality
left testis	UBERON:0004533	92.33	gold quality
testis	UBERON:0000473	92.07	gold quality
right testis	UBERON:0004534	91.48	gold quality
adult organism	UBERON:0007023	90.70	gold quality
secondary oocyte	CL:0000655	89.04	gold quality
ganglionic eminence	UBERON:0004023	88.85	gold quality
bone marrow	UBERON:0002371	87.01	gold quality
embryo	UBERON:0000922	86.77	gold quality
adrenal tissue	UBERON:0018303	86.65	gold quality
sperm	CL:0000019	86.50	gold quality
male germ cell	CL:0000015	85.14	gold quality
bone marrow cell	CL:0002092	82.87	gold quality
rectum	UBERON:0001052	82.31	gold quality
trabecular bone tissue	UBERON:0002483	81.36	gold quality
lymph node	UBERON:0000029	81.06	gold quality
calcaneal tendon	UBERON:0003701	80.84	gold quality
vermiform appendix	UBERON:0001154	80.74	gold quality
endometrium epithelium	UBERON:0004811	80.24	gold quality
tibia	UBERON:0000979	80.02	gold quality
granulocyte	CL:0000094	79.33	gold quality
right ovary	UBERON:0002118	79.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	78.84	gold quality
left ovary	UBERON:0002119	78.73	gold quality
leukocyte	CL:0000738	78.42	gold quality
tonsil	UBERON:0002372	78.00	gold quality
mononuclear cell	CL:0000842	77.96	gold quality
monocyte	CL:0000576	77.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4, HES1, SP1

miRNA regulators (miRDB)

79 targeting DBF4, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
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-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-7161-5P	99.68	68.92	1592

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 85.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 28)

• results suggest that E2F regulates the ASK promoter through an atypical mode of recognition of the target site (PMID:12015319)
• The HuDbf4 gene has of 12 exons over a 33-kb region. The MluI cell-cycle box is needed for core promoter activation. The Sp1 upregulator & HES-1 repressor coordinately determine promoter efficiency. Transcription initiations occur at -220, -235 and -245. (PMID:12420215)
• Results demonstrate a DNA damage checkpoint that targets Cdc7/Dbf4 protein kinase. (PMID:12535533)
• Cdc7-Dbf4 kinase efficiently phosphorylates p150. (PMID:16826239)
• Taken together, these results indicate that Cdc7/Dbf4 phosphorylation of MCM2 is essential for the initiation of DNA replication in mammalian cells. (PMID:16899510)
• Overexpression of Dbf4 abrogates the S checkpoint response to ultraviolet radiation but not ionizing radiation. (PMID:17276990)
• There is the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggest that up-regulation of ASK/Dbf4 is a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma. (PMID:17768177)
• Cdc7/Dbf4 kinase activity inhibition affects specific phosphorylation sites on MCM2 in cancer cells (PMID:18286467)
• ASK/Dbf4, a novel cell survival gene in melanoma is transcriptionally regulated by E2F1. (PMID:18503552)
• A strong origin of replication at the DBF4 promoter locus, which contains two initiation zones, two origin recognition complex (ORC) binding sites and two DNase I-hypersensitive regions, is identified. (PMID:18536724)
• increased Cdc7-Dbf4 abundance may be a common occurrence in human malignancies (PMID:18714392)
• These results indicate that Ddk functions as an upstream regulator to monitor S-phase checkpoint signaling. (PMID:19111665)
• Data document the role of DBF4 as a key player in nitrogen-containing bisphosphonate-induced cytotoxicity, thus explaining the effects on the cell-cycle. (PMID:19744312)
• The interaction with LEDGF relieves autoinhibition of Cdc7-ASK kinase, imposed by the C terminus of ASK. (PMID:19864417)
• Dbf4 regulates the Cdc5 Polo-like kinase through a distinct non-canonical binding interaction (PMID:21036905)
• bipartite interaction between Cdc7 and Dbf4/ASK subunits facilitates ATP binding and substrate recognition by the Cdc7 kinase. (PMID:21536671)
• Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) protein to regulate intra-S-phase checkpoint. (PMID:22123827)
• The anti-invasive and cell cycle arrest-inducing effects of nitrogen-containing bisphosphonates are not DBF4 mediated in human breast cancer cells. (PMID:24287290)
• Histone H3 lysine 9 (H3K9) acetylation was most prevalent when the Dbf4 transcription level was highest whereas the H3K9me3 level was greatest during and just after replication. (PMID:27341472)
• 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)
• Both CDC7 and DBF4 promoters bind E2F, suggesting that increased E2F activity in RB1 mutant cancers promotes increased DDK expression. Surprisingly, increased DDK expression levels are also correlated with both increased chemoresistance and genome-wide mutation frequencies. (PMID:28448802)
• High DBF4 expression is associated with oral cancer. (PMID:29209046)
• CDC7-DBF4 kinase (DDK) has a primary role in the replication checkpoint to promote single-stranded DNA accumulation at stalled forks, which is required to initiate a robust checkpoint response and cell cycle arrest to maintain genome integrity. (PMID:30157471)
• Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis. (PMID:33377973)
• Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma. (PMID:34975331)
• DBF4 Dependent Kinase Inhibition Suppresses Hepatocellular Carcinoma Progression and Potentiates Anti-Programmed Cell Death-1 Therapy. (PMID:37497004)
• The prognostic significance and potential mechanism of DBF4 zinc finger in hepatocellular carcinoma. (PMID:38724606)
• DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks. (PMID:38865090)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dbf4	ENSDARG00000074796
mus_musculus	Dbf4	ENSMUSG00000002297
rattus_norvegicus	Dbf4	ENSRNOG00000050482
drosophila_melanogaster	chif	FBGN0000307

Paralogs (1): DBF4B (ENSG00000161692)

Protein

Protein identifiers

Protein DBF4 homolog A — Q9UBU7 (reviewed: Q9UBU7)

Alternative names: Activator of S phase kinase, Chiffon homolog A, DBF4-type zinc finger-containing protein 1

All UniProt accessions (3): Q9UBU7, B4DXK0, F8WF77

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at ‘Ser-40’ and ‘Ser-53’ and then is involved in regulating the initiation of DNA replication during cell cycle.

Subunit / interactions. Forms a complex with CDC7. Note that CDC7 forms distinct complex either with DBF4A or DBF4B. Such complexes are stable upon replication stress. Interacts with MEN1, MCM2, ORC2, ORC4 and ORC6. Interacts (via IBM motifs) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in testis and thymus. Expressed also in most cancer cells lines.

Post-translational modifications. Phosphorylation increases its interaction with PSIP1.

Induction. Induced in G1 phase at low level, increased during G1-S phase and remain high during S and G2-M phase.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBU7-1	1	yes
Q9UBU7-2	2

RefSeq proteins (4): NP_001304989, NP_001304990, NP_001304991, NP_006707* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006572	Znf_DBF	Domain
IPR038545	Znf_DBF_sf	Homologous_superfamily
IPR051590	Replication_Regulatory_Kinase	Family

Pfam: PF07535

UniProt features (49 total): modified residue 12, strand 6, mutagenesis site 5, binding site 4, helix 4, sequence conflict 3, domain 2, splice variant 2, sequence variant 2, region of interest 2, short sequence motif 2, compositionally biased region 2, chain 1, zinc finger region 1, turn 1

Structure

Experimental structures (PDB)

7 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
4F99	X-RAY DIFFRACTION	2.33
4F9B	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBU7-F1	55.17	0.23

Functional residue map

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

Ligand- & substrate-binding residues (4): 296; 299; 309; 315

Post-translational modifications (12): 273, 312, 345, 354, 359, 381, 413, 508, 553, 625, 667, 669

Mutagenesis-validated functional residues (5):

Position	Phenotype
625	phosphomimetic mutant. increased interaction with psip1.
631	loss of interaction with psip1; when associated with a-634.
634	loss of interaction with psip1; when associated with a-631.
667	phosphomimetic mutant. increased interaction with psip1; when associated with d-669.
669	phosphomimetic mutant. increased interaction with psip1; when associated with d-667.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-68962	Activation of the pre-replicative complex

MSigDB gene sets: 279 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, MODULE_97, REACTOME_DNA_REPLICATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, BASSO_B_LYMPHOCYTE_NETWORK, XU_GH1_AUTOCRINE_TARGETS_UP, BROWNE_HCMV_INFECTION_8HR_UP, GOBP_CELL_CYCLE_DNA_REPLICATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS

GO Biological Process (4): G1/S transition of mitotic cell cycle (GO:0000082), DNA replication (GO:0006260), positive regulation of nuclear cell cycle DNA replication (GO:0010571), regulation of cell cycle phase transition (GO:1901987)

GO Molecular Function (6): nucleic acid binding (GO:0003676), enzyme activator activity (GO:0008047), zinc ion binding (GO:0008270), protein serine/threonine kinase activator activity (GO:0043539), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), nuclear body (GO:0016604), Dbf4-dependent protein kinase complex (GO:0031431), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
G2/M Checkpoints	1
DNA Replication Pre-Initiation	1
G1/S Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
DNA metabolic process	1
DNA biosynthetic 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
regulation of cell cycle process	1
cell cycle phase transition	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
transition metal ion binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear protein-containing complex	1
serine/threonine protein kinase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DBF4	CDC7	O00311	999
DBF4	TICRR	Q7Z2Z1	979
DBF4	CDC45	O75419	969
DBF4	MCM4	P33991	968
DBF4	CDT1	Q9H211	902
DBF4	CDC6	Q99741	898
DBF4	MCM3	P25205	891
DBF4	TOPBP1	Q92547	862
DBF4	MCM10	Q7L590	857
DBF4	CHEK2	O96017	819
DBF4	MCM5	P33992	794
DBF4	GINS4	Q9BRT9	792
DBF4	MCM6	Q14566	776
DBF4	MCM7	P33993	774
DBF4	RAD52	P43351	748

IntAct

37 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	BLMH	psi-mi:“MI:0915”(physical association)	0.560
DBF4	CHRNA7	psi-mi:“MI:0915”(physical association)	0.560
DBF4	GFAP	psi-mi:“MI:0915”(physical association)	0.560
DBF4	HSPD1	psi-mi:“MI:0915”(physical association)	0.560
NEFL	DBF4	psi-mi:“MI:0915”(physical association)	0.560
PRKN	DBF4	psi-mi:“MI:0915”(physical association)	0.560
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
DBF4	TARDBP	psi-mi:“MI:0915”(physical association)	0.400
DBF4	CHAF1A	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
CDC7	AMY1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): DBF4 (Affinity Capture-MS), DBF4 (Two-hybrid), HDGFRP2 (Affinity Capture-MS), CDC7 (Affinity Capture-MS), NME6 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), DBF4 (Two-hybrid), MCM2 (Biochemical Activity), MCM2 (Biochemical Activity), MCM4 (Biochemical Activity), MCM6 (Biochemical Activity), MCM7 (Biochemical Activity), DBF4 (Reconstituted Complex), DBF4 (Two-hybrid), ORC1 (Two-hybrid)

ESM2 similar proteins: A0P8Z5, B0KYV5, B1WC58, B2RYR0, F1LR10, F6SNN2, O75128, O75410, P51826, P61590, P61591, P61592, P61593, P61594, Q3USH1, Q501R9, Q5IFK1, Q5PQK4, Q5R8C5, Q5SU73, Q5SWA1, Q5U5Q9, Q6NZF1, Q6P1D7, Q6P7W0, Q6PJW8, Q6Y685, Q6ZSG2, Q6ZVT6, Q7TT79, Q80XI1, Q80XJ2, Q80YR6, Q86T90, Q8BFU3, Q8C9B9, Q8IY92, Q8IYW5, Q8ND24, Q8NEM0

Diamond homologs: O59836, P32325, Q99MU0, Q9QZ41, Q9UBU7, Q9Y7J1, Q283Q6, Q28FY7, Q7ZZH7, Q8NFT6

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ATM	down-regulates	DBF4	phosphorylation
ATR	down-regulates	DBF4	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1849 predictions. Top by Δscore:

Variant	Effect	Δscore
7:87884973:TTCTA:T	acceptor_loss	1.0000
7:87884977:A:AG	acceptor_gain	1.0000
7:87884977:AGC:A	acceptor_gain	1.0000
7:87884978:G:GG	acceptor_gain	1.0000
7:87884978:GC:G	acceptor_gain	1.0000
7:87884978:GCG:G	acceptor_gain	1.0000
7:87884978:GCGA:G	acceptor_gain	1.0000
7:87885133:G:GT	donor_gain	1.0000
7:87885154:ACACA:A	donor_gain	1.0000
7:87885155:CACA:C	donor_gain	1.0000
7:87885156:ACA:A	donor_gain	1.0000
7:87885156:ACAG:A	donor_loss	1.0000
7:87885157:CA:C	donor_gain	1.0000
7:87885157:CAGTA:C	donor_loss	1.0000
7:87885158:AGTAA:A	donor_loss	1.0000
7:87885159:G:GG	donor_gain	1.0000
7:87885159:G:T	donor_loss	1.0000
7:87885160:TA:T	donor_loss	1.0000
7:87885161:AA:A	donor_loss	1.0000
7:87887324:TACA:T	acceptor_loss	1.0000
7:87887327:AGGAT:A	acceptor_loss	1.0000
7:87887976:A:AG	acceptor_gain	1.0000
7:87897336:GCCA:G	donor_gain	1.0000
7:87897340:G:GG	donor_gain	1.0000
7:87900835:G:GT	donor_gain	1.0000
7:87900879:G:GG	donor_gain	1.0000
7:87904286:TTTTA:T	acceptor_loss	1.0000
7:87904287:TTTA:T	acceptor_loss	1.0000
7:87904288:TTAG:T	acceptor_loss	1.0000
7:87904290:A:AC	acceptor_loss	1.0000

AlphaMissense

4487 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:87884991:T:C	F78L	0.999
7:87884993:T:A	F78L	0.999
7:87884993:T:G	F78L	0.999
7:87885016:T:C	L86P	0.999
7:87887363:C:A	A162D	0.999
7:87878158:T:C	F51S	0.998
7:87878160:T:G	Y52D	0.998
7:87878218:T:C	L71P	0.998
7:87878224:G:A	G73E	0.998
7:87900840:T:C	C296R	0.998
7:87878223:G:A	G73R	0.997
7:87878223:G:C	G73R	0.997
7:87884992:T:C	F78S	0.997
7:87887371:T:A	W165R	0.997
7:87887371:T:C	W165R	0.997
7:87897322:G:C	K221N	0.997
7:87897322:G:T	K221N	0.997
7:87900841:G:A	C296Y	0.997
7:87900842:T:G	C296W	0.997
7:87900849:T:C	C299R	0.997
7:87904347:T:A	V327D	0.997
7:87878197:T:C	L64P	0.996
7:87878209:T:A	I68N	0.996
7:87885019:T:A	I87N	0.996
7:87887362:G:C	A162P	0.996
7:87887387:T:C	L170P	0.996
7:87897314:T:C	F219L	0.996
7:87897316:T:A	F219L	0.996
7:87897316:T:G	F219L	0.996
7:87900851:C:G	C299W	0.996

dbSNP variants (sampled 300 via entrez): RS1000043358 (7:87901652 A>C,G), RS1000203144 (7:87876477 C>T), RS1000331620 (7:87896912 A>C), RS1000432458 (7:87903639 G>A), RS1000569876 (7:87904883 C>T), RS1000633753 (7:87899898 TCA>T), RS1000767386 (7:87905137 T>C), RS1000799200 (7:87892224 C>T), RS1000883636 (7:87883035 G>T), RS1000927954 (7:87891874 T>G), RS1000954995 (7:87898333 G>A), RS1000999245 (7:87888316 T>C), RS1001067681 (7:87898045 G>A,T), RS1001152389 (7:87894839 T>C), RS1001245518 (7:87895254 T>C,G)

Disease associations

OMIM: gene MIM:604281 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1287	Metabolite levels	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010548	xanthine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111377 (PROTEIN COMPLEX), CHEMBL4483 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 63 (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

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

Binding affinities (BindingDB)

90 measured of 231 human assays (231 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
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
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
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
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
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
6-cyclopropyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	5 nM
2-(2-aminopyrimidin-4-yl)-7-ethyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	5 nM
2-(2-aminopyrimidin-4-yl)-7-cyclobutyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	5 nM
2-(2-aminopyrimidin-4-yl)-7,7-diethyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	5 nM
(7R)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	5 nM
2-(2-aminopyrimidin-4-yl)-1-(2,2,2-trifluoroethyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	5 nM
16-methyl-8-thia-3,5,10-triazatetracyclo[7.7.0.0^{2,7}.0^{11,15}]hexadeca-1(16),2(7),3,5,9,11(15)-hexaen-6-amine	KI	5 nM
6-(propan-2-yl)-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	6 nM
7,7-diethyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	6 nM
2-(2-aminopyrimidin-4-yl)-7-methyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	6 nM
2-(2-aminopyrimidin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	7 nM
2-(2-aminopyrimidin-4-yl)-7-[2-(benzyloxy)ethyl]-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	7 nM
2-[2-(phenylamino)pyrimidin-4-yl]-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	7 nM
2-(2-aminopyrimidin-4-yl)-6-(2-methylpropyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	8 nM
2-(2-aminopyrimidin-4-yl)-1-ethyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	8 nM
2-(3-fluoropyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	9 nM
JMC502647 Compound 8	IC50	10 nM
7-methyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	10 nM
7-(propan-2-yl)-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	10 nM
2-(2-aminopyrimidin-4-yl)-7-(3,3,3-trifluoropropyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	10 nM
2-(2-aminopyrimidin-4-yl)-6-cyclopropyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	11 nM
2-(2-aminopyrimidin-4-yl)-6-(propan-2-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	12 nM
2-(2-aminopyrimidin-4-yl)-7-(3-hydroxypropyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	12 nM
2-(2-aminopyrimidin-4-yl)-1-propyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	12 nM
6-methyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	13 nM
2-(2-aminopyrimidin-4-yl)-1-(2-methylpropyl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	13 nM
2-{1H-pyrrolo[2,3-b]pyridin-4-yl}-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	14 nM
2-(2-aminopyrimidin-4-yl)-1-cyclobutyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	14 nM
2-(2-aminopyrimidin-4-yl)-7-phenyl-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	19 nM
7-phenyl-2-(pyridin-4-yl)-1H,4H,5H,6H,7H-pyrrolo[3,2-c]pyridin-4-one	IC50	20 nM

ChEMBL bioactivities

318 potent at pChembl≥5 of 334 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
9.85	Ki	0.14	nM	CHEMBL1958416
9.80	IC50	0.16	nM	CHEMBL4436649
9.80	IC50	0.16	nM	CHEMBL4462898
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
9.60	Ki	0.25	nM	CHEMBL1958418
9.59	IC50	0.26	nM	SIMUROSERTIB
9.52	Ki	0.3	nM	CHEMBL1958406
9.39	IC50	0.41	nM	CHEMBL4439133
9.37	IC50	0.43	nM	CHEMBL4570191
9.36	IC50	0.44	nM	CHEMBL4439133
9.30	Ki	0.5	nM	CHEMBL505372
9.30	Ki	0.5	nM	CHEMBL1958404
9.30	Ki	0.5	nM	CHEMBL1958408
9.28	IC50	0.53	nM	CHEMBL4543158
9.27	Kd	0.541	nM	CHEMBL4083927
9.27	IC50	0.54	nM	SIMUROSERTIB
9.22	IC50	0.6	nM	CHEMBL4089159
9.21	IC50	0.61	nM	CHEMBL4569914
9.16	IC50	0.69	nM	CHEMBL3093076
9.15	IC50	0.7	nM	CHEMBL4083927
9.15	IC50	0.71	nM	CHEMBL4440266
9.14	IC50	0.72	nM	CHEMBL4570191
9.07	IC50	0.85	nM	CHEMBL3093075
9.04	IC50	0.91	nM	CHEMBL4587191
9.00	IC50	1	nM	CHEMBL2016996
9.00	IC50	1	nM	CHEMBL2016862
9.00	IC50	1	nM	CHEMBL2016856
9.00	IC50	1	nM	CHEMBL3093074
9.00	IC50	1	nM	CHEMBL4214023
9.00	IC50	1	nM	CHEMBL4572218
9.00	Ki	1	nM	CHEMBL444981
8.96	IC50	1.1	nM	CHEMBL3093080
8.96	IC50	1.1	nM	CHEMBL4087760
8.96	Ki	1.1	nM	CHEMBL1958409
8.92	IC50	1.2	nM	CHEMBL4078941
8.92	IC50	1.2	nM	CHEMBL4213805
8.92	IC50	1.2	nM	CHEMBL4529213
8.90	Kd	1.26	nM	CHEMBL4098392
8.89	IC50	1.3	nM	CHEMBL4462574
8.85	IC50	1.4	nM	CHEMBL4070822
8.85	Ki	1.4	nM	CHEMBL1958407
8.82	IC50	1.5	nM	CHEMBL3093078
8.82	IC50	1.5	nM	CHEMBL4080673
8.82	IC50	1.5	nM	CHEMBL4062209

PubChem BioAssay actives

413 with measured affinity, of 565 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
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
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
6-(cyclohexylamino)-4-(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	0.0005	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
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
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
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
6-(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	0.0013	uM
4-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1H-pyrimidin-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	0.0014	uM
2-(methylaminomethyl)-6-(5-methyl-1H-pyrazol-4-yl)-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	0.0014	uM
N-[(R)-cyclopropyl-(2-fluorophenyl)methyl]-5-(7H-pyrrolo[2,3-d]pyrimidin-5-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	0.0015	uM
2-(cyclopentylmethyl)-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	0.0015	uM
2-[(dimethylamino)methyl]-6-(5-methyl-1H-pyrazol-4-yl)-3H-thieno[3,2-d]pyrimidin-4-one;dihydrochloride	1453925: 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 60 mins followed by 50 uM ATP addition by TR-FRET assay	ic50	0.0015	uM
6-(5-methyl-1H-pyrazol-4-yl)spiro[1,3-dihydrothieno[3,2-d]pyrimidine-2,1’-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	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Cisplatin	decreases reaction, increases expression, decreases expression	2
Formaldehyde	decreases expression	2
Quercetin	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
geraniol	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric oxide	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
deguelin	increases expression	1
GW 4064	increases expression	1
poly(propyleneimine)	decreases expression	1
pyrimidifen	increases expression	1
oligofectamine	increases expression	1
jinfukang	decreases expression	1
incobotulinumtoxinA	decreases expression	1
picoxystrobin	increases expression	1

ChEMBL screening assays

100 unique, capped per target: 100 binding

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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SK38	HAP1 DBF4 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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