BUB1

Summary

BUB1 (BUB1 mitotic checkpoint serine/threonine kinase, HGNC:1148) is a protein-coding gene on chromosome 2q13, encoding Mitotic checkpoint serine/threonine-protein kinase BUB1 (O43683). Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. It is a selective cancer dependency (DepMap: 74.9% of cell lines).

This gene encodes a serine/threonine-protein kinase that play a central role in mitosis. The encoded protein functions in part by phosphorylating members of the mitotic checkpoint complex and activating the spindle checkpoint. This protein also plays a role in inhibiting the activation of the anaphase promoting complex/cyclosome. This protein may also function in the DNA damage response. Mutations in this gene have been associated with aneuploidy and several forms of cancer. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 699 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly 30, primary, autosomal recessive (Moderate, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 1,540 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 87
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 74.9% of screened cell lines
• MANE Select transcript: NM_004336

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1148
Approved symbol	BUB1
Name	BUB1 mitotic checkpoint serine/threonine kinase
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	hBUB1, BUB1A
Ensembl gene	ENSG00000169679
Ensembl biotype	protein_coding
OMIM	602452
Entrez	699

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000302759, ENST00000409311, ENST00000420328, ENST00000436916, ENST00000447014, ENST00000465029, ENST00000466333, ENST00000468927, ENST00000477481, ENST00000478175, ENST00000490632, ENST00000535254, ENST00000666956, ENST00000671097, ENST00000902357, ENST00000902358, ENST00000922602, ENST00000922603, ENST00000922604, ENST00000922605, ENST00000922606

RefSeq mRNA: 3 — MANE Select: NM_004336 NM_001278616, NM_001278617, NM_004336

CCDS: CCDS33273, CCDS62984, CCDS62985

Canonical transcript exons

ENST00000302759 — 25 exons

Exon	Start	End
ENSE00001146554	110639742	110639848
ENSE00001146562	110641034	110641205
ENSE00001507328	110641307	110641464
ENSE00003459197	110674306	110674365
ENSE00003465185	110653436	110653523
ENSE00003481918	110661582	110661841
ENSE00003483692	110641642	110641803
ENSE00003487692	110655739	110655916
ENSE00003497511	110674086	110674224
ENSE00003523914	110649234	110649377
ENSE00003536122	110666263	110666414
ENSE00003538844	110667797	110667849
ENSE00003542626	110650546	110650784
ENSE00003558608	110642119	110642234
ENSE00003583605	110667521	110667705
ENSE00003610719	110669453	110669553
ENSE00003620869	110658614	110658742
ENSE00003635414	110659978	110660036
ENSE00003642648	110677970	110678063
ENSE00003649478	110672661	110672857
ENSE00003657909	110657036	110657117
ENSE00003683110	110658410	110658520
ENSE00003690725	110657546	110657645
ENSE00003787303	110670525	110670568
ENSE00003876978	110637528	110638159

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.1073 / max 725.4731, expressed in 1465 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30125	22.1073	1465

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.64	gold quality
ganglionic eminence	UBERON:0004023	92.92	gold quality
right testis	UBERON:0004534	92.46	gold quality
left testis	UBERON:0004533	92.04	gold quality
secondary oocyte	CL:0000655	91.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.56	gold quality
testis	UBERON:0000473	91.08	gold quality
embryo	UBERON:0000922	90.31	gold quality
oocyte	CL:0000023	87.19	gold quality
bone marrow cell	CL:0002092	85.42	gold quality
bone marrow	UBERON:0002371	83.59	gold quality
mucosa of transverse colon	UBERON:0004991	81.71	gold quality
adrenal tissue	UBERON:0018303	81.69	gold quality
trabecular bone tissue	UBERON:0002483	81.60	gold quality
vermiform appendix	UBERON:0001154	80.95	gold quality
stromal cell of endometrium	CL:0002255	80.21	gold quality
rectum	UBERON:0001052	80.07	gold quality
lower esophagus mucosa	UBERON:0035834	79.49	gold quality
lymph node	UBERON:0000029	78.30	gold quality
esophagus mucosa	UBERON:0002469	75.72	gold quality
caecum	UBERON:0001153	75.71	gold quality
colonic epithelium	UBERON:0000397	75.62	gold quality
spleen	UBERON:0002106	74.02	gold quality
sperm	CL:0000019	73.22	gold quality
male germ cell	CL:0000015	72.90	gold quality
endometrium epithelium	UBERON:0004811	72.58	silver quality
tonsil	UBERON:0002372	70.75	gold quality
cortical plate	UBERON:0005343	70.60	gold quality
thymus	UBERON:0002370	70.53	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	665.33
E-GEOD-110499	yes	412.96
E-CURD-122	yes	21.36
E-MTAB-6678	yes	8.09
E-ANND-3	yes	6.65
E-GEOD-99795	no	231.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1

miRNA regulators (miRDB)

33 targeting BUB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-4327	97.21	67.71	676
HSA-MIR-6847-3P	96.50	67.30	582

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1, were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers (PMID:11782350)
• As part of a common complex in checkpoint-activated cells, Bub1 monitors different spindle events compared to BubR1 and integrates different signals into a single signal that is then relayed to the downstream cell cycle machinery. (PMID:11792804)
• Reduced expression and aberrant transcription of the hBUB1 gene were detected in acute myeloid leukemia specimens. (PMID:11999574)
• mutations in leukemia and lymphoma cells (PMID:12096343)
• Results suggest that mutation of the Bub1 gene might not play a role in human stomach and oral carcinogenesis. (PMID:12375025)
• mitotic checkpoint kinases BubR1 and BuB1, by binding to beta-adaptins, may play novel roles in the regulation of vesicular intracellular traffic (PMID:12419313)
• The checkpoint pathway can be abrogated by mutations in BUB1 in the pancreatic cancer cell line Hs766T. (PMID:12655561)
• No apparent selection trend was established with neoplastic progression or aneuploidy for BUB1 in Barrett esophagus. (PMID:15013707)
• Bub1 protects centromeric cohesion through Shugoshin in mitosis (PMID:15604152)
• Bub1 defines the persistent cohesion site along the mitotic chromosome by affecting Shugoshin localization. (PMID:15723797)
• Bub1 is cleaved during apoptosis (PMID:15818396)
• Altered expression is associated with therapy failure and death in patients with multiple types of cancer. (PMID:15931389)
• Data suggest that Bub1 and Aurora B function in parallel pathways that promote formation of stable bipolar kinetochore-microtubule attachments. (PMID:15933723)
• The two spindle checkpoint arms respond to different spindle cues: whereas the Bub1 arm monitors kinetochore-microtubule attachment, the aurora B arm monitors biorientation. (PMID:16046481)
• expression of wild-type Bub1 suppressed multinuclei formation induced by HTLV-I Tax protein both in A549 and HeLa cells. (PMID:16449967)
• Results indicate that increased expression of the human Bub1 gene is closely linked to abnormal cell proliferation in malignant conditions. (PMID:16525682)
• Phosphorylation of Bub1 at T609 by Cdk1 creates a docking site for the PBD of Plk1 and facilitates the kinetochore recruitment of Plk1. (PMID:16760428)
• Bub1, an anaphase-promoting complex/ cyclosome (APC/C) inhibitor, is also an APC/C substrate. (PMID:17158872)
• Bub1 compromise triggers p53-dependent senescence, which limits the production of aneuploid and potentially cancerous cells. (PMID:17488820)
• Kinetochoe localization of Sgo1 depends on AurB and Bub1. (PMID:17617734)
• BUB1 mediation of caspase-independent mitotic death determines cell fate. (PMID:17620410)
• Bub1 is essential for postimplantation embryogenesis and proliferation of primary embryonic fibroblasts. Bub1 inactivation in adult males inhibits proliferation in seminiferous tubules, reducing sperm production and causing infertility. (PMID:17925231)
• These observations suggest that Bub1 not only regulates the cell cycle, but also may be involved in the cytoskeletal control in interphase cells. (PMID:18036341)
• hBUB1, hBUBR1 and hMAD2 expressions in anaplastic thyroid cancer were significantly higher than those in diffuse cancer. hBUBR1 and hMAD2 expressions in advanced DTCs were significantly higher than those in non-advanced DTCs. (PMID:18383837)
• domain amphiphilicity is of higher importance than amino acid sequence specificity in the determination of protein adsorption and interfacial activity (PMID:18547097)
• BUB1 and BUBR1 overexpression plays a role in cytogenetic and morphologic progression of clear cell renal cell cancer (PMID:18791270)
• data suggest that large T antigen, via Bub1 binding, breaches genome integrity mechanisms, leading to DNA damage responses, p53 stabilization, and tetraploidy. (PMID:18922873)
• The KEN boxes of Bub1 are specifically required for the spindle checkpoint in human cells. (PMID:18995837)
• the spindle checkpoint kinase Bub1 contributes to the maintenance of Sgo1 steady-state protein levels in an APC/C-independent mechanism. (PMID:19015261)
• structure provides insight into the molecular basis of Blinkin-specific recognition by BUB1 and, on a broader perspective, of the mechanism that mediates kinetochore localization of BUB1 in checkpoint-activated cells (PMID:19141287)
• Results suggest a novel molecular mechanism leading to aneuploidy involving interference of TAp73alpha with Bub1 and Bub3 resulting in an altered mitotic checkpoint. (PMID:19182530)
• Depletion of the outer kinetochore protein hBub1 upon activation of SAC primarily triggers early cell death mediated by p53. (PMID:19242126)
• P53 physically interacts with hBub1 at kinetochores in response to mitotic spindle damage suggesting a direct role for hBub1 in the suppression of p53 mediated cell death. (PMID:19252416)
• Bub1 can regulate chromosome segregation in a kinetochore-independent manner. (PMID:19487456)
• Findings strongly suggest that the loss of spindle assembly checkpoint proteins, such as Bub1 and Mad2, may cause spontaneous miscarriages. (PMID:20643875)
• the interaction between LANA and the kinetochore proteins CENP-F and Bub1 is important for KSHV genome tethering and its segregation to new daughter cells (PMID:20660191)
• findings show phosphorylation of histone H3-threonine 3 mediated by Haspin cooperates with Bub1-mediated histone 2A-serine 121 phosphorylation in targeting the chromosomal passenger complex to the inner centromere in fission yeast and human cells (PMID:20929775)
• Bub1 expression could be regulated by estradiol and paclitaxel in endometrial carcinoma Ishikawa cells. (PMID:21092550)
• h-KNL1 functions to connect Bub1 and BubR1 with the hMis12, Ndc80, and Zwint-1 complexes. (PMID:21199919)
• Results establish that Bub1 has oncogenic properties and suggest that Aurora B is a critical target through which overexpressed Bub1 drives aneuploidization and tumorigenesis. (PMID:21646403)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	bub1	ENSDARG00000077029
mus_musculus	Bub1	ENSMUSG00000027379
rattus_norvegicus	Bub1	ENSRNOG00000032778
drosophila_melanogaster	Bub1	FBGN0031696
drosophila_melanogaster	BubR1	FBGN0263855
caenorhabditis_elegans	bub-1	WBGENE00000275
caenorhabditis_elegans	san-1	WBGENE00004721

Paralogs (1): BUB1B (ENSG00000156970)

Protein

Protein identifiers

Mitotic checkpoint serine/threonine-protein kinase BUB1 — O43683 (reviewed: O43683)

Alternative names: BUB1A

All UniProt accessions (6): A0A590UJ99, A0A590UK50, C9IYH4, C9JQA4, C9JRC7, O43683

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A. Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis.

Subunit / interactions. Interacts with BUB3 and KNL1. Interacts (when phosphorylated) with PLK1. The BUB1-BUB3 complex interacts with MAD1L1. (Microbial infection) Interacts with SV40 Large T antigen; this interaction induces activation of a DNA damage response and promotes p53/TP53 stabilization and phosphorylation. (Microbial infection) Interacts with herpes virus 8 protein LANA1.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Tissue specificity. High expression in testis and thymus, less in colon, spleen, lung and small intestine. Expressed in fetal thymus, bone marrow, heart, liver, spleen and thymus. Expression is associated with cells/tissues with a high mitotic index.

Post-translational modifications. Upon spindle-assembly checkpoint activation it is hyperphosphorylated and its kinase activity toward CDC20 is stimulated. Phosphorylation at Thr-609 is required for interaction with PLK1, phosphorylation at this site probably creates a binding site for the POLO-box domain of PLK1, thus enhancing the PLK1-BUB1 interaction. Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.

Disease relevance. Microcephaly 30, primary, autosomal recessive (MCPH30) [MIM:620183] A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH30 is characterized by small head, poor overall growth, and global developmental delay with variably impaired intellectual development. Affected individuals may also have variable congenital anomalies, including atrial septal defect, dysmorphic facial features, tracheal stenosis, and anomalies of the skin and teeth. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Autophosphorylated when the cells enters mitosis.

Domain organisation. The KEN box is required for its ubiquitination and degradation. BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.

Induction. Inhibited by phorbol 12-myristate 13-acetate (PMA).

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O43683-1	1	yes
O43683-2	2
O43683-3	3

RefSeq proteins (3): NP_001265545, NP_001265546, NP_004327* (*=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
IPR013212	Mad3/Bub1_I	Domain
IPR015661	Bub1/Mad3	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069, PF08311

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 (94 total): helix 25, strand 15, modified residue 13, mutagenesis site 11, sequence variant 7, region of interest 6, short sequence motif 3, domain 2, compositionally biased region 2, binding site 2, splice variant 2, sequence conflict 2, turn 2, chain 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7B1F	X-RAY DIFFRACTION	1.75
6F7B	X-RAY DIFFRACTION	2
4QPM	X-RAY DIFFRACTION	2.2
4R8Q	X-RAY DIFFRACTION	2.31
5DMZ	X-RAY DIFFRACTION	2.4
7B1H	X-RAY DIFFRACTION	2.4
4A1G	X-RAY DIFFRACTION	2.6
7B1J	X-RAY DIFFRACTION	2.9
2LAH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43683-F1	63.91	0.31

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): 917 (proton acceptor)

Ligand- & substrate-binding residues (2): 793–801; 821

Post-translational modifications (13): 307, 314, 331, 375, 525, 563, 593, 596, 609, 655, 661, 668, 672

Mutagenesis-validated functional residues (11):

Position	Phenotype
106	loss of interaction with knl1.
122	loss of interaction with knl1.
130	partial rescue of the spindle-assembly checkpoint activity. increased rate of chromosome congression errors. impaired lo
535	loss of ubiquitination and cdh1-dependent degradation; when associated with a-536 and a-537.
536	loss of ubiquitination and cdh1-dependent degradation; when associated with a-535 and a-537.
537	loss of ubiquitination and cdh1-dependent degradation; when associated with a-535 and a-536.
609	diminished interaction with plk1.
625	loss of ubiquitination and cdh1-dependent degradation; when associated with a-626 and a-627.
626	loss of ubiquitination and cdh1-dependent degradation; when associated with a-625 and a-627.
627	loss of ubiquitination and cdh1-dependent degradation; when associated with a-625 and a-626.
821	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 642 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GNF2_CKS1B, GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, MORF_ESPL1, TSENG_IRS1_TARGETS_UP, MORF_BUB1, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, MORF_RRM1

GO Biological Process (11): apoptotic process (GO:0006915), chromosome segregation (GO:0007059), regulation of sister chromatid cohesion (GO:0007063), mitotic spindle assembly checkpoint signaling (GO:0007094), cell division (GO:0051301), meiotic sister chromatid cohesion, centromeric (GO:0051754), regulation of chromosome segregation (GO:0051983), positive regulation of maintenance of mitotic sister chromatid cohesion, centromeric (GO:2000720), chromatin remodeling (GO:0006338), protein phosphorylation (GO:0006468), intracellular signal transduction (GO:0035556)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), histone H2A kinase activity (GO:0140995), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): kinetochore (GO:0000776), outer kinetochore (GO:0000940), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane (GO:0016020), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of cell cycle process	2
protein kinase activity	2
intracellular membraneless organelle	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell cycle process	1
sister chromatid cohesion	1
regulation of chromosome organization	1
mitotic cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
cellular process	1
meiotic sister chromatid cohesion	1
centromeric sister chromatid cohesion	1
chromosome segregation	1
positive regulation of maintenance of mitotic sister chromatid cohesion	1
maintenance of mitotic sister chromatid cohesion, centromeric	1
regulation of maintenance of mitotic sister chromatid cohesion, centromeric	1
chromatin organization	1
phosphorylation	1
protein modification process	1
intracellular anatomical structure	1
signal transduction	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
histone kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
condensed chromosome, centromeric region	1
supramolecular complex	1
kinetochore	1

Protein interactions and networks

STRING

3274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BUB1	BUB3	O43684	999
BUB1	CDC20	Q12834	993
BUB1	BUB1B	O60566	989
BUB1	AURKB	Q96GD4	985
BUB1	KNL1	Q8NG31	972
BUB1	CCNB2	O95067	970
BUB1	CDK1	P06493	964
BUB1	KIF2C	Q99661	964
BUB1	TTK	P33981	946
BUB1	MAD2L1	Q13257	940
BUB1	SGO1	Q5FBB7	938
BUB1	PLK1	P53350	937
BUB1	CENPE	Q02224	935
BUB1	ESPL1	Q14674	919
BUB1	CENPF	P49454	904

IntAct

129 interactions, top by confidence:

A	B	Type	Score
BUB3	BUB1	psi-mi:“MI:0915”(physical association)	0.800
BUB1	BUB3	psi-mi:“MI:0915”(physical association)	0.800
BUB1	BUB1B	psi-mi:“MI:0915”(physical association)	0.750
BUB1	ARIH2	psi-mi:“MI:0915”(physical association)	0.740
CDC20	BUB1	psi-mi:“MI:0914”(association)	0.730
BUB1	KNL1	psi-mi:“MI:0915”(physical association)	0.690
BUB3	ZNF207	psi-mi:“MI:0914”(association)	0.690
BUB1	KNL1	psi-mi:“MI:0407”(direct interaction)	0.680
BUB1	NDC80	psi-mi:“MI:0914”(association)	0.670
BUB1	NDC80	psi-mi:“MI:0915”(physical association)	0.670
HSF1	KPNA3	psi-mi:“MI:0914”(association)	0.640
CRK	BUB1	psi-mi:“MI:0407”(direct interaction)	0.590
BUB1	CRK	psi-mi:“MI:0915”(physical association)	0.590
Cdc20	BUB1	psi-mi:“MI:0914”(association)	0.560
Cdc20	BUB1	psi-mi:“MI:0915”(physical association)	0.560
MAP1LC3B	BUB1	psi-mi:“MI:0407”(direct interaction)	0.540
MAP1LC3B	BUB1	psi-mi:“MI:0915”(physical association)	0.540
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
BRINP3	BUB1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530

BioGRID (215): BUB3 (Two-hybrid), BUB1 (Affinity Capture-RNA), BUB1 (Affinity Capture-MS), BUB1 (Affinity Capture-MS), BUB1 (Affinity Capture-MS), BUB1B (Affinity Capture-MS), CASC5 (Affinity Capture-MS), CDC20 (Affinity Capture-MS), RAE1 (Affinity Capture-MS), RABL6 (Affinity Capture-MS), BPTF (Affinity Capture-MS), MIS12 (Affinity Capture-MS), CRK (Two-hybrid), ARIH2 (Two-hybrid), CDC20 (Protein-peptide)

ESM2 similar proteins: A0MZ66, A2APB8, A4IG59, A4IH24, A5A6J4, A6H6Z7, B0BM24, E2RYF8, E7F7X0, F4I2H7, O13024, O43683, O60566, O95990, P13505, P14317, P92204, Q0IHP2, Q28E45, Q2KI00, Q32N93, Q3B820, Q3TGF2, Q5EAW4, Q5NVP3, Q5RAF2, Q5U4F3, Q62736, Q659C4, Q66KE9, Q68FU8, Q6AY14, Q6DDV8, Q6NUF4, Q6PKG0, Q78TU8, Q7L590, Q84ZT9, Q8CB59, Q8CH02

Diamond homologs: F4IVI0, F4J6F6, O08901, O22806, O43683, O94324, O94751, P41695, P47074, P92199, Q852L0, Q8LPI7, Q93Z18, O59767, P06244, Q21776, Q54CV5, Q5Q0U5, Q822K5, O60566, Q9Z1S0

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
BUB1	up-regulates	PLK1	binding
CDK1	up-regulates	BUB1	phosphorylation
KNL1	up-regulates	BUB1	binding
BUB1	up-regulates	Mitotic_checkpoint
ATM	up-regulates	BUB1	phosphorylation
BUB1	“down-regulates activity”	CDC20	phosphorylation
BUB1	unknown	H2AC11	phosphorylation
TTK	“up-regulates activity”	BUB1	phosphorylation
BUB1	“up-regulates quantity by stabilization”	SGO1	phosphorylation
AURKB	“up-regulates activity”	BUB1	phosphorylation
PLK1	“up-regulates activity”	BUB1	phosphorylation
BUB1	“up-regulates activity”	STAT3	phosphorylation
BUB1	“up-regulates activity”	TP53	phosphorylation
BUB1	“up-regulates activity”	CENPE	relocalization
BUB1	“up-regulates activity”	MAD1L1	relocalization
BUB1	“up-regulates activity”	MAD2L1	relocalization
BUB1	“up-regulates activity”	BUB3	relocalization
BUB1	“up-regulates activity”	BUB1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 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
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	5	38.7×	5e-06
Inactivation of APC/C via direct inhibition of the APC/C complex	5	31.6×	1e-05
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	6	30.9×	2e-06
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	6	29.8×	2e-06
APC/C-mediated degradation of cell cycle proteins	7	28.7×	3e-07
Regulation of mitotic cell cycle	7	28.7×	3e-07
Regulation of APC/C activators between G1/S and early anaphase	7	26.4×	4e-07
APC/C:Cdc20 mediated degradation of mitotic proteins	6	26.1×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
attachment of spindle microtubules to kinetochore	5	43.3×	2e-05
mitotic spindle assembly checkpoint signaling	8	41.6×	1e-08
mitotic sister chromatid segregation	6	26.8×	2e-05
regulation of mitotic cell cycle	5	11.2×	7e-03
insulin receptor signaling pathway	5	10.3×	8e-03
MAPK cascade	7	9.9×	1e-03
canonical Wnt signaling pathway	7	9.9×	1e-03
protein-containing complex assembly	7	7.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1540 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	971
Likely benign	507
Benign	9

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1806482	NM_004336.5(BUB1):c.2625+1G>A	Pathogenic
1806483	NM_004336.5(BUB1):c.2197dup (p.Ala733fs)	Pathogenic
1808718	GRCh37/hg19 2q13(chr2:111366256-113127751)x1	Pathogenic
2684642	GRCh37/hg19 2q12.2-13(chr2:107029681-113127751)x1	Pathogenic
6759	NM_004336.5(BUB1):c.3069del (p.His1024fs)	Pathogenic
7082	NM_004336.5(BUB1):c.422+1G>A	Pathogenic
7083	NM_004336.5(BUB1):c.1475C>A (p.Ser492Tyr)	Pathogenic
3377649	NM_004336.5(BUB1):c.1430dup (p.Pro478fs)	Likely pathogenic

SpliceAI

3391 predictions. Top by Δscore:

Variant	Effect	Δscore
2:110639734:ATACT:A	donor_loss	1.0000
2:110639737:CTCA:C	donor_loss	1.0000
2:110639738:TCACC:T	donor_loss	1.0000
2:110639739:CA:C	donor_loss	1.0000
2:110639740:A:C	donor_loss	1.0000
2:110639741:C:CT	donor_loss	1.0000
2:110641634:ATACT:A	donor_loss	1.0000
2:110641635:TACTT:T	donor_loss	1.0000
2:110641636:ACTT:A	donor_loss	1.0000
2:110641638:TTA:T	donor_loss	1.0000
2:110641640:A:AC	donor_gain	1.0000
2:110641640:ACTA:A	donor_loss	1.0000
2:110641641:C:CA	donor_gain	1.0000
2:110641641:CT:C	donor_gain	1.0000
2:110641641:CTA:C	donor_gain	1.0000
2:110641641:CTAA:C	donor_gain	1.0000
2:110641641:CTAAT:C	donor_gain	1.0000
2:110642114:TTTA:T	donor_loss	1.0000
2:110642115:TTACC:T	donor_loss	1.0000
2:110642116:TACC:T	donor_loss	1.0000
2:110642117:ACCTT:A	donor_loss	1.0000
2:110642118:CCTT:C	donor_loss	1.0000
2:110642236:T:C	acceptor_gain	1.0000
2:110649379:T:C	acceptor_gain	1.0000
2:110649379:T:TC	acceptor_gain	1.0000
2:110649387:A:AC	acceptor_gain	1.0000
2:110650544:A:AC	donor_gain	1.0000
2:110650545:C:CC	donor_gain	1.0000
2:110650790:CG:C	acceptor_gain	1.0000
2:110650791:G:GC	acceptor_gain	1.0000

AlphaMissense

7212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:110638140:A:G	W1028R	0.997
2:110638140:A:T	W1028R	0.997
2:110641152:T:A	D946V	0.996
2:110642119:C:A	K821N	0.996
2:110642119:C:G	K821N	0.996
2:110641139:A:C	S950R	0.995
2:110641139:A:T	S950R	0.995
2:110641141:T:G	S950R	0.995
2:110641782:A:G	W829R	0.995
2:110641782:A:T	W829R	0.995
2:110638004:A:G	L1073P	0.994
2:110641681:A:C	S862R	0.994
2:110641681:A:T	S862R	0.994
2:110641683:T:G	S862R	0.994
2:110641152:T:G	D946A	0.993
2:110642188:A:C	F798L	0.993
2:110642188:A:T	F798L	0.993
2:110642190:A:G	F798L	0.993
2:110641076:A:C	F971L	0.992
2:110641076:A:T	F971L	0.992
2:110641078:A:G	F971L	0.992
2:110641151:G:C	D946E	0.992
2:110641151:G:T	D946E	0.992
2:110641333:T:A	K919N	0.992
2:110641333:T:G	K919N	0.992
2:110641104:A:G	F962S	0.991
2:110641045:A:G	W982R	0.989
2:110641045:A:T	W982R	0.989
2:110641331:G:T	P920Q	0.989
2:110641780:C:A	W829C	0.989

dbSNP variants (sampled 300 via entrez): RS1000014323 (2:110676294 G>A), RS1000016162 (2:110645176 G>A), RS1000231057 (2:110640425 T>C), RS1000263021 (2:110648196 A>T), RS1000276123 (2:110675941 A>G), RS1000349217 (2:110656407 C>T), RS1000422642 (2:110656863 T>C), RS1000455716 (2:110647873 T>C), RS1000620274 (2:110677643 G>A), RS1000733440 (2:110648571 C>T), RS1000882657 (2:110677483 T>C), RS1001265477 (2:110665459 T>C), RS1001295322 (2:110653204 T>C), RS1001354213 (2:110658565 T>A,C), RS1001387956 (2:110670371 C>T)

Disease associations

OMIM: gene MIM:602452 | disease phenotypes: MIM:114500, MIM:620183

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 30, primary, autosomal recessive	Moderate	Autosomal recessive
mosaic variegated aneuploidy syndrome	Supportive	Autosomal dominant
familial colorectal cancer	Limited	Autosomal dominant
colorectal cancer	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
colorectal cancer	Limited	AD

Mondo (6): colorectal cancer (MONDO:0005575), microcephaly 30, primary, autosomal recessive (MONDO:0859342), colon carcinoma (MONDO:0002032), psychotic disorder (MONDO:0005485), familial colorectal cancer (MONDO:0023113), mosaic variegated aneuploidy syndrome (MONDO:0000141)

Orphanet (1): NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000062	Ambiguous genitalia
HP:0000175	Cleft palate
HP:0000185	Cleft soft palate
HP:0000201	Pierre-Robin sequence
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000325	Triangular face
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000445	Wide nose
HP:0000452	Choanal stenosis
HP:0000457	Depressed nasal ridge
HP:0000478	Abnormality of the eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000637	Long palpebral fissure
HP:0000821	Hypothyroidism
HP:0000924	Abnormality of the skeletal system
HP:0000929	Abnormal skull morphology

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536987	Mosaic variegated aneuploidy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1772932 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 199,101 (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
CHEMBL3301622	GILTERITINIB	4	2,395
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL1088752	LOSMAPIMOD	3	865
CHEMBL2087361	ICOTINIB	3	2,802
CHEMBL495727	AT-9283	2	1,376
CHEMBL564829	MILCICLIB	2	821
CHEMBL3545328	XL-019	1	715
CHEMBL482967	CYC-116	1	651
CHEMBL598797	CUDC-101	1	2,156

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Bub family

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
compound 2-1-1 [PMID: 24900824]	Inhibition	8.3	pIC50
compound 2-3-2 [PMID: 24900824]	Inhibition	8.22	pIC50
compound 2-3-1 [PMID: 24900824]	Inhibition	8.05	pIC50
compound 2-13-1 [PMID: 24900824]	Inhibition	7.52	pIC50
BAY-524	Inhibition	6.35	pIC50
BAY-320	Inhibition	6.17	pIC50

Binding affinities (BindingDB)

593 measured of 711 human assays (711 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[3-[[2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl]oxymethyl]oxetan-3-yl]methanol	IC50	2.4 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[1-[(6-chloro-2-fluoro-3-methylphenyl)methyl]indazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	2.6 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[1-[(2,6-difluoro-3-methoxyphenyl)methyl]indazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	2.6 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
3-anilino-6-prop-2-enyl-2-pyridin-4-yl-1,5,6,7-tetrahydroindol-4-one	IC50	3 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
1-[3,5-difluoro-4-[[3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]indazol-1-yl]methyl]phenyl]ethanone	IC50	3 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
[3-[[2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl]oxymethyl]oxetan-3-yl]methanol	IC50	3.3 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl]oxyethanol	IC50	3.3 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
Preparation of 5-(2-aminoethoxy)-2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine	IC50	3.4 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[1-(4-ethoxy-2,6- difluorobenzyl)-1H- indazol-3-yl]-5- (morpholin-2- ylmethoxy)-N- (pyridin-4- yl)pyrimidin-4-amine	IC50	3.4 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[1-[(4-cyclopropyl-2,6-difluorophenyl)methyl]indazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	3.9 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
(6RS)-6-[(Ethylsulfanyl)methyl]-3-(phenylamino)-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one	IC50	4 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(6R)-3-anilino-6-(2-hydroxypropan-2-yl)-2-pyridin-4-yl-1,5,6,7-tetrahydroindol-4-one	IC50	4 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(4aS,5aS)-3-anilino-2-pyridin-4-yl-4a,5,5a,6-tetrahydro-1H-cyclopropa[f]indol-4-one	IC50	4 nM	US-10308629: 1H-pyrrol-3-amines
N-[4-[(4aR,5aR)-3-anilino-5a-methyl-4-oxo-1,4a,5,6-tetrahydrocyclopropa[f]indol-2-yl]-2-pyridinyl]-2,6-difluorobenzamide	IC50	4 nM	US-10308629: 1H-pyrrol-3-amines
2-[1-[(2-chloro-4,5-dimethylphenyl)methyl]indazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	4.4 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[(E)-[(2,6-difluoro-3-methoxyphenyl)methyl-phenylhydrazinylidene]methyl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	4.5 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
1-[(4-ethoxy-2,6-difluorophenyl)methyl]-N’-[(E)-2-methoxy-1-(pyridin-4-ylamino)ethenyl]-N-methylideneindazole-3-carboximidamide	IC50	4.6 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
(2R)-3-[2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl]oxypropane-1,2-diol	IC50	4.6 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
N-[4-[3-anilino-6-(chloromethyl)-4-oxo-1,5,6,7-tetrahydroindol-2-yl]-2-pyridinyl]acetamide	IC50	4.61 nM	US-10428044: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
4-({2-[4-chloro-5-cyclopropyl-1-(4-ethoxy-2,6-difluorobenzyl)-1H-pyrazol-3-yl]pyrimidin-4-yl}amino)-N-methylnicotinamide	IC50	4.7 nM	US-9765058: Substituted benzylpyrazoles
2-[1-[(2-chloro-4-methoxyphenyl)methyl]indazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	4.7 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol	IC50	4.7 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
4-({2-[1-(2- fluorobenzyl)- 1H-indazol-3-yl]- 5-(2- hydroxyethoxy)- pyrimidin-4- yl}amino)-N- methylpyridine- 3-carboxamide	IC50	4.7 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
1-[(2,6-difluorophenyl)methyl]-3-(5-methoxypyrimidin-2-yl)indazole	IC50	4.8 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
(2S)-3-[2-[1-[(2-fluorophenyl)methyl]indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl]oxypropane-1,2-diol	IC50	4.8 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]indazol-3-yl]-5-(2-methylsulfinylethoxy)-N-pyridin-4-ylpyrimidin-4-amine	IC50	4.91 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
(6RS)-6-Ethenyl-3-(phenylamino)-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one	IC50	5 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(6RS)-3-(Phenylamino)-6-[(propan-2-ylsulfanyl)methyl]-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one	IC50	5 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(6RS)—N-Methyl-N-(2-methylpropyl)-4-oxo-3-(phenylamino)-2-(pyridin-4-yl)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide	IC50	5 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
Methyl (6RS)-2-[3-(2-methoxyethoxy)pyridin-4-yl]-4-oxo-3-(phenylamino)-4,5,6,7-tetrahydro-1H-indol-6-carboxylate	IC50	5 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(6RS)-2-2-[(4-Fluorobenzoyl)amino]pyridin-4-yl-N,N-dimethyl-4-oxo-3-(phenylamino)-4,5,6,7-tetrahydro-1H-indol-6-carboxamide	IC50	5 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(6S)-3-anilino-2-(3-fluoro-4-pyridinyl)-N,N-dimethyl-4-oxo-1,5,6,7-tetrahydroindole-6-carboxamide	IC50	5 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
3-anilino-6-(2-hydroxypropan-2-yl)-2-pyridin-4-yl-1,5,6,7-tetrahydroindol-4-one	IC50	5 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(4aR,5aR)-3-anilino-5a-methyl-2-pyridin-4-yl-1,4a,5,6-tetrahydrocyclopropa[f]indol-4-one	IC50	5 nM	US-10308629: 1H-pyrrol-3-amines
N-[4-[(7R)-3-anilino-7-methyl-4-oxo-5,6,7,8-tetrahydro-1H-cyclohepta[b]pyrrol-2-yl]-2-pyridinyl]acetamide	IC50	5 nM	US-10308629: 1H-pyrrol-3-amines
4-({2-[1-(2,6- difluoro-4- hydroxybenzyl)-1H- indazol-3-yl]-5- methoxypyrimidin-4- yl}amino)pyridine-3- carboxamide	IC50	5.03 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
trans-(1R,2S)-N-[4-(3-anilino-6,6-dimethyl-4-oxo-5,7-dihydro-1H-indol-2-yl)-2-pyridinyl]-2-fluorocyclopropane-1-carboxamide	IC50	5.03 nM	US-10428044: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
3-anilino-6-(chloromethyl)-2-pyridin-4-yl-1,5,6,7-tetrahydroindol-4-one	IC50	5.05 nM	US-10428044: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]indazol-3-yl]-N-pyridin-4-ylpyrimidin-4-amine	IC50	5.2 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
Preparation of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine hydrochloride (1:1)	IC50	5.2 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
1-[2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl]oxy-3-piperidin-1-ylpropan-2-ol	IC50	5.4 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
4-({5-methoxy-2-[1- (4-propylbenzyl)- 1H-indazol-3- yl]pyrimidin-4- yl}amino)pyridine-3- carboxamide	IC50	5.4 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
2-[1-[(2,6-difluoro-3-methylphenyl)methyl]indazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	5.5 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
3-anilino-6-propan-2-yl-2-pyridin-4-yl-1,5,6,7-tetrahydroindol-4-one	IC50	5.57 nM	US-10428044: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
2-[4-chloro-5-cyclopropyl-1-(4-ethoxy-2,6-difluorobenzyl)-1H-pyrazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amine	IC50	5.6 nM	US-9765058: Substituted benzylpyrazoles
2-[1-[[4-(difluoromethoxy)-2,6-difluorophenyl]methyl]indazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	IC50	5.6 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
Preparation of 2-[1-(4-ethoxy-2,6-difluorobenzyl)-1H-indazol-3-yl]-5-[2-(methylsulfonyl)ethoxy]-N-(pyridin-4-yl)pyrimidin-4-amine	IC50	5.7 nM	US-10266548: Substituted benzylindazoles for use as Bub1 kinase inhibitors in the treatment of hyperproliferative diseases
Preparation of 6-ethyl-3-(phenylamino)-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one	IC50	5.93 nM	US-10428044: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
(6RS)-6-[(Ethylsulfonyl)methyl]-3-(phenylamino)-2-(pyridin-4-yl)-1,5,6,7-tetrahydro-4H-indol-4-one	IC50	6 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones
Methyl (6RS)-2-2-[(4-fluorobenzoyl)amino]pyridin-4-yl-4-oxo-3-(phenylamino)-4,5,6,7-tetrahydro-1H-indol-6-carboxylate	IC50	6 nM	US-10227299: 3-amino-1,5,6,7-tetrahydro-4H-indol-4-ones

ChEMBL bioactivities

1138 potent at pChembl≥5 of 1153 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL5084426
8.89	IC50	1.3	nM	CHEMBL5084426
8.68	Kd	2.1	nM	CHEMBL5084426
8.62	IC50	2.4	nM	CHEMBL6062775
8.59	IC50	2.6	nM	CHEMBL5783916
8.59	IC50	2.6	nM	CHEMBL5855460
8.59	IC50	2.58	nM	CHEMBL5839408
8.52	IC50	3	nM	CHEMBL5882408
8.52	IC50	3	nM	CHEMBL6023600
8.52	IC50	3	nM	CHEMBL5939177
8.48	Kd	3.3	nM	CHEMBL5084426
8.48	IC50	3.3	nM	CHEMBL5084426
8.48	IC50	3.3	nM	CHEMBL5887250
8.48	IC50	3.3	nM	CHEMBL5823098
8.47	IC50	3.4	nM	CHEMBL5981039
8.47	IC50	3.4	nM	CHEMBL5859564
8.47	IC50	3.35	nM	CHEMBL5996908
8.46	IC50	3.45	nM	CHEMBL5824886
8.45	IC50	3.55	nM	CHEMBL5964570
8.41	IC50	3.9	nM	CHEMBL6026096
8.40	IC50	4	nM	CHEMBL5758090
8.40	IC50	4	nM	CHEMBL5966205
8.40	IC50	4	nM	CHEMBL5905008
8.40	IC50	4	nM	CHEMBL5970251
8.40	IC50	4	nM	CHEMBL5863089
8.40	IC50	4	nM	CHEMBL5831228
8.40	IC50	3.96	nM	CHEMBL5934271
8.39	IC50	4.04	nM	CHEMBL5928383
8.37	IC50	4.3	nM	CHEMBL5084426
8.37	IC50	4.23	nM	CHEMBL5827652
8.36	IC50	4.4	nM	CHEMBL5789895
8.36	IC50	4.38	nM	CHEMBL5923078
8.35	IC50	4.5	nM	CHEMBL5910836
8.35	IC50	4.52	nM	CHEMBL5838069
8.35	IC50	4.49	nM	CHEMBL5978396
8.34	IC50	4.6	nM	CHEMBL5882079
8.34	IC50	4.6	nM	CHEMBL6004380
8.34	IC50	4.61	nM	CHEMBL5807771
8.33	IC50	4.7	nM	CHEMBL6037720
8.33	IC50	4.7	nM	CHEMBL6058399
8.33	IC50	4.7	nM	CHEMBL5902891
8.33	IC50	4.7	nM	CHEMBL5793847
8.32	IC50	4.8	nM	CHEMBL6035819
8.32	IC50	4.8	nM	CHEMBL5870041
8.31	IC50	4.91	nM	CHEMBL5817709
8.30	IC50	5	nM	CHEMBL3260324
8.30	IC50	5	nM	CHEMBL5758924
8.30	IC50	5	nM	CHEMBL5786113
8.30	IC50	5	nM	CHEMBL6065158
8.30	IC50	5	nM	CHEMBL5878626

PubChem BioAssay actives

19 with measured affinity, of 280 total; 19 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-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]-5-methoxy-N-pyridin-4-ylpyrimidin-4-amine	1137947: Inhibition of Bub1 kinase (unknown origin) by TR-FRET kinase assay	ic50	0.0050	uM
[3-[[2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl]oxymethyl]oxetan-3-yl]methanol	1137947: Inhibition of Bub1 kinase (unknown origin) by TR-FRET kinase assay	ic50	0.0060	uM
5-[2-(dimethylamino)ethoxy]-2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]-N-pyridin-4-ylpyrimidin-4-amine	1137947: Inhibition of Bub1 kinase (unknown origin) by TR-FRET kinase assay	ic50	0.0090	uM
4-[[2-[1-[(2-fluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]-5-(2-methylsulfonylethoxy)pyrimidin-4-yl]amino]pyridine-3-carboxamide	1137947: Inhibition of Bub1 kinase (unknown origin) by TR-FRET kinase assay	ic50	0.0300	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147963: Binding affinity to human BUB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0825	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0940	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1110	uM
Erlotinib	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1130	uM
Gilteritinib	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1910	uM
3-[[(1R,2S)-2-aminocyclohexyl]amino]-5-(1H-indol-7-ylamino)-1,2,4-triazine-6-carboxamide	1199663: Competitive binding affinity to human BUB1	kd	0.2400	uM
N-[4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]phenyl]pyrrolidine-2-carboxamide	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3900	uM
4-(cyclopropylamino)-2-[4-(4-ethylsulfonylpiperazin-1-yl)anilino]pyrimidine-5-carboxamide;hydrochloride	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4370	uM
ethyl 4-[[5-(2-ethoxycarbonylphenoxy)-2-[1-[(2-fluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]pyrimidin-4-yl]amino]pyridine-3-carboxylate	1137947: Inhibition of Bub1 kinase (unknown origin) by TR-FRET kinase assay	ic50	0.5000	uM
7-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyheptanamide	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.9610	uM
6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-N-(2,2-dimethylpropyl)pyridine-3-carboxamide	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.9210	uM
4-[[2-[1-[(2-fluorophenyl)methyl]-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]-5-(2-hydroxyethoxy)pyrimidin-4-yl]-(2-hydroxyethyl)amino]pyridine-3-carboxamide	1137947: Inhibition of Bub1 kinase (unknown origin) by TR-FRET kinase assay	ic50	2.0000	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.7090	uM
N-(3-ethynylphenyl)-2,5,8,11-tetraoxa-15,17-diazatricyclo[10.8.0.014,19]icosa-1(12),13,15,17,19-pentaen-18-amine	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.9120	uM
Sunitinib	1424926: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.5070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	4
Quercetin	affects cotreatment, increases expression, decreases expression, decreases phosphorylation	4
Valproic Acid	decreases expression, increases expression	4
bisphenol A	affects expression, decreases expression	3
Acetaminophen	decreases expression, increases expression	3
Cisplatin	affects expression, decreases expression, affects cotreatment	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
methylmercuric chloride	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
chromium hexavalent ion	increases abundance, decreases reaction, increases phosphorylation, decreases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Cadmium	decreases expression	2
Caffeine	affects cotreatment, increases expression, increases phosphorylation	2
Doxorubicin	decreases expression	2
Tretinoin	decreases expression	2
Tunicamycin	decreases expression	2
Zinc	increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Vitamin K 3	affects expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1

ChEMBL screening assays

86 unique, capped per target: 84 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1072193	Binding	Inhibition of BUB1	Identification of potent pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinase inhibitors. — J Med Chem
CHEMBL5444420	Functional	Affinity Phenotypic Cellular interaction: (Cell-proliferation assay (crystal violet, median anti-proliferative activity against 43 human and mouse tumor cell lines)) EUB0001548a BUB1	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5400	VACO 400	Cancer cell line	Male
CVCL_5401	VACO 429	Cancer cell line	Male
CVCL_B1LN	Abcam HeLa BUB1 KO	Cancer cell line	Female
CVCL_SF93	HAP1 BUB1 (-) 1	Cancer cell line	Male
CVCL_SF94	HAP1 BUB1 (-) 2	Cancer cell line	Male
CVCL_SF95	HAP1 BUB1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	PHASE4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer