KIF11

Summary

KIF11 (kinesin family member 11, HGNC:6388) is a protein-coding gene on chromosome 10q23.33, encoding Kinesin-like protein KIF11 (P52732). Motor protein required for establishing a bipolar spindle and thus contributing to chromosome congression during mitosis. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis.

Source: NCBI Gene 3832 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 1,053 total — 132 pathogenic, 53 likely-pathogenic
• Phenotypes (HPO): 95
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6388
Approved symbol	KIF11
Name	kinesin family member 11
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	Eg5, HKSP, TRIP5
Ensembl gene	ENSG00000138160
Ensembl biotype	protein_coding
OMIM	148760
Entrez	3832

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

ENST00000260731, ENST00000676621, ENST00000676647, ENST00000676757, ENST00000677720, ENST00000937277, ENST00000937278

RefSeq mRNA: 1 — MANE Select: NM_004523 NM_004523

CCDS: CCDS7422

Canonical transcript exons

ENST00000260731 — 22 exons

Exon	Start	End
ENSE00000932880	92648212	92648434
ENSE00000986575	92593130	92593452
ENSE00000986592	92645363	92645642
ENSE00000986593	92649835	92649986
ENSE00000986594	92650401	92650517
ENSE00000986595	92653665	92655395
ENSE00001007273	92613377	92613619
ENSE00001007274	92616737	92616832
ENSE00001007275	92628808	92628895
ENSE00001007276	92613040	92613130
ENSE00001007277	92607159	92607237
ENSE00001007278	92609020	92609205
ENSE00001007279	92639794	92639900
ENSE00001007280	92637387	92637545
ENSE00001007281	92633623	92633795
ENSE00001007282	92621385	92621473
ENSE00001007283	92606619	92606716
ENSE00001007284	92632486	92632693
ENSE00001007285	92630176	92630364
ENSE00001007286	92609385	92609509
ENSE00001007287	92637184	92637309
ENSE00001007288	92606265	92606397

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 97.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.0686 / max 354.5567, expressed in 1620 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106243	13.2907	1411
106242	2.8416	923
106241	1.0570	606
106239	0.8221	420
106244	0.7242	416
106245	0.2737	128
106240	0.0592	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.84	gold quality
ganglionic eminence	UBERON:0004023	94.06	gold quality
embryo	UBERON:0000922	92.33	gold quality
secondary oocyte	CL:0000655	90.76	gold quality
endometrium epithelium	UBERON:0004811	90.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.50	gold quality
bone marrow	UBERON:0002371	84.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.01	gold quality
trabecular bone tissue	UBERON:0002483	83.82	gold quality
esophagus squamous epithelium	UBERON:0006920	82.68	gold quality
bone marrow cell	CL:0002092	81.71	gold quality
stromal cell of endometrium	CL:0002255	80.56	gold quality
oocyte	CL:0000023	79.73	gold quality
gingival epithelium	UBERON:0001949	79.42	gold quality
rectum	UBERON:0001052	78.81	gold quality
epithelium of esophagus	UBERON:0001976	78.65	gold quality
vermiform appendix	UBERON:0001154	78.57	gold quality
adrenal tissue	UBERON:0018303	78.08	gold quality
oral cavity	UBERON:0000167	77.09	gold quality
esophagus mucosa	UBERON:0002469	76.84	gold quality
squamous epithelium	UBERON:0006914	76.37	gold quality
gingiva	UBERON:0001828	76.18	gold quality
mucosa of transverse colon	UBERON:0004991	76.07	gold quality
amniotic fluid	UBERON:0000173	75.39	gold quality
testis	UBERON:0000473	75.21	gold quality
lymph node	UBERON:0000029	75.08	gold quality
thymus	UBERON:0002370	75.01	gold quality
right testis	UBERON:0004534	74.62	gold quality
caecum	UBERON:0001153	74.31	gold quality
tongue squamous epithelium	UBERON:0006919	73.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	8.54
E-ANND-3	yes	6.98
E-MTAB-6819	no	733.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN

miRNA regulators (miRDB)

106 targeting KIF11, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-579-3P	99.86	71.66	3628

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• ATPase pathway for monomeric Eg5 is more similar to conventional kinesin than the spindle motors Ncd and Kar3, where ADP product release is rate-limiting for steady-state turnover (PMID:15247293)
• Monastrol causes aberrant interactions with the microtubule, and reversals at the ATP hydrolysis step which alter the ability of Eg5 to generate force, thereby yielding a nonproductive Mt.Eg5 complex that cannot establish or maintain the bipolar spindle (PMID:15665380)
• model of movement of the mitotic motor Eg5 (PMID:16115880)
• L5 may be an element in the pathway that links the state of the nucleotide-binding site to the neck linker in Eg5 kinesin motors (PMID:16434397)
• The Eg5-513-5His velocity data were described by a minimal, three-state model where a force-dependent transition follows nucleotide binding. (PMID:16604065)
• Data show that the Eg5-513 dimer binds microtubules with both heads to two adjacent tubulin heterodimers along the same microtubule protofilament, and that this binding is inhibited by monastrol. (PMID:16642039)
• Eg5 is downstream of and regulated by Bcr-Abl tyrosine kinase in Philadelphia chromosome positive cells. Inhibition of Eg5 expression or its activity blocks cell cycle progression and induces cell death independent of the cellular response to Imatinib (PMID:16969080)
• microtubule-Eg5 complex binds MgATP tightly, followed by rapid ATP hydrolysis with a subsequent slow step that limits steady-state turnover. (PMID:17014086)
• dimeric Eg5 is the first kinesin motor identified to have a rate-limiting ATP hydrolysis step (PMID:17062577)
• Inhibition of KSP induces apoptosis independently of p53 and that p53 is dispensable for spindle checkpoint function. Thus, KSP inhibitors should be active in p53-deficient tumors. (PMID:17101792)
• Crystal structure (2.7A) of the complex between human Eg5 and a new keto derivative of monastrol (named mon-97), a potent antimitotic inhibitor. (PMID:17251189)
• Single-nucleotide polymorphisms in the KIF11 gene are associated with susceptibility to type 2 diabetes across the boundary of race. (PMID:17971426)
• characterization of selective ATP competitive inhibitors of the human mitotic kinesin KSP (PMID:17999913)
• Dimeric Eg5 appears to undergo a conformational change shortly after collision with the microtubule that primes the motor for its characteristically short processive runs (PMID:18037705)
• The cocrystal structure of the motor domain of HsEg5 in complex with CK0238273 at a 2.15 A resolution was reported. (PMID:18503753)
• The Eg5 gene, a member of the kinesin-5 family, plays critical roles in proper mitotic spindle function, and is a potential microtubule-related target for proliferating cancer cells. (PMID:18512732)
• The neck linker and the neck are involved not only in motility generation in general and in determination of movement direction, but also in velocity regulation. (PMID:18640125)
• These results suggest possible involvement of XB-S in the function of Eg5. (PMID:18679583)
• the rotational pitch of microtubule sliding conveniently reports on the processivity of the driving motors, confirming that two-headed Eg5 is much less processive than two-headed kinesin-1 (PMID:18806799)
• a novel function for Parkin in modulating the expression of Eg5 through the Hsp70-JNK-c-Jun signaling pathway. (PMID:18845538)
• KIF11 is critical for proper spindle assembly in the area of cell cycle inhibition (PMID:19545421)
• KIF11 inhibitor, ARRY-520, as a substitute for Paclitaxel in type I ovarian cancer cells is reported. (PMID:19619321)
• Data show the crystal structure of the Eg5 motor domain complexed with a potent antimitotic inhibitor STLC (S-trityl-L-cysteine) to 2.0 A resolution. (PMID:19793049)
• analysis of a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses (PMID:19802393)
• The thermodynamic aspects of nucleotide and inhibitor (ispinesib and monastrol) binding to the motor domain of wild-type Eg5 and its D130V and A133D mutants were studied. (PMID:19824700)
• there is an association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes in the Chinese population (PMID:19862325)
• For the first time at a cellular level, the propensity of selected Eg5 point mutants to confer drug resistance confirms the target specificity of monastrol and S-trityl-L-cysteine for Eg5. (PMID:19896928)
• In a series of 428 psoriatic patients anti-hsEG5 (NuMA-2) autoantibodies were found only in a patient, at a titer of 1:640, without any apparent clinical relevance. (PMID:19951065)
• Data show that 4-oxo-4-HPR inhibited tubulin polymerization and modulated gene expression of spindle aberration associated genes Kif 1C, Kif 2A, Eg5, Tara, tankyrase-1, centractin, and TOGp. (PMID:19996280)
• ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism. (PMID:20018897)
• Eg5 kinesin has a role in ATP hydrolysis and structural transitions (PMID:20154092)
• Allosteric drug discrimination is coupled to mechanochemical changes in the kinesin-5 motor core (PMID:20299460)
• B23 regulates microtubule dynamics by directly inhibiting Eg5 ATPase activity (PMID:20404347)
• The results define the energy landscape of a kinesin ATPase cycle in the absence and presence of microtubules and shed light on the role of molecular motor mechanochemistry in cellular microtubule dynamics. (PMID:20558732)
• Binding to kinesin I ensures properly assembled and functioning Kv3.1 channels are transported into axons. (PMID:21106837)
• Loop L5 acts as a conformational latch in the mitotic kinesin Eg5. (PMID:21148480)
• correlates with poor differentiation of bladder cancer and represents an independent prognostic factor in predicting early intravesical recurrence in non-muscle invasive bladder carcinoma patients (PMID:21449971)
• The authors report that in G2 phase polo-like kinase 1 (Plk1) can trigger centrosome separation independently of Cdk1 by phosphorylating the motor protein Eg5. (PMID:21522128)
• Abeta impairs the assembly and maintenance of the mitotic spindle. Mechanistically, these defects result from Abeta’s inhibition of mitotic motor kinesins, including Eg5, KIF4A and MCAK. (PMID:21566458)
• Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. (PMID:21642957)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	kif11	ENSDARG00000010948
mus_musculus	Kif11	ENSMUSG00000012443
rattus_norvegicus	Kif11	ENSRNOG00000056069
drosophila_melanogaster	nod	FBGN0002948
drosophila_melanogaster	Klp61F	FBGN0004378
drosophila_melanogaster	CG32318	FBGN0052318
caenorhabditis_elegans		WBGENE00000257

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), KIF17 (ENSG00000117245), KIF14 (ENSG00000118193), KIF18A (ENSG00000121621), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), CENPE (ENSG00000138778), KIF21A (ENSG00000139116), KIFC3 (ENSG00000140859), KIF2B (ENSG00000141200), KIF2C (ENSG00000142945), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), KIF15 (ENSG00000163808), KIF6 (ENSG00000164627), KIF27 (ENSG00000165115), KIF7 (ENSG00000166813), KIFC2 (ENSG00000167702), KIF5C (ENSG00000168280), KIF5B (ENSG00000170759), KIF18B (ENSG00000186185), KIF24 (ENSG00000186638), KIF19 (ENSG00000196169), KIF13B (ENSG00000197892), KIF4B (ENSG00000226650)

Protein

Protein identifiers

Kinesin-like protein KIF11 — P52732 (reviewed: P52732)

Alternative names: Kinesin-like protein 1, Kinesin-like spindle protein HKSP, Kinesin-related motor protein Eg5, Thyroid receptor-interacting protein 5

All UniProt accessions (4): P52732, A0A7I2V3A9, A0A7I2V3V3, A0A7I2YQY4

UniProt curated annotations — full annotation on UniProt →

Function. Motor protein required for establishing a bipolar spindle and thus contributing to chromosome congression during mitosis. Required in non-mitotic cells for transport of secretory proteins from the Golgi complex to the cell surface.

Subunit / interactions. Interacts with the thyroid hormone receptor in the presence of thyroid hormone. Component of a large chromatin remodeling complex, at least composed of MYSM1, PCAF, RBM10 and KIF11/TRIP5. Interacts (via C-terminus) with the kinase NEK6 in both interphase and mitosis. Interacts with RARRES1 and AGBL2. Interacts with TPX2.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle pole.

Post-translational modifications. Phosphorylated exclusively on serine during S phase, but on both serine and Thr-926 during mitosis, so controlling the association of KIF11 with the spindle apparatus (probably during early prophase). A subset of this protein primarily localized at the spindle pole is phosphorylated by NEK6 during mitosis; phosphorylation is required for mitotic function. Ubiquitinated at Lys-1034 by UHRF1 via ‘Lys-63’-linked ubiquitin chains, leading to interaction with spindle assembly factor TPX2, thereby ensuring accurate distribution to the spindles during metaphase.

Disease relevance. Microcephaly with or without chorioretinopathy, lymphedema, or impaired intellectual development (MCLMR) [MIM:152950] An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. BimC subfamily.

RefSeq proteins (1): NP_004514* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR019821	Kinesin_motor_CS	Conserved_site
IPR025901	Kinesin-assoc_MT-bd_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily
IPR047149	KIF11-like	Family
IPR047241	KIF11-like_kin_motor_dom	Domain

Pfam: PF00225, PF13931

Enzyme classification (BRENDA):

• EC 5.6.1.3 — plus-end-directed kinesin ATPase (BRENDA: 34 organisms, 94 substrates, 257 inhibitors, 53 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	45
ALEXA FLUOR 647 ATP	0.032	1
METHYLANTHRANILOYL-ATP	0.0004	1
ADP	—	0
PHOSPHATE	—	0

UniProt features (64 total): strand 21, helix 17, sequence variant 5, modified residue 5, mutagenesis site 4, turn 4, cross-link 2, coiled-coil region 2, chain 1, domain 1, sequence conflict 1, binding site 1

Structure

Experimental structures (PDB)

62 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3ZCW	X-RAY DIFFRACTION	1.69
6TLE	X-RAY DIFFRACTION	1.75
1X88	X-RAY DIFFRACTION	1.8
6G6Y	X-RAY DIFFRACTION	1.8
2PG2	X-RAY DIFFRACTION	1.85
1Q0B	X-RAY DIFFRACTION	1.9
2X7C	X-RAY DIFFRACTION	1.9
8YHH	X-RAY DIFFRACTION	1.95
3K5E	X-RAY DIFFRACTION	1.97
2WOG	X-RAY DIFFRACTION	2
3L9H	X-RAY DIFFRACTION	2
5JV3	X-RAY DIFFRACTION	2.01
1II6	X-RAY DIFFRACTION	2.1
2FME	X-RAY DIFFRACTION	2.1
2UYI	X-RAY DIFFRACTION	2.1
2UYM	X-RAY DIFFRACTION	2.11
3HQD	X-RAY DIFFRACTION	2.19
2X2R	X-RAY DIFFRACTION	2.2
5ZO8	X-RAY DIFFRACTION	2.2
6TRL	X-RAY DIFFRACTION	2.2
3CJO	X-RAY DIFFRACTION	2.28
2FKY	X-RAY DIFFRACTION	2.3
2GM1	X-RAY DIFFRACTION	2.3
2X7D	X-RAY DIFFRACTION	2.3
4ZCA	X-RAY DIFFRACTION	2.3
4ZHI	X-RAY DIFFRACTION	2.3
2X7E	X-RAY DIFFRACTION	2.4
3K3B	X-RAY DIFFRACTION	2.4
4AS7	X-RAY DIFFRACTION	2.4
4A5Y	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52732-F1	74.46	0.17

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 (1): 105–112

Post-translational modifications (7): 477, 1034, 146, 458, 925, 926, 1033

Mutagenesis-validated functional residues (4):

Position	Phenotype
926	no mitotic phosphorylation. no binding to spindle apparatus.
1033	still binds to the mitotic spindle but mitotic progression is impaired.
1034	significantly diminished interaction with tpx2.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 578 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GNF2_CKS1B, GOBP_CHROMOSOME_ORGANIZATION, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, MORF_ESPL1, GNF2_CENPF, MORF_BUB1, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, PAL_PRMT5_TARGETS_UP, CROONQUIST_NRAS_SIGNALING_DN, TTTGTAG_MIR520D

GO Biological Process (11): mitotic cell cycle (GO:0000278), microtubule-based movement (GO:0007018), spindle organization (GO:0007051), mitotic spindle organization (GO:0007052), mitotic centrosome separation (GO:0007100), regulation of mitotic centrosome separation (GO:0046602), spindle elongation (GO:0051231), cell division (GO:0051301), mitotic spindle assembly (GO:0090307), spindle assembly (GO:0051225), mitotic nuclear division (GO:0140014)

GO Molecular Function (8): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), plus-end-directed microtubule motor activity (GO:0008574), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), protein binding (GO:0005515)

GO Cellular Component (16): spindle pole (GO:0000922), nucleus (GO:0005634), spindle (GO:0005819), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), membrane (GO:0016020), protein-containing complex (GO:0032991), ciliary basal body (GO:0036064), mitotic spindle (GO:0072686), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), spindle microtubule (GO:0005876)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Adaptive Immune System	1
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
mitotic nuclear division	3
spindle organization	3
spindle	3
sperm flagellum	3
microtubule-based process	2
cell cycle process	2
mitotic cell cycle	2
mitotic cell cycle process	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
cell cycle	1
microtubule cytoskeleton organization	1
microtubule cytoskeleton organization involved in mitosis	1
centrosome separation	1
mitotic centrosome separation	1
regulation of cell cycle process	1
nuclear chromosome segregation	1
cellular process	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
chromosome segregation	1
membraneless organelle assembly	1
nuclear division	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
microtubule motor activity	1
kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
microtubule associated complex	1

Protein interactions and networks

STRING

3372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF11	DLGAP5	Q15398	922
KIF11	BUB1B	O60566	875
KIF11	CDK1	P06493	869
KIF11	CDC20	Q12834	825
KIF11	HHEX	Q03014	824
KIF11	AURKA	O14965	817
KIF11	AURKB	Q96GD4	804
KIF11	CKAP5	Q14008	802
KIF11	DCTN1	Q14203	802
KIF11	SLC30A8	Q8IWU4	791
KIF11	TPX2	Q9ULW0	790
KIF11	PLK1	P53350	776
KIF11	MAD2L1	Q13257	775
KIF11	BUB1	O43683	774
KIF11	CCNB1	P14635	763

IntAct

96 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TFDP3	E2F3	psi-mi:“MI:0914”(association)	0.530
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
GATA3	PRMT5	psi-mi:“MI:0914”(association)	0.350
MTA1	PRMT5	psi-mi:“MI:0914”(association)	0.350
TACC3	DHRS2	psi-mi:“MI:0914”(association)	0.350
Anapc13	ANAPC15	psi-mi:“MI:0914”(association)	0.350
KIF11	ILVBL	psi-mi:“MI:0914”(association)	0.350
KIF11	MAP4	psi-mi:“MI:0914”(association)	0.350
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
PB2		psi-mi:“MI:0914”(association)	0.350
ABCA1	DMD	psi-mi:“MI:0914”(association)	0.350
KATNAL2	CDK1	psi-mi:“MI:0914”(association)	0.350
CASP1	KIF11	psi-mi:“MI:0914”(association)	0.350
CBY2	KIF11	psi-mi:“MI:0914”(association)	0.350
TNIP3	RNH1	psi-mi:“MI:0914”(association)	0.350
ELK4	MYO1C	psi-mi:“MI:0914”(association)	0.350
FYN	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
KATNIP		psi-mi:“MI:0914”(association)	0.350
PAK4	SNRPE	psi-mi:“MI:0914”(association)	0.350

BioGRID (320): KIF11 (Affinity Capture-MS), KIF11 (Protein-peptide), KIF11 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), PI4K2A (Co-fractionation), SNRNP70 (Co-fractionation), KIF11 (Affinity Capture-MS), KIF11 (Proximity Label-MS), KIF11 (Biochemical Activity), ADARB2 (Affinity Capture-MS)

ESM2 similar proteins: B2GU58, B3H6Z8, B7EJ91, B9F2Y7, B9F7C8, F4IIS5, F4IJK6, F4K0J3, O23826, O95239, P17120, P24339, P28025, P28738, P33174, P33175, P33176, P34540, P46863, P52732, P56536, P82266, Q0WQJ7, Q10E64, Q12840, Q2PQA9, Q2VIQ3, Q498L9, Q58G59, Q5R9K7, Q5W7C6, Q61768, Q6FXI5, Q6P9L6, Q6P9P6, Q6QLM7, Q7M6Z4, Q7M6Z5, Q7TSP2, Q86VH2

Diamond homologs: A0A068FIK2, A0JN40, A1ZAJ2, A8BB91, A8BKD1, B1AVY7, B2GU58, B7EJ91, B7ZNG0, B9F7C8, B9FAF3, B9FUF9, F1M4A4, F1QN54, F4IIS5, F4K0J3, O14782, O15066, O23826, O35066, O35071, O35787, O43093, O43896, O55165, O60333, O88658, O95239, P17120, P17210, P23678, P28025, P28741, P28742, P33173, P33174, P46863, P46867, P46869, P46871

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
ARRY-520	down-regulates	KIF11	“chemical inhibition”
N-(3-aminopropyl)-N-[(1R)-1-[7-chloro-4-oxo-3-(phenylmethyl)-2-quinazolinyl]-2-methylpropyl]-4-methylbenzamide	down-regulates	KIF11	“chemical inhibition”
940929-33-9	down-regulates	KIF11	“chemical inhibition”
KIF11	up-regulates	Spindle_assembly
KIF11	up-regulates	“Plus-end directed sliding movement”
NEK6	“up-regulates activity”	KIF11	phosphorylation
CDK1	“up-regulates activity”	KIF11	phosphorylation
PTEN	“up-regulates activity”	KIF11	dephosphorylation
CDK1	up-regulates	KIF11	phosphorylation
NEK7	“up-regulates activity”	KIF11	phosphorylation
TPX2	“down-regulates activity”	KIF11	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Dengue Virus Genome Translation and Replication	5	19.8×	1e-03
SARS-CoV-1-host interactions	5	11.0×	5e-03
G2/M Checkpoints	6	10.1×	4e-03
G2/M DNA damage checkpoint	6	9.0×	4e-03
SARS-CoV-2-host interactions	6	8.9×	4e-03
Cell Cycle Checkpoints	7	7.8×	4e-03
mRNA Splicing - Major Pathway	10	6.8×	1e-03
Transcriptional Regulation by TP53	8	6.2×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of protein ubiquitination	6	14.4×	2e-03
mRNA splicing, via spliceosome	10	7.7×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1053 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	132
Likely pathogenic	53
Uncertain significance	338
Likely benign	349
Benign	96

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064447	NM_004523.4(KIF11):c.2922G>T (p.Pro974=)	Pathogenic
1068438	NM_004523.4(KIF11):c.388-2A>T	Pathogenic
1068577	NM_004523.4(KIF11):c.1680_1686dup (p.His563fs)	Pathogenic
1069460	NM_004523.4(KIF11):c.366_370del (p.Asn122fs)	Pathogenic
1070069	NM_004523.4(KIF11):c.157C>T (p.Arg53Ter)	Pathogenic
1071386	NC_000010.10:g.(?94405120)(94405399_?)del	Pathogenic
1071653	NM_004523.4(KIF11):c.601del (p.Glu201fs)	Pathogenic
1073666	NM_004523.4(KIF11):c.1873_1875+1del	Pathogenic
1074360	NM_004523.4(KIF11):c.631dup (p.Tyr211fs)	Pathogenic
1074507	NM_004523.4(KIF11):c.1057_1058insTACTTTG (p.Ala353fs)	Pathogenic
1074892	NM_004523.4(KIF11):c.2441del (p.Glu814fs)	Pathogenic
1075762	NM_004523.4(KIF11):c.1768dup (p.Thr590fs)	Pathogenic
1076032	NM_004523.4(KIF11):c.305_306del (p.Phe102fs)	Pathogenic
1076596	NM_004523.4(KIF11):c.2759del (p.Asp920fs)	Pathogenic
1198357	NM_004523.4(KIF11):c.2775_2777delinsATTAATGTCCGTTAAAGGT (p.Thr926fs)	Pathogenic
1206547	NM_004523.4(KIF11):c.439del (p.Thr148fs)	Pathogenic
1297165	NM_004523.4(KIF11):c.2932_2933dup (p.Val978_Glu979insTer)	Pathogenic
1299334	NM_004523.4:c.(1217+1_1218-1)_(1494+1_1495-1)del	Pathogenic
1338285	NM_004523.4(KIF11):c.2018dup (p.Glu674fs)	Pathogenic
1338455	NM_004523.4(KIF11):c.2105del (p.Lys702fs)	Pathogenic
1372060	NM_004523.4(KIF11):c.2521del (p.Glu841fs)	Pathogenic
1388223	NM_004523.4(KIF11):c.2351_2352del (p.Arg784fs)	Pathogenic
1418931	NM_004523.4(KIF11):c.605_606insA (p.Thr203fs)	Pathogenic
1444687	NM_004523.4(KIF11):c.1973del (p.Phe658fs)	Pathogenic
1459199	NM_004523.4(KIF11):c.338_339del (p.Phe113fs)	Pathogenic
1459635	NC_000010.10:g.(?94392223)(94393572_?)del	Pathogenic
1679262	NM_004523.4(KIF11):c.2441_2442insTTCTT (p.Glu814fs)	Pathogenic
1687208	NM_004523.4(KIF11):c.2304_2305del (p.His768fs)	Pathogenic
1687289	NM_004523.4(KIF11):c.2507_2510del (p.Ser835_Ser836insTer)	Pathogenic
1697182	NM_004523.4(KIF11):c.2402_2403del (p.His800_Ser801insTer)	Pathogenic

SpliceAI

3042 predictions. Top by Δscore:

Variant	Effect	Δscore
10:92593423:G:T	donor_gain	1.0000
10:92593449:GCAGG:G	donor_loss	1.0000
10:92593450:CAG:C	donor_loss	1.0000
10:92593451:AG:A	donor_loss	1.0000
10:92593452:GG:G	donor_loss	1.0000
10:92593453:GT:G	donor_loss	1.0000
10:92593454:T:A	donor_loss	1.0000
10:92606260:TATA:T	acceptor_loss	1.0000
10:92606261:ATAG:A	acceptor_loss	1.0000
10:92606262:TAG:T	acceptor_loss	1.0000
10:92606263:A:AG	acceptor_gain	1.0000
10:92606264:G:A	acceptor_loss	1.0000
10:92606264:G:GA	acceptor_gain	1.0000
10:92606264:GACC:G	acceptor_gain	1.0000
10:92606376:G:GT	donor_gain	1.0000
10:92606377:A:T	donor_gain	1.0000
10:92606604:A:AG	acceptor_gain	1.0000
10:92606613:C:CA	acceptor_gain	1.0000
10:92606616:TA:T	acceptor_loss	1.0000
10:92606617:A:AG	acceptor_gain	1.0000
10:92606617:AG:A	acceptor_gain	1.0000
10:92606617:AGGT:A	acceptor_gain	1.0000
10:92606618:G:GA	acceptor_gain	1.0000
10:92606618:GG:G	acceptor_gain	1.0000
10:92606618:GGT:G	acceptor_gain	1.0000
10:92606618:GGTG:G	acceptor_gain	1.0000
10:92606618:GGTGT:G	acceptor_gain	1.0000
10:92606712:TTTGC:T	donor_gain	1.0000
10:92606713:TTGC:T	donor_gain	1.0000
10:92606714:TGC:T	donor_gain	1.0000

AlphaMissense

6975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:92593452:G:C	R26T	1.000
10:92606694:G:C	G96R	1.000
10:92606695:G:A	G96D	1.000
10:92606695:G:T	G96V	1.000
10:92607163:G:C	G105R	1.000
10:92607164:G:A	G105D	1.000
10:92607164:G:T	G105V	1.000
10:92607178:G:A	G110R	1.000
10:92607178:G:C	G110R	1.000
10:92607179:G:A	G110E	1.000
10:92607179:G:T	G110V	1.000
10:92607182:A:T	K111I	1.000
10:92607191:C:A	T114K	1.000
10:92607194:T:A	M115K	1.000
10:92607194:T:G	M115R	1.000
10:92607199:G:C	G117R	1.000
10:92607229:T:A	W127R	1.000
10:92607229:T:C	W127R	1.000
10:92609032:G:C	G134R	1.000
10:92609033:G:A	G134D	1.000
10:92609033:G:T	G134V	1.000
10:92609045:G:C	R138P	1.000
10:92609099:T:A	V156D	1.000
10:92609129:A:T	E166V	1.000
10:92609144:T:C	L171P	1.000
10:92609474:G:C	R221S	1.000
10:92609474:G:T	R221S	1.000
10:92613041:C:A	R234S	1.000
10:92613044:T:C	S235P	1.000
10:92613047:C:G	H236D	1.000

dbSNP variants (sampled 300 via entrez): RS1000078542 (10:92594112 G>C,T), RS1000161810 (10:92618135 T>A), RS1000200079 (10:92648794 T>C), RS1000257100 (10:92637312 A>G), RS1000288162 (10:92636923 C>G), RS1000301725 (10:92647942 C>T), RS1000302708 (10:92592174 T>C), RS1000370612 (10:92614595 A>ATTTAAT), RS1000459195 (10:92655037 A>G), RS1000466052 (10:92595881 C>T), RS1000489199 (10:92629749 A>G), RS1000639037 (10:92649621 AG>A), RS1000653363 (10:92635431 C>T), RS1000657523 (10:92592457 G>T), RS1000699357 (10:92597010 C>A,T)

Disease associations

OMIM: gene MIM:148760 | disease phenotypes: MIM:152950, MIM:268000, MIM:276900, MIM:133780, MIM:615502, MIM:251270

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliopathy	Definitive	Autosomal dominant
microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability	Definitive	AD

Mondo (17): microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability (MONDO:0007918), neutropenia (MONDO:0001475), lymphopenia (MONDO:0003783), microcephaly (MONDO:0001149), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118), neurodevelopmental disorder (MONDO:0700092), long QT syndrome (MONDO:0002442), Usher syndrome (MONDO:0019501), lymphedema (MONDO:0019297), intellectual disability (MONDO:0001071), exudative vitreoretinopathy 1 (MONDO:0007589), CTCF-related neurodevelopmental disorder (MONDO:0014213), hereditary ataxia (MONDO:0100309), optic atrophy (MONDO:0003608)

Orphanet (12): Microcephaly-lymphedema-chorioretinopathy syndrome (Orphanet:2526), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Usher syndrome (Orphanet:886), Familial exudative vitreoretinopathy (Orphanet:891), Retinopathy of prematurity (Orphanet:90050), CTCF-related neurodevelopmental disorder (Orphanet:363611), OBSOLETE: Syndromic rod-cone dystrophy (Orphanet:98661), Hereditary ataxia (Orphanet:183518), OBSOLETE: Lymphedema (Orphanet:79383), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), Autosomal recessive chorioretinopathy-microcephaly syndrome (Orphanet:2518)

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000179	Thick lower lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000478	Abnormality of the eye
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000488	Retinopathy
HP:0000492	Abnormal eyelid morphology
HP:0000494	Downslanted palpebral fissures
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000540	Hypermetropia
HP:0000541	Retinal detachment
HP:0000545	Myopia

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001033_8	Type 2 diabetes	7.000000e-06
GCST004131_111	Inflammatory bowel disease	5.000000e-07
GCST006394_72	Intraocular pressure	1.000000e-08
GCST006412_112	Intraocular pressure	2.000000e-09
GCST007797_46	Asthma onset (childhood vs adult)	8.000000e-07
GCST007798_125	Asthma	1.000000e-12
GCST007800_69	Asthma (childhood onset)	3.000000e-20
GCST008833_16	Type 2 diabetes	1.000000e-09
GCST008916_68	Asthma	7.000000e-10
GCST009863_11	Insulin-related traits (multivariate analysis)	2.000000e-14
GCST010042_51	Asthma	1.000000e-12
GCST010043_16	Asthma	1.000000e-12
GCST010660_2	Triglyceride levels	9.000000e-06
GCST010661_7	Blood glucose levels	7.000000e-06
GCST011569_5	Pancreatic beta-cell glucose sensitivity	3.000000e-07

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004847	age at onset
EFO:0004467	insulin measurement
EFO:0004530	triglyceride measurement
EFO:0004468	glucose measurement
EFO:0006842	diabetes mellitus biomarker

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D008209	Lymphedema	C15.604.496
D008231	Lymphopenia	C15.378.243.750.605; C15.378.553.546.605; C20.673.627
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
C536382	Exudative vitreoretinopathy 1 (supp.)
C531684	Hereditary spinal ataxia (supp.)
C537711	Lymphedema, microcephaly and chorioretinopathy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4581 (SINGLE PROTEIN), CHEMBL6193844 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195559 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 16,971 (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
CHEMBL51483	GOSSYPOL	3	13,973
CHEMBL1829433	AZD-4877	2	150
CHEMBL2105661	LITRONESIB	2	47
CHEMBL228814	ISPINESIB	2	1,396
CHEMBL2347655	FILANESIB	2	512
CHEMBL2325429	SB-743921	1	893

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — Kinesins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
AZD4877	Inhibition	8.7	pIC50

Binding affinities (BindingDB)

119 measured of 195 human assays (195 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CID148124	IC50	0.2 nM
(2S)-N-[(1R)-1-[2-benzyl-5-(2,5-difluorophenyl)-1,2,4-triazol-3-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]-2-hydroxypropanamide	IC50	0.6 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(1S)-1-[2-benzyl-5-(2,5-difluorophenyl)-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]oxolane-2-carboxamide	IC50	0.69 nM	US-8546434: Triazole compounds as KSP inhibitors
(2R,6S)-N-[(1R)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]-2,6-dimethylmorpholine-4-carboxamide	IC50	0.74 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S,6R)-N-[(1R)-1-[2-benzyl-5-(2,5-difluorophenyl)-1,2,4-triazol-3-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]-2,6-dimethylmorpholine-4-carboxamide	IC50	0.83 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(1R)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]-2-hydroxypropanamide	IC50	0.83 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(1R)-1-[5-benzyl-2-(2,5-difluorophenyl)-1,3-thiazol-4-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]-2-hydroxypropanamide	IC50	0.84 nM	US-8748626: Oxazole and thiazole compounds as KSP inhibitors
(2S)-N-[(1S)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]-2-hydroxypropanamide	IC50	0.87 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(1S)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]oxolane-2-carboxamide	IC50	0.9 nM	US-8546434: Triazole compounds as KSP inhibitors
N-[(1R)-1-[2-benzyl-5-(2,5-difluorophenyl)-1,2,4-triazol-3-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]oxolane-2-carboxamide	IC50	0.96 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1S)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]oxolane-2-carboxamide	IC50	1.23 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1S)-1-[2-benzyl-5-(2,5-difluorophenyl)-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]oxolane-2-carboxamide	IC50	1.4 nM	US-8546434: Triazole compounds as KSP inhibitors
N-[(1R)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]oxolane-2-carboxamide	IC50	1.46 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1S)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]-2-hydroxypropanamide	IC50	1.49 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1S)-1-[2-benzyl-5-(2,5-difluorophenyl)-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]-2-hydroxypropanamide	IC50	2.34 nM	US-8546434: Triazole compounds as KSP inhibitors
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1R)-1-[5-benzyl-2-(2,5-difluorophenyl)-1,3-oxazol-4-yl]-2,2-dimethylpropyl]-2-hydroxypropanamide	IC50	2.54 nM	US-8748626: Oxazole and thiazole compounds as KSP inhibitors
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1R)-1-[5-benzyl-2-(2,5-difluorophenyl)-1,3-thiazol-4-yl]-2,2-dimethylpropyl]-2-hydroxypropanamide	IC50	2.6 nM	US-8748626: Oxazole and thiazole compounds as KSP inhibitors
(2S)-N-[(1R)-1-[5-benzyl-2-(2,5-difluorophenyl)-1,3-oxazol-4-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]-2-hydroxypropanamide	IC50	7.18 nM	US-8748626: Oxazole and thiazole compounds as KSP inhibitors
(2S)-N-[(1R)-1-[5-benzyl-2-(2,5-difluorophenyl)-1,3-thiazol-4-yl]-2,2-dimethylpropyl]-N-[[(3S,4R)-4-fluoropyrrolidin-3-yl]methyl]oxolane-2-carboxamide	IC50	10 nM	US-8748626: Oxazole and thiazole compounds as KSP inhibitors
(2S)-N-[(1S)-1-[5-(2,5-difluorophenyl)-2-[(3-fluorophenyl)methyl]-1,2,4-triazol-3-yl]-2-methoxy-2-methylpropyl]-N-[[(3S,4R)-1-ethyl-4-fluoropyrrolidin-3-yl]methyl]oxolane-2-carboxamide	IC50	49.4 nM	US-8546434: Triazole compounds as KSP inhibitors
(2R)-2-amino-3-{[(4-methylphenyl)diphenylmethyl]sulfanyl}propanoic acid	KI	100 nM
(4R)-4-(3-hydroxyphenyl)-N,N,7,8-tetramethyl-1,2,3,4-tetrahydroisoquinoline-2-carboxamide	IC50	104 nM
6-[4-(Trifluoromethyl)phenyl]-3,4-dihydro-2(1H)-quinolinone	KI	109 nM
methyl (2R)-2-amino-3-[(triphenylmethyl)sulfanyl]propanoate	KI	120 nM
(2R)-2-amino-3-[(2-methyl-1,1-diphenylpropyl)sulfanyl]propanoic acid	KI	150 nM
2-[(triphenylmethyl)sulfanyl]ethan-1-amine	KI	150 nM
(2R)-2-amino-3-{[(4-fluorophenyl)diphenylmethyl]sulfanyl}propanoic acid	KI	150 nM
(2R)-2-amino-3-[(1,1-diphenylpentyl)sulfanyl]propanoic acid	KI	175 nM
(2R)-2-amino-3-[(cyclohexyldiphenylmethyl)sulfanyl]propanoic acid	KI	175 nM
(2R)-2-amino-3-[(naphthalen-2-yldiphenylmethyl)sulfanyl]propanoic acid	KI	200 nM
(2R)-2-amino-3-[(2H-1,3-benzodioxol-5-yldiphenylmethyl)sulfanyl]propanoic acid	KI	200 nM
(2R)-2-amino-3-{[(4-chlorophenyl)diphenylmethyl]sulfanyl}propanoic acid	KI	200 nM
(2R)-2-amino-3-{[(4-methoxyphenyl)diphenylmethyl]sulfanyl}propanoic acid	KI	200 nM
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1S)-1-[5-benzyl-2-(2,5-difluorophenyl)-1,3-thiazol-4-yl]-2,2-dimethylpropyl]-2-hydroxypropanamide	IC50	216 nM	US-8748626: Oxazole and thiazole compounds as KSP inhibitors
(2R)-2-amino-3-{[(4-bromophenyl)diphenylmethyl]sulfanyl}propanoic acid	KI	250 nM
N-[2-[2-[2-[2-[2-[(E)-4-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-4-oxobut-2-enoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methyl-2-phenyl-1,3,4-thiadiazole-3-carboxamide	IC50	275 nM	US-20250136619: HETEROBIFUNCTIONAL COMPOUNDS AND THEIR USE IN TREATING DISEASE
4-(3-hydroxyphenyl)-N,N,7,8-tetramethyl-1,2,3,4-tetrahydroisoquinoline-2-carboxamide	IC50	306 nM
4-(3-hydroxyphenyl)-7-iodo-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-2-carboxamide	IC50	317 nM
8-ethyl-4-(3-hydroxyphenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-2-carboxamide	IC50	344 nM
(2R)-2-amino-3-[(1,1-diphenylpropyl)sulfanyl]propanoic acid	KI	450 nM
6-(3-hydroxyphenyl)-N,N-dimethyl-4-azatricyclo[8.4.0.0^{2,7}]tetradeca-1(10),2(7),8,11,13-pentaene-4-carboxamide	IC50	477 nM
3-N,3-N-diethyl-5-methyl-2-N-(thiophene-2-)-4,5,6,7-tetrahydro-1-benzothiophene-2,3-diamido	IC50	480 nM
4-(3-hydroxyphenyl)-N,N,7-trimethyl-1,2,3,4-tetrahydroisoquinoline-2-carboxamide	IC50	595 nM
methyl (2S)-2-[(2R)-2-amino-3-[(triphenylmethyl)sulfanyl]propanamido]-3-methylbutanoate	KI	600 nM
(2R)-2-amino-3-{[bis(4-methoxyphenyl)(phenyl)methyl]sulfanyl}propanoic acid	KI	600 nM
4-(3-hydroxyphenyl)-7-methoxy-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-2-carboxamide	IC50	617 nM
(2S)-N-[(3S)-3-amino-4-fluorobutyl]-N-[(1S)-1-[5-benzyl-2-(2,5-difluorophenyl)-1,3-oxazol-4-yl]-2,2-dimethylpropyl]-2-hydroxypropanamide	IC50	631 nM	US-8748626: Oxazole and thiazole compounds as KSP inhibitors
10-(3-hydroxyphenyl)-N,N-dimethyl-3-oxa-12-azatricyclo[7.4.0.0^{2,6}]trideca-1(9),2(6),7-triene-12-carboxamide	IC50	639 nM
(2S)-2-amino-3-(triphenylmethoxy)propanoic acid	KI	750 nM
7-bromo-4-(3-hydroxyphenyl)-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-2-carboxamide	IC50	808 nM

ChEMBL bioactivities

1124 potent at pChembl≥5 of 1256 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.85	IC50	0.14	nM	SB-743921
9.70	IC50	0.2	nM	CHEMBL4239814
9.70	IC50	0.2	nM	CHEMBL247044
9.57	IC50	0.271	nM	CHEMBL5778625
9.40	IC50	0.4	nM	CHEMBL398478
9.35	IC50	0.446	nM	CHEMBL5951006
9.34	IC50	0.457	nM	CHEMBL5842292
9.33	IC50	0.47	nM	CHEMBL5827710
9.30	Ki	0.5	nM	SB-743921
9.30	IC50	0.5	nM	CHEMBL206115
9.30	IC50	0.5	nM	CHEMBL250127
9.22	IC50	0.6	nM	CHEMBL3645244
9.21	IC50	0.621	nM	CHEMBL5745316
9.16	IC50	0.69	nM	CHEMBL3645253
9.13	IC50	0.74	nM	CHEMBL3645243
9.09	IC50	0.82	nM	CHEMBL400042
9.08	IC50	0.83	nM	CHEMBL3645242
9.08	IC50	0.83	nM	CHEMBL3645246
9.08	IC50	0.84	nM	CHEMBL3680846
9.08	IC50	0.827	nM	CHEMBL5943907
9.06	IC50	0.87	nM	CHEMBL3645252
9.05	IC50	0.9	nM	CHEMBL3645250
9.05	IC50	0.9	nM	CHEMBL241754
9.05	IC50	0.9	nM	CHEMBL251142
9.03	IC50	0.944	nM	CHEMBL5788500
9.02	IC50	0.96	nM	CHEMBL3645241
9.02	IC50	0.964	nM	CHEMBL5909134
9.00	EC50	1	nM	CHEMBL3403387
9.00	IC50	1	nM	CHEMBL240704
9.00	IC50	1	nM	CHEMBL398396
9.00	IC50	1	nM	CHEMBL240497
9.00	IC50	1	nM	CHEMBL250126
9.00	IC50	1	nM	CHEMBL399378
9.00	IC50	1	nM	CHEMBL429553
9.00	IC50	1	nM	CHEMBL1829430
8.97	IC50	1.07	nM	CHEMBL5614288
8.96	IC50	1.11	nM	CHEMBL5856994
8.96	IC50	1.1	nM	CHEMBL1277017
8.92	Ki	1.2	nM	CHEMBL2325410
8.92	IC50	1.2	nM	ISPINESIB MESYLATE
8.92	IC50	1.2	nM	CHEMBL381526
8.92	IC50	1.2	nM	CHEMBL246603
8.91	IC50	1.23	nM	CHEMBL3645247
8.90	IC50	1.26	nM	CHEMBL5752563
8.89	IC50	1.3	nM	CHEMBL262736
8.89	IC50	1.3	nM	CHEMBL427688
8.85	IC50	1.4	nM	CHEMBL3645251
8.85	IC50	1.4	nM	CHEMBL392148
8.85	Ki	1.4	nM	CHEMBL1222153
8.84	IC50	1.46	nM	CHEMBL3645245

PubChem BioAssay actives

1207 with measured affinity, of 1879 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
(2E,5Z)-2-[(4-acetyl-5-methyl-5-phenyl-1,3,4-thiadiazol-2-yl)imino]-5-[(2-nitrophenyl)methylidene]-1,3-thiazolidin-4-one	1398518: Inhibition of MT-stimulated EG5 ATPase activity (unknown origin) by pyruvate kinase/lactate dehydrogenase enzyme coupled photometric assay	ic50	<0.0001	uM
N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxochromen-2-yl)-2-methylpropyl]-4-methylbenzamide	765745: Inhibition of microtubule-stimulated ATPase activity of N-terminal His-6-tagged human wild type Eg5 (1 to 368) expressed in Escherichia coli BL21 by pyruvate kinase/lactate dehydrogenase-linked assay	ic50	0.0001	uM
1-[(4R)-4-[3-(dimethylamino)propyl]-2-(2-fluoro-5-methylphenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	309337: Inhibition of kinesin spindle protein by ATPase assay	ic50	0.0002	uM
1-[(4S)-4-[3-(dimethylamino)propyl]-2-(2-fluoro-5-methylphenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	1398519: Inhibition EG5 (unknown origin)	ic50	0.0002	uM
Docetaxel	1799372: Wild-type IC95 biaryl selected from Article 10.1038/nchembio.2007.34: “ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism.”	ic50	0.0002	uM
1-[(3R,3aR)-8-fluoro-3-(3-morpholin-4-ylpropyl)-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0004	uM
6-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-quinolin-2-one	1799374: HCT116-D130V not selected from Article 10.1038/nchembio.2007.34: “ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism.”	ic50	0.0004	uM
1-[(3R,3aR)-3-(3-aminopropyl)-8-fluoro-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0005	uM
N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-3-fluoro-4-methylbenzamide	1799370: Wild-type HCT116 from Article 10.1038/nchembio.2007.34: “ATP-competitive inhibitors of the mitotic kinesin KSP that function via an allosteric mechanism.”	ic50	0.0005	uM
(2S)-2-amino-2-cyclopropyl-1-[(2S)-4-(2,5-difluorophenyl)-2-(3-hydroxyphenyl)-2,5-dihydropyrrol-1-yl]ethanone	263198: Inhibition of KSP by ATPase assay	ic50	0.0005	uM
1-[(5R)-5-[(2S)-3-amino-2-fluoropropyl]-3-(2,5-difluorophenyl)-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0008	uM
1-[3-[(3R,3aR)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl]-4-methyl-1,4-diazepan-5-one	309415: Inhibition of kinesin spindle protein	ic50	0.0009	uM
1-[(5S)-5-(3-aminopropyl)-3-(2,5-difluorophenyl)-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0009	uM
N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)propyl]-4-methylbenzamide	620415: Inhibition of human recombinant C-terminal His6-tagged KSP ATPase activity after 1 hr by malachite green assay	ic50	0.0010	uM
1-[(5S)-5-[3-(2-azabicyclo[2.2.1]heptan-2-yl)propyl]-3-(2,5-difluorophenyl)-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0010	uM
1-[(3R,3aR)-8-chloro-3-[3-(dimethylamino)propyl]-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0010	uM
1-[(3R,3aR)-8-methyl-3-(3-morpholin-4-ylpropyl)-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0010	uM
1-[(3R,3aR)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-chloro-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0010	uM
1-[(5S)-3-(2,5-difluorophenyl)-5-[3-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]propyl]-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0010	uM
1-[(5S)-3-(2,5-difluorophenyl)-5-[3-[(3S)-3-fluoropyrrolidin-1-yl]propyl]-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0010	uM
1-[1-(1H-indol-3-yl)-6-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-2-yl]butan-1-one	487602: Inhibition of human Eg5 expressed in Escherichia coli assessed as microtubule-activated ATPase activity by spectrophotometry	ic50	0.0010	uM
1-[(2S,3’R)-3’-(2-aminoethyl)-5-(2,5-difluorophenyl)-6’-fluorospiro[1,3,4-thiadiazole-2,4’-2,3-dihydrochromene]-3-yl]ethanone	1195161: Inhibition of KSP in human HCT116 cells assessed as phos-histone H3 level by immunofluorescent assay	ec50	0.0010	uM
4-(furan-2-yl)-N-(4-methoxyphenyl)-6-methyl-4,7-dihydro-1H-pyrazolo[5,4-b]pyridine-5-carboxamide	537124: Inhibition of human full-length Eg5 ATPase activity expressed in Escherichia coli assessed as release of inorganic phosphate after 30 mins	ic50	0.0011	uM
(2S)-2-amino-1-[(2S)-4-(2,5-difluorophenyl)-2-(3-hydroxyphenyl)-2,5-dihydropyrrol-1-yl]-3-methylbutan-1-one	263198: Inhibition of KSP by ATPase assay	ic50	0.0012	uM
1-[2-(2,5-difluorophenyl)-4-[3-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl]-4-phenyl-3H-pyrazol-5-yl]ethanone	309337: Inhibition of kinesin spindle protein by ATPase assay	ic50	0.0012	uM
N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-4-methylbenzamide;methanesulfonic acid	740791: Inhibition of Eg5 (unknown origin)	ic50	0.0012	uM
(2R)-2-amino-3-[(3,4-dimethylphenyl)-diphenylmethyl]sulfanylpropanoic acid	728344: Inhibition of human N-terminal His6-tagged Eg5 (1 to 368 amino acid residues) motor domain basal ATPase activity expressed in Escherichia coli BL21 (DE3) by pyruvate kinase/lactate dehydrogenase-coupled assay	ki	0.0012	uM
(2S)-1-[(2S)-4-(2,5-difluorophenyl)-2-(3-hydroxyphenyl)-2,5-dihydropyrrol-1-yl]-2-hydroxy-3,3-dimethylbutan-1-one	263198: Inhibition of KSP by ATPase assay	ic50	0.0013	uM
1-[(5S)-3-(2,5-difluorophenyl)-5-phenyl-5-(3-pyrrolidin-1-ylpropyl)-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0013	uM
1-[(5S)-3-(2,5-difluorophenyl)-5-[3-(dimethylamino)propyl]-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0014	uM
1-[3-[(3R,3aR)-2-acetyl-8-fluoro-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-3-yl]propyl]-1,4-diazepan-5-one	309415: Inhibition of kinesin spindle protein	ic50	0.0015	uM
1-[(3R,3aR)-3-[3-(dimethylamino)propyl]-8-fluoro-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0016	uM
1-[(3R,3aR)-3-[3-(4-acetylpiperazin-1-yl)propyl]-8-fluoro-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309337: Inhibition of kinesin spindle protein by ATPase assay	ic50	0.0016	uM
1-[(3R,3aR)-3-[3-(dimethylamino)propyl]-8-methyl-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0018	uM
1-[(5S)-3-(2,5-difluorophenyl)-5-[3-(3-fluoroazetidin-1-yl)propyl]-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0018	uM
1-[(5S)-3-(2,5-difluorophenyl)-5-(3-morpholin-4-ylpropyl)-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0018	uM
1-[(3aR)-8-chloro-3-(3-morpholin-4-ylpropyl)-3-phenyl-3a,4-dihydropyrazolo[5,1-c][1,4]benzoxazin-2-yl]ethanone	309415: Inhibition of kinesin spindle protein	ic50	0.0018	uM
(5S)-5-(3-aminopropyl)-3-(2,5-difluorophenyl)-N,N-dimethyl-5-phenyl-4H-pyrazole-1-carboxamide	265609: Inhibition of KSP by ATPase assay	ic50	0.0019	uM
N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide	620415: Inhibition of human recombinant C-terminal His6-tagged KSP ATPase activity after 1 hr by malachite green assay	ic50	0.0020	uM
1-[4-[3-(4-acetylpiperazin-1-yl)propyl]-2-(2-fluoro-5-methylphenyl)-4-phenyl-3H-pyrazol-5-yl]ethanone	309337: Inhibition of kinesin spindle protein by ATPase assay	ic50	0.0020	uM
1-[(5S)-3-(2,5-difluorophenyl)-5-[3-[2-methoxyethyl(methyl)amino]propyl]-5-phenyl-4H-pyrazol-1-yl]ethanone	301179: Inhibition of KSP by ATPase assay	ic50	0.0020	uM
N-[[(2R,4aS,5R,10bS)-5-phenyl-9-propan-2-yl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-2-yl]methyl]-3-(dimethylamino)propane-1-sulfonamide	466475: Inhibition of ATPase activity of human recombinant EG5 assessed as ATP hydrolysis by pyruvate kinase-lactate dehydrogenase coupled assay	ic50	0.0020	uM
N-[[(2R,4aS,5R,10bS)-9-chloro-7-fluoro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quinolin-2-yl]methyl]-2-(dimethylamino)ethanesulfonamide	466475: Inhibition of ATPase activity of human recombinant EG5 assessed as ATP hydrolysis by pyruvate kinase-lactate dehydrogenase coupled assay	ic50	0.0020	uM
1-[(2S,3’R)-3’-(2-aminoethyl)-5-(2,5-difluorophenyl)spiro[1,3,4-thiadiazole-2,4’-2,3-dihydrochromene]-3-yl]ethanone	1195161: Inhibition of KSP in human HCT116 cells assessed as phos-histone H3 level by immunofluorescent assay	ec50	0.0020	uM
(2S)-2-amino-2-cyclopropyl-1-[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydropyrrol-1-yl]ethanone	263184: Inhibition of KSP	ic50	0.0020	uM
1-[2-(2,5-difluorophenyl)-4-[3-(dimethylamino)propyl]-4-phenyl-3H-pyrazol-5-yl]ethanone	309337: Inhibition of kinesin spindle protein by ATPase assay	ic50	0.0021	uM
(2R)-2-amino-3-[diphenyl(5,6,7,8-tetrahydronaphthalen-2-yl)methyl]sulfanylpropanoic acid	728344: Inhibition of human N-terminal His6-tagged Eg5 (1 to 368 amino acid residues) motor domain basal ATPase activity expressed in Escherichia coli BL21 (DE3) by pyruvate kinase/lactate dehydrogenase-coupled assay	ki	0.0021	uM
(5S)-5-(3-aminopropyl)-3-(2,5-difluorophenyl)-N,N-dimethyl-5-phenyl-2H-pyrrole-1-carboxamide	295456: Inhibition of KSP	ic50	0.0022	uM
N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-4-methylbenzamide	1525541: Inhibition of Kinesin Eg5 (unknown origin)	ki	0.0023	uM
N-(4-methoxyphenyl)-6-methyl-4-thiophen-2-yl-4,7-dihydro-1H-pyrazolo[5,4-b]pyridine-5-carboxamide	537124: Inhibition of human full-length Eg5 ATPase activity expressed in Escherichia coli assessed as release of inorganic phosphate after 30 mins	ic50	0.0025	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression, affects expression	6
sodium arsenite	decreases expression, increases abundance, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	4
Resveratrol	decreases expression, affects cotreatment, increases expression	3
Cisplatin	affects expression, affects reaction, decreases expression	3
Estradiol	increases expression	3
Cyclosporine	decreases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
methylparaben	decreases expression, increases expression	2
bisphenol AF	affects binding, affects folding, decreases reaction, increases reaction	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Doxorubicin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
FR900359	affects phosphorylation	1
echimidine	decreases expression, increases metabolic processing	1
dicrotophos	decreases expression	1
3-tritylthio-L-alanine	affects binding, decreases activity	1
urushiol	increases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
methylselenic acid	decreases expression	1
nobiletin	decreases expression	1
titanium dioxide	affects expression	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	decreases expression	1

ChEMBL screening assays

193 unique, capped per target: 185 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002142	Binding	Inhibition of basal ATPase activity of human Eg5	Structure of human Eg5 in complex with a new monastrol-based inhibitor bound in the R configuration. — J Biol Chem
CHEMBL860813	Functional	Inhibition of Eg5 by ATPase assay	Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl-tetrahydroisoquinoline lead series. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00125723	PHASE4	COMPLETED	FIRST - Study of Pegfilgrastim Administered in the First and Subsequent Cycles of Myelosuppressive Chemotherapy
NCT00194857	PHASE4	TERMINATED	Treatment of Anemia and Neutropenia in HIV/HCV Coinfected Patients Treated With Pegylated Interferon and Ribavirin
NCT00257790	PHASE4	COMPLETED	The Tobramycin Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01114165	PHASE4	COMPLETED	Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
NCT01135589	PHASE4	UNKNOWN	Micafungin Prevention Study for Fungal Disease in Child Receiving Allogenic Hematopoietic Stem Cell Transplantation
NCT01571518	PHASE4	UNKNOWN	Prevention of Neutropenia After Using G-CSF With TAC Chemotherapy
NCT02621905	PHASE4	COMPLETED	Steady-State Comparative Bioavailability Study in Prophylaxis Patients of Lozanoc® 50 mg With Sporanox® 100 mg
NCT02967341	PHASE4	UNKNOWN	Blood Draw Validation for Ciprofloxacin Pharmacokinetic Research in Pediatric Cancer Patients
NCT04009941	PHASE4	COMPLETED	Efficacy and Safety of 4.5mg PEG-rhG-CSF Per Cycle in Preventing Neutropenia After Intensive Chemotherapy for Breast Cancer
NCT04904614	PHASE4	COMPLETED	Letermovir Use in Heart Transplant Recipients
NCT05626530	PHASE4	RECRUITING	Letermovir for Secondary Prophylaxis in Solid Organ Transplant Recipients
NCT06145321	PHASE4	ACTIVE_NOT_RECRUITING	Continuous Versus Bolus Administration of G-CSF in Children With Cancer
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00001338	PHASE3	COMPLETED	A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00002658	PHASE3	UNKNOWN	Combination Chemotherapy, Biological Therapy, and Bone Marrow Transplantation in Treating Patients With Acute Myeloid Leukemia
NCT00002719	PHASE3	COMPLETED	Combination Chemotherapy With or Without G-CSF in Treating Older Patients With Acute Myeloid Leukemia
NCT00003739	PHASE3	COMPLETED	Antibiotic Therapy With or Without G-CSF in Treating Children With Neutropenia and Fever Caused by Chemotherapy
NCT00020865	PHASE3	UNKNOWN	Levofloxacin Compared With Cefepime in Treating Cancer Patients With Fever and Neutropenia
NCT00035594	PHASE3	COMPLETED	Pegfilgrastim as Support to Advanced Breast Cancer Patients Receiving Chemotherapy
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00107081	PHASE3	TERMINATED	Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
NCT00445497	PHASE3	UNKNOWN	Early Hospital Discharge or Standard Inpatient Care in Cancer Patients Receiving Antibiotics for Febrile Neutropenia
NCT00529282	PHASE3	TERMINATED	A Study of Ceftobiprole in Patients With Fever and Neutropenia.
NCT00627393	PHASE3	COMPLETED	Safety and Effectiveness of Granulocyte Transfusions in Resolving Infection in People With Neutropenia (The RING Study)
NCT00770172	PHASE3	COMPLETED	G-CSF in Preventing Neutropenia in Patients With Solid Tumors Who Are Receiving Chemotherapy
NCT00784368	PHASE3	COMPLETED	A Pharmacokinetic Study of JK1211(Itraconazole [Itrizole]) Oral Solution in Participants With Deep Mycosis and Those With Febrile Neutropenia Suspected of Fungal Infection
NCT00806351	PHASE3	TERMINATED	An Evaluation Of The Effectiveness And Safety Of Anidulafungin Compared To Caspofungin For The Treatment Of Serious Fungal Infection Due To Candida In Patients With A Dysfunctional Immune System
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01307579	PHASE3	COMPLETED	Caspofungin Versus Fluconazole in Preventing Invasive Fungal Infections (IFI) in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia
NCT01371656	PHASE3	COMPLETED	Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation
NCT01560195	PHASE3	UNKNOWN	A Study of Pegylated rhG-CSF as Support to Advanced Non-Small-Cell Lung Cancer (NSCLC) Patients Receiving Chemotherapy Receiving Chemotherapy
NCT01611051	PHASE3	COMPLETED	A Study Comparing Pegylated rhG-CSF and rhG-CSF as Support to Breast Cancer Patients Receiving Chemotherapy
NCT02238873	PHASE3	UNKNOWN	Pegfilgrastim on Day +3 Compared to Day +1 After Salvage Chemotherapy for Patients With Refractory or Relapsed Aggressive Lymphoma
NCT02414581	PHASE3	COMPLETED	Mouthwash With Chlorhexidine 0.12%/Ethyl Alcohol 7% Compared to Ethyl Alcohol 7%
NCT02643420	PHASE3	COMPLETED	SPI-2012 vs Pegfilgrastim in the Management of Neutropenia in Participants With Breast Cancer With Docetaxel and Cyclophosphamide (ADVANCE)