KIF18A

Summary

KIF18A (kinesin family member 18A, HGNC:29441) is a protein-coding gene on chromosome 11p14.1, encoding Kinesin-like protein KIF18A (Q8NI77). Microtubule-depolymerizing kinesin which plays a role in chromosome congression by reducing the amplitude of preanaphase oscillations and slowing poleward movement during anaphase, thus suppressing chromosome movements. It is a selective cancer dependency (DepMap: 86.1% of cell lines).

KIF18A is a member of the kinesin superfamily of microtubule-associated molecular motors (see MIM 148760) that use hydrolysis of ATP to produce force and movement along microtubules (Luboshits and Benayahu, 2005 [PubMed 15878648]).

Source: NCBI Gene 81930 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 130 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 86.1% of screened cell lines
• MANE Select transcript: NM_031217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29441
Approved symbol	KIF18A
Name	kinesin family member 18A
Location	11p14.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434G2226, PPP1R99
Ensembl gene	ENSG00000121621
Ensembl biotype	protein_coding
OMIM	611271
Entrez	81930

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 3 retained_intron

ENST00000263181, ENST00000526288, ENST00000531047, ENST00000533466, ENST00000903297, ENST00000903298, ENST00000903299, ENST00000924689, ENST00000924690, ENST00000924691, ENST00000924692, ENST00000924693, ENST00000924694

RefSeq mRNA: 1 — MANE Select: NM_031217 NM_031217

CCDS: CCDS7867

Canonical transcript exons

ENST00000263181 — 17 exons

Exon	Start	End
ENSE00000988245	28036217	28036664
ENSE00000988246	28035387	28035494
ENSE00000988247	28023741	28023850
ENSE00001098289	28062395	28062516
ENSE00001098291	28058926	28059161
ENSE00001098293	28069259	28069423
ENSE00001158458	28097623	28097993
ENSE00001183727	28020619	28021282
ENSE00002141478	28108064	28108156
ENSE00003514886	28094643	28094800
ENSE00003534163	28088524	28088721
ENSE00003538176	28084632	28084808
ENSE00003606259	28090617	28090727
ENSE00003617027	28091409	28091513
ENSE00003619719	28083169	28083243
ENSE00003620894	28077007	28077169
ENSE00003659982	28082856	28082968

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 90.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3659 / max 620.4743, expressed in 1262 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119091	8.2582	1257
119090	0.1077	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	90.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.15	gold quality
secondary oocyte	CL:0000655	82.86	gold quality
oocyte	CL:0000023	82.50	gold quality
ganglionic eminence	UBERON:0004023	82.45	gold quality
sperm	CL:0000019	82.33	gold quality
male germ cell	CL:0000015	79.62	gold quality
embryo	UBERON:0000922	79.25	gold quality
testis	UBERON:0000473	76.26	gold quality
left testis	UBERON:0004533	75.91	gold quality
right testis	UBERON:0004534	75.68	gold quality
stromal cell of endometrium	CL:0002255	73.93	gold quality
bone marrow	UBERON:0002371	72.81	gold quality
trabecular bone tissue	UBERON:0002483	72.51	gold quality
adrenal tissue	UBERON:0018303	71.44	gold quality
rectum	UBERON:0001052	68.69	gold quality
bone marrow cell	CL:0002092	67.65	silver quality
lymph node	UBERON:0000029	66.08	gold quality
vermiform appendix	UBERON:0001154	64.44	gold quality
esophagus mucosa	UBERON:0002469	63.42	gold quality
lower esophagus mucosa	UBERON:0035834	62.81	gold quality
mucosa of transverse colon	UBERON:0004991	62.60	gold quality
caecum	UBERON:0001153	60.69	gold quality
cortical plate	UBERON:0005343	60.62	gold quality
thymus	UBERON:0002370	60.58	silver quality
smooth muscle tissue	UBERON:0001135	60.27	gold quality
endometrium	UBERON:0001295	60.27	gold quality
duodenum	UBERON:0002114	58.32	gold quality
calcaneal tendon	UBERON:0003701	57.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, JUN

miRNA regulators (miRDB)

46 targeting KIF18A, 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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-3925-5P	99.21	67.90	1466

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 86.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 39)

• Kif18A is a dual-functional kinesin and a key component of chromosome congression. (PMID:17346968)
• Kif18A regulates kinetochore microtubule dynamics to control mitotic chromosome positioning. (PMID:18267093)
• The current study sheds light on MS-KIF18A a microtubule-dependent kinesin and adds insights on the post-translational modifications that potentially control the protein cellular distribution and its co-association with cytoskeletal proteins. (PMID:18680169)
• Studies strongly suggest that chromosome congression defects as the result of KIF18A depletion is at least in part mediated through destabilizing kinetochore CENP-E. (PMID:19625775)
• The kinesin-8 Kif18A dampens microtubule plus-end dynamics. (PMID:20153196)
• High Kif18A is associated with breast carcinogenesis. (PMID:20595236)
• Kif18A overexpression is associated with colorectal cancer progression. (PMID:21213216)
• Kinesin (KIF18A) can be potentially used as a blood biomarker to identify asbestosis patients at risk of developing lung cancer. (PMID:21231887)
• The heightened processivity of Kif18A, conferred by its tail domain, thus promotes concentration of Kif18A at K-MT plus ends, where it suppresses their dynamics to control chromosome movements. (PMID:21884977)
• Kif18A controls spindle length independently of its role in chromosome positioning. This is mediated by an ATP-independent spindle microtubule (MT) binding site at C-terminal end of the Kif18A tail that has a strong affinity for MTs in vitro and in cells. (PMID:21885282)
• there is a mutual regulation of kinetochore MT plus-end dynamics and Kif18A accumulation, which may contribute to the highly regulated and ordered changes in kinetochore spindle microtubule dynamics during chromosome congression and oscillation (PMID:22104080)
• Kif18A (kinesin-8) attenuates centromere movement by directly promoting microtubule pausing in a concentration- dependent manner. (PMID:22595673)
• Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex. (PMID:23288039)
• the motion of yeast (Kip3) and human (Kif18A) kinesin-8s (PMID:23746518)
• Cdk1-mediated inhibitory phosphorylation of Kif18A promotes chromosome oscillations in early metaphase. PP1 induces metaphase plate thinning by directly dephosphorylating Kif18A. (PMID:25048371)
• data support a model in which microtubule-attenuating kinesins are molecularly “tuned” to control the dynamics of specific subsets of spindle microtubules (PMID:25208566)
• that the human mitotic kinesin-8, KIF18A, directly interacts with PP1gamma through a conserved RVxF motif (PMID:25281536)
• a biomarker for hepatocellular carcinoma diagnosis and an independent predictor of overall survival (PMID:25431949)
• Confocal microscopy shows that cells expressing SUMO-resistant Kif18A display a compromised dissociation of BubR1 from kinetochores after anaphase onset. (PMID:25884224)
• KIF18a role in microtubule assembly (PMID:26912793)
• Low post translational modifications of KIF18A protein is associated with neoplasms. (PMID:28209915)
• High KIF18A expression is associated with invasion and metastasis of hepatocellular carcinoma. (PMID:29466986)
• These findings shed new light on the role of Kif18A in chromosome segregation and demonstrate that the spindle assembly checkpoint can be activated at kinetochores that are occupied by fully functional k-Mts that lack tension. (PMID:30122526)
• KIF18A expression is a predictive biomarker of drug resistance to endocrine therapy in breast cancer. (PMID:30306428)
• These results support a model in which KIF18A’s neck linker length permits efficient navigation of obstacles to reach K-fiber ends during mitosis. (PMID:30655363)
• High KIF18A expression is associated with lung adenocarcinoma. (PMID:30817091)
• this study showed that KIF18A is overexpressed in patients with LUAD, further confirming that a high KIF18A expression level is correlated with higher pathologic tumor status stage, poorer tumor differentiation, lymph node metastasis, and tumor stage. (PMID:30907518)
• High KIF18A expression in prostate cancer patients predicts a poor prognosis. (PMID:31451680)
• phylogenetic analysis revealed that the KIF18A gene family is remarkably conserved across vertebrates. (PMID:31677127)
• The expression of the Kif18A protein by immunohistochemistry was higher in nonsmall cell lung cancer tissues than in normal tissues, and was associated with tumor differentiation, lymph node metastasis, and TNM staging. (PMID:31977917)
• Kinesin KIF18A is a novel PUM-regulated target promoting mitotic progression and survival of a human male germ cell line. (PMID:32094263)
• Selective and ATP-competitive kinesin KIF18A inhibitor suppresses the replication of influenza A virus. (PMID:32253833)
• Knockdown of Circ_CCNB2 Sensitizes Prostate Cancer to Radiation Through Repressing Autophagy by the miR-30b-5p/KIF18A Axis. (PMID:32716640)
• Chromosomally unstable tumor cells specifically require KIF18A for proliferation. (PMID:33619254)
• KIF18A knockdown reduces proliferation, migration, invasion and enhances radiosensitivity of esophageal cancer. (PMID:33872988)
• Length-dependent poleward flux of sister kinetochore fibers promotes chromosome alignment. (PMID:35926461)
• KIF18A inactivates hepatic stellate cells and alleviates liver fibrosis through the TTC3/Akt/mTOR pathway. (PMID:38372748)
• Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma. (PMID:38446308)
• KIF18A promotes cervical squamous cell carcinoma progression by activating the PI3K/AKT pathway through upregulation of CENPE. (PMID:39331093)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kif18a	ENSMUSG00000027115
rattus_norvegicus	Kif18a	ENSRNOG00000005037

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), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), KIF11 (ENSG00000138160), 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 KIF18A — Q8NI77 (reviewed: Q8NI77)

Alternative names: Marrow stromal KIF18A

All UniProt accessions (1): Q8NI77

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-depolymerizing kinesin which plays a role in chromosome congression by reducing the amplitude of preanaphase oscillations and slowing poleward movement during anaphase, thus suppressing chromosome movements. May stabilize the CENPE-BUB1B complex at the kinetochores during early mitosis and maintains CENPE levels at kinetochores during chromosome congression.

Subunit / interactions. Interacts with CENPE and ESR1.

Subcellular location. Cell projection. Ruffle. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. Glycosylated. Ubiquitinated.

Induction. By estrogen.

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

RefSeq proteins (1): NP_112494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027640	Kinesin-like_fam	Family
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00225

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)
• EC 5.6.1.4 — minus-end-directed kinesin ATPase (BRENDA: 25 organisms, 54 substrates, 17 inhibitors, 11 Km, 31 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	—	45
ATP	0.0001–0.059	9
ALEXA FLUOR 647 ATP	0.032	1
METHYLANTHRANILOYL-ATP	0.0004	1
ADP	—	0
PHOSPHATE	—	0

UniProt features (50 total): strand 14, helix 11, cross-link 5, modified residue 3, sequence variant 3, turn 3, compositionally biased region 3, region of interest 2, sequence conflict 2, chain 1, domain 1, coiled-coil region 1, binding site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3LRE	X-RAY DIFFRACTION	2.2
9YMG	X-RAY DIFFRACTION	2.41
9DI0	ELECTRON MICROSCOPY	3.1
5OGC	ELECTRON MICROSCOPY	4.8
7RSI	ELECTRON MICROSCOPY	4.9
5OCU	ELECTRON MICROSCOPY	5.2
5OAM	ELECTRON MICROSCOPY	5.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI77-F1	67.91	0.39

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): 113–120

Post-translational modifications (8): 695, 838, 24, 683, 794, 868, 874, 674

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2132295	MHC class II antigen presentation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
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-8856688	Golgi-to-ER retrograde transport
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 270 (showing top): GOBP_CHROMOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_ESTRADIOL, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CHROMOSOME_LOCALIZATION, GOCC_KINESIN_COMPLEX, GOCC_RUFFLE, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ORGANELLE_FISSION

GO Biological Process (10): mitotic sister chromatid segregation (GO:0000070), microtubule-based movement (GO:0007018), microtubule depolymerization (GO:0007019), mitotic metaphase chromosome alignment (GO:0007080), male meiotic nuclear division (GO:0007140), protein transport (GO:0015031), regulation of microtubule cytoskeleton organization (GO:0070507), cellular response to estradiol stimulus (GO:0071392), seminiferous tubule development (GO:0072520), mitotic cell cycle (GO:0000278)

GO Molecular Function (11): actin binding (GO:0003779), ATP binding (GO:0005524), microtubule binding (GO:0008017), plus-end-directed microtubule motor activity (GO:0008574), ATP hydrolysis activity (GO:0016887), microtubule plus-end binding (GO:0051010), tubulin-dependent ATPase activity (GO:0070463), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), microtubule motor activity (GO:0003777), protein binding (GO:0005515)

GO Cellular Component (16): kinetochore (GO:0000776), ruffle (GO:0001726), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), kinesin complex (GO:0005871), caveola (GO:0005901), microtubule cytoskeleton (GO:0015630), mitotic spindle astral microtubule (GO:0061673), mitotic spindle midzone (GO:1990023), cytoskeleton (GO:0005856), microtubule (GO:0005874), spindle microtubule (GO:0005876), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Adaptive Immune System	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	3
cellular anatomical structure	3
mitotic nuclear division	2
mitotic cell cycle process	2
intracellular membraneless organelle	2
mitotic spindle	2
sister chromatid segregation	1
microtubule-based process	1
microtubule polymerization or depolymerization	1
protein depolymerization	1
supramolecular fiber organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
male gamete generation	1
meiotic cell cycle	1
meiotic nuclear division	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
microtubule cytoskeleton organization	1
regulation of microtubule-based process	1
regulation of cytoskeleton organization	1
response to estradiol	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
male gonad development	1
tube development	1
reproductive structure development	1
cell cycle	1
cytoskeletal protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
microtubule motor activity	1
ribonucleoside triphosphate phosphatase activity	1
microtubule binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1

Protein interactions and networks

STRING

2104 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIF18A	CIB3	Q96Q77	825
KIF18A	DLGAP5	Q15398	714
KIF18A	AURKB	Q96GD4	681
KIF18A	CENPA	P49450	653
KIF18A	NUF2	Q9BZD4	649
KIF18A	SKA1	Q96BD8	628
KIF18A	CENPF	P49454	618
KIF18A	CKAP5	Q14008	591
KIF18A	CENPE	Q02224	571
KIF18A	KATNA1	O75449	560
KIF18A	CLASP1	Q7Z460	557
KIF18A	KIF2C	Q99661	554
KIF18A	KIFC1	Q9BW19	554
KIF18A	CENPK	Q9BS16	527
KIF18A	CENPB	P07199	523

IntAct

62 interactions, top by confidence:

A	B	Type	Score
CDC16	BUB1B	psi-mi:“MI:0914”(association)	0.790
CDC23	BUB1B	psi-mi:“MI:0914”(association)	0.790
PPP1CA	KIF18A	psi-mi:“MI:0915”(physical association)	0.790
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
ANAPC4	NEK2	psi-mi:“MI:0914”(association)	0.620
KIF18A	ANAPC4	psi-mi:“MI:0915”(physical association)	0.620
KIFBP	KIF3C	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PPP1CA	PQBP1	psi-mi:“MI:0914”(association)	0.510
PPP1R7	CCDC85C	psi-mi:“MI:0914”(association)	0.510
Ppp1cb	MYO1C	psi-mi:“MI:0914”(association)	0.350
Cdc16	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Cdc26		psi-mi:“MI:0914”(association)	0.350
Cdc26	PEX10	psi-mi:“MI:0914”(association)	0.350
Kif18b	EIF2AK2	psi-mi:“MI:0914”(association)	0.350
KIF18A	NCOR1	psi-mi:“MI:0914”(association)	0.350
Kifbp	TPM1	psi-mi:“MI:0914”(association)	0.350
SAMD1		psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.350
LYPD4	DPYSL4	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): KIF18A (Affinity Capture-MS), KIF18A (Affinity Capture-Western), KIF18A (Biochemical Activity), KIF18A (Affinity Capture-MS), KIF18A (Affinity Capture-MS), KIF18A (Affinity Capture-MS), KIF18A (Proximity Label-MS), CSE1L (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), PSMD5 (Affinity Capture-MS), TCF3 (Affinity Capture-MS), ICAM5 (Affinity Capture-MS), TTC3 (Affinity Capture-MS), MKNK1 (Affinity Capture-MS), ITM2B (Affinity Capture-MS)

ESM2 similar proteins: A2YFR6, A2ZRG4, A3BE68, B3H6Z8, B9EUM5, B9FL70, B9FS33, B9FTR1, B9FUF9, B9G8P1, F4HZF0, F4I1T9, F4IAR2, F4IBQ9, F4IGL2, F4IL57, F4J2M6, F4J394, F4JDI6, F4JQ51, F4JUI9, F4JX00, F4JZ68, F4KEC6, L0N7N1, O14343, O59751, O81635, Q0IMS9, Q10MN5, Q27IK6, Q27IK7, Q651Z7, Q6H638, Q6H647, Q6Z9D2, Q75LL2, Q7X7H4, Q80WE4, Q8C0N1

Diamond homologs: A0A068FIK2, A0JN40, A1ZAJ2, A8BB91, A8BKD1, B1AVY7, B7ZC32, B9FUF9, B9GE13, D3YXS5, F1M4A4, F1QN54, F4J1U4, F4K0J3, F8WLE0, L0N7N1, O14782, O15066, O35066, O35071, O35787, O43093, O43896, O55165, O60282, O60333, O88658, O95239, P17210, P23678, P28738, P28741, P33173, P33174, P33175, P33176, P34540, P46863, P46865, P46867

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
KIF18A	up-regulates	“Plus-end directed sliding movement”
APC-c	“down-regulates quantity by destabilization”	KIF18A	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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	85.7×	1e-07
Inactivation of APC/C via direct inhibition of the APC/C complex	5	70.2×	3e-07
APC-Cdc20 mediated degradation of Nek2A	6	68.6×	3e-08
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	6	68.6×	3e-08
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	6	66.1×	3e-08
APC/C:Cdc20 mediated degradation of mitotic proteins	6	57.9×	6e-08
APC/C-mediated degradation of cell cycle proteins	6	54.5×	6e-08
Regulation of mitotic cell cycle	6	54.5×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
cell division	10	9.4×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3111 predictions. Top by Δscore:

Variant	Effect	Δscore
11:28023851:C:CC	acceptor_gain	1.0000
11:28023852:T:C	acceptor_gain	1.0000
11:28023852:T:TC	acceptor_gain	1.0000
11:28057689:TTA:T	donor_gain	1.0000
11:28059157:ATACT:A	acceptor_gain	1.0000
11:28059158:TACT:T	acceptor_gain	1.0000
11:28059160:CT:C	acceptor_gain	1.0000
11:28059162:C:CC	acceptor_gain	1.0000
11:28059164:A:C	acceptor_gain	1.0000
11:28059166:A:C	acceptor_gain	1.0000
11:28059169:C:CT	acceptor_gain	1.0000
11:28059175:A:C	acceptor_gain	1.0000
11:28062387:GTAC:G	donor_loss	1.0000
11:28062388:TACT:T	donor_loss	1.0000
11:28062389:A:AC	donor_gain	1.0000
11:28062389:ACTC:A	donor_loss	1.0000
11:28062390:C:CC	donor_gain	1.0000
11:28062390:CTCA:C	donor_gain	1.0000
11:28062391:TCA:T	donor_loss	1.0000
11:28062392:CA:C	donor_loss	1.0000
11:28062393:A:AC	donor_gain	1.0000
11:28062393:ACG:A	donor_gain	1.0000
11:28062394:C:CA	donor_gain	1.0000
11:28062394:CG:C	donor_gain	1.0000
11:28062394:CGC:C	donor_gain	1.0000
11:28062394:CGCT:C	donor_gain	1.0000
11:28062394:CGCTT:C	donor_gain	1.0000
11:28062514:TTC:T	acceptor_gain	1.0000
11:28062515:TC:T	acceptor_gain	1.0000
11:28062515:TCC:T	acceptor_loss	1.0000

AlphaMissense

5964 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:28084652:C:G	A352P	0.999
11:28084654:C:G	R351P	0.999
11:28084660:G:T	A349D	0.999
11:28084661:C:G	A349P	0.999
11:28084669:A:G	L346P	0.999
11:28084669:A:T	L346H	0.999
11:28088654:A:G	L256P	0.999
11:28090674:C:A	R214S	0.999
11:28090674:C:G	R214S	0.999
11:28090675:C:G	R214T	0.999
11:28094654:A:G	S158P	0.999
11:28084734:A:C	C324W	0.998
11:28084759:A:G	L316S	0.998
11:28084765:C:G	R314P	0.998
11:28084776:A:C	S310R	0.998
11:28084776:A:T	S310R	0.998
11:28084778:T:G	S310R	0.998
11:28088567:A:G	L285P	0.998
11:28088645:A:G	L259P	0.998
11:28088648:T:C	D258G	0.998
11:28088666:G:T	A252D	0.998
11:28090675:C:A	R214M	0.998
11:28094656:A:T	V157D	0.998
11:28094707:A:G	L140P	0.998
11:28094788:C:T	G113D	0.998
11:28097637:C:T	G104E	0.998
11:28084664:A:G	Y348H	0.997
11:28084707:A:C	S333R	0.997
11:28084707:A:T	S333R	0.997
11:28084709:T:G	S333R	0.997

dbSNP variants (sampled 300 via entrez): RS1000028230 (11:28021344 G>A), RS1000120745 (11:28021015 T>A,C), RS1000153201 (11:28070046 C>T), RS1000162722 (11:28042691 C>A), RS1000200234 (11:28054208 T>C), RS1000214067 (11:28071515 A>G), RS1000214779 (11:28050833 T>C), RS1000238910 (11:28091004 T>C), RS1000252411 (11:28053859 A>G), RS1000272338 (11:28099634 C>A), RS1000293721 (11:28022510 A>C), RS1000326840 (11:28086622 A>T), RS1000402770 (11:28105697 G>A), RS1000420206 (11:28070418 C>G,T), RS1000432552 (11:28035623 C>G)

Disease associations

OMIM: gene MIM:611271 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006030_6	Chloride levels	1.000000e-08
GCST007433_6	Fulminant type 1 diabetes	8.000000e-09
GCST009391_24	Metabolite levels	7.000000e-06
GCST90000050_66	Age at first birth	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009101	age at first birth measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523403 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 69 (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
CHEMBL5084301	AMG-650	1	69

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

Binding affinities (BindingDB)

116 measured of 782 human assays (782 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US12084420, Compound 140a	KI	0.5 nM	US-12084420: Indoline compounds for inhibiting KIF18A
N-(4-(5-(2-(3,3-Difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	1 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
2-Hydroxy-N-(4-(5-(6-methyl-2-(3,3,3-trifluoropropoxy)pyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)ethane-1-sulfonamide	IC50	1 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(4,4-Difluoropiperidin-1-yl)-6-methylpyridin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	1 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(6,6-Difluoro-3-azabicyclo[3.1.0]hexan-3-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	1 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
US12084420, Compound 140b	KI	1.4 nM	US-12084420: Indoline compounds for inhibiting KIF18A
N-(4-(5-(2-(4,4-Difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(4-fluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro [2.5]octan-6-yl)phenyl)-2-hydroxyethanesulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(4,4-Difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(4,4-Difluoropiperidin-1-yl)-6-ethylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(4-Fluoropiperidin-1-yl)-6-methylpyridin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro [2.5]octan-6-yl)phenyl)-2-hydroxyethane-sulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(4,4-Difluorocyclohexyl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
(2S)-N-[3-(6-azaspiro[2.5]octan-6-yl)-4-[4-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]pyrazol-1-yl]phenyl]-1-hydroxypropane-2-sulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(3,3-Difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	2 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(3-azabicyclo[3.1.0]hexan-3-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	3 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(6-Methyl-2-(3,3,3-trifluoropropoxy)pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	3 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(1-(3,3-Difluorocyclobutyl)-6-oxo-1,6-dihydropyridazin-3-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	3 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
1-(3,4-dichlorophenyl)-3-(1-morpholin-4-yl-1-phenylpropan-2-yl)urea	IC50	3.6 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
N-[[3-carbamoyl-7-(diethylamino)chromen-2-ylidene]amino]pyridine-4-carboxamide	IC50	3.7 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
N-[3-(6-azaspiro[2.5]octan-6-yl)-4-[4-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]triazol-1-yl]phenyl]-2-hydroxyethanesulfonamide	IC50	4 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(6-(4,4-Difluoropiperidin-1-yl)-4-methylpyridin-2-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro [2.5]octan-6-yl)phenyl)-2-hydroxyethanesulfonamide	IC50	4 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(3-Fluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	4 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(4,4-Difluoropiperidin-1-yl)pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	5 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
(2R)-N-[3-(6-azaspiro[2.5]octan-6-yl)-4-[4-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]pyrazol-1-yl]phenyl]-1-hydroxypropane-2-sulfonamide	IC50	5 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(6-Methyl-2-(3,3,3-trifluoropropoxy)pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	5 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(4,4-Difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(4-methylpiperidin-1-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	5 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(2-(3,3-Difluoropyrrolidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	7 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(6,6-Difluoro-3-azabicyclo[3.1.0]hexan-3-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	7 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(4-Fluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	7 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
2-[3-[5-chloro-4-(3,4-dimethylanilino)-6-oxopyridazin-1-yl]-1-adamantyl]acetic acid	IC50	7.6 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
N-(4-(5-(2-((3S,4R)-3,4-Difluoropyrrolidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	8 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(Difluoromethyl)-6-(4,4-difluoropiperidin-1-yl)pyridin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	8 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
US12084420, Compound 336a	IC50	8.5 nM	US-12084420: Indoline compounds for inhibiting KIF18A
N-(4-(4-(2-(4,4-Difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(4-fluoro-4-methylpiperidin-1-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	9 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(4,4-Difluoropiperidin-1-yl)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	9 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(4-(4,4-Difluoropiperidin-1-yl)-1,3,5-triazin-2-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro [2.5]octan-6-yl)phenyl)-2-hydroxyethanesulfonamide	IC50	9 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-[5-acetyl-6-[(E)-2-(dimethylamino)ethenyl]-2-oxopyran-3-yl]benzamide	IC50	10 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
2-Hydroxy-N-(4-(5-(6-methyl-2-(5-azaspiro[2.4]heptan-5-yl)pyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)ethane-1-sulfonamide	IC50	10 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(5-(6-Methyl-2-(3,3,5,5-tetrafluoropiperidin-1-yl)pyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	10 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
6-methyl-2-nitro-3-(2-phenoxyethoxy)pyridine	IC50	10.2 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
4-[(E)-(1,3-diphenylpyrazol-4-yl)methylideneamino]-3-pyridin-4-yl-1H-1,2,4-triazole-5-thione	IC50	10.7 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
US12084420, Compound 24a	IC50	11 nM	US-12084420: Indoline compounds for inhibiting KIF18A
N-(4-(5-(2-(3,3-Difluoroazetidin-1-yl)-6-methylpyrimidin-4-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	11 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
(2R)-N-[3-(6-azaspiro[2.5]octan-6-yl)-4-[5-[2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl]-1,3,4-oxadiazol-2-yl]phenyl]-1-hydroxypropane-2-sulfonamide	IC50	11 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(4-(4-(2-(4,4-Difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	11 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
N-(3-(4,4-Difluoropiperidin-1-yl)-4-(4-(2-(4,4-difluoropiperidin-1-yl)-6-methylpyrimidin-4-yl)-1H-pyrazol-1-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	11 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
3-[2-(2,4-dichlorophenyl)ethoxy]-6-methyl-2-nitropyridine	IC50	11.3 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
2-[3-[5-chloro-4-(3,5-dimethylanilino)-6-oxopyridazin-1-yl]-1-adamantyl]acetic acid	IC50	11.3 nM	US-20250382298: NITROGEN-CONTAINING COMPOUND AND USE THEREOF
N-(4-(5-(4-Methyl-6-(3-(trifluoromethyl)piperidin-1-yl)pyridin-2-yl)-1,3,4-oxadiazol-2-yl)-3-(6-azaspiro[2.5]octan-6-yl)phenyl)-2-hydroxyethane-1-sulfonamide	IC50	12 nM	US-20250250264: KIF18A INHIBITOR AND USE THEREOF
US12084420, Compound 204	IC50	13 nM	US-12084420: Indoline compounds for inhibiting KIF18A

ChEMBL bioactivities

1097 potent at pChembl≥5 of 1099 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.54	IC50	2.9	nM	CHEMBL6103265
8.41	IC50	3.9	nM	CHEMBL6078192
8.18	IC50	6.6	nM	CHEMBL6102102
8.09	IC50	8.2	nM	CHEMBL6102935
8.06	IC50	8.7	nM	CHEMBL6074553
7.92	IC50	12	nM	CHEMBL4776977
7.92	IC50	12	nM	CHEMBL4755023
7.92	IC50	12	nM	CHEMBL4784192
7.89	IC50	13	nM	CHEMBL5070813
7.85	IC50	14	nM	CHEMBL4777623
7.85	IC50	14	nM	CHEMBL4752657
7.84	IC50	14.5	nM	CHEMBL6078335
7.82	IC50	15	nM	CHEMBL5075318
7.82	IC50	15	nM	CHEMBL6082902
7.80	IC50	16	nM	CHEMBL4777759
7.80	IC50	16	nM	CHEMBL4746340
7.80	IC50	16	nM	CHEMBL5081181
7.80	IC50	16	nM	CHEMBL5094304
7.80	IC50	16	nM	CHEMBL5091710
7.77	IC50	17	nM	CHEMBL4750775
7.77	IC50	17	nM	CHEMBL4779888
7.77	IC50	17	nM	CHEMBL5087614
7.77	IC50	17	nM	CHEMBL5075165
7.77	IC50	17	nM	AMG-650
7.76	IC50	17.4	nM	CHEMBL4751673
7.75	IC50	18	nM	CHEMBL4743241
7.75	IC50	17.6	nM	CHEMBL4776120
7.75	IC50	18	nM	CHEMBL4740783
7.75	IC50	18	nM	CHEMBL5092103
7.75	IC50	18	nM	CHEMBL5072943
7.75	IC50	18	nM	CHEMBL5078662
7.72	IC50	19	nM	CHEMBL5087385
7.70	IC50	20	nM	CHEMBL5094252
7.70	IC50	20	nM	CHEMBL5069425
7.70	IC50	20	nM	CHEMBL5093636
7.70	IC50	20	nM	CHEMBL5079933
7.70	IC50	20	nM	CHEMBL5767954
7.70	IC50	19.8	nM	CHEMBL6102989
7.68	IC50	21	nM	CHEMBL5079028
7.66	IC50	22	nM	CHEMBL5093289
7.66	IC50	22	nM	CHEMBL5080068
7.66	IC50	22	nM	CHEMBL5086712
7.66	IC50	22	nM	CHEMBL5081961
7.64	IC50	23	nM	CHEMBL5069902
7.64	IC50	23	nM	CHEMBL5085000
7.64	IC50	23	nM	CHEMBL5081092
7.64	IC50	23	nM	CHEMBL5082550
7.64	IC50	23	nM	CHEMBL5081140
7.63	IC50	23.6	nM	CHEMBL6082896
7.62	IC50	24	nM	CHEMBL5082968

PubChem BioAssay actives

43 with measured affinity, of 47 total; 42 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-(6-azaspiro[2.5]octan-6-yl)-4-(2-hydroxyethylsulfonylamino)-N-(5-methyl-6-morpholin-4-yl-2-pyridinyl)benzamide	1725677: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0120	uM
2-(6-azaspiro[2.5]octan-6-yl)-4-(2-hydroxyethylsulfamoyl)-N-[6-(3,3,3-trifluoropropoxy)-2-pyridinyl]benzamide	1725677: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0120	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(4,4-difluoropiperidin-1-yl)phenyl]-4-(2-hydroxyethylsulfonylamino)benzamide	1709724: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 80 mins by ADP-Glo reagent based assay	ic50	0.0120	uM
2-(6-azaspiro[2.5]octan-6-yl)-4-[[(2S)-1-hydroxypropan-2-yl]sulfonylamino]-N-[6-(3,3,3-trifluoropropoxy)-2-pyridinyl]benzamide	1725677: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0140	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[6-(3,3-difluoroazetidin-1-yl)-4-methyl-2-pyridinyl]-4-(methanesulfonamido)benzamide	1725677: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0140	uM
2-(6-azaspiro[2.5]octan-6-yl)-4-[[(2R)-1-hydroxypropan-2-yl]sulfonylamino]-N-[6-(3,3,3-trifluoropropoxy)-2-pyridinyl]benzamide	1725677: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0160	uM
2-(6-azaspiro[2.5]octan-6-yl)-4-(2-hydroxyethylsulfamoyl)-N-[6-[(2R)-2-methylmorpholin-4-yl]-2-pyridinyl]benzamide	1725677: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0160	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluoropiperidin-1-yl)-4-pyridinyl]-4-(2-hydroxyethylsulfonylamino)benzamide	1726177: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0170	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[2-(4,4-difluorocyclohexyl)-6-methylpyrimidin-4-yl]-4-(2-hydroxyethylsulfonylamino)benzamide	1726177: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0170	uM
2-(6-azaspiro[2.5]octan-6-yl)-4-[[(2S)-1-hydroxypropan-2-yl]sulfonylamino]-N-[2-[(2R)-2-methylmorpholin-4-yl]pyrimidin-4-yl]benzamide	1726177: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0174	uM
N-[2-(5-azaspiro[2.4]heptan-5-yl)-6-methylpyrimidin-4-yl]-2-(6-azaspiro[2.5]octan-6-yl)-4-(2-hydroxyethylsulfonylamino)benzamide	1726177: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0176	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(2-cyclobutyloxy-6-methylpyrimidin-4-yl)-4-(2-hydroxyethylsulfonylamino)benzamide	1726177: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0180	uM
2-(6-azaspiro[2.5]octan-6-yl)-4-(2-hydroxyethylsulfonylamino)-N-[2-[(1-hydroxy-2-methylpropan-2-yl)amino]-6-methylpyrimidin-4-yl]benzamide	1726177: Inhibition of recombinant human His-tagged KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and measured after 15 mins by ADP-Glo kinase assay	ic50	0.0180	uM
N-[2-(6-azaspiro[2.5]octan-6-yl)-4-(2-hydroxyethylsulfonylamino)phenyl]-3-piperidin-1-ylbenzamide	1709724: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 80 mins by ADP-Glo reagent based assay	ic50	0.0260	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(tert-butylsulfamoyl)phenyl]-4-(propan-2-ylsulfonylamino)benzamide	1709724: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 80 mins by ADP-Glo reagent based assay	ic50	0.0260	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(tert-butylsulfamoyl)phenyl]-4-(methanesulfonamido)benzamide	1709724: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 80 mins by ADP-Glo reagent based assay	ic50	0.0270	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(tert-butylsulfamoyl)phenyl]-4-(methylsulfamoyl)benzamide	1709724: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 80 mins by ADP-Glo reagent based assay	ic50	0.0290	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(4,4-difluoropiperidin-1-yl)-2-fluorophenyl]-4-(2-hydroxyethylsulfonylamino)benzamide	1709724: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 80 mins by ADP-Glo reagent based assay	ic50	0.0290	uM
2-(6-azaspiro[2.5]octan-6-yl)-6-(2-hydroxyethylsulfonylamino)-N-[3-[3-(trifluoromethyl)diazirin-3-yl]phenyl]pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.0320	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(tert-butylsulfamoyl)phenyl]-4-[(1-methylcyclopropyl)sulfonylamino]benzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.0610	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[6-(cyclopentylsulfamoyl)-2-pyridinyl]-4-[(1-hydroxy-2-methylpropan-2-yl)amino]benzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.0800	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[6-(tert-butylsulfamoyl)-2-pyridinyl]-6-[(1-hydroxy-2-methylpropan-2-yl)amino]pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.0810	uM
2-(6-azaspiro[2.5]octan-6-yl)-6-(1,3-dihydroxypropan-2-ylamino)-N-[3-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.0900	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(6-cyclopentylsulfonyl-2-pyridinyl)-4-(2-hydroxyethylamino)benzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.0920	uM
3-(6-azaspiro[2.5]octan-6-yl)-N-[6-(tert-butylsulfamoyl)-2-pyridinyl]-5-(methanesulfonamido)pyrazine-2-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.0960	uM
3-(6-azaspiro[2.5]octan-6-yl)-N-[3-(tert-butylsulfamoyl)phenyl]-5-[(1-hydroxy-2-methylpropan-2-yl)amino]pyrazine-2-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.1350	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[6-(tert-butylsulfamoyl)-2-pyridinyl]-4-[(1-hydroxy-2-methylpropan-2-yl)amino]benzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.1400	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(6-cyclopentylsulfonyl-2-pyridinyl)-4-[(2-hydroxy-2-methylpropyl)amino]benzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.1650	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[6-(tert-butylsulfamoyl)-2-pyridinyl]-4-[[1-(hydroxymethyl)cyclopropyl]amino]benzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.1660	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(6-cyclopentylsulfonyl-2-pyridinyl)-4-[2-hydroxyethyl(methyl)amino]benzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.2530	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(tert-butylsulfamoyl)phenyl]pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.3200	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(6-cyclopentylsulfonyl-2-pyridinyl)-4-methoxybenzamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.3600	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(3-cyclopentylsulfonylphenyl)pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.4100	uM
5-(4-chlorophenyl)-N-(3-piperidin-1-ylsulfonylphenyl)-1H-pyrazole-4-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.5200	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(cyclopropylsulfamoyl)phenyl]pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	0.5800	uM
N-(3-cyclopentylsulfonylphenyl)-2-(4,4-dimethylpiperidin-1-yl)pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	1.2500	uM
1-(benzenesulfonyl)-4-chloro-2-nitrobenzene	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	1.7000	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(3-pyrrolidin-1-ylsulfonylphenyl)pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	1.8300	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-(3-propan-2-ylsulfonylphenyl)pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	3.1500	uM
N-(3-cyclopentylsulfonylphenyl)-2-(4,4-difluoropiperidin-1-yl)pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	5.3100	uM
N-(3-cyclopentylsulfonylphenyl)-2-piperidin-1-ylpyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	6.1600	uM
2-(6-azaspiro[2.5]octan-6-yl)-N-[3-(oxetan-3-ylsulfonyl)phenyl]pyridine-3-carboxamide	1921121: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in Trichoplusia ni insect cells assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 30 mins followed by ATP addition and further incubated for 15 mins by ADP-Glo reagent based assay	ic50	8.8800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Coumestrol	affects cotreatment, increases expression, affects reaction	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
arsenite	decreases reaction, affects binding	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases acetylation, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric oxide	decreases expression	1
hydroquinone	decreases expression	1
phenanthridone	increases metabolic processing	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects binding, decreases reaction, affects localization, increases metabolic processing	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
thieno(2,3-c)isoquinolin-5-one	increases metabolic processing	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4372732	Binding	Inhibition of Kif18A (unknown origin) assessed as reduction in Alexa-594 labelled microtubule gliding at 30 uM measured every 2 secs for 20 secs by epifluorescence microscopic analysis relative to control	Dual inhibition of Kif15 by oxindole and quinazolinedione chemical probes. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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