Table 3.

Inhibitors targeting proteins involved in centrosome clustering (CC).

Inhibitors Targeting	Enzymes	Pathways	Protein Target	Inhibitor	Mechanism of Action of Inhibitors	Clinical Trial
Centrosome Clustering (CC)	Stathmin	STAT3–Stathmin	STAT3	Stattic	Blocks STAT3 to inhibit stathmin depolymerase function, allowing stathmin to remain active to depolymerize microtubules [112].	Pre-clinical development.
				Napabucasin(BBI-608)	Blocks STAT3 to inhibit stathmin depolymerase function, allowing stathmin to remain active to depolymerize microtubules [112].	Phase I-III clinical trials including trials in combination with other compounds in patients with pancreatic, metastatic colorectal cancer, gastric, gastro-esophageal junction cancer and non-squamous, non-small cell lung cancer. https://clinicaltrials.gov/ct2/results?cond=cancer&term=BBI-608&cntry=&state=&city=&dist=&Search=Search
	APC/C Cdc20/CDH1	Mitotic progression	Anaphase-promoting Complex	ProTAME	Disrupts APC3–Cdc20 IR-tail binding interaction and prevents its activation by Cdc20 and Cdh1 [119,120].	Pre-clinical development.
	APC/C Cdc20			Apcin	Disrupts D-box interaction between Cdc20 and the substrate [120].	Pre-clinical development [122].
	HSET	Mitotic spindle assembly	HSET	CW069	Binds to loop 5 cleft of HSET motor domain causing selective allosteric inhibition of HSET [45,123].	Pre-clinical development.
				AZ82	Blocks the ATP binding pocket and binds specifically to the KIFC1/microtubule (MT) binary complex, inhibiting the MT-stimulated KIFC1 enzymatic activity [45].	Pre-clinical development [124,125].
	α/β Tubulin	microtubule dynamics	Tubulin	Griseofulvin	Decreases the dynamicity of microtubules, leading to multipolar spindles and inducing mitotic arrest [126].	Preclinical development [127].
				GF-15	Disrupts microtubule dynamics, leading to multipolar spindles [128].	Pre-clinical development [128,129].
	Poly (ADP-ribose) polymerase	DNA damage	PARP5a (TNKS1) PARP1, 2, 6	AZ0108	NAD+ competitive inhibitor [130].	Pre-clinical development [130].
			PARP-1	PJ-34	Induces G2/M arrest in cancer cells via p21 gene activation and subsequent cell death via centrosome declustering [124].	Pre-clinical development [131,132].
			PARP-1, 2	Veliparib (ABT-888)	Inhibits PARP catalytic activity and, to a lesser extent, exerts PARP trapping activity [133].	Phase I/II/III trials in a range of human malignancies, alone and in combination with other agents. https://clinicaltrials.gov/ct2/results?term=veliparib&cond=Cancer&age_v=&gndr=&type=&rslt=&phase=2&phase=3&Search=Apply
			Non-specific PARP inhibitor/cysteine-containing proteins	Iniparib (BSI-201)	A non-selective modifier of cysteine-containing proteins (protein-reactive compound), rather than a bona fide PARP inhibitor [134,135].	Phase I/II/III trials in breast, ovarian, uterine, lung and advanced solid tumours, both alone and in combination with other agents. https://clinicaltrials.gov/ct2/results?cond=Cancer&term=Iniparib&cntry=&state=&city=&dist=
	Coiled-Coil Containing Protein 3 (TACC3) Colonic and Hepatic Tumour Overexpressed gene (ch-TOG)	Actin and mitotic microtubule organization	Integrin-linked Kinase (ILK)	QLT-0267	Inhibits kinase activity of ILK in an ATP-competitive manner and disrupts TACC3 phosphorylation [129].	Pre-clinical development [136].
	Hsp70	Nek6–Hsp72	Hsp70 Hsp72	VER-155008	ATP competitive inhibitor of Hsp 70 which blocks the nucleotide-binding domain and prevents substrate binding [137].	Pre-clinical development [138].
	N/A	N/A	N/A	CCCI-01	Inhibits centrosome clustering, promoting spindle multipolarity and cell death selectively in cancer cells [139].	Pre-clinical development [139].
	End Binding Protein-1 (EB1), cytoplasmic linker protein-170 (CLIP-170)	Microtubule dynamics	EB1, CLIP-170	EM011	Disrupts microtubule dynamicity and induces G2/M arrest in cancer cells followed by apoptotic cell death [140].	Pre-clinical development [141].
	Cofilin	Actin destabilization	Cofilin Platelet-derived Growth Factor Receptor (PDGFR)-a and -b and FLT3	Crenolanib (CP-868596)	An ATP competitive inhibitor which induces spindle multipolarity in cells with CA by activating cofilin [142].	Phase I–III clinical trials in D842V PDGFRA gene-mutated tumours, advanced gastrointestinal stromal tumours and acute myeloid leukaemia. https://clinicaltrials.gov/ct2/results?cond=cancer&term=Crenolanib&cntry=&state=&city=&dist=&Search=Search
	Cofilin	Actin destabilization	Cofilin PDGFR-b	CP-673451	An ATP competitive inhibitor which induces spindle multipolarity in cells with CA by activating cofilin [142].	Pre-clinical development [143].