PLK-1 Targeted Inhibitors and Their Potential against Tumorigenesis

Table 3

Cancer cell lines and xenografts are sensitive to inhibitors.

(a)  

Number	Inhibitors	Cell lines	Xenografts	Animal models	Clinical phase tested cancers	References
1	Scytonemin	Myeloma cells, Jurkat T cells	NA	NA	T-cell leukemia, non-Hodgkin lymphoma	[8, 12]
2	ON01910.Na	HCT-116 colorectal cancer cells, pancreatic cancer cell lines, myelodysplastic syndrome, HL-60, MDS-L, Jurkat, and Ramos, cervical carcinoma	Head and neck squamous cell carcinoma	NA	B-cell chronic lymphocytic leukemia (CLL), brain tumor	[36, 67, 77, 78]
3	Wortmannin	HL-60 cells, MDA-MB-435, MDAMB-231, MCF-7, T-47D, and NCI/ADR	NA	NA	Breast cancer	[17]
4	HMN-176	MDR1 resistant cell lines of ovarian cancer	Gastric, breast, lung human tumor xenograft	Mouse	NA	[21, 22]
5	NMS-P937	Hematological and solid cancer cell lines and <120 cancer cell lines	HCT-116 xenograft tumor model	Rodent and nonrodent	AML, advance and metastatic solid tumor	[20, 29]
6	GSK461364A	120 cancer cell lines, colo205, HT29, A549, MX-1, SKOV-3, HN5, MCF7, N87, PC-3, RKO and so forth	U2OS tumor	Nude mice	Colon, lung, breast, ovarian, colorectal, gastric, prostate, Had and neck squamous cell carcinoma, brain metastasis of brain cancer, non-Hodgkin	[24–26]
7	BI 2536	HeLa	NA	HCT-116 tumor-bearing nude mice	NSCLC, pancreatic, hormone-refractory prostate cancer, relapsed or refractory acute myeloid leukemia and small lung cancer, cervical cancer	[11, 16, 31, 64]
8	BI 6727	Ewing sarcomas, leukemia, medulloblastomas, neuroblasblastoma, osteo- and rhabdomyosarcomas	NSCLC tumor model, Taxane-resistant CXB1 xenograft model of colorectal, RMS-1 xenograft model of rhabdoblastoma in pediatrics tumor	NA	Colon pancreatic and bread cancer, advance or metastatic solid tumor, platinum-resistant/refractory ovarian cancer, pediatric cancer	[34, 65]
9	Cyclapolin 1	Hela	NA	NA	Cervical cancer	[42]
10	DAP-81	NA	NA	NA	NA	[43]
11	ZK-thiazolidinone	Caco2, HeLa, MCF-7	NA	NA	Human and mouse colon, breast, cervical cancer	[44]
12	PHA-680626	NA	NA	NA	NA	[15]
13	SBE13	HeLa	NA	NA	Cervical cancer	[45]
14	Compound 36	NA	NA	HeLa xenograft bearing rats	NA	[27, 46]
15	LFM-A13	Breast and glioblastoma	NA	Mouse and rat tumor models	Human leukemic B-cell precursors	[47, 48, 68]
16	RO3280	H82, H69, colo205, HT-29, MDA-MB-468, PC3	NA	Mouse xenograft model	Leukemic, lung, colon, breast, prostate	[49, 50]
17	Compound 15	HCT-116 Colorectal cancer cell lines	NA	NA	NA	[51]
18	Compound 38	HCT-116 Colorectal cancer cell lines	NA	NA	NA	[52]
19	TAK-960	TP53, KRAS mutated and MDR1 resistant cancer cell lines	NA	HT-29 colorectal cancer xenograft model, MV4-11 human leukemic model	NA	[53]
20	TKM-080301	NA	NA	Implanted xenograft intrahepatically and subcutaneously	Hepatic metastases, specific neuroendocrine tumors and adrenocortical carcinoma	[69]

(b)  

Number	PBD inhibitors	Cell lines	Mode of action	References
21	Poloxipan	NA	Inhibits PLK-1-PBD binding manner	[72]
22	Poloxin	NA	Interferes with PLK-1-PBD functions in vitro and in vivo	[27, 57]
23	PPG	NA	Inhibits PBD-dependent binding in vitro and in vivo by 2-hydroxyl group	[27, 71]
24	Aristolactam AIIIa	HCT-8/V colon resistant cell lines	Inhibit PBD domain ad as well as kinase domain	[73]
25	MQSpTPL	NA	PoloBoxtide is recognized by pincer grip like pocket PB1 and PB2	[55, 60, 61, 74]
26	LLCSpTPNG	NA	LLCSpTPNG is recognized by the trp414 residue of PB1	[75]
27	PLHSpT	NA	The side-chain of N-terminal Pro docked into a surrounding core of hydrophobic amino acid Trp414, Phe535, and Arg516 residue	[41, 76]

NA = not available.