Table 1.

Survivin therapeutics- Drug targets and mechanism of action in various cancers

Drug	Target	Mechanism of action	Cancers
Inhibitors of Survivin Transcription
FL118	Survivin Promotor	Multiple mechanisms leading to transcriptional inhibition	Head and Neck, Cervical, Ovarian, Pancreatic, Prostate, Leukaemia, Lung and CSCs [116, 117, 235, 236]
YM155	SP1 binding site of Survivin Promotor	DNA damage and S phase arrest	Leukaemia, Neuroblastoma, Gastric, Pancreatic, Liver, Prostate, NSCLC [119]
Tolfenamic Acid	SP1 and SP3	Loss of DNA binding specificity leading to transcriptional repression	Pancreatic, Ovarian and Ewing Sarcoma [122, 123]
Teremprocol	SP1 and cdc2	Transcriptional Repression	Lung, Colorectal, Breast, Prostate, Liver [124, 125]
Mithramycin A	SP1 and SP3	Loss of DNA binding specificity of SP1	Ewing Sarcoma, LSCs [126, 127, 225]
Protein-Protein interaction inhibitors
Survivin-Survivin interaction inhibitors
Abbot 8 LQZ7 LQZ7F	Survivin	Binds to survivin dimer interface	Cervical, Pancreatic [128, 129]
Survivin-Smac interaction inhibitors
Piperine Withanone UC112 4 g 10f	Survivin	Bind to Survivin at Smac binding region, increases survivin expression	Melanoma, Pancreas, Breast and Colorectal [130–133]
Survivin-Hsp90 interaction inhibitors
Shepherdin AICAR 17AAG NVP-922	HSP90/ Survivin complex	Disruption of survivin Hsp90 interaction and proteasomal degradation	Prostate, Cervical, Melanoma, Colorectal, Chronic myelogenous Leukaemia [133–140]
Mitotic Inhibitor
Indinavir	Survivin	Inhibit Aurora B phosphorylation and CPC complex formation	Breast [141]
S12		Microtubule dynamics	Medulloblastoma, Cervical, Osteosarcoma, Breast [141]
LLP3		Affect survivin-Ran stability, and spindle formation	Colorectal, Cervical, GSC [64]
Flavopiridol	CDKs	Hyperphosphorylation at 34th position, mitotic block	Ovarian, Breast, Cervical [142]
Purvalanol A	P34 cdc2		Gastric, Ovarian [143]
NU6140	CDK2	Transcriptional inhibition and caspase activation	Cervical, Ovarian [144]
Cephalochro min	CDK2/ Cyclin -E CDK4/ Cyclin-D1	Mitochondrial disruption and cell cycle arrest	Lung [145]
Inhibitors of Signalling molecules
Prodigiosin	P53	Caspase activation	Breast, Liver, Colorectal, Leukaemia, CSCs [146]
Omega 3 fatty acids			Colon, Acute Myeloid Leukaemia, CSCs [147, 148, 232]
Nutlin 3a	Integrin-α5β1 MDM2	P53 and mTOR dependent downregulation	Glioblastoma [149, 150]
RG7388	MDM2		Neuroblastoma [149]
Rapamycin	mTOR	Binds to FKBP12	Glioblastoma, Leukaemia, Lymphoma, Multiplemyeloma [151]
MK2206	Akt	Inhibit Survivin-XIAP complex	Glioblastoma [152]
SH5	Akt	Inhibit phosphatidyl inositol binding domain and Akti-X	Chronic myeloid leukaemia, lung and Prostate [153, 154]
TG101209	JAK2	–	CML, Lung [163, 164]
Gefitinib	EGFR	Dephosphorylation of EGFR	Lung, Breast [157]
Lapatinib	EGFR and HER-2	Upregulation of BMI and attenuation of ErbB1 and ErbB2 phosphorylation	Pancreatic, Breast and Ovarian [155, 156]
Trastuzumab	ErbB2	Transcriptional inactivation thorough β-Catenin/TCF	Breast [214]
Wnt-2Ab	Wnt		Lung [215]
PD153035	MAPK/ EGFR	H4 acetylation via TSA activation	Breast, Ovarian, Pancreatic, Lung, Colorectal and Blood [158–160]
AG1478
PD98059
CI1040	MEK	Blocking phosphorylation of ERK	Leukaemia, Breast, Keratinocytes [161]
U0126
Bay-11-7057	IKK	Degradation of IĸB and inhibition of NF-ĸB	Pancreatic and Endothelial [182]
SD1029	JAK2	Combined inhibition of IAPs	Breast, Ovarian [168]
Panepoxyd- one	NF-ĸB	Regulation of IAPs	Breast [162]
Limonoids		Increase caspase 2 activity	Cervical [172]
Arctigenin	Stat3	Phosphorylation of Stat3,	NSCLC, Ovarian [165, 166]
Resveratrol		–	Cervical [169]
Tambjamine	JAK2 and IL-6	Stat3 phosphorylation	Lung [167]
GDP366	Survivin	Chromosomal Instability, Senescence	Leukaemia, Colon, Cervical [183]
Curcumin	NF-ĸB, Stat3, Akt	Multiple mechanisms	Breast, Ovarian, Liver cholangiocarcinoma [170, 243]
Etodolac Celecoxib	Cox2	PI3K/Akt suppression	Glioblastoma, Colon, Liver [173–175]
AKAP145	TGF-β	Dissociates Survivin/XIAP complex	Colon [184]
Metformin Phenformin		Affects Stat3, TGF-β and SMAD	Rectal [185, 226]
Salinomycin		Survivin downregulation	Renal cancer and CSCs [222]
IGC-001	β-catenin	Transcription inhibition and caspase activation	Colon [179], CSCs [237–239]
Emodin		Wnt /β-Catenin signalling regulation	Pancreatic [176, 177]
WM-127	Wnt	Supress β-catenin /TCF signalling induces Bax expression	Liver [178]
Xanthohumol Bulbine Futescens	Notch	Survivin suppression and affects stemness	Breast, Liver, Ovarian [180, 181]
SNS-032	CDK7/9	Downregulation of Survivin	Uveal melanoma [219]
Sabutoclax,	IL-6/Stat3		Breast CSCs [229]
CEP-1347	P38/MAPK		Ovarian CSCs [234]
Brexpiprazol	–	Reduction of Survivin	Pancreas, Lung, Brain CSCs [240]
AS602801	–	Combined downregulation of survivin and MDR1	Ovarian CSCs [248, 249]
Cardamonin	Stat 3	Survivin downregulation	GSCs [244]
Apigenin	PI3K/Akt	p53 and Apaf1 upregulation	Pancreatic CSCs[242]
PD173074	FGFR1	FGFR1/Scr/NF-ĸB axis	Pancreatic ductal adenocarcinoma CSCs [228]
mRNA Inhibitors
LY2181301 (AO)	3′ untranslated region	Target mRNA cleaving, caspase activation	Lymphoma, Leukaemia, Melanoma, Breast [187]
SPC3042 (AO)	Exon 4	Target mRNA cleaving	Prostate, Lung [187, 189]
Oligo4003 (AO)	232–251 nucleotides	Nuclear condensation, Apoptosome formation	Lung [190]
siRNA (RNAi)	Binding to RISC to Target RNA	Target RNA cleaving	Pancreatic, Breast, Colorectal, Glioblastomas [183, 233, 234]
miRNA (RNAi)	3’-UTR	Target RNA cleaving	Prostate, Pancreatic, Lung, Gastric, Breast, Liver, Bladder, CSCs [194–198, 253–256]
Ribozymes	GUC(294) or CUA(110) of 3’ end	Hydrolysis of phosphodiester bond	Melanoma, Prostate [201, 202]