Table 1

Compounds downregulating vimentin expression

Name of moleculeTypeEffectsModes of actionModelsReference
17-DMCHAGGeldanamycin derivativeAntimigratory;
antiproliferative
Inhibits HSP90; induces the proteasome-dependent degradation of androgen receptorHuman prostate cancer cells; tumour-bearing mice79
Alpha-lipoic acid*Acid;
antioxidant
Inhibitor of EMT;
antiproliferative
Inhibits TGF-ß; activates AMPK and downregulates mTOR-S6 signallingHuman thyroid cancer cells; tumour-bearing mice80
Apigenin*†Flavonoid derivativeAntiapoptosis;
pro-proliferative;
antifibrotic
Decreases miR-34aMouse mesothelial peritoneal cells81
Berberine*Alkaloid derivativeInhibitor of EMT;
antiproliferative
Decreases PI3/AKT, Ras-Raf-ERK and TGF-ß1 signallingMouse neuroblastoma cells82
BergamottinFuranocoumarin derivativeInhibitor of EMT;
antimigratory
Decreases PI3K/AKT/mTOR, TGF-ß signallingHuman lung adenocarcinoma cells83
Beta-asaronePhenylpropanoid derivativeInhibitor of EMT;
antimigratory
Decreases hnRNP A2/B1, MMP-9, p-STAT3 expressionHuman glioma cells84
Beta-lapachoneQuinone derivativeInhibitor of EMT;
antimigratory;
proapoptosis
Induces apoptosis through caspase-3, -8 and -9 activation and poly(ADP-ribose) cleavage; decreases MMP-2 and MMP-9Mouse colon cancer cells; tumour-bearing mice85
BHXPyrazoline derivativeInhibitor of EMT;
antimigratory;
proapoptosis
Inhibits Wnt/β-catenin signallingHuman breast cancer cells; tumour-bearing mice86
BMS345541Selective I kappa B kinase inhibitorInhibitor of EMT;
anti-inflammatory
Inhibits NF–κB/RelA pathwayHuman epithelial cells; polyinosinic–polycytidylic acid-treated mice87
Chrysin*Flavonoid derivativeInhibitor of EMT;
antimigratory
Reduces MMP-2 activity; induces zona occludens protein-1 and occludin expressionHuman renal epithelial cells; db/db mice88
ChrysotobibenzylInhibitor of EMT;
antimigratory
Decreases integrins (β1, β3, αν), p-FAK, p-AKT, caveolin-1 expressionHuman lung cancer cells89
CisplatinAnticancerInhibitor of EMT;
antimigratory;
antiproliferative
Reduces YAP activityHuman colon cancer cells; tumour-bearing mice90
Compound 11Selective class I HDAC inhibitorInhibitor of EMT;
antiproliferative
Decreases p-AKT, p-ERK activityHuman colorectal cancer cells; tumour-bearing mice91
Curcumin*Polyphenolic compoundInhibitor of EMT;
antimigratory;
antiproliferative
Decreases TGF-ß/Smad2/3 signallingHuman thyroid cancer cells92
CypripedinPhenanthrenequinone derivativeInhibitor of EMT;
antimigratory
Decreases AKT/GSK-3β signallingHuman lung cancer cells93
D-4FApolipoprotein A-I mimeticInhibitor of EMT;
antifibrotic
Inhibits TGF-ß1Human alveolar epithelial cells94
DehydroepiandrosteroneSteroidInhibitor of EMT;
antimigratory
Decreases N-cadherin and Snail expressionHuman breast cancer cells; tumour-bearing mice95
DictamnineAlkaloidInhibitor of EMT;
antiproliferative; proapoptosis
Decreases mTOR/p70S6K/eIF4E and MAPK signallingHuman lung cancer cells96
Ginsenoside Rg3*†Steroidal saponinInhibitor of EMT;
antimigratory;
proapoptosis
Inhibits LncRNA colon cancer-associated transcript 1 expression and PI3K/AKT signalling; inhibits MAPK and NF–κB signallingHuman colorectal cancer cells; lung cancer cells; tumour-bearing mice97 98
Hydrogen sulfide*†Inhibitor of EndMT; decrease ER stress; vasodilator; cardioprotectiveDecreases Smad2 and Src signallingHuman umbilical vein endothelial cells99
HydroxygenkwaninFlavonoid derivativeAntimigratory;
antiproliferative
Activates p21 signallingHuman oral squamous cell carcinoma44
Icariin*†Flavonoid derivativeAntimigratory;
antiproliferative;
proapoptosis
Inhibits PI3K, AKT and MEK/ERK signalling; decreases miR-625-3p and MMP-9 expressionHuman thyroid cancer cells100
Icariside IIFlavonol glycosideInhibitor of EMT;
antimigratory
Inhibits NF-κB and AKT/GSK-3ß signallingHuman lung cancer cells; tumour-bearing mice101
Inositol*†LipidInhibitor of EMT;
antimigratory
Inhibits PI3K/AKT and NF-κB signallingHuman breast cancer cells102
Melatonin*†HormoneInhibitor of EMT;
antimigratory;
antiproliferative
Inhibits PI3K/AKT signalling;
decreases MMP-2, MMP-9, NF-κB p65 expression
Human ovarian cancer cells;
gastric cancer cells; tumour-bearing mice
103 104
Metapristone*RU486 derivativeAntimigratory;
antiproliferative;
proapoptosis
Decreases AKT and ERK phosphorylation and Bcl-2; upregulates total p53 and Bax expressionMouse skin melanoma cells105
Metformin*†Biguanide derivative; antidiabeticInhibitor of EMT;
antimigratory
Downregulates HIF-1alpha, CAIX, miR-34a, SNAIL1 and ZEB1; upregulates miR-200a, miR-200c and miR-429Human cervical squamous cancer cells; human colorectal cancer cell106 107
MoscatilinBibenzyl derivativeInhibitor of EMT;
proapoptosis
Decreases ERK and AKT activity; downregulates caveolin-1 levelHuman lung cancer cells108
N-acetylcysteine*AntioxidantReduce fibrosis;
anti-inflammatory
Enhances antioxidant enzyme activities; downregulates oxidising enzymes’ expressionCrystalline silica-induced pulmonary fibrosis mice model109
Niclosamide*†AntihelminthicInhibitor of EMT;
antimigratory
Inhibits Wnt/β-catenin signallingHuman oral squamous cell carcinoma110
NorcantharidinCantharidin derivativeInhibitor of EMT;
antimigratory
Inhibits αvβ6-ERK-Ets1 signallingHuman colon cancer cells111
Osthole*Coumarin derivativeInhibitor of EMT;
antimigratory;
antiproliferative;
proapoptosis
Decreases MMP-2, MMP-9, Smad-3, Snail-1, Twist-1 expressionHuman renal cell carcinoma112
PAC*Curcumin analogueInhibitor of EMT;
antimigratory;
antiproliferative
Inhibits JAK2/STAT3, AKT/mTOR and MEK/ERK signalling; inhibits STAT3/cyclin D1 pathwayHuman colorectal cancer cells; tumour-bearing mice113
PalbociclibSelective CDK4/6 inhibitorInhibitor of EMT;
antimigratory
Inhibits c-Jun/COX-2 signallingHuman breast cancer cells; tumour-bearing mice114
PargylineLysine-specific demethylase 1 inhibitorInhibitor of EMT;
antimigratory
Reduces prostate-specific antigenHuman prostate cancer cells; tumour-bearing mice115
PhyscionAnthraquinone derivativeInhibitor of EMT;
antimigratory
Activates ROS/AMPK/GSK3β signalling; inhibits SOX2Human colorectal cancer cells116
Pterostilbene*†AntioxidantInhibitor of EMT;
antimigratory
Reduces Src/Fak signalling; upregulates miR-205 expressionHuman breast cancer cells; tumour-bearing mice117
Salidroside*Glucopyranoside derivativeInhibitor of EMT;
antimigratory;
antiproliferative
Downregulates miR-891b expression; inhibits PI3K/AKT/mTOR and NF-κB signallingWilms' tumour cells; mouse prostate cancer118
Selenium*†MetalInhibitor of EMTDownregulates genes involved in cellular migration, inflammation and mesenchymal markers; upregulates genes involved in epithelial markersHuman prostate119
Simvastatin*†StatinInhibitor of EMT;
antifibrotic
Decreases Toll-like receptor 4 and NF-κB signallingHuman biliary epithelial cells120
Sinomenine*†AlkaloidAntimigratory;
antiproliferative
Downregulates miR-23a expression; inhibits PI3K/AKT and JAK/STAT signallingHuman prostate cancer cells121
SwainsonineIndolizidine alkaloidAntimigratory;
antiproliferative;
proapoptosis
Downregulates miR-92a, inhibits PI3K/AKT/mTOR signallingHuman glioblastoma cells122
Tanshinone IIA*†Lipophilic compoundInhibitor of EMT;
antimigratory;
antiproliferative
Inhibits STAT3-CCL2 signallingHuman bladder cancer cells123
Tetramethylpyrazine nitroneTetramethylpyrazine derivativeReduces brain infarction; preserves neurological functionDecrease expression of neuroinflammatory markersCynomolgus macaques brain ischaemic stroke model124
TetrandrineAlkaloidInhibitor of EMT;
antimigratory
Reduces glioma-associated oncogene family zinc finger 1 (Gli-1) expressionHuman bladder cancer cells125
ToosendaninAlkaloidInhibitor of EMT;
antimigratory;
antiproliferative
Inhibits AKT/mTOR signallingHuman pancreatic cancer cells; tumour-bearing mice126
Triptolide*†Diterpenoid derivativeAntifibroticInhibits TLR4-induced NF-κB/IL-1β immune pathway; inhibits NF-κB/TNF-α/VCAM-1 inflammatory pathway; downregulates TGF-β1/α-SMA/vimentin fibrosis pathwayDiabetic rats127
Valproic acid*†AcidInhibitor of EMT;
antiproliferative
Downregulates Smad4 expression; upregulates transcriptional intermediary factor-1γ (TIF1γ) expressionHuman prostate carcinoma cells; tumour-bearing mice128 129
Wogonin*Flavonoid derivativeInhibitor of EMT;
antimigratory
Inhibits IL-6/STAT3 signalling pathwayHuman alveolar adenocarcinoma cells130
  • A selection of compounds downregulating vimentin expression and their major cellular and molecular effects. Some of these molecules already have FDA approval, thus can be immediately used to set up clinical trials against COVID-19.

  • *Indicates the compounds have been referenced by the FDA; the latter group of drugs is briefly discussed in the text.

  • †Indicates the compounds that have been reported to play a role in acute lung injury.

  • AMPK, AMP-activated protein kinase; ANG, Angiotensin; Bax, Bcl-2–associated X; Bcl-2, B-cell lymphoma 2; CCL2, Chemokine ligand 2; 17-DMCHAG, 17-(6-(3,4-dimethoxycinnamamido)hexylamino)-17-demethoxy-geldanamycin; eIF4E, Eukaryotic translation initiation factor 4E; EMT, epithelial to mesenchymal transition; EndMT, endothelial to mesenchymal transition; ER, endoplasmic reticulum; ERK, Extracellular signal-regulated kinase; FAK, Focal adhesion kinase; FDA, Food and Drug Administration; GSK-3, Glycogen synthase kinase-3; HDAC, Histone deacetylase; HIF, Hypoxia Inducible Factor; hRNP, Heterogeneous Nuclear Ribonucleoprotein; HSP, Heat Shock Protien; IL, Interleukin; JAK2, Janus kinase 2; LncRNA, Long noncoding RNAs; MAPK, Mitogen-activated protein kinase; MMP, Matrix metallopeptidase; mTOR, Mechanistic target of rapamycin; NF-κB, nuclear factor-kappa B; PEA3, polyoma enhancer activator 3; PI3K, Phosphatidylinositol 3-kinase; ROS, Reactive oxygen species; SMA, Smooth muscle actin; Smad, small mothers against decapentaplegic transcription factor; STAT3, Signal transducer and activator of transcription 3; TGF, Transforming growth factor; TLR4, Toll-like receptor 4; TNF, Tumor necrosis factor; VCAM, Vascular cell adhesion molecule; YAP, Yes-associated protein.