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"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2017/04/30

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Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections.

Curr Top Med Chem. 2017;17(10):1157-1176

Authors: Soo VW, Kwan BW, Quezada H, Castillo-Juárez I, Pérez-Eretza B, García-Contreras SJ, Martínez-Vázquez M, Wood TK, García-Contreras R

Abstract
Despite the fact that bacterial infections are one of the leading causes of death worldwide and that mortality rates are increasing at alarming rates, no new antibiotics have been produced by the pharmaceutical industry in more than a decade. The situation is so dire that the World Health Organization warned that we may enter a "post-antibiotic era" within this century; accordingly, bacteria resistant against all known antibiotics are becoming common and already producing untreatable infections. Although several novel approaches to combat bacterial infections have been proposed, they have yet to be implemented in clinical practice. Hence, we propose that a more plausible and faster approach is the utilization of drugs originally developed for other purposes besides antimicrobial activity. Among these are some anticancer molecules proven effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria; some of which also protect animals from infections and recently are undergoing clinical trials. In this review, we highlight the similarities between cancer cells/tumors and bacterial infections, and present evidence that supports the utilization of some anticancer drugs, including 5-fluorouracil (5-FU), gallium (Ga) compounds, and mitomycin C, as antibacterials. Each of these drugs has some promising properties such as broad activity (all three compounds), dual antibiotic and antivirulence properties (5-FU), efficacy against multidrug resistant strains (Ga), and the ability to kill metabolically dormant persister cells which cause chronic infections (mitomycin C).

PMID: 27697046 [PubMed - indexed for MEDLINE]

Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron.

J Pharmacol Toxicol Methods. 2017 Apr 20;:

Authors: Korstanje C, Suzuki M, Yuno K, Sato S, Ukai M, Schneidkraut MJ, Yan GX

Abstract
INTRODUCTION: Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron.
METHODS: Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (IKr, IKs, Ito, INa, and ICa,L), on QT-interval, subendocardial APD90, Tpeak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QTc) in conscious dogs.
RESULTS: In conscious dogs, mirabegron (0.01-10mg/kg, p.o.) dose-dependently increased HR, reduced SBP but DBP was unchanged. Propranolol blocked the decrease in SBP and attenuated HR increase at 100mg/kg mirabegron. Mirabegron, at 30, 60, or 100mg/kg, p.o., had no significant effect on the QTc interval. In paced dog ventricular wedge, neither mirabegron nor metabolites M5, M11, M12, M14, and M16 prolonged QT, altered transmural dispersion of repolarization, induced premature ventricular contractions, or induced ventricular tachycardia. Mirabegron nor its metabolites inhibited IKr, IKs, Ito INa, or ICa,L at clinically relevant concentrations.
DISCUSSION: Up to exposure levels well exceeding human clinical exposure no discernible effects on ion channel conductance or on arrhythmogenic parameters in ventricular wedge resulted for mirabegron, or its main metabolites, confirming human cardiac safety findings. In vivo, dose-related increases in HR with effects markedly higher than seen clinically, was mediated in part by cross-activation of beta-1 adrenoceptors. This non-clinical cardiac safety test program therefore proved predictive for human cardiac safety for mirabegron.

PMID: 28434969 [PubMed - as supplied by publisher]

The Molecular Revolution in Cutaneous Biology: Emerging Landscape in Genomic Dermatology: New Mechanistic Ideas, Gene Editing, and Therapeutic Breakthroughs.

J Invest Dermatol. 2017 May;137(5):e123-e129

Authors: Titeux M, Izmiryan A, Hovnanian A

Abstract
Stunning technological advances in genomics have led to spectacular breakthroughs in the understanding of the underlying defects, biological pathways and therapeutic targets of skin diseases leading to new therapeutic interventions. Next-generation sequencing has revolutionized the identification of disease-causing genes and has a profound impact in deciphering gene and protein signatures in rare and frequent skin diseases. Gene addition strategies have shown efficacy in junctional EB and in recessive dystrophic EB (RDEB). TALENs and Cripsr/Cas9 have emerged as highly efficient new tools to edit genomic sequences to creat new models and to correct or disrupt mutated genes to treat human diseases. Therapeutic approaches have not been limited to DNA modification and strategies at the mRNA, protein and cellular levels have also emerged, some of which have already proven clinical efficacy in RDEB. Improved understanding of the pathogenesis of skin disorders has led to the development of specific drugs or repurposing of existing medicines as in basal cell nevus syndrome, alopecia areata, melanoma and EB simplex. These discoveries pave the way for improved targeted personalized medicine for rare and frequent diseases. It is likely that a growing number of orphan skin diseases will benefit from combinatory new therapies in a near future.

PMID: 28411843 [PubMed - indexed for MEDLINE]

Mechanistic insights into epigenetic modulation of ethanol consumption.

Alcohol. 2017 Mar 12;:

Authors: Ponomarev I, Stelly CE, Morikawa H, Blednov YA, Mayfield RD, Harris RA

Abstract
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking. Decitabine but not SAHA reduced ethanol consumption in both tests. We further investigated decitabine's effects on the brain's reward pathway by gene expression profiling in the ventral tegmental area (VTA), using RNA sequencing and electrophysiological recordings from VTA dopaminergic neurons. Decitabine-induced decreases in EOD drinking were associated with global changes in gene expression, implicating regulation of cerebral blood flow, extracellular matrix organization, and neuroimmune functions in decitabine actions. In addition, an in vivo administration of decitabine shortened ethanol-induced excitation of VTA dopaminergic neurons in vitro, suggesting that decitabine reduces ethanol drinking via changes in the reward pathway. Taken together, our data suggest a contribution of both neuronal and non-neuronal mechanisms in the VTA in the regulation of ethanol consumption. Decitabine and other epigenetic compounds have been approved for cancer treatment, and understanding their mechanisms of actions in the brain may assist in repurposing these drugs and developing novel therapies for central disorders, including drug addiction.

PMID: 28433417 [PubMed - as supplied by publisher]

Repurposed drugs targeting eIF2α-P-mediated translational repression prevent neurodegeneration in mice.

Brain. 2017 Apr 19;:

Authors: Halliday M, Radford H, Zents KAM, Molloy C, Moreno JA, Verity NC, Smith E, Ortori CA, Barrett DA, Bushell M, Mallucci GR

Abstract
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss. Re-establishing translation rates by inhibition of eIF2α-P activity, genetically or pharmacologically, restores memory and prevents neurodegeneration and extends survival. However, the experimental compounds used preclinically are unsuitable for use in humans, due to associated toxicity or poor pharmacokinetic properties. To discover compounds that have anti-eIF2α-P activity suitable for clinical use, we performed phenotypic screens on a NINDS small molecule library of 1040 drugs. We identified two compounds, trazodone hydrochloride and dibenzoylmethane, which reversed eIF2α-P-mediated translational attenuation in vitro and in vivo. Both drugs were markedly neuroprotective in two mouse models of neurodegeneration, using clinically relevant doses over a prolonged period of time, without systemic toxicity. Thus, in prion-diseased mice, both trazodone and dibenzoylmethane treatment restored memory deficits, abrogated development of neurological signs, prevented neurodegeneration and significantly prolonged survival. In tauopathy-frontotemporal dementia mice, both drugs were neuroprotective, rescued memory deficits and reduced hippocampal atrophy. Further, trazodone reduced p-tau burden. These compounds therefore represent potential new disease-modifying treatments for dementia. Trazodone in particular, a licensed drug, should now be tested in clinical trials in patients.

PMID: 28430857 [PubMed - as supplied by publisher]

Growth-suppressive activity of raloxifene on liver cancer cells by targeting IL-6/GP130 signaling.

Oncotarget. 2017 Apr 06;:

Authors: Wang Y, Ma H, Zhao C, Liu T, Yan D, Jou D, Li H, Zhang C, Lü J, Li C, Lin J, Li S, Lin L

Abstract
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning. The possible effect of Raloxifene in STAT3 signaling or liver cancer cells is still unclear.
RESULTS: Raloxifene inhibited the P-STAT3 stimulated by IL-6, but not the induction of STAT1 and STAT6 phosphorylation by IFN-γ, IFN-α, and IL-4. Raloxifene inhibited STAT3 phosphorylation and resulted in the induction apoptosis on human liver cancer cell-lines. Raloxifene inhibited the targets of STAT3, such as Bcl-2, Bcl-xl and survivin and cell viability, cell migration, and colony formation in liver cancer cells. Further, daily administration of Raloxifene suppressed the Hep-G2 tumor growth in mice in vivo.
MATERIALS AND METHODS: The inhibitory effect on STAT3 phosphorylation and activity as well as cell viability, migration, and colony forming ability by Raloxifene was examined in human liver cancer cells. Tumor growth was detected via mouse xenograft tumor mode.
CONCLUSIONS: Our results suggest that Raloxifene is a potent IL-6/GP130 inhibitor and may be a chemoprevention agent for liver cancer by targeting persistent STAT3 signaling.

PMID: 28430601 [PubMed - as supplied by publisher]

Benserazide, a dopadecarboxylase inhibitor, suppresses tumor growth by targeting hexokinase 2.

J Exp Clin Cancer Res. 2017 Apr 20;36(1):58

Authors: Li W, Zheng M, Wu S, Gao S, Yang M, Li Z, Min Q, Sun W, Chen L, Xiang G, Li H

Abstract
BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy.
METHODS: Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity. Enzyme inhibition, cytotoxicity, apoptosis, intracellular ATP level, mitochondrial membrane potential (MMP), glucose uptake and lactate production experiments were undertaken in SW480 cells to identify Benz as a HK2 inhibitor. Western blot was used to test protein expression. SW480 cells xenograft mouse models were used for in vivo study. Nano-particles of Benz were prepared to improve the antitumor efficacy and tumor targeting of Benz. HPLC was used to measure the concentration of free Benz in tumor tissues.
RESULTS: Benserazide (Benz), was identified as a selective HK2 inhibitor, could specifically bind to HK2 and significantly inhibit HK2 enzymatic activity in vitro. In addition, Benz reduced glucose uptake, lactate production and intracellular ATP level, and could cause cell apoptosis and an increased loss of MMP as well. In vivo study indicated that intraperitoneal (ip) injection of Benz at 300 and 600 mg/Kg suppressed cancer growth in tumor-bearing mice and no toxicity shown. To further improve the antitumor efficacy and tumor targeting of Benz, nano-particles of Benz was prepared. Liposomal Benz at 100 and 200 mg/Kg performed potent inhibitory effects on tumor-bearing mice, showing reduced dose and better efficacy.
CONCLUSIONS: Our study provides a new direction for the development of Benz and its analogues as novel antitumor agents for cancer therapy.

PMID: 28427443 [PubMed - in process]

Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma.

Oncotarget. 2017 Apr 04;8(14):22811-22824

Authors: Furuta T, Sabit H, Dong Y, Miyashita K, Kinoshita M, Uchiyama N, Hayashi Y, Hayashi Y, Minamoto T, Nakada M

Abstract
BACKGROUND: Glycogen synthase kinase (GSK)-3β has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3β activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ).
MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3β in the primary tumor. GBM cells and a mouse model were examined for the effects of GSK3β-inhibitory drugs, cimetidine, lithium, olanzapine, and valproate. The safety and efficacy of the cocktail of these drugs (CLOVA cocktail) in combination with TMZ were tested in the mouse model and in a clinical study for recurrent GBM patients.
RESULTS: Activation of GSK3β in the tumor inversely correlated with patient survival as an independent prognostic factor. CLOVA cocktail significantly inhibited cell invasion and proliferation. The patients treated with CLOVA cocktail in combination with TMZ showed increased survival compared to the control group treated with TMZ alone.
CONCLUSIONS: Repositioning of the GSK3β-inhibitory drugs improved the prognosis of refractory GBM patients with active GSK3β in tumors. Combination of CLOVA cocktail and TMZ is a promising approach for recurrent GBM.

PMID: 28423558 [PubMed - in process]

Drug Repurposing Patent Applications October-December 2016.

Assay Drug Dev Technol. 2017 Apr;15(3):120-126

Authors: Mucke HAM

PMID: 28418694 [PubMed - in process]

Validating the Predicted Effect of Astemizole and Ketoconazole Using a Drosophila Model of Parkinson's Disease.

Assay Drug Dev Technol. 2017 Apr;15(3):106-112

Authors: Styczyńska-Soczka K, Zechini L, Zografos L

Abstract
Parkinson's disease is a growing threat to an ever-ageing population. Despite progress in our understanding of the molecular and cellular mechanisms underlying the disease, all therapeutics currently available only act to improve symptoms and do not stop the disease process. It is therefore imperative that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson's. Drug repurposing has been recognized as being equally as promising as de novo drug discovery in the field of neurodegeneration and Parkinson's disease specifically. In this work, we utilize a transgenic Drosophila model of Parkinson's disease, made by expressing human alpha-synuclein in the Drosophila brain, to validate two repurposed compounds: astemizole and ketoconazole. Both have been computationally predicted to have an ameliorative effect on Parkinson's disease, but neither had been tested using an in vivo model of the disease. After treating the flies in parallel, results showed that both drugs rescue the motor phenotype that is developed by the Drosophila model with age, but only ketoconazole treatment reversed the increased dopaminergic neuron death also observed in these models, which is a hallmark of Parkinson's disease. In addition to validating the predicted improvement in Parkinson's disease symptoms for both drugs and revealing the potential neuroprotective activity of ketoconazole, these results highlight the value of Drosophila models of Parkinson's disease as key tools in the context of in vivo drug discovery, drug repurposing, and prioritization of hits, especially when coupled with computational predictions.

PMID: 28418693 [PubMed - in process]

Drug Repurposing Patent Applications January-March 2017.

Assay Drug Dev Technol. 2017 Apr;15(3):127-132

Authors: Mucke HAM

PMID: 28418692 [PubMed - in process]

Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses.

Molecules. 2016 Jun 28;21(7):

Authors: Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA

Abstract
In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders.

PMID: 27367653 [PubMed - indexed for MEDLINE]

Some Remarks on Prediction of Drug-Target Interaction with Network Models.

Curr Top Med Chem. 2017 Apr 14;:

Authors: Zhang SW, Yan XY

Abstract
System-level understanding of the relationships between drugs and targets is very important for enhancing drug research, especially for drug function repositioning. The experimental methods used to determine drug-target interactions are usually time-consuming, tedious and expensive, and sometimes lack reproducibility. Thus, it is highly desired to develop computational methods for efficiently and effectively analyzing and detecting new drug-target interaction pairs. With the explosive growth of different types of omics data, such as genome, pharmacology, phenotypic, and other kinds of molecular networks, numerous computational approaches have been developed to predict drug-target interactions (DTI). In this review, we make a survey on the recent advances in predicting drug-target interaction with network-based models from the following aspects: i) Available public data sources and benchmark datasets, ii) Drug/target similarity metrics, iii) Network construction, iv) Common network algorithms, v) Performance comparison of existing network-based DTI predictors.

PMID: 28413948 [PubMed - as supplied by publisher]

Molecular therapies for inherited epidermolysis bullosa.

G Ital Dermatol Venereol. 2016 Aug;151(4):397-402

Authors: Has C

Abstract
Inherited epidermolysis bullosa (EB) comprises rare genetic disorders characterized by formation of blisters and erosions of skin and mucous membranes after minor mechanical trauma. The molecular basis and the pathomechanisms of the main EB types have been largely deciphered in the past decades. The burden of the disease is high and quality of life strongly affected. The treatment is still symptomatic aiming to support wound healing and resolve complications. Numerous experimental therapeutic approaches for EB have been explored in the last years, most of them dedicated to dystrophic EB. Although gene and cell therapies have been already applied in patients, molecular therapies including gene editing and repurposing of small molecules are currently very attractive. Recent data on the effect of small molecules, like aminoglycosides and angiotensin receptor blockers in preclinical models for dystrophic EB are encouraging. The efficacy in patients remains to be proven in clinical trials. Therapeutic efficacy, as well as unexpected outcomes must be carefully monitored.

PMID: 27149615 [PubMed - indexed for MEDLINE]

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections.

Curr Opin Virol. 2017 Apr 12;24:1-8

Authors: Bauer L, Lyoo H, van der Schaar HM, Strating JR, van Kuppeveld FJ

Abstract
Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues. As an alternative approach, host-targeting inhibitors with potential broad-spectrum activity have been identified. Furthermore, drug repurposing screens have recently uncovered promising new inhibitors with disparate viral and host targets. Together, these findings raise hope for the development of (broad-range) anti-enteroviral drugs.

PMID: 28411509 [PubMed - as supplied by publisher]

The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans.

Front Microbiol. 2017;8:535

Authors: Joffe LS, Schneider R, Lopes W, Azevedo R, Staats CC, Kmetzsch L, Schrank A, Del Poeta M, Vainstein MH, Rodrigues ML

Abstract
Cryptococcus neoformans is the most lethal pathogen of the central nervous system. The gold standard treatment of cryptococcosis, a combination of amphotericin B with 5-fluorocytosine, involves broad toxicity, high costs, low efficacy, and limited worldwide availability. Although the need for new antifungals is clear, drug research and development (R&D) is costly and time-consuming. Thus, drug repurposing is an alternative to R&D and to the currently available tools for treating fungal diseases. Here we screened a collection of compounds approved for use in humans seeking for those with anti-cryptococcal activity. We found that benzimidazoles consist of a broad class of chemicals inhibiting C. neoformans growth. Mebendazole and fenbendazole were the most efficient antifungals showing in vitro fungicidal activity. Since previous studies showed that mebendazole reaches the brain in biologically active concentrations, this compound was selected for further studies. Mebendazole showed antifungal activity against phagocytized C. neoformans, affected cryptococcal biofilms profoundly and caused marked morphological alterations in C. neoformans, including reduction of capsular dimensions. Amphotericin B and mebendazole had additive anti-cryptococcal effects. Mebendazole was also active against the C. neoformans sibling species, C. gattii. To further characterize the effects of the drug a random C. gattii mutant library was screened and indicated that the antifungal activity of mebendazole requires previously unknown cryptococcal targets. Our results indicate that mebendazole is as a promising prototype for the future development of anti-cryptococcal drugs.

PMID: 28400768 [PubMed - in process]

Baseline Regularization for Computational Drug Repositioning with Longitudinal Observational Data.

IJCAI (U S). 2016 Jul;2016:2521-2528

Authors: Kuang Z, Thomson J, Caldwell M, Peissig P, Stewart R, Page D

Abstract
Computational Drug Repositioning (CDR) is the knowledge discovery process of finding new indications for existing drugs leveraging heterogeneous drug-related data. Longitudinal observational data such as Electronic Health Records (EHRs) have become an emerging data source for CDR. To address the high-dimensional, irregular, subject and time-heterogeneous nature of EHRs, we propose Baseline Regularization (BR) and a variant that extend the one-way fixed effect model, which is a standard approach to analyze small-scale longitudinal data. For evaluation, we use the proposed methods to search for drugs that can lower Fasting Blood Glucose (FBG) level in the Marshfield Clinic EHR. Experimental results suggest that the proposed methods are capable of rediscovering drugs that can lower FBG level as well as identifying some potential blood sugar lowering drugs in the literature.

PMID: 28392671 [PubMed - in process]

The Drug Repurposing Hub: a next-generation drug library and information resource.

Nat Med. 2017 Apr 07;23(4):405-408

Authors: Corsello SM, Bittker JA, Liu Z, Gould J, McCarren P, Hirschman JE, Johnston SE, Vrcic A, Wong B, Khan M, Asiedu J, Narayan R, Mader CC, Subramanian A, Golub TR

PMID: 28388612 [PubMed - in process]

Proton pump inhibitor ilaprazole suppresses cancer growth by targeting T-cell-originated protein kinase.

Oncotarget. 2017 Mar 27;:

Authors: Zheng M, Luan S, Gao S, Cheng L, Hao B, Li J, Chen Y, Hou X, Chen L, Li H

Abstract
T-cell-originated protein kinase (TOPK) is highly and frequently expressed in various cancer tissues and plays an indispensable role in the mitosis of cancer cells, and therefore, it is an important target for drug treatment of tumor. Ilaprazole was identified to be a potent TOPK inhibitor. The data indicated that ilaprazole inhibited TOPK activities with high affinity and selectivity. In vitro studies showed that ilaprazole inhibited TOPK activities in HCT116, ES-2, A549, SW1990 cancer cells. Moreover, knockdown of TOPK in these cells decreased their sensitivities to ilaprazole. Results of an in vivo study demonstrated that gavage of ilaprazole in HCT116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after ilaprazole treatment. Our results suggested that ilaprazole inhibited the cancer growth by targeting TOPK both in vitro and in vivo.

PMID: 28388576 [PubMed - as supplied by publisher]