Targeting epithelial-mesenchymal plasticity in cancer: clinical and preclinical advances in therapy and monitoring.

Biochem J. 2017 Sep 20;474(19):3269-3306

Authors: Bhatia S, Monkman J, Toh AKL, Nagaraj SH, Thompson EW

Abstract
The concept of epithelial-mesenchymal plasticity (EMP), which describes the dynamic flux within the spectrum of phenotypic states that invasive carcinoma cells may reside, is being increasingly recognised for its role in cancer progression and therapy resistance. The myriad of events that are able to induce EMP, as well as the more recently characterised control loops, results in dynamic transitions of cancerous epithelial cells to more mesenchymal-like phenotypes through an epithelial-mesenchymal transition (EMT), as well as the reverse transition from mesenchymal phenotypes to an epithelial one. The significance of EMP, in its ability to drive local invasion, generate cancer stem cells and facilitate metastasis by the dissemination of circulating tumour cells (CTCs), highlights its importance as a targetable programme to combat cancer morbidity and mortality. The focus of this review is to consolidate the existing knowledge on the strategies currently in development to combat cancer progression via inhibition of specific facets of EMP. The prevalence of relapse due to therapy resistance and metastatic propensity that EMP endows should be considered when designing therapy regimes, and such therapies should synergise with existing chemotherapeutics to benefit efficacy. To further improve upon EMP-targeted therapies, it is imperative to devise monitoring strategies to assess the impact of such treatments on EMP-related phenomenon such as CTC burden, chemosensitivity/-resistance and micrometastasis in patients.

PMID: 28931648 [PubMed - indexed for MEDLINE]

Pharmacological approach for drug repositioning against cardiorenal diseases.

J Med Invest. 2017;64(3.4):197-201

Authors: Zamami Y, Imanishi M, Takechi K, Ishizawa K

Abstract
New applications of approved clinically used drugs are being discovered. Drug repositioning is a proposed strategy for developing these drugs as therapeutic agents for different diseases. Currently, approximately 2000 drugs are used in Japan. However, the compound targets and pathways involved in the pharmacological actions of 70-80% of these drugs have not been adequately clarified. Pharmacological examination of approved drugs is an important task in drug repositioning and vital for improving drug development efficiency. This review reports that angiotensin II type 1 receptor blockers show receptor-independent effects against reactive oxygen species generation in renal cells. Additionally, nitrosonifedipine has an antioxidative effect and protects endothelial cells against oxidative stress, and pioglitazone has multiple effects that improve dysfunctions in vascular control regulated by adrenergic and calcitonin gene-related peptide-containing nerves in animal models of diabetes. These data suggest that some approved drugs could be useful for treating cardiorenal diseases. Since cardiorenal diseases are likely to have chronic pathological conditions and require chronic drug administration, highly safe drugs are needed. Compared to newly developed drugs, drug repositioning of approved drugs with safety information is considered a particularly useful technique for searching new treatments for cardiorenal diseases. J. Med. Invest. 64: 197-201, August, 2017.

PMID: 28954981 [PubMed - in process]

A perspective on genomic-guided anthelmintic discovery and repurposing using Haemonchus contortus.

Infect Genet Evol. 2016 Jun;40:368-73

Authors: Preston S, Jabbar A, Gasser RB

Abstract
High-throughput molecular and computer technologies have become instrumental for systems biological explorations of parasites. Investigating the genomes and transcriptomes of different developmental stages of parasitic nematodes can provide insights into gene expression, regulation and function in the parasite, which is a significant step toward understanding their biology as well as host interactions and disease. This article covers aspects of a talk given at the MEEGID XII conference in Thailand in 2014. Here, we refer to recent studies of the genomes and transcriptomes of socioeconomically important parasitic nematodes of animals; provide an account of the barber's pole worm (Haemonchus contortus) and emerging drug resistance problems in this and related worms; we also propose a genomic-guided drug discovery and repurposing approach, involving the prediction of the druggable genome, prioritization of drug targets, screening of compound libraries against H. contortus and, briefly, a hit-to-lead optimization approach. We conclude by indicating prospects that molecular tool kits for nematodes provide to the scientific community for future comparative genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological and epidemiological investigations, and as a basis for biotechnological outcomes and translation.

PMID: 26144657 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2017/09/24

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Systematic integration of biomedical knowledge prioritizes drugs for repurposing.

Elife. 2017 Sep 22;6:

Authors: Himmelstein DS, Lizee A, Hessler C, Brueggeman L, Chen SL, Hadley D, Green A, Khankhanian P, Baranzini SE

Abstract
The ability to computationally predict whether a compound treats a disease would improve the economy and success rate of drug approval. This study describes Project Rephetio to systematically model drug efficacy based on 755 existing treatments. First, we constructed Hetionet (neo4j.het.io), an integrative network encoding knowledge from millions of biomedical studies. Hetionet v1.0 consists of 47,031 nodes of 11 types and 2,250,197 relationships of 24 types. Data was integrated from 29 public resources to connect compounds, diseases, genes, anatomies, pathways, biological processes, molecular functions, cellular components, pharmacologic classes, side effects, and symptoms. Next, we identified network patterns that distinguish treatments from non-treatments. Then we predicted the probability of treatment for 209,168 compound-disease pairs (het.io/repurpose). Our predictions validated on two external sets of treatment and provided pharmacological insights on epilepsy, suggesting they will help prioritize drug repurposing candidates. This study was entirely open and received realtime feedback from 40 community members.

PMID: 28936969 [PubMed - as supplied by publisher]

Metformin as a repurposed therapy in advanced non-small cell lung cancer (NSCLC): results of a phase II trial.

Invest New Drugs. 2017 Sep 22;:

Authors: Parikh AB, Kozuch P, Rohs N, Becker DJ, Levy BP

Abstract
Background Metformin has been shown to have anti-neoplastic activity in non-small cell lung cancer (NSCLC) in both preclinical and observational studies, however this has never been prospectively evaluated. This single-arm phase II trial, while not fully accrued, is the first known prospective study evaluating the use of metformin with chemotherapy in advanced NSCLC. Methods Patients received carboplatin AUC 5 + pemetrexed 500 mg/m2 IV every 21 days for 4 cycles. For patients who achieved at least stable disease, maintenance pemetrexed was administered until progression or toxicity. Metformin was initiated at 1000 mg/day for week 1, 1500 mg/day for week 2, then 2000 mg/day thereafter, in divided doses. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and adverse events (AE). Tumor tissue was tested for LKB1/STK11 mutations, and non-fasting serum insulin levels were longitudinally assessed. Results Of a planned 50 patients, 14 were enrolled. ORR was 23% and median PFS was 3.9 months. Median OS was 11.7 months. No LKB1/STK11 mutations were identified. The most common AE were fatigue (42.9%), anemia, and nausea (28.6% each). The most common grade III AE was nausea (14.3%). No grade IV AE occurred. Mean duration of metformin treatment was 5.6 months. Conclusion Adding metformin to chemotherapy for advanced NSCLC was safe but did not significantly improve clinical outcomes compared to historical phase III controls. These results are limited by the small sample size; larger trials are needed.

PMID: 28936567 [PubMed - as supplied by publisher]

Psilocybin: Good Trip or Bad Trip.

Clin Pharmacol Ther. 2017 Oct;102(4):580-584

Authors: Sellers EM

Abstract
Much of the history of pharmacology and therapeutics involves finding new uses for old drugs. The latest rediscovery is that of psychedelic drugs. Since they can cause profound distortions of perception and were once used as part of religious ceremonies, such research may seem unusual at this time.

PMID: 28548221 [PubMed - indexed for MEDLINE]

Use of an anti-viral drug, Ribavirin, as an anti-glioblastoma therapeutic.

Oncogene. 2017 May 25;36(21):3037-3047

Authors: Volpin F, Casaos J, Sesen J, Mangraviti A, Choi J, Gorelick N, Frikeche J, Lott T, Felder R, Scotland SJ, Eisinger-Mathason TSK, Brem H, Tyler B, Skuli N

Abstract
The median survival for glioblastoma patients is ~15 months despite aggressive surgery and radio-chemotherapy approaches. Thus, developing new therapeutics is necessary to improve the treatment of these invasive brain tumors, which are known to show high levels of the eukaryotic initiation factor, eIF4E, a potent oncogene. Ribavirin, the only clinically approved drug known to target eIF4E, is an anti-viral molecule currently used in hepatitis C treatment. Here, we report the effect of ribavirin on proliferation, cell cycle, cell death and migration of several human and murine glioma cell lines, as well as human glioblastoma stem-like cells, in vitro. In addition, we tested ribavirin efficacy in vivo, alone and in combination with temozolomide and radiation. Our work showed that ribavirin inhibits glioma cell growth and migration, and increases cell cycle arrest and cell death, potentially through modulation of the eIF4E, EZH2 and ERK pathways. We also demonstrate that ribavirin treatment in combination with temozolomide or irradiation increases cell death in glioma cells. Finally and most importantly, ribavirin treatment in vivo significantly enhances chemo-radiotherapy efficacy and improves survival of rats and mice orthotopically implanted with gliosarcoma tumors or glioma stem-like cells, respectively. On the basis of these results, we propose that ribavirin represents a new therapeutic option for glioblastoma patients as an enhancer of the cytotoxic effects of temozolomide and radiotherapy.

PMID: 27941882 [PubMed - indexed for MEDLINE]

Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration-Approved Drugs.

Pharmacol Rev. 2017 Oct;69(4):479-496

Authors: Coussens NP, Braisted JC, Peryea T, Sittampalam GS, Simeonov A, Hall MD

Abstract
High-throughput screening (HTS) of small-molecule libraries accelerates the discovery of chemical leads to serve as starting points for probe or therapeutic development. With this approach, thousands of unique small molecules, representing a diverse chemical space, can be rapidly evaluated by biologically and physiologically relevant assays. The origins of numerous United States Food and Drug Administration-approved cancer drugs are linked to HTS, which emphasizes the value in this methodology. The National Institutes of Health Molecular Libraries Program made HTS accessible to the public sector, enabling the development of chemical probes and drug-repurposing initiatives. In this work, the impact of HTS in the field of oncology is considered among both private and public sectors. Examples are given for the discovery and development of approved cancer drugs. The importance of target validation is discussed, and common assay approaches for screening are reviewed. A rigorous examination of the PubChem database demonstrates that public screening centers are contributing to early-stage drug discovery in oncology by focusing on new targets and developing chemical probes. Several case studies highlight the value of different screening strategies and the potential for drug repurposing.

PMID: 28931623 [PubMed - in process]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2017/09/21

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Drug repurposing may generate novel approaches to treating depression.

J Pharm Pharmacol. 2017 Sep 18;:

Authors: Ebada ME

Abstract
OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression. This short review discusses the progress made in repurposing drugs for antidepressant actions.
KEY FINDINGS: Drugs being repurposed as antidepressants act on novel drug targets, thereby treating resistant depression and improving remission rate. Drugs such as ketamine, dextromethorphan/quinidine and scopolamine are rapidly acting antidepressants targeting glutamate receptors. Nimodipine and quetiapine are efficient add-on therapy for late-life depression. Anti-inflammatory drugs, statins, insulin sensitizers, minocycline could remarkably contribute to treating refractory depression.
SUMMARY: Drug repurposing represents an alternative approach to cope with major obstacles, including financial insufficiency and unavoidable long lag evaluation time, undermining the classical pathway of developing new hit compounds into clinically approved antidepressants.

PMID: 28925030 [PubMed - as supplied by publisher]

Exploring the anti-proliferative activity of Pelargonium sidoides DC with in silico target identification and network pharmacology.

Mol Divers. 2017 Sep 18;:

Authors: Pereira ASP, Bester MJ, Apostolides Z

Abstract
Pelargonium sidoides DC (Geraniaceae) is a medicinal plant indigenous to Southern Africa that has been widely evaluated for its use in the treatment of upper respiratory tract infections. In recent studies, the anti-proliferative potential of P. sidoides was shown, and several phenolic compounds were identified as the bioactive compounds. Little, however, is known regarding their anti-proliferative protein targets. In this study, the anti-proliferative mechanisms of P. sidoides through in silico target identification and network pharmacology methodologies were evaluated. The protein targets of the 12 phenolic compounds were identified using the target identification server PharmMapper and the server for predicting Drug Repositioning and Adverse Reactions via the Chemical-Protein Interactome (DRAR-CPI). Protein-protein and protein-pathway interaction networks were subsequently constructed with Cytoscape 3.4.0 to evaluate potential mechanisms of action. A total of 142 potential human target proteins were identified with the in silico target identification servers, and 90 of these were found to be related to cancer. The protein interaction network was constructed from 86 proteins involved in 209 interactions with each other, and two protein clusters were observed. A pathway enrichment analysis identified over 80 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched with the protein targets and included several pathways specifically related to cancer as well as various signaling pathways that have been found to be dysregulated in cancer. These results indicate that the anti-proliferative activity of P. sidoides may be multifactorial and arises from the collective regulation of several interconnected cell signaling pathways.

PMID: 28924942 [PubMed - as supplied by publisher]

A network integration approach for drug-target interaction prediction and computational drug repositioning from heterogeneous information.

Nat Commun. 2017 Sep 18;8(1):573

Authors: Luo Y, Zhao X, Zhou J, Yang J, Zhang Y, Kuang W, Peng J, Chen L, Zeng J

Abstract
The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery and repositioning. In this work, we develop a computational pipeline, called DTINet, to predict novel drug-target interactions from a constructed heterogeneous network, which integrates diverse drug-related information. DTINet focuses on learning a low-dimensional vector representation of features, which accurately explains the topological properties of individual nodes in the heterogeneous network, and then makes prediction based on these representations via a vector space projection scheme. DTINet achieves substantial performance improvement over other state-of-the-art methods for drug-target interaction prediction. Moreover, we experimentally validate the novel interactions between three drugs and the cyclooxygenase proteins predicted by DTINet, and demonstrate the new potential applications of these identified cyclooxygenase inhibitors in preventing inflammatory diseases. These results indicate that DTINet can provide a practically useful tool for integrating heterogeneous information to predict new drug-target interactions and repurpose existing drugs.Network-based data integration for drug-target prediction is a promising avenue for drug repositioning, but performance is wanting. Here, the authors introduce DTINet, whose performance is enhanced in the face of noisy, incomplete and high-dimensional biological data by learning low-dimensional vector representations.

PMID: 28924171 [PubMed - in process]

Review of Experimental Compounds Demonstrating Anti-Toxoplasma Activity.

Antimicrob Agents Chemother. 2016 Dec;60(12):7017-7034

Authors: McFarland MM, Zach SJ, Wang X, Potluri LP, Neville AJ, Vennerstrom JL, Davis PH

Abstract
Toxoplasma gondii is a ubiquitous apicomplexan parasite capable of infecting humans and other animals. Current treatment options for T. gondii infection are limited and most have drawbacks, including high toxicity and low tolerability. Additionally, no FDA-approved treatments are available for pregnant women, a high-risk population due to transplacental infection. Therefore, the development of novel treatment options is needed. To aid this effort, this review highlights experimental compounds that, at a minimum, demonstrate inhibition of in vitro growth of T. gondii When available, host cell toxicity and in vivo data are also discussed. The purpose of this review is to facilitate additional development of anti-Toxoplasma compounds and potentially to extend our knowledge of the parasite.

PMID: 27600037 [PubMed - indexed for MEDLINE]

Uncovering novel repositioning opportunities using the Open Targets platform.

Drug Discov Today. 2017 Sep 14;:

Authors: Khaladkar M, Koscielny G, Hasan S, Agarwal P, Dunham I, Rajpal D, Sanseau P

Abstract
The recently developed Open Targets platform consolidates a wide range of comprehensive evidence associating known and potential drug targets with human diseases. We have harnessed the integrated data from this platform for novel drug repositioning opportunities. Our computational workflow systematically mines data from various evidence categories and presents potential repositioning opportunities for drugs that are marketed or being investigated in ongoing human clinical trials, based on evidence strength on target-disease pairing. We classified these novel target-disease opportunities in several ways: (i) number of independent counts of evidence; (ii) broad therapy area of origin; and (iii) repositioning within or across therapy areas. Finally, we elaborate on one example that was identified by this approach.

PMID: 28919242 [PubMed - as supplied by publisher]

Promethazine Hydrochloride Inhibits Ectopic Fat Cell Formation in Skeletal Muscle.

Am J Pathol. 2017 Sep 14;:

Authors: Kasai T, Nakatani M, Ishiguro N, Ohno K, Yamamoto N, Morita M, Yamada H, Tsuchida K, Uezumi A

Abstract
Fatty degeneration of skeletal muscle leads to muscle weakness and loss of function. Preventing fatty degeneration in skeletal muscle is important, but no drug has been used clinically. In this study, we performed drug repositioning using human platelet-derived growth factor receptor α (PDGFRα)-positive mesenchymal progenitors that have been proved to be an origin of ectopic adipocytes in skeletal muscle. We found that promethazine hydrochloride (PH) inhibits adipogenesis in a dose-dependent manner without cell toxicity. PH inhibited expression of adipogenic markers and also suppressed phosphorylation of cAMP response element binding protein (CREB), which was reported to be a primary regulator of adipogenesis. We established a mouse model of tendon rupture with intramuscular fat deposition and confirmed that emerged ectopic adipocytes are derived from PDGFRα(+) cells using lineage tracing mice. When these injured mice were treated with PH, formation of ectopic adipocytes was significantly suppressed. Our results demonstrated that PH inhibits PDGFRα(+) mesenchymal progenitor-dependent ectopic adipogenesis in skeletal muscle and suggest that treatment with PH can be a promising approach to prevent fatty degeneration of skeletal muscle.

PMID: 28919111 [PubMed - as supplied by publisher]

Phase I Clinical Trial Results of Auranofin, a Novel Antiparasitic Agent.

Antimicrob Agents Chemother. 2017 Jan;61(1):

Authors: Capparelli EV, Bricker-Ford R, Rogers MJ, McKerrow JH, Reed SL

Abstract
Under an NIH priority to identify new drugs to treat class B parasitic agents, we performed high-throughput screens, which identified the activity of auranofin (Ridaura) against Entamoeba histolytica and Giardia intestinalis, major causes of water- and foodborne outbreaks. Auranofin, an orally administered, gold (Au)-containing compound that was approved by the FDA in 1985 for treatment of rheumatoid arthritis, was effective in vitro and in vivo against E. histolytica and both metronidazole-sensitive and -resistant strains of Giardia We now report the results of an NIH-sponsored phase I trial to characterize the pharmacokinetics (PK) and safety of auranofin in healthy volunteers using modern techniques to measure gold levels. Subjects received orally 6 mg (p.o.) of auranofin daily, the recommended dose for rheumatoid arthritis, for 7 days and were followed for 126 days. Treatment-associated adverse events were reported by 47% of the subjects, but all were mild and resolved without treatment. The mean gold maximum concentration in plasma (Cmax) at day 7 was 0.312 μg/ml and the half-life (t1/2) 35 days, so steady-state blood levels would not be reached in short-term therapy. The highest concentration of gold, 13 μM (auranofin equivalent), or more than 25× the 50% inhibitory concentration (IC50) for E. histolytica and 4× that for Giardia, was in feces at 7 days. Modeling of higher doses (9 and 21 mg/day) was performed for systemic parasitic infections, and plasma gold levels of 0.4 to 1.0 μg/ml were reached after 14 days of treatment at 21 mg/day. This phase I trial supports the idea of the safety of auranofin and provides important PK data to support its potential use as a broad-spectrum antiparasitic drug. (This study has been registered at ClinicalTrials.gov under identifier NCT02089048.).

PMID: 27821451 [PubMed - indexed for MEDLINE]

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Antimicrob Agents Chemother. 2016 Sep;60(9):5111-21

Authors: Hennessy E, Adams C, Reen FJ, O'Gara F

Abstract
Statins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called "pleiotropic effects," which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and in vitro and in vivo virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents.

PMID: 27324773 [PubMed - indexed for MEDLINE]

Repurposing the Nonsteroidal Anti-inflammatory Drug Diflunisal as an Osteoprotective, Antivirulence Therapy for Staphylococcus aureus Osteomyelitis.

Antimicrob Agents Chemother. 2016 Sep;60(9):5322-30

Authors: Hendrix AS, Spoonmore TJ, Wilde AD, Putnam NE, Hammer ND, Snyder DJ, Guelcher SA, Skaar EP, Cassat JE

Abstract
Staphylococcus aureus osteomyelitis is a common and debilitating invasive infection of bone. Treatment of osteomyelitis is confounded by widespread antimicrobial resistance and the propensity of bacteria to trigger pathological changes in bone remodeling that limit antimicrobial penetration to the infectious focus. Adjunctive therapies that limit pathogen-induced bone destruction could therefore limit morbidity and enhance traditional antimicrobial therapies. In this study, we evaluate the efficacy of the U.S. Food and Drug Administration-approved, nonsteroidal anti-inflammatory (NSAID) compound diflunisal in limiting S. aureus cytotoxicity toward skeletal cells and in preventing bone destruction during staphylococcal osteomyelitis. Diflunisal is known to inhibit S. aureus virulence factor production by the accessory gene regulator (agr) locus, and we have previously demonstrated that the Agr system plays a substantial role in pathological bone remodeling during staphylococcal osteomyelitis. Consistent with these observations, we find that diflunisal potently inhibits osteoblast cytotoxicity caused by S. aureus secreted toxins independently of effects on bacterial growth. Compared to commonly used NSAIDs, diflunisal is uniquely potent in the inhibition of skeletal cell death in vitro Moreover, local delivery of diflunisal by means of a drug-eluting, bioresorbable foam significantly limits bone destruction during S. aureus osteomyelitis in vivo Collectively, these data demonstrate that diflunisal potently inhibits skeletal cell death and bone destruction associated with S. aureus infection and may therefore be a useful adjunctive therapy for osteomyelitis.

PMID: 27324764 [PubMed - indexed for MEDLINE]

From malaria to cancer: Computational drug repositioning of amodiaquine using PLIP interaction patterns.

Sci Rep. 2017 Sep 12;7(1):11401

Authors: Salentin S, Adasme MF, Heinrich JC, Haupt VJ, Daminelli S, Zhang Y, Schroeder M

Abstract
Drug repositioning identifies new indications for known drugs. Here we report repositioning of the malaria drug amodiaquine as a potential anti-cancer agent. While most repositioning efforts emerge through serendipity, we have devised a computational approach, which exploits interaction patterns shared between compounds. As a test case, we took the anti-viral drug brivudine (BVDU), which also has anti-cancer activity, and defined ten interaction patterns using our tool PLIP. These patterns characterise BVDU's interaction with its target s. Using PLIP we performed an in silico screen of all structural data currently available and identified the FDA approved malaria drug amodiaquine as a promising repositioning candidate. We validated our prediction by showing that amodiaquine suppresses chemoresistance in a multiple myeloma cancer cell line by inhibiting the chaperone function of the cancer target Hsp27. This work proves that PLIP interaction patterns are viable tools for computational repositioning and can provide search query information from a given drug and its target to identify structurally unrelated candidates, including drugs approved by the FDA, with a known safety and pharmacology profile. This approach has the potential to reduce costs and risks in drug development by predicting novel indications for known drugs and drug candidates.

PMID: 28900272 [PubMed - in process]