Benzimidazole Ribonucleosides: Novel Drug Candidates for the Prevention and Treatment of Cytomegalovirus Diseases

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.

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Missing Novelty in Drug Development

Review of Financial Studies ◽

10.1093/rfs/hhab024 ◽

2021 ◽

Author(s):

Joshua Krieger ◽

Danielle Li ◽

Dimitris Papanikolaou

Keyword(s):

Radical Innovation ◽

Chemical Similarity ◽

Net Worth ◽

Drug Candidates ◽

Pharmaceutical Firms ◽

External Finance ◽

Fda Approval ◽

Novel Drugs ◽

Positive Shock ◽

Novel Drug

Abstract We provide evidence that risk aversion leads pharmaceutical firms to underinvest in radical innovation. We introduce a new measure of drug novelty based on chemical similarity and show that firms face a risk-reward trade-off: novel drug candidates are less likely to obtain FDA approval but are based on more valuable patents. Consistent with a simple model of costly external finance, we show that a positive shock to firms’ net worth leads firms to develop more novel drugs. This suggests that even large firms may behave as though they are risk averse, reducing their willingness to investment in potentially valuable radical innovation.

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Developing novel chemical entities for the treatment of lysosomal storage disorders: an academic perspective

AJP Renal Physiology ◽

10.1152/ajprenal.00393.2015 ◽

2015 ◽

Vol 309 (12) ◽

pp. F996-F999 ◽

Cited By ~ 7

Author(s):

James A. Shayman

Keyword(s):

Drug Targets ◽

Lysosomal Storage ◽

Federal Drug Administration ◽

Drug Candidates ◽

Gaucher Disease Type 1 ◽

Biotechnology Companies ◽

Approved Drugs ◽

Novel Drug ◽

Early Drug

Historically, most Federal Drug Administration-approved drugs were the result of “in-house” efforts within large pharmaceutical companies. Over the last two decades, this paradigm has steadily shifted as the drug industry turned to startups, small biotechnology companies, and academia for the identification of novel drug targets and early drug candidates. This strategic pivot has created new opportunities for groups less traditionally associated with the creation of novel therapeutics, including small academic laboratories, for engagement in the drug discovery process. A recent example of the successful development of a drug that had its origins in academia is eliglustat tartrate, an oral agent for Gaucher disease type 1.

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Harnessing the medicinal properties of Cussonia barteri Seem. (Araliaceae) in drug development. A review

Herba Polonica ◽

10.2478/hepo-2018-0018 ◽

2018 ◽

Vol 64 (3) ◽

pp. 50-61 ◽

Cited By ~ 1

Author(s):

Ighodaro Igbe ◽

Osaze Edosuyi ◽

Agbonlahor Okhuarobo

Keyword(s):

Drug Development ◽

Antioxidant Activities ◽

Biological Activities ◽

Stem Bark ◽

Deciduous Tree ◽

Drug Candidates ◽

Medicinal Properties ◽

Phytochemical Constituents ◽

Anti Inflammatory ◽

Novel Drug

Summary Cussonia barteri Seem (Araliaceae) is a deciduous tree growing in savannah of Africa. Ethnomedicinally, it is used in Africa as an analgesic, anti-malarial, anti-inflammatory, anti-anaemic, anti-diarhoea, anti-poison, ani-pyschotic and anti-epileptic agent. This review provides a brief summary on the phytochemical screenings, ethnomedicinal and pharmacological applications of various parts of C. barteri. Leaves, stem bark and seed of C. barteri have been shown to be rich in saponins, flavonoids, phenols, sugars and alkaloids. Some of these constituents have been isolated and elucidated from C. barteri. Several compounds isolated from plant include triterpenes, saponins, polyenyne and quinic esters. Phytochemical constituents are also partly responsible for biological activities of C. barteri. Extracts and components isolated from the plant have demonstrated neuropharmacological, anti-larvicidal, anti-microbial, anti-inflammatory and antioxidant activities. Overall, the insights provided by this review reinforce the potential of C. barteri for drug development and create the need for further scientific probe of constituents of the plant with the aim of developing novel drug candidates.

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Current targets and drug candidates for prevention and treatment of SARS-CoV-2 (COVID-19) infection

Reviews in Cardiovascular Medicine ◽

10.31083/j.rcm.2020.03.118 ◽

2020 ◽

Vol 21 (3) ◽

pp. 365

Author(s):

Ramesh K. Goyal ◽

Jaseela Majeed ◽

Rajiv Tonk ◽

Mahaveer Dhobi ◽

Bhoomika Patel ◽

...

Keyword(s):

Drug Candidates ◽

Prevention And Treatment

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PERSPECTIVE INSIGHT AND APPLICATION OF IN-SILICO TOOL AS VIRTUAL SCREENING METHOD FOR LEAD DESIGNING AND DEVELOPMENT

Journal of medical pharmaceutical and allied sciences ◽

10.22270/jmpas.v10i6.1908 ◽

2021 ◽

Vol 11 (6) ◽

pp. 16-24

Author(s):

Hemant U Chikhale

Keyword(s):

In Silico ◽

Screening Method ◽

Lead Discovery ◽

Environmental Technology ◽

Lead Structure ◽

Drug Candidates ◽

Underlying Principle ◽

Novel Drug ◽

Investigative Process ◽

Specific Illness

Humans are now in a bioinformatics and chemo informatics century, where we can foresee data across domains like as healthcare, the environmental, technology, and public health. The use of information sharing in silico methodologies has impacted sickness administration by predicting the absorption, distribution, metabolism, excretion, and toxicity (ADMET) patterns of synthetic compounds and efficient and environmentally succeeding pharmaceuticals upfront. The purpose of lead discovery and design is to create the appearance of novel drug candidates that can attach to a specific illness cause. The lead investigative process starts with the recognition of the lead structure, which is followed by the synthesis of its analogs and their estimation in order to produce a candidate for lead improvement. The finding of the proper lead exact is the fundamental and primary worked in the traditional lead discovery progression, and the use of computer (in silico) approaches is widely used in lead innovation. A medicinal chemist's passion for building lead structure is piqued by biomolecules, which are often made up of DNA, RNA, and proteins (such as enzymes, receptors, transporters, and ion channels). The underlying principle of such nuts and bolts is noteworthy to be acquainted with their pharmacological implication to the disease under examination. The motive of this review piece of writing is to emphasize several of the in silico methods that are used in lead discovery and to express the applications of these computational methods.

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Discovery of novel drug candidates based on herbaric acid derivates as potential inhibitors of the hedgehog signaling pathway in cervical cancer therapeutics

Journal of Physics Conference Series ◽

10.1088/1742-6596/1442/1/012052 ◽

2020 ◽

Vol 1442 ◽

pp. 012052

Author(s):

M A F Nasution ◽

A A Parikesit ◽

U S F Tambunan

Keyword(s):

Cervical Cancer ◽

Signaling Pathway ◽

Hedgehog Signaling ◽

Cancer Therapeutics ◽

Hedgehog Signaling Pathway ◽

Drug Candidates ◽

Potential Inhibitors ◽

Novel Drug

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Homology Modeling and Virtual Screening Studies of Antigen MLAA-42 Protein: Identification of Novel Drug Candidates against Leukemia—An In Silico Approach

Computational and Mathematical Methods in Medicine ◽

10.1155/2020/8196147 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Ihsan A. Shehadi ◽

Huda R. M. Rashdan ◽

Aboubakr H. Abdelmonsef

Keyword(s):

Virtual Screening ◽

Homology Modeling ◽

Protein Identification ◽

Binding Affinities ◽

Monocytic Leukemia ◽

Drug Candidates ◽

Promising Target ◽

Leukemia Treatment ◽

Potent Drug ◽

Novel Drug

Monocytic leukemia-associated antigen-42 (MLAA-42) is associated with excessive cell division and progression of leukemia. Thus, human MLAA-42 is considered as a promising target for designing of new lead molecules for leukemia treatment. Herein, the 3D model of the target was generated by homology modeling technique. The model was then evaluated using various cheminformatics servers. Moreover, the virtual screening studies were performed to explore the possible binding patterns of ligand molecules to MLAA’s active site pocket. Thirteen ligand molecules from the ChemBank™ database were identified as they showed good binding affinities, scaffold diversity, and preferential ADME properties which may act as potent drug candidates against leukemia. The study provides the way to identify novel therapeutics with optimal efficacy, targeting MLAA-42.

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Full-length and C-terminal neurogranin in Alzheimer’s disease cerebrospinal fluid analyzed by novel ultrasensitive immunoassays

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00748-6 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Annika Öhrfelt ◽

Julien Dumurgier ◽

Henrik Zetterberg ◽

Agathe Vrillon ◽

Nicholas J. Ashton ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Single Molecule ◽

Full Length ◽

The Novel ◽

Drug Candidates ◽

Postsynaptic Protein ◽

Coefficients Of Variation ◽

Assay Precision ◽

Novel Drug

Abstract Background Neurogranin (Ng) is a neuron-specific and postsynaptic protein that is abundantly expressed in the brain, particularly in the dendritic spine of the hippocampus and cerebral cortex. The enzymatic cleavage of Ng produces fragments that are released into cerebrospinal (CSF), which have been shown to be elevated in Alzheimer’s disease (AD) patients and predict cognitive decline. Thus, quantification of distinctive cleavage products of Ng could elucidate different features of the disease. Methods In this study, we developed novel ultrasensitive single molecule array (Simoa) assays for measurement of full-length neurogranin (FL-Ng) and C-terminal neurogranin (CT-Ng) fragments in CSF. The Ng Simoa assays were evaluated in CSF samples from AD patients (N = 23), mild cognitive impairment due to AD (MCI-AD) (N = 18), and from neurological controls (N = 26). Results The intra-assay repeatability and inter-assay precision of the novel methods had coefficients of variation below 7% and 14%, respectively. CSF FL-Ng and CSF CT-Ng median concentrations were increased in AD patients (6.02 ng/L, P < 0.00001 and 452 ng/L, P = 0.00001, respectively) and in patients with MCI-AD (5.69 ng/L, P < 0.00001 and 566 ng/L, P < 0.00001) compared to neurological controls (0.644 ng/L and 145 ng/L). The median CSF ratio of CT-Ng/FL-Ng were decreased in AD patients (ratio = 101, P = 0.008) and in patients with MCI-AD (ratio = 115, P = 0.016) compared to neurological controls (ratio = 180). CSF of FL-Ng, CT-Ng, and ratio of CT-Ng/FL-Ng could each significantly differentiate AD patients from controls (FL-Ng, AUC = 0.907; CT-Ng, AUC = 0.913; CT-Ng/FL-Ng, AUC = 0.775) and patients with MCI-AD from controls (FL-Ng, AUC = 0.937; CT-Ng, AUC = 0.963; CT-Ng/FL-Ng, AUC = 0.785). Conclusions Assessments of the FL-Ng and CT-Ng levels in CSF with the novel sensitive immunoassays provide a high separation of AD from controls, even in early phase of the disease. The novel Ng assays are robust and highly sensitive and may be valuable tools to study synaptic alteration in AD, as well as to monitor the effect on synaptic integrity of novel drug candidates in clinical trials.

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