scholarly journals Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Hyeong-Min Lee ◽  
Yuna Kim
Keyword(s):  
Drug Discovery ◽  
De Novo ◽  
Drug Repurposing ◽  
Cost Effective ◽  
Neuropsychiatric Disorders ◽  
Mechanisms Of Action ◽  
Drug Discovery And Development ◽  
Cost Effective Method ◽  
Alternative Approach ◽  
Target Effects

Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

Developing Novel Anticancer Drugs for Targeted Populations: An Update

2020 ◽  
Vol 26 ◽  
Author(s):  
Tadesse Bekele Tafesse ◽  
Mohammed Hussen Bule ◽  
Fazlullah Khan ◽  
Mohammad Abdollahi ◽  
Mohsen Amini
Keyword(s):  
Drug Discovery ◽  
Drug Development ◽  
Anticancer Drugs ◽  
Anticancer Drug ◽  
Development Process ◽  
De Novo ◽  
Drug Repurposing ◽  
Drug Discovery And Development ◽  
Probability Of Success ◽  
Selection Of

Background: Due to higher failure rates, lengthy time and high cost of the traditional de novo drug discovery and development process; the rate of opportunity to get new, safe and efficacious drugs for the targeted population including pediatric patients with cancer becomes sluggish. Objectives: This paper discusses the development of novel anticancer drugs focusing on the identification and selection of target anticancer drug development for the targeted population. Methods: Information presented in this review was obtained from different databases including PUBMED, SCOPUS, Web of Science, and EMBASE. Various keywords were used as search terms. Results: The pharmaceutical companies currently are executing drug repurposing as an alternative means to accelerate the drug development process that reduces the risk of failure, time and cost, which takes 3-12 years with almost 25% overall probability of success as compared to de novo drug discovery and development process (10-17 years) which has less than 10% probability of success. An alternative strategy to the traditional de novo drug discovery and development process, called drug repurposing, is also presented. Conclusion: Therefore, to continue with the progress of developing novel anticancer drugs towards the targeted population, identification and selection of the target to the specific disease type is important considering the aspects of the age of the patient and the disease stages such as each cancer types are different when we consider the disease at a molecular level. Drug repurposing technique becomes an influential alternative strategy to discover and develop novel anticancer drug candidates.

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

2020 ◽  
Author(s):  
Sanaa Bardaweel
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Antimalarial Drug ◽  
Drug Repurposing ◽  
Spike Protein ◽  
Diabetic Patients ◽  
Potential Drug ◽  
Chemokine Production ◽  
Drug Discovery And Development ◽  
Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

scholarly journals Safety, Efficacy, and Patient Acceptability of the Copper T-380A Intrauterine Contraceptive Device

2011 ◽  
Vol 4 ◽  
pp. CMWH.S5332
Author(s):  
Anita L. Nelson
Keyword(s):  
Intrauterine Device ◽  
Cost Effective ◽  
Mechanisms Of Action ◽  
Contraceptive Device ◽  
Menstrual Blood Loss ◽  
First Line ◽  
Medical Problems ◽  
Patient Acceptability ◽  
Cost Effective Method ◽  
Intrauterine Contraceptive

The ParaGard Copper T 380A intrauterine device (CuT380A) provides reversible contraception that is as effective as sterilization for up to 20 years. The CuT380A is a mainstream, first-line contraceptive option for most healthy women, including nulligravid women, as well as many women who have serious medical problems. Because it is the most cost-effective method of birth control, the CuT380A is the preferred IUD, except for women who desire lighter or no menstrual blood loss. Surveys reveal that 95% of US CuT380A users are “very” or “somewhat” satisfied with their method. This article describes current candidates for IUD use, discusses the mechanisms of action of the CuT380A, provides guidance to reduce barriers to IUD access, suggests counseling points for patients, and outlines techniques to reduce the risks and side effects that can be associated with use of the CuT380A.

Recent Drug-Repurposing-Driven Advances in the Discovery of Novel Antibiotics

2019 ◽  
Vol 26 (28) ◽  
pp. 5363-5388 ◽  
Author(s):  
Ananda Kumar Konreddy ◽  
Grandhe Usha Rani ◽  
Kyeong Lee ◽  
Yongseok Choi
Keyword(s):  
Drug Discovery ◽  
Bacterial Infections ◽  
De Novo ◽  
Genetic Disorder ◽  
Antibacterial Properties ◽  
Drug Repurposing ◽  
Global Public Health ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Novel Antibiotics

: Drug repurposing is a safe and successful pathway to speed up the novel drug discovery and development processes compared with de novo drug discovery approaches. Drug repurposing uses FDA-approved drugs and drugs that failed in clinical trials, which have detailed information on potential toxicity, formulation, and pharmacology. Technical advancements in the informatics, genomics, and biological sciences account for the major success of drug repurposing in identifying secondary indications of existing drugs. Drug repurposing is playing a vital role in filling the gap in the discovery of potential antibiotics. Bacterial infections emerged as an ever-increasing global public health threat by dint of multidrug resistance to existing drugs. This raises the urgent need of development of new antibiotics that can effectively fight multidrug-resistant bacterial infections (MDRBIs). The present review describes the key role of drug repurposing in the development of antibiotics during 2016–2017 and of the details of recently FDA-approved antibiotics, pipeline antibiotics, and antibacterial properties of various FDA-approved drugs of anti-cancer, anti-fungal, anti-hyperlipidemia, antiinflammatory, anti-malarial, anti-parasitic, anti-viral, genetic disorder, immune modulator, etc. Further, in view of combination therapies with the existing antibiotics, their potential for new implications for MDRBIs is discussed. The current review may provide essential data for the development of quick, safe, effective, and novel antibiotics for current needs and suggest acuity in its effective implications for inhibiting MDRBIs by repurposing existing drugs.

scholarly journals Gliptin Repurposing for COVID-19

2020 ◽  
Author(s):  
Matthew Groves ◽  
Alexander Domling ◽  
Angel Jonathan Ruiz Moreno ◽  
Atilio Reyes Romero ◽  
Constantinos Neochoritis ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Drug Class ◽  
De Novo ◽  
Drug Repurposing ◽  
Therapeutic Modality ◽  
Antidiabetic Drug ◽  
Short Term ◽  
Computational Screening ◽  
Approved Drugs

<i>De novo</i> drug discovery of any therapeutic modality (e.g. antibodies, vaccines or small molecules) historically takes years from idea/preclinic to the market and it is therefore not a short-term solution for the current SARS-CoV-2 pandemic. Therefore, drug repurposing – the discovery novel indication areas for already approved drugs - is perhaps the only approach able to yield a short term relieve. Here we describe computational screening results suggesting that certain members of the drug class of gliptins are inhibitors of the two SARS-CoV-2 proteases 3CLpro and PLpro. The oral bioavailable antidiabetic drug class of gliptins are safe and have been introduced clinically since 2006 and used by millions of patients since then. Based on our repurposing hypothesis the nitrile containing gliptins deserve further investigation as potential anti-COVID19 drugs.

A short de novo synthesis of nucleoside analogs

Science ◽  
2020 ◽  
Vol 369 (6504) ◽  
pp. 725-730 ◽  
Author(s):  
Michael Meanwell ◽  
Steven M. Silverman ◽  
Johannes Lehmann ◽  
Bharanishashank Adluri ◽  
Yang Wang ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Viral Infections ◽  
De Novo ◽  
Nucleoside Analogs ◽  
Aldol Reactions ◽  
Displacement Reaction ◽  
De Novo Synthesis ◽  
One Pot ◽  
Drug Discovery And Development ◽  
Locked Nucleic Acids

Nucleoside analogs are commonly used in the treatment of cancer and viral infections. Their syntheses benefit from decades of research but are often protracted, unamenable to diversification, and reliant on a limited pool of chiral carbohydrate starting materials. We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted acetaldehydes are fluorinated and then directly engaged in enantioselective aldol reactions in a one-pot reaction. A subsequent intramolecular fluoride displacement reaction provides a functionalized nucleoside analog. The versatility of this process is highlighted in multigram syntheses of d- or l-nucleoside analogs, locked nucleic acids, iminonucleosides, and C2′- and C4′-modified nucleoside analogs. This de novo synthesis creates opportunities for the preparation of diversity libraries and will support efforts in both drug discovery and development.

scholarly journals Implications of de novo mutations in guiding drug discovery: A study of four neuropsychiatric disorders

2017 ◽  
Author(s):  
Hon-Cheong So ◽  
Yui-Hang Wong
Keyword(s):  
Drug Discovery ◽  
De Novo ◽  
Neuropsychiatric Disorders ◽  
Lipid Lowering ◽  
De Novo Mutations ◽  
Histone Deacetylase Inhibition ◽  
Gene Set ◽  
Drug Candidates ◽  
Drug Classes ◽  
Sequencing Studies

AbstractRecent studies have suggested an important role of de novo mutations (DNMs) in neuropsychiatric disorders. As DNMs are not subject to elimination due to evolutionary pressure, they are likely to have greater disruptions on biological functions. While a number of sequencing studies have been performed on neuropsychiatric disorders, the implications of DNMs for drug discovery remain to be explored.In this study, we employed a gene-set analysis approach to address this issue. Four neuropsychiatric disorders were studied, including schizophrenia (SCZ), autistic spectrum disorders (ASD), intellectual disability (ID) and epilepsy. We first identified gene-sets associated with different drugs, and analyzed whether the gene-set pertaining to each drug overlaps with DNMs more than expected by chance. We also assessed which medication classes are enriched among the prioritized drugs. We discovered that neuropsychiatric drug classes were indeed significantly enriched for DNMs of all four disorders; in particular, antipsychotics and antiepileptics were the most strongly enriched drug classes for SCZ and epilepsy respectively. Interestingly, we revealed enrichment of several unexpected drug classes, such as lipid-lowering agents for SCZ and anti-neoplastic agents. By inspecting individual hits, we also uncovered other interesting drug candidates or mechanisms (e.g. histone deacetylase inhibition and retinoid signaling) that might warrant further investigations. Taken together, this study provided evidence for the usefulness of DNMs in guiding drug discovery or repositioning.

scholarly journals COMPUTER AIDED DRUG DESIGN: A MINI-REVIEW

2020 ◽  
Vol 9 (5) ◽  
pp. 2584-2591
Author(s):  
Aateka Y Barrawaz
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Development Process ◽  
De Novo ◽  
Computer Aided Drug Design ◽  
Drug Discovery And Development ◽  
Research Activities ◽  
Complex Process ◽  
Computer Aided ◽  
New Chemical Entities

New drug discovery and development process is considered much complex process which is time consuming and resources accommodating too. So computer aided drug design are being broadly used to enhance the effectiveness of the drug discovery and development process which ultimately saves time and resources. Various approaches to Computer aided drug design are evaluated to shows potential techniques in accordance with their needs. Two approaches are considered to designing of drug first one is structure-based and second one is Ligand based drug designs. In this review, we are discussing about highly effective and powerful techniques for drug discovery and development as well as various methods of Computer aided drug design like molecular docking at virtual screening for lead identification, QSAR, molecular homology, de-novo design, molecular modeling and optimization. It also elaborate about different software used in Computer aided drug design, different application of Computer aided drug design etc. Major objectives of Computer aided drug design are to commence collaborative foundation of research activities and to discover new chemical entities for novel therapeutics drugs

scholarly journals Drug Repurposing for Targeting Acute Leukemia With KMT2A (MLL)—Gene Rearrangements

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexia Tsakaneli ◽  
Owen Williams
Keyword(s):  
Drug Discovery ◽  
Acute Leukemia ◽  
De Novo ◽  
Complex Function ◽  
Drug Repurposing ◽  
Therapeutic Approaches ◽  
Vast Number ◽  
Mll Gene ◽  
Oncogenic Pathways ◽  
Mechanistic Basis

The treatment failure rates of acute leukemia with rearrangements of the Mixed Lineage Leukemia (MLL) gene highlight the need for novel therapeutic approaches. Taking into consideration the limitations of the current therapies and the advantages of novel strategies for drug discovery, drug repurposing offers valuable opportunities to identify treatments and develop therapeutic approaches quickly and effectively for acute leukemia with MLL-rearrangements. These approaches are complimentary to de novo drug discovery and have taken advantage of increased knowledge of the mechanistic basis of MLL-fusion protein complex function as well as refined drug repurposing screens. Despite the vast number of different leukemia associated MLL-rearrangements, the existence of common core oncogenic pathways holds the promise that many such therapies will be broadly applicable to MLL-rearranged leukemia as a whole.

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