COVID-19 drug candidate pipeline, an overview

Background: Glioblastomas (GBMs) are aggressive malignant brain tumors. Although chemotherapy with temozolomide (TMZ) can extend patient survival, most patients eventually demonstrate resistance. Therefore, novel therapeutic agents that overcome TMZ chemoresistance are required to improve patient outcomes. Purpose: Drug screening is an efficient method to find new therapeutic agents from existing drugs. In this study, we explored a novel anti-glioma agent by drug screening and analyzed its function with respect to GBM treatment for future clinical applications. Methods: Drug libraries containing 1,301 diverse chemical compounds were screened against two glioma stem cell (GSC) lines for drug candidate selection. The effect of selected agents on GSCs and glioma was estimated through viability, proliferation, sphere formation, and invasion assays. Combination therapy was performed to assess its ability to enhance TMZ cytotoxicity against GBM. To clarify the mechanism of action, we performed methylation-specific polymerase chain reaction, gelatin zymography, and western blot analysis. Results: The acyl-CoA synthetase inhibitor 2-fluoropalmitic acid (2-FPA) was selected as a candidate anti-glioma agent. 2-FPA suppressed the viability and stem-like phenotype of GSCs. It also inhibited proliferation and invasion of glioma cell lines. Combination therapy of 2-FPA with TMZ synergistically enhanced the efficacy of TMZ. 2-FPA suppressed the expression of phosphor-ERK, CD133, and SOX-2; reduced MMP-2 activity; and increased methylation of the MGMT promoter. Conclusion: 2-FPA was identified as a potential therapeutic agent against GBM. To extend these findings, physiological studies are required to examine the efficacy of 2-FPA against GBM in vivo.

Download Full-text

Toxicokinetics in Drug Development: An Overview of Toxicokinetic Application in the Development of PNU-101017, an Anxiolytic Drug Candidate

Current Drug Metabolism ◽

10.2174/1389200003338992 ◽

2000 ◽

Vol 1 (3) ◽

pp. 243-254 ◽

Cited By ~ 4

Author(s):

W. Zhong ◽

M. Williams ◽

D. Branstetter

Keyword(s):

Drug Development ◽

Drug Candidate ◽

Anxiolytic Drug

Download Full-text

Tamarix articulata (T. articulata) - An Important Halophytic Medicinal Plant with Potential Pharmacological Properties

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190318120103 ◽

2019 ◽

Vol 20 (4) ◽

pp. 285-292 ◽

Cited By ~ 5

Author(s):

Abdullah M. Alnuqaydan ◽

Bilal Rah

Keyword(s):

Medicinal Plant ◽

Biological Activities ◽

Wide Spectrum ◽

Biological Properties ◽

In Vivo Model ◽

Drug Candidate ◽

Phytochemical Analysis ◽

Pharmacological Properties

Background:Tamarix Articulata (T. articulata), commonly known as Tamarisk or Athal in Arabic region, belongs to the Tamaricaece species. It is an important halophytic medicinal plant and a good source of polyphenolic phytochemical(s). In traditional medicines, T. articulata extract is commonly used, either singly or in combination with other plant extracts against different ailments since ancient times.Methods:Electronic database survey via Pubmed, Google Scholar, Researchgate, Scopus and Science Direct were used to review the scientific inputs until October 2018, by searching appropriate keywords. Literature related to pharmacological activities of T. articulata, Tamarix species, phytochemical analysis of T. articulata, biological activities of T. articulata extracts. All of these terms were used to search the scientific literature associated with T. articulata; the dosage of extract, route of administration, extract type, and in-vitro and in-vivo model.Results:Numerous reports revealed that T. articulata contains a wide spectrum of phytochemical(s), which enables it to have a wide window of biological properties. Owing to the presence of high content of phytochemical compounds like polyphenolics and flavonoids, T. articulata is a potential source of antioxidant, anti-inflammatory and antiproliferative properties. In view of these pharmacological properties, T. articulata could be a potential drug candidate to treat various clinical conditions including cancer in the near future.Conclusion:In this review, the spectrum of phytochemical(s) has been summarized for their pharmacological properties and the mechanisms of action, and the possible potential therapeutic applications of this plant against various diseases discussed.

Download Full-text

The Plausible role of Indian Traditional Medicine in combating Corona Virus (SARS-CoV 2): a mini-review

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200807111359 ◽

2020 ◽

Vol 21 ◽

Author(s):

Adithya J ◽

Bhagyalakshmi Nair ◽

Aishwarya S ◽

Lekshmi R. Nath

Keyword(s):

Specific Treatment ◽

Ocimum Sanctum ◽

Drug Candidate ◽

Asparagus Racemosus ◽

Traditional System ◽

Traditional Medicines ◽

Contagious Nature ◽

Community Transmission ◽

Novel Virus

: SARS-CoV 2 is a novel virus strain of Coronavirus, reported in China in late December 2019. Its highly contagious nature in humans has prompted WHO to designate the ongoing pandemic as a Public Health Emergency of International Concern. At this moment, there is no specific treatment and the therapeutic strategies to deal with the infection are only supportive, and prevention aimed at reducing community transmission. A permanent solution for the pandemic, which has brought the world economy to the edge of collapse, is the need of the hour. This situation has brought intense research in traditional systems of medicine. Indian Traditional System, Ayurveda has a clear concept of the cause and treatment of pandemics. Through this review, information on the potential antiviral traditional medicines along with their immunomodulatory pathways is discussed. We have covered the seven most important Indian traditional plants with antiviral properties :Withaniasomnifera (L.) Dunal(family: Solanaceae),Tinosporacordifolia(Thunb.)Miers (family:Menispermaceae),Phyllanthusemblica L.(family:Euphorbiaceae),Asparagus racemosus L.(family:Liliaceae), Glycyrrhizaglabra L.(family:Fabaceae), Ocimum sanctum L.(family:Lamiaceae) and Azadirachta indica A.Juss(family:Meliaceae)in this review. An attempt is also made to bring into limelight the importance of dietary polyphenol, Quercetin which is a potential drug candidate in the making against the SARS-CoV2 virus.

Download Full-text

Conformation as the Therapeutic Target for Neurodegenerative Diseases

Current Alzheimer Research ◽

10.2174/1567205014666170116152622 ◽

2017 ◽

Vol 14 (4) ◽

pp. 393-402 ◽

Cited By ~ 6

Author(s):

Rajaraman Krishnan ◽

Franz Hefti ◽

Haim Tsubery ◽

Michal Lulu ◽

Ming Proschitsky ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Neurodegenerative Diseases ◽

Protein Misfolding ◽

Specific Binding ◽

Drug Candidate ◽

High Affinity ◽

Novel Approach ◽

Multiple Protein ◽

Clinical Benefits ◽

Effective Drugs

Therapeutic strategies that target pathways of protein misfolding and the toxicity of intermediates along these pathways are mainly at discovery and early development stages, with the exception of monoclonal antibodies that have mainly failed to produce convincing clinical benefits in late stage trials. The clinical failures represent potentially critical lessons for future neurodegenerative disease drug development. More effective drugs may be achieved by pursuing the following two strategies. First, conformational targeting of aggregates of misfolded proteins, rather than less specific binding that includes monomer subunits, which vastly outnumber the toxic targets. Second, since neurodegenerative diseases frequently include more than one potential protein pathology, generic targeting of aggregates by shape might also be a crucial feature of a drug candidate. Incorporating both of these critical features into a viable drug candidate along with high affinity binding has not been achieved with small molecule approaches or with antibody fragments. Monoclonal antibodies developed so far are not broadly acting through conformational recognition. Using GAIM (General Amyloid Interaction Motif) represents a novel approach that incorporates high affinity conformational recognition for multiple protein assemblies, as well as recognition of an array of assemblies along the misfolding pathway between oligomers and fibers. A GAIM-Ig fusion, NPT088, is nearing clinical testing.

Download Full-text

Plant Extracts and their Secondary Metabolites as Modulators of Kinases

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200224100219 ◽

2020 ◽

Vol 20 (12) ◽

pp. 1093-1104 ◽

Cited By ~ 2

Author(s):

Muhammad Shoaib Ali Gill ◽

Hammad Saleem ◽

Nafees Ahemad

Keyword(s):

Signal Transduction ◽

Secondary Metabolites ◽

Plant Extracts ◽

Cell Biology ◽

Kinase Inhibitor ◽

Plant Secondary Metabolites ◽

Biological Properties ◽

Drug Candidate ◽

New Chemical Entities ◽

Natural Flora

Natural Products (NP), specifically from medicinal plants or herbs, have been extensively utilized to analyze the fundamental mechanisms of ultimate natural sciences as well as therapeutics. Isolation of secondary metabolites from these sources and their respective biological properties, along with their lower toxicities and cost-effectiveness, make them a significant research focus for drug discovery. In recent times, there has been a considerable focus on isolating new chemical entities from natural flora to meet the immense demand for kinase modulators, and also to overcome major unmet medical challenges in relation to signal transduction pathways. The signal transduction systems are amongst the foremost pathways involved in the maintenance of life and protein kinases play an imperative part in these signaling pathways. It is important to find a kinase inhibitor, as it can be used not only to study cell biology but can also be used as a drug candidate for cancer and metabolic disorders. A number of plant extracts and their isolated secondary metabolites such as flavonoids, phenolics, terpenoids, and alkaloids have exhibited activities against various kinases. In the current review, we have presented a brief overview of some important classes of plant secondary metabolites as kinase modulators. Moreover, a number of phytocompounds with kinase inhibition potential, isolated from different plant species, are also discussed.

Download Full-text