scholarly journals REMDESIVIR IN THE TREATMENT OF COVID-19: A SHORT OUTLINE

2021 ◽  
Vol 9 (09) ◽  
pp. 128-131
Author(s):  
Pydala Sai Prasanna ◽  
◽  
Ragam Swetha Samrajyam ◽  
Kasani Chitti Ramya ◽  
Ambati Sujatha ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Viral Replication ◽  
Clinical Development ◽  
Nucleotide Analogue

We look at the clinical development of remdesivir, a prodrug that has been shown to inhibit SARS-CoV-2 replication, indicating that it could be used to treat COVID-19. Remdesivir is a nucleotide analogue prodrug that disrupts viral replication and was first tested in clinical trials in 2014 to combat the Ebola outbreak.The ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2, was later demonstrated by numerous virology laboratories. Well go over how remdesivir was discovered, how it works, and what studies are currenty being done to see how effective it is in the clinic.

New Anti-VEGF Drugs in Ophthalmology

2020 ◽  
Vol 21 (12) ◽  
pp. 1194-1200
Author(s):  
Claudio Campa
Keyword(s):  
Clinical Trials ◽  
Delivery System ◽  
Clinical Development ◽  
Advanced Stage ◽  
Phase 3 ◽  
Anti Vegf

: This review focuses on 5 new anti-VEGF drugs in the advanced stage of clinical development (i.e., phase 3): conbercept, brolucizumab, port delivery system with ranibizumab, abicipar pegol and faricimab. : Results of clinical trials and the advantages of each drug compared to the available molecules are discussed in detail.

scholarly journals WEE1 Inhibitor: Clinical Development

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Anthony Kong ◽  
Hisham Mehanna
Keyword(s):  
Clinical Trials ◽  
Tp53 Mutation ◽  
Predictive Biomarker ◽  
Concurrent Chemotherapy ◽  
Clinical Development ◽  
Novel Agents ◽  
The Novel ◽  
Grade 3 ◽  
Chemotherapy Agents

Abstract Purpose of Review WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents. Recent Findings Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. Summary There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

scholarly journals The exosome journey: from biogenesis to uptake and intracellular signalling

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sonam Gurung ◽  
Dany Perocheau ◽  
Loukia Touramanidou ◽  
Julien Baruteau
Keyword(s):  
Clinical Trials ◽  
Plasma Membrane ◽  
Scientific Community ◽  
Cell Types ◽  
Clinical Applications ◽  
Clinical Development ◽  
Intracellular Signalling ◽  
Clinical Settings ◽  
Health And Disease ◽  
Adequate Definition

AbstractThe use of exosomes in clinical settings is progressively becoming a reality, as clinical trials testing exosomes for diagnostic and therapeutic applications are generating remarkable interest from the scientific community and investors. Exosomes are small extracellular vesicles secreted by all cell types playing intercellular communication roles in health and disease by transferring cellular cargoes such as functional proteins, metabolites and nucleic acids to recipient cells. An in-depth understanding of exosome biology is therefore essential to ensure clinical development of exosome based investigational therapeutic products. Here we summarise the most up-to-date knowkedge about the complex biological journey of exosomes from biogenesis and secretion, transport and uptake to their intracellular signalling. We delineate the major pathways and molecular players that influence each step of exosome physiology, highlighting the routes of interest, which will be of benefit to exosome manipulation and engineering. We highlight the main controversies in the field of exosome research: their adequate definition, characterisation and biogenesis at plasma membrane. We also delineate the most common identified pitfalls affecting exosome research and development. Unravelling exosome physiology is key to their ultimate progression towards clinical applications.

Clinical Trials and Machine Learning: Regulatory Approach Review

2021 ◽  
Vol 16 ◽  
Author(s):  
Diego Alejandro Dri ◽  
Maurizio Massella ◽  
Donatella Gramaglia ◽  
Carlotta Marianecci ◽  
Sandra Petraglia
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Clinical Trials ◽  
Patient Safety ◽  
Drug Discovery ◽  
Clinical Applications ◽  
Clinical Development ◽  
Regulatory Approach ◽  
National Competent Authorities ◽  
Review Current

: Machine Learning, a fast-growing technology, is an application of Artificial Intelligence that has significantly contributed to drug discovery and clinical development. In the last few years, the number of clinical applications based on Machine Learning has constantly been growing. Moreover, it is now also impacting National Competent Authorities during the assessment of most recently submitted Clinical Trials that are designed, managed, or generating data deriving from the use of Machine Learning or Artificial Intelligence technologies. We review current information available on the regulatory approach to Clinical Trials and Machine Learning. We also provide inputs for further reasoning and potential indications, including six actionable proposals for regulators to proactively drive the upcoming evolution of Clinical Trials within a strong regulatory framework, focusing on patient safety, health protection, and fostering immediate access to effective treatments.

scholarly journals Edaravone in Amyotrophic Lateral Sclerosis’Lessons from the Clinical Development Program and the Importance of a Strategic Clinical Trial Design

US Neurology ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. 47 ◽  
Author(s):  
Said R Beydoun ◽  
Jeffrey Rosenfeld
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Amyotrophic Lateral Sclerosis ◽  
Trial Design ◽  
Development Program ◽  
Clinical Trial Design ◽  
Clinical Development ◽  
Disease Heterogeneity ◽  
Clinical Development Program ◽  
Lateral Sclerosis

Edaravone significantly slows progression of amyotrophic lateral sclerosis (ALS), and is the first therapy to receive approval by the Food and Drug Administration (FDA) for the disease in 22 years. Approval of edaravone has marked a new chapter in pharmaceutical development since the key trial included a novel strategic clinical design involving cohort enrichment. In addition, approval was based on clinical trials that had a relatively small patient number and were performed outside of the US. Edaravone was developed through a series of clinical trials in Japan where it was determined that a well-defined subgroup of patients was required to reveal a treatment effect within the study period. Amyotrophic lateral sclerosis is associated with wide-ranging disease heterogeneity (both within the spectrum of ALS phenotypes as well as in the rate of progression). The patient cohort enrichment strategy aimed to address this heterogeneity and should now be considered as a viable, and perhaps preferred, trial design for future studies. Future research incorporating relevant biomarkers may help to better elucidate edaravone’s mechanism of action, pharmacodynamics, and subsequently ALS phenotypes that may preferentially benefit from treatment. In this review, we discuss the edaravone clinical development program, outline the strategic clinical trial design, and highlight important lessons for future trials.

scholarly journals Macrophage checkpoint blockade: results from initial clinical trials, binding analyses, and CD47-SIRPα structure–function

2020 ◽  
Vol 3 (2) ◽  
pp. 80-94 ◽  
Author(s):  
AbdelAziz R Jalil ◽  
Jason C Andrechak ◽  
Dennis E Discher
Keyword(s):  
Clinical Trials ◽  
Regulatory Protein ◽  
Clinical Results ◽  
Structural Features ◽  
Clinical Development ◽  
Combination Therapies ◽  
Syngeneic Mouse ◽  
Solid Malignancies ◽  
Anti Cancer ◽  
Tumor Types

Abstract The macrophage checkpoint is an anti-phagocytic interaction between signal regulatory protein alpha (SIRPα) on a macrophage and CD47 on all types of cells – ranging from blood cells to cancer cells. This interaction has emerged over the last decade as a potential co-target in cancer when combined with other anti-cancer agents, with antibodies against CD47 and SIRPα currently in preclinical and clinical development for a variety of hematological and solid malignancies. Monotherapy with CD47 blockade is ineffective in human clinical trials against many tumor types tested to date, except for rare cutaneous and peripheral lymphomas. In contrast, pre-clinical results show efficacy in multiple syngeneic mouse models of cancer, suggesting that many of these tumor models are more immunogenic and likely artificial compared to human tumors. However, combination therapies in humans of anti-CD47 with agents such as the anti-tumor antibody rituximab do show efficacy against liquid tumors (lymphoma) and are promising. Here, we review such trials as well as key interaction and structural features of CD47-SIRPα.

scholarly journals Everything in Moderation: Lessons Learned by Exploiting Moderate Replication Stress in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1320 ◽  
Author(s):  
Nazareth ◽  
Jones ◽  
Gabrielli
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Replication Stress ◽  
Cytotoxic Chemotherapy ◽  
Clinical Development ◽  
Lessons Learned ◽  
The Poor ◽  
Damage Response ◽  
Specific Vulnerability

The poor selectivity of standard cytotoxic chemotherapy regimens causes severe side-effects in patients and reduces the quality of life during treatment. Targeting cancer-specific vulnerabilities can improve response rates, increase overall survival and limit toxic side effects in patients. Oncogene-induced replication stress serves as a tumour specific vulnerability and rationale for the clinical development of inhibitors targeting the DNA damage response (DDR) kinases (CHK1, ATR, ATM and WEE1). CHK1 inhibitors (CHK1i) have served as the pilot compounds in this class and their efficacy in clinical trials as single agents has been disappointing. Initial attempts to combine CHK1i with chemotherapies agents that enhance replication stress (such as gemcitabine) were reported to be excessively toxic. More recently, it has emerged that combining CHK1i with subclinical doses of replication stress inducers is more effective, better tolerated and more compatible with immunotherapies. Here we focus on the lessons learned during the clinical development of CHK1i with the goal of improving the design of future clinical trials utilizing DDR inhibitors to target replication stress in cancer.

scholarly journals Stenoparib, an Inhibitor of Cellular Poly(ADP-Ribose) Polymerase, Blocks Replication of the SARS-CoV-2 and HCoV-NL63 Human Coronaviruses In Vitro

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathan E. Stone ◽  
Sierra A. Jaramillo ◽  
Ashley N. Jones ◽  
Adam J. Vazquez ◽  
Madison Martz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Viral Replication ◽  
Phase Ii ◽  
Parp Inhibitor ◽  
Target Range ◽  
Phase Ii Clinical Trials ◽  
Human Coronaviruses ◽  
Respiratory Coronavirus

ABSTRACT By late 2020, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused tens of millions of infections and over 1 million deaths worldwide. A protective vaccine and more effective therapeutics are urgently needed. We evaluated a new poly(ADP-ribose) polymerase (PARP) inhibitor, stenoparib, that recently advanced to phase II clinical trials for treatment of ovarian cancer, for activity against human respiratory coronaviruses, including SARS-CoV-2, in vitro. Stenoparib exhibits dose-dependent suppression of SARS-CoV-2 multiplication and spread in Vero E6 monkey kidney and Calu-3 human lung adenocarcinoma cells. Stenoparib was also strongly inhibitory to the human seasonal respiratory coronavirus HCoV-NL63. Compared to remdesivir, which inhibits viral replication downstream of cell entry, stenoparib impedes entry and postentry processes, as determined by time-of-addition (TOA) experiments. Moreover, a 10 μM dosage of stenoparib—below the approximated 25.5 μM half-maximally effective concentration (EC50)—combined with 0.5 μM remdesivir suppressed coronavirus growth by more than 90%, indicating a potentially synergistic effect for this drug combination. Stenoparib as a stand-alone or as part of combinatorial therapy with remdesivir should be a valuable addition to the arsenal against COVID-19. IMPORTANCE New therapeutics are urgently needed in the fight against COVID-19. Repurposing drugs that are either already approved for human use or are in advanced stages of the approval process can facilitate more rapid advances toward this goal. The PARP inhibitor stenoparib may be such a drug, as it is currently in phase II clinical trials for the treatment of ovarian cancer and its safety and dosage in humans have already been established. Our results indicate that stenoparib possesses strong antiviral activity against SARS-CoV-2 and other coronaviruses in vitro. This activity appears to be based on multiple modes of action, where both pre-entry and postentry viral replication processes are impeded. This may provide a therapeutic advantage over many current options that have a narrower target range. Moreover, our results suggest that stenoparib and remdesivir in combination may be especially potent against coronavirus infection.

scholarly journals An overview on Coronaviruses family from past to Covid-19: introduce some inhibitors as antiviruses from Gillan’s plants

2020 ◽  
Vol 10 (3) ◽  
pp. 5575-5585 ◽  
Keyword(s):  
Physical Chemistry ◽  
Clinical Trials ◽  
Herbal Medicine ◽  
Virus Infection ◽  
Molecular Modelling ◽  
High Accuracy ◽  
Clinical Development ◽  
Binding Interaction ◽  
Active Constituents ◽  
Nmr Study

Among the herbal medicine that commonly used in relieving diseases we choose 4 species as the source for active constituents to be examined as its potential as anti SARS-CoV-2, namely Matrine, Cytarabine, Gemcitabine and Vidarabine from which are extracted from Gillan ‘s plants such as Trshvash, Chuchaq, Cote D’Couto and Khlvash in Iran. The mechanisms by which these agents exercise their antivirus action are calculated via analyzing of NMR and physical chemistry properties via docking. The drugs which are discussed in this article, some of them are in pre-clinical trials or clinical development and some are available in market such as Matrine, Cytarabine, Gemcitabine and Vidarabine. In this work, we have optimized and discussed about several active compounds which are extracted from famous plants through NMR study. These data in high-accuracy determine for anti-SARS-CoV-NSPs confirm our molecular modelling and also exhibited that Cytarabine, a compound found in Chuchaq, and Matrine from Trshvash, bind to those receptors with lower energies compared to the respected reference compounds. These finding indicated that both compounds possess better binding interaction and may inhibit the initial virus infection to the host cell

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