Anti-obesity Drugs: From Animal Models to Clinical Efficacy

2008 ◽  
pp. 271-315 ◽  
Author(s):  
Colin T. Dourish ◽  
John P.H. Wilding ◽  
Jason C.G. Halford
Keyword(s):  
Animal Models ◽  
Clinical Efficacy ◽  
Obesity Drugs

Protein degradation: a validated therapeutic strategy with exciting prospects

2017 ◽  
Vol 61 (5) ◽  
pp. 517-527 ◽  
Author(s):  
Honorine Lebraud ◽  
Tom D. Heightman
Keyword(s):  
Animal Models ◽  
Protein Degradation ◽  
Small Molecules ◽  
Cancer Patients ◽  
Clinical Efficacy ◽  
Therapeutic Strategy ◽  
Substrate Recognition ◽  
Pharmacological Targets ◽  
Preclinical Animal Models

In a time of unprecedented challenges in developing potent, selective and well-tolerated protein inhibitors as therapeutics, drug hunters are increasingly seeking alternative modalities to modulate pharmacological targets. Selective inhibitors are achievable for only a fraction of the proteome, and are not guaranteed to elicit the desired response in patients, especially when pursuing targets identified through genetic knockdown. Targeted protein degradation holds the potential to expand the range of proteins that can be effectively modulated. Drugs inducing protein degradation through misfolding or by modulating cereblon (CRBN) substrate recognition are already approved for treatment of cancer patients. The last decade has seen the development of proteolysis targeting chimeras (PROTACs), small molecules that elicit proteasomal degradation by causing protein polyubiquitination. These have been used to degrade a range of disease-relevant proteins in cells, and some show promising efficacy in preclinical animal models, although their clinical efficacy and tolerability is yet to be proven. This review introduces current strategies for protein degradation with an emphasis on PROTACs and the role of click chemistry in PROTAC research through the formation of libraries of preclicked PROTACs or in-cell click-formed PROTACs (CLIPTACs).

scholarly journals Systematic review and meta-analysis of temozolomide in animal models of glioma: was clinical efficacy predicted?

2013 ◽  
Vol 108 (1) ◽  
pp. 64-71 ◽  
Author(s):  
T C Hirst ◽  
H M Vesterinen ◽  
E S Sena ◽  
K J Egan ◽  
M R Macleod ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Clinical Efficacy ◽  
Meta Analysis

scholarly journals How Do Tumor-Treating Fields Work?

2020 ◽  
pp. 19-35
Author(s):  
Kristen W. Carlson ◽  
Jack A. Tuszynski ◽  
Socrates Dokos ◽  
Nirmal Paudel ◽  
Thomas Dreeben ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Clinical Efficacy ◽  
Brain Cancer ◽  
Mechanisms Of Action ◽  
Great Promise ◽  
Tumor Treating Fields ◽  
Cancer Types

AbstractSince approved by the FDA for the treatment of glioblastoma brain cancer in 2015, tumor-treating fields (TTFields) have rapidly become the fourth modality to treat cancer, along with surgery, chemotherapy, and radiation [1]. TTFields are now in clinical trials for a variety of cancer types. While efficacy has been proven in the clinic, the higher efficacy is demonstrated in vitro and in animal models, which indicates much greater clinical efficacy is possible. To attain the great promise of TTFields, uncovering the mechanisms of action (MoA) is necessary.

Ischemia, reperfusion and preconditioning: traditional and new approaches for treatment of myocardial infarction

2016 ◽  
Vol 14 (3) ◽  
pp. 3-11
Author(s):  
Abdrei V. Lyubimov ◽  
Petr D. Shabanov
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Trials ◽  
Animal Models ◽  
Clinical Efficacy ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Katp Channels ◽  
Instrumental Control ◽  
Pharmacological Preconditioning

The review is devoted to the questions of improvement of the efficacy of myocardial infarction treatment by means of pharmacological drugs possessing pre- or postconditioning effect. The proofs of clinical efficacy of reperfusional therapy of the myocardial infarction are observed using examples of adenosine, activators of KATP channels (diazoxide and nicorandil), opiates (fentanyl, morphine) and some other drugs. The data are analyzed from the point of modern view of molecular mechanisms of hypoxia, the findings of objective laboratory and instrumental control in therapy of myocardial infarction in differend known clinical trials. It is concluded that pharmacological preconditioning is perspective approach in therapy of the acute myocardial infarction both in animal models and in humans.

scholarly journals Reply to “Drug Susceptibility of Genetically Engineered Trypanosoma cruzi Strains and Sterile Cure in Animal Models as a Criterion for Potential Clinical Efficacy of Anti-T. cruzi Drugs”

2015 ◽  
Vol 59 (12) ◽  
pp. 7925-7925 ◽  
Author(s):  
Amanda Fortes Francisco ◽  
Michael D. Lewis ◽  
Shiromani Jayawardhana ◽  
Martin C. Taylor ◽  
Eric Chatelain ◽  
...  
Keyword(s):  
Animal Models ◽  
Trypanosoma Cruzi ◽  
Clinical Efficacy ◽  
Drug Susceptibility ◽  
Genetically Engineered

scholarly journals Fc-engineered antibody therapeutics with improved efficacy against COVID-19

2021 ◽  
Author(s):  
Jeffrey Ravetch ◽  
Rachel Yamin ◽  
Andrew Jones ◽  
Hans-Heinrich Hoffmann ◽  
Kevin Kao ◽  
...  
Keyword(s):  
Weight Loss ◽  
Monoclonal Antibodies ◽  
Animal Models ◽  
Clinical Efficacy ◽  
Clinical Benefit ◽  
Effector Function ◽  
Antibody Therapeutics ◽  
Limited Efficacy ◽  
High Doses ◽  
Full Protection

Abstract Monoclonal antibodies (mAbs) with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefit in cases of mild to moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1-4. Treatment generally requires the administration of high doses of these mAbs with limited efficacy in preventing disease complications or mortality among hospitalized COVID-19 patients5. Here we report the development and evaluation of Fc-optimized anti-SARS-CoV-2 mAbs with superior potency to prevent or treat COVID-19 disease. In several animal models of COVID-19 disease6,7, we demonstrate that selective engagement of activating FcγRs results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection upon SARS-CoV-2 challenge and treatment of pre-infected animals. Our results highlight the importance of FcγR pathways in driving antibody-mediated antiviral immunity, while excluding any pathogenic or disease-enhancing effects of FcγR engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered mAbs with optimal Fc effector function and improved clinical efficacy against COVID-19 disease.

scholarly journals In Vitro Activities of Omadacycline and Comparators against Anaerobic Bacteria

2018 ◽  
Vol 62 (4) ◽  
pp. e00047-18 ◽  
Author(s):  
Laure Stapert ◽  
Cindy Wolfe ◽  
Dean Shinabarger ◽  
Andrea Marra ◽  
Chris Pillar
Keyword(s):  
Clostridium Difficile ◽  
Animal Models ◽  
Clostridium Perfringens ◽  
Clinical Efficacy ◽  
Broad Spectrum ◽  
Anaerobic Bacteria ◽  
Content Type ◽  
Skin Structure ◽  
Anaerobic Infections

ABSTRACT Omadacycline (OMC), a broad-spectrum aminomethylcycline, has shown clinical efficacy in anaerobic acute bacterial skin and skin structure infections (ABSSSI) and in animal models of intra-abdominal anaerobic infections. Here, the in vitro activity of OMC against clinically relevant anaerobes was similar to that of tigecycline, with MIC90 values of 1 to 8 μg/ml against Bacteroides spp., 0.5 μg/ml against Clostridium difficile, Prevotella spp., and Porphyromonas asaccharolytica, 1 μg/ml against Peptostreptococcus spp., and 16 μg/ml against Clostridium perfringens.

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