scholarly journals Molecular Features of Non-Selective Small Molecule Antagonists of the Bradykinin Receptors

2020 ◽  
Vol 13 (9) ◽  
pp. 259 ◽  
Author(s):  
Bahareh Rasaeifar ◽  
Patricia Gomez-Gutierrez ◽  
Juan J. Perez
Keyword(s):  
Present Report ◽  
Drug Repurposing ◽  
Lung Edema ◽  
Bradykinin Receptors ◽  
Molecular Features ◽  
Acute Lung Failure ◽  
Selective Antagonists ◽  
Bradykinin Antagonist ◽  
Lung Failure ◽  
Approved Drugs

Angiotensin converting enzyme 2 (ACE2) downregulation is a key negative factor for the severity of lung edema and acute lung failure observed in patients infected with SARS-CoV-2. ACE2 downregulation affects the levels of diverse peptide mediators of the renin-agiotensin-aldestosterone and kallikrein-kinin systems, compromising vascular hemostasis. Increasing evidence suggests that the inflammatory response observed in covid-19 patients is initiated by the action of kinins on the bradykinin receptors. Accordingly, the use of bradykinin antagonists should be considered as a strategy for therapeutic intervention against covid-19 illness progression. Presently, icatibant is the only bradykinin antagonist drug approved. In the present report, we investigated the molecular features characterizing non-selective antagonists targeting the bradykinin receptors and carried out a in silico screening of approved drugs, aimed at the identification of compounds with a non-selective bradykinin antagonist profile that can be evaluated for drug repurposing. The study permitted to identify eight compounds as prospective non-selective antagonists of the bradykinin receptors, including raloxifene; sildenafil; cefepime; cefpirome; imatinib; ponatinib; abemaciclib and entrectinib.

Acute lung failure due to hypereosinophilic syndrome after pneumonectomy

2019 ◽  
Author(s):  
G Yavuz ◽  
T Kauke ◽  
OM Glück ◽  
T Weig ◽  
K Milger-Kneidinger ◽  
...  
Keyword(s):  
Hypereosinophilic Syndrome ◽  
Acute Lung Failure ◽  
Lung Failure

Transport of newborns with acute lung failure in the pre-ECMO situation and on ECMO

2006 ◽  
Vol 210 (S 5) ◽  
Author(s):  
F Loersch ◽  
R Gerull ◽  
S Hien ◽  
S Demirakca ◽  
I Jester ◽  
...  
Keyword(s):  
Acute Lung Failure ◽  
Lung Failure

Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug Repurposing Study

2018 ◽  
Vol 14 (2) ◽  
pp. 106-116 ◽  
Author(s):  
Olujide O. Olubiyi ◽  
Maryam O. Olagunju ◽  
James O. Oni ◽  
Abidemi O. Olubiyi
Keyword(s):  
Drug Repurposing ◽  
Structural Basis ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Screening of an FDA-Approved Library for Novel Drugs against Y. pestis

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
David Gur ◽  
Theodor Chitlaru ◽  
Emanuelle Mamroud ◽  
Ayelet Zauberman
Keyword(s):  
Drug Repurposing ◽  
Mortality Rates ◽  
Systematic Screening ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Therapy Initiation ◽  
Novel Drugs ◽  
Resistant Strains ◽  
Approved Drugs ◽  
Fda Approved Drugs

Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset. To overcome the emergence of antibiotic resistant strains, we attempted a systematic screening of Food and Drug Administration (FDA)-approved drugs to identify alternative compounds which may possess antibacterial activity against Y. pestis. Here, we describe a drug-repurposing approach, which led to the identification of two antibiotic-like activities of the anticancer drugs bleomycin sulfate and streptozocin that have the potential for designing novel antiplague therapy approaches. The inhibitory characteristics of these two drugs were further addressed as well as their efficiency in affecting the growth of Y. pestis strains resistant to doxycycline and ciprofloxacin, antibiotics recommended for plague treatment.

scholarly journals Discovery of a Bradykinin B2 Partial Agonist Profile of Raloxifene in a Drug Repurposing Campaign

2020 ◽  
Vol 22 (1) ◽  
pp. 257
Author(s):  
Patricia Gomez-Gutierrez ◽  
Juan J. Perez
Keyword(s):  
Virtual Screening ◽  
Molecular Mechanisms ◽  
Partial Agonist ◽  
Drug Repurposing ◽  
Cytokine Storm ◽  
Bradykinin Receptors ◽  
Screening Process ◽  
Bradykinin Antagonists ◽  
Illness Progression

Covid-19 urges a deeper understanding of the underlying molecular mechanisms involved in illness progression to provide a prompt therapeutical response with an adequate use of available drugs, including drug repurposing. Recently, it was suggested that a dysregulated bradykinin signaling can trigger the cytokine storm observed in patients with severe Covid-19. In the scope of a drug repurposing campaign undertaken to identify bradykinin antagonists, raloxifene was identified as prospective compound in a virtual screening process. The pharmacodynamics profile of raloxifene towards bradykinin receptors is reported in the present work, showing a weak selective partial agonist profile at the B2 receptor. In view of this new profile, its possible use as a therapeutical agent for the treatment of severe Covid-19 is discussed.

scholarly journals Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3193
Author(s):  
Christina Pfab ◽  
Luisa Schnobrich ◽  
Samir Eldnasoury ◽  
André Gessner ◽  
Nahed El-Najjar
Keyword(s):  
Clinical Trials ◽  
Antimicrobial Agents ◽  
Large Body ◽  
Drug Repurposing ◽  
Extensive Discussion ◽  
Attrition Rates ◽  
Beneficial Effects ◽  
Stage Of Development ◽  
Development Costs ◽  
Approved Drugs

The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Acute Lung Failure

2011 ◽  
Vol 32 (05) ◽  
pp. 607-625 ◽  
Author(s):  
Rob Sweeney ◽  
Daniel McAuley ◽  
Michael Matthay
Keyword(s):  
Acute Lung Failure ◽  
Lung Failure

scholarly journals Angiotensin-converting enzyme 2 protects from severe acute lung failure

Nature ◽  
2005 ◽  
Vol 436 (7047) ◽  
pp. 112-116 ◽  
Author(s):  
Yumiko Imai ◽  
Keiji Kuba ◽  
Shuan Rao ◽  
Yi Huan ◽  
Feng Guo ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Acute Lung Failure ◽  
Lung Failure

scholarly journals Potential 2019-nCoV 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches

2020 ◽  
Author(s):  
Alex Zhavoronkov ◽  
Vladimir Aladinskiy ◽  
Alexander Zhebrak ◽  
Bogdan Zagribelnyy ◽  
Victor Terentiev ◽  
...  
Keyword(s):  
Homology Modelling ◽  
Drug Repurposing ◽  
Hiv Protease ◽  
Learning Approaches ◽  
Protein Targets ◽  
Chemical Libraries ◽  
Internal Resources ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Novel Drug

<div> <div> <div> <p>The emergence of the 2019 novel coronavirus (2019-nCoV), for which there is no vaccine or any known effective treatment created a sense of urgency for novel drug discovery approaches. One of the most important 2019-nCoV protein targets is the 3C-like protease for which the crystal structure is known. Most of the immediate efforts are focused on drug repurposing of known clinically-approved drugs and virtual screening for the molecules available from chemical libraries that may not work well. For example, the IC50 of lopinavir, an HIV protease inhibitor, against the 3C-like protease is approximately 50 micromolar. In an attempt to address this challenge, on January 28th, 2020 Insilico Medicine decided to utilize a part of its generative chemistry pipeline to design novel drug-like inhibitors of 2019-nCoV and started generation on January 30th. It utilized three of its previously validated generative chemistry approaches: crystal-derived pocked- based generator, homology modelling-based generation, and ligand-based generation. Novel druglike compounds generated using these approaches are being published at www.insilico.com/ncov-sprint/ and will be continuously updated. Several molecules will be synthesized and tested using the internal resources; however, the team is seeking collaborations to synthesize, test, and, if needed, optimize the published molecules. </p> </div> </div> </div>

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