Using a Recombinant Metagenomic Lipase for Enantiomeric Separation of Pharmaceutically Important Drug Intermediates

2019 ◽  
pp. 77-101
Author(s):  
Rakesh Kumar ◽  
Uttam Chand Banerjee ◽  
Jagdeep Kaur
Keyword(s):  
Enantiomeric Separation ◽  
Important Drug ◽  
Drug Intermediates

Discovery of an Unexpected Similarity in Ligand Binding Between BRD4 and PPARγ

2019 ◽  
Author(s):  
Lina Humbeck ◽  
Jette Pretzel ◽  
Saskia Spitzer ◽  
Oliver Koch
Keyword(s):  
Cancer Therapy ◽  
Drug Targets ◽  
Synergistic Effects ◽  
Complex Structure ◽  
Peroxisome Proliferator ◽  
Resistance Development ◽  
Peroxisome Proliferator Activated Receptor ◽  
Starting Point ◽  
Fundamental Research ◽  
Important Drug

Knowledge about interrelationships between different proteins is crucial in fundamental research for the elucidation of protein networks and pathways. Furthermore, it is especially critical in chemical biology to identify further key regulators of a disease and to take advantage of polypharmacology effects. A comprehensive scaffold-based analysis uncovered an unexpected relationship between bromodomain-containing protein 4 (BRD4) and peroxisome-proliferator activated receptor gamma (PPARγ). They are both important drug targets for cancer therapy and many more important diseases. Both proteins share binding site similarities near a common hydrophobic subpocket which should allow the design of a polypharmacology-based ligand targeting both proteins. Such a dual-BRD4-PPARγ-modulator could show synergistic effects with a higher efficacy or delayed resistance development in, for example, cancer therapy. Thereon, a complex structure of sulfasalazine was obtained that involves two bromodomains and could be a potential starting point for the design of a bivalent BRD4 inhibitor.

A Prospective Review on Phyto-pharmacological Aspects of Vitex negundo Linn.

2019 ◽  
Vol 05 ◽  
Author(s):  
Mohd Faisal Khan ◽  
Poonam Arora ◽  
Mahaveer Dhobi
Keyword(s):  
Chlorogenic Acid ◽  
Biological Activities ◽  
Volatile Oil ◽  
Vitex Negundo ◽  
Bioactive Constituents ◽  
Traditional System ◽  
Comprehensive Information ◽  
Medicinal Properties ◽  
Main Components ◽  
Important Drug

Background: Vitex negundo Linn. commonly known as five leave chase tree is an ethnobotanically important drug in traditional system of medicine. The plant is widely distributed in India, China and other Asian and American countries. Objective: The review aims at presenting comprehensive information with respect to ethnopharmacological rele-vance and recent findings on phytochemical and biological activities of Vitex negundo. Method: Literature was collected from various sources such as pubmed, scopus, science direct, and others. Results: Extracts and secondary metabolites of this plant, particularly those from roots and leaves, possess useful pharmacological activities such as anti-inflammatory, antitumor, antioxidant, antimicrobial, galactagogue, antigas-tric, antiflatulant, antiparasitic, analgesic, hepatoprotective and antihypertensive, some of which have been vali-dated scientifically. All parts of plant especially leave and roots contain a large number of bioactive phytoconstitu-ents including flavonoids, iridoids, lignans, volatile oil, terpenes, coumarins, phenolic and steroidal compounds which impart it multiple medicinal properties. Vitexin, isovitexin, viridifol, caffeic acid, chlorogenic acid and iso-chlorogenic acid are the main components. Conclusion: The review emphasises the medicinal importance of Vitex negundo and its bioactive constituents in traditional system of medicine.

scholarly journals Qualification of translational safety biomarkers

2021 ◽  
pp. 153537022110021
Author(s):  
John-Michael Sauer ◽  
Amy C Porter
Keyword(s):  
Skeletal Muscle ◽  
Drug Development ◽  
Vascular Injury ◽  
Validation Studies ◽  
Safety Assessment ◽  
Regulatory Agencies ◽  
Development Studies ◽  
Clinical Validation ◽  
Development Tools ◽  
Important Drug

Safety biomarkers are important drug development tools, both preclinically and clinically. It is a straightforward process to correlate the performance of nonclinical safety biomarkers with histopathology, and ideally, the biomarker is useful in all species commonly used in safety assessment. In clinical validation studies, where histopathology is not feasible, safety biomarkers are compared to the response of standard biomarkers and/or to clinical adjudication. Worldwide, regulatory agencies have put in place processes to qualify biomarkers to provide confidence in the manner of use and interpretation of biomarker data in drug development studies. This paper describes currently qualified safety biomarkers which can be utilized to monitor for nephrotoxicity and cardiotoxicity and ongoing projects to qualify safety biomarkers for liver, skeletal muscle, and vascular injury. In many cases, the development and use of these critical drug development tools is dependent upon partnerships and the precompetitive sharing of data to support qualification efforts.

scholarly journals Molecular and Pharmacological Characterization of the Interaction between Human Geranylgeranyltransferase Type I and Ras-Related Protein Rap1B

2021 ◽  
Vol 22 (5) ◽  
pp. 2501
Author(s):  
Sonja Hinz ◽  
Dominik Jung ◽  
Dorota Hauert ◽  
Hagen S. Bachmann
Keyword(s):  
Protein Function ◽  
Tumor Development ◽  
Cysteine Residue ◽  
Type I ◽  
Pharmacological Characterization ◽  
Anti Cancer ◽  
And Function ◽  
Caax Motif ◽  
Important Drug

Geranylgeranyltransferase type-I (GGTase-I) represents an important drug target since it contributes to the function of many proteins that are involved in tumor development and metastasis. This led to the development of GGTase-I inhibitors as anti-cancer drugs blocking the protein function and membrane association of e.g., Rap subfamilies that are involved in cell differentiation and cell growth. In the present study, we developed a new NanoBiT assay to monitor the interaction of human GGTase-I and its substrate Rap1B. Different Rap1B prenylation-deficient mutants (C181G, C181S, and ΔCQLL) were designed and investigated for their interaction with GGTase-I. While the Rap1B mutants C181G and C181S still exhibited interaction with human GGTase-I, mutant ΔCQLL, lacking the entire CAAX motif (defined by a cysteine residue, two aliphatic residues, and the C-terminal residue), showed reduced interaction. Moreover, a specific, peptidomimetic and competitive CAAX inhibitor was able to block the interaction of Rap1B with GGTase-I. Furthermore, activation of both Gαs-coupled human adenosine receptors, A2A (A2AAR) and A2B (A2BAR), increased the interaction between GGTase-I and Rap1B, probably representing a way to modulate prenylation and function of Rap1B. Thus, A2AAR and A2BAR antagonists might be promising candidates for therapeutic intervention for different types of cancer that overexpress Rap1B. Finally, the NanoBiT assay provides a tool to investigate the pharmacology of GGTase-I inhibitors.

Aatrilal (Ammi majus L.), an important drug of Unani system of medicine: A review

2021 ◽  
Vol 276 ◽  
pp. 114144
Author(s):  
Qamrul Islam Usmani ◽  
Nasreen Jahan ◽  
Mohd Aleem ◽  
Syed Ameer Hasan
Keyword(s):  
Ammi Majus ◽  
Important Drug

Chiral separation and analysis of antifungal drugs by chromatographic and electromigration techniques: Results achieved in 2010–2020

2021 ◽  
Vol 40 (1) ◽  
pp. 220-252
Author(s):  
Giovanni D’Orazio ◽  
Chiara Fanali ◽  
Chiara Dal Bosco ◽  
Alessandra Gentili ◽  
Salvatore Fanali
Keyword(s):  
Gas Chromatography ◽  
Pharmaceutical Industry ◽  
State Of The Art ◽  
Stationary Phases ◽  
Enantiomeric Separation ◽  
Antifungal Drugs ◽  
Chiral Discrimination ◽  
Food Science ◽  
Industry Environment ◽  
Metabolic Activities

Abstract The determination and separation of enantiomers is an interesting and important topic of research in various fields, e.g., biochemistry, food science, pharmaceutical industry, environment, etc. Although these compounds possess identical physicochemical properties, a pair of enantiomers often has different pharmacological, toxicological, and metabolic activities. For this reason, chiral discrimination by using chromatographic and electromigration techniques has become an urgent need in the pharmaceutical field. This review intends to offer the “state of the art” about the separation of chiral antifungal drugs and several related precursors by both liquid and gas chromatography, as well as electromigration methods. This overview is organized into two sections. The first one describes general considerations on chiral antifungal drugs. The second part deals with the main analytical methods for the enantiomeric discrimination of these drugs, including a brief description of chiral selectors and stationary phases. Moreover, many recent applications attesting the great interest of analytical chemists in the field of enantiomeric separation are presented.

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