MDM2-p53 Interaction Inhibitors: The Current State-of-Art and Updated Patent Review (2010-Present)

2020 ◽  
Vol 14 (4) ◽  
pp. 324-369 ◽  
Author(s):  
Rafał Rusiecki ◽  
Jakub Witkowski ◽  
Joanna Jaszczewska-Adamczak
Keyword(s):  
Therapeutic Potential ◽  
Research Work ◽  
Academic Research ◽  
Tumor Suppressor P53 ◽  
Research Groups ◽  
Current State ◽  
Mouse Double Minute ◽  
Patent Review ◽  
Main Emphasis ◽  
Double Minute

Background: Mouse Double Minute 2 protein (MDM2) is a cellular regulator of p53 tumor suppressor (p53). Inhibition of the interaction between MDM2 and p53 proteins is a promising anticancer therapy. Objective: This updated patent review is an attempt to compile the research and achievements of the various researchers working on small molecule MDM2 inhibitors from 2010 to date. We provide an outlook into the future for therapy based on MDM2 inhibition by presenting an overview of the most relevant patents which have recently appeared in the literature. Methods: Literature and recent patents focusing on the anticancer potential of MDM2-p53 interaction inhibitors and its applications have been analyzed. We put the main emphasis on the most perspective compounds which are or were examined in clinical trials. Results: Literature data indicated that MDM2 inhibitors are therapeutically effective in specific types of cancer or non-cancer diseases. A great number of patents and research work around new MDM2- p53 interaction inhibitors, possible combinations, new indications, clinical regimens in previous years prove that this targeted therapy is in the scope of interest for many business and academic research groups. Conclusion: Novel MDM2 inhibitors thanks to higher potency and better ADME properties have shown effectiveness in preclinical and clinical development however the final improvement of therapeutic potential for MDM2 inhibitors might depend on the useful combination therapy and exploring new cancer and non-cancer indications.

scholarly journals Discovery, X-ray structure and CPP-conjugation enabled uptake of p53/MDM2 macrocyclic peptide inhibitors

2021 ◽  
Author(s):  
Anselm Schneider ◽  
Jörg Kallen ◽  
Johannes Ottl ◽  
Patrick C Reid ◽  
Sebastien Ripoche ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Peptide Inhibitors ◽  
Negative Regulator ◽  
Tumor Suppressor P53 ◽  
X Ray ◽  
Mouse Double Minute ◽  
Double Minute ◽  
Important Negative Regulator ◽  
Display Technique ◽  
Macrocyclic Peptide

Mouse double minute 2 homolog (MDM2, Hdm2) is an important negative regulator of the tumor suppressor p53. Using a mRNA based display technique to screen a library of >1012 in...

scholarly journals Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice

2021 ◽  
Vol 218 (5) ◽  
Author(s):  
Jing Qu ◽  
Shan-Zhong Yang ◽  
Yi Zhu ◽  
Ting Guo ◽  
Victor J. Thannickal ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Therapeutic Potential ◽  
Matrix Stiffness ◽  
Genetic Ablation ◽  
Aged Mice ◽  
Mouse Double Minute ◽  
Double Minute ◽  
P53 Activation ◽  
Lung Matrix

Aging is a strong risk factor and an independent prognostic factor for progressive human idiopathic pulmonary fibrosis (IPF). Aged mice develop nonresolving pulmonary fibrosis following lung injury. In this study, we found that mouse double minute 4 homolog (MDM4) is highly expressed in the fibrotic lesions of human IPF and experimental pulmonary fibrosis in aged mice. We identified MDM4 as a matrix stiffness–regulated endogenous inhibitor of p53. Reducing matrix stiffness down-regulates MDM4 expression, resulting in p53 activation in primary lung myofibroblasts isolated from IPF patients. Gain of p53 function activates a gene program that sensitizes lung myofibroblasts to apoptosis and promotes the clearance of apoptotic myofibroblasts by macrophages. Destiffening of the fibrotic lung matrix by targeting nonenzymatic cross-linking or genetic ablation of Mdm4 in lung (myo)fibroblasts activates the Mdm4–p53 pathway and promotes lung fibrosis resolution in aged mice. These findings suggest that mechanosensitive MDM4 is a molecular target with promising therapeutic potential against persistent lung fibrosis associated with aging.

Cooperation and Competition

2017 ◽  
Author(s):  
Ken Peach
Keyword(s):  
Graduate Students ◽  
Particle Physics ◽  
Life Sciences ◽  
Academic Research ◽  
Research Groups ◽  
Experimental Science ◽  
Multidisciplinary Research ◽  
Common Goal ◽  
Physical Sciences ◽  
Research Sector

This chapter discusses the need for cooperation (or collaboration) to be balanced with competition, including between research groups, within a university or laboratory and between the academic research sector and industry. Healthy competition is a great motivator but unhealthy competition can be disastrous. While it is still possible for an individual scientist working alone or with a couple of graduate students or postdocs to make ground-breaking discoveries, today much experimental science requires large teams working collaboratively on a common goal or set of goals. While this trend is most evident in particle physics and astronomy, it is also present in the other physical sciences and the life sciences. Collaboration brings together more resources–physical, financial and intellectual–to address major challenges that would otherwise be beyond the scope of any individual or group. Multidisciplinary research and interdisciplinary research are examples of cooperation between different disciplines.

scholarly journals Biological Properties and Prospects for the Application of Eugenol—A Review

2021 ◽  
Vol 22 (7) ◽  
pp. 3671
Author(s):  
Magdalena Ulanowska ◽  
Beata Olas
Keyword(s):  
Body Weight ◽  
Aromatic Compound ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Biological Properties ◽  
Clove Oil ◽  
Current State ◽  
Potential Component ◽  
Anti Inflammatory ◽  
High Concentrations

Eugenol is a phenolic aromatic compound obtained mainly from clove oil. Due to its known antibacterial, antiviral, antifungal, anticancer, anti-inflammatory and antioxidant properties, it has long been used in various areas, such as cosmetology, medicine, and pharmacology. However, high concentrations can be toxic. A dose of 2.5 mg/kg body weight is regarded as safe. This paper reviews the current state of knowledge regarding the activities and application of eugenol and its derivatives and recent research of these compounds. This review is based on information concerning eugenol characteristics and recent research from articles in PubMed. Eugenol remains of great interest to researchers, since its multidirectional action allows it to be a potential component of drugs and other products with therapeutic potential against a range of diseases.

Appendix: Publication venues, academic research groups, and funding agencies

2013 ◽  
pp. 127-127
Author(s):  
Sandeep K. S. Gupta ◽  
Tridib Mukherjee ◽  
Krishna Kumar Venkatasubramanian
Keyword(s):  
Academic Research ◽  
Research Groups ◽  
Funding Agencies

Vascular surgery: What increases the flow of students to the speciality?

Vascular ◽  
2018 ◽  
Vol 27 (3) ◽  
pp. 338-344 ◽  
Author(s):  
Mohammed Adil A Turki ◽  
Alexander Zargaran ◽  
Aasim Murtaza ◽  
Amal Thomas ◽  
Harry Spiers ◽  
...  
Keyword(s):  
Vascular Surgery ◽  
Medical Curriculum ◽  
Research Work ◽  
Academic Research ◽  
Undergraduate Curriculum ◽  
Significant Rise ◽  
Surgical Skills ◽  
Positive Perception ◽  
Vascular Surgeon ◽  
Diverse Range

Objectives Vascular surgery is in increasing demand due to the higher prevalence of cardiovascular disease in the general population. Meanwhile, applications to join the speciality have been in decline in the last few years. St George’s Surgical Society held a one-day conference to expose undergraduates to the speciality in the hope that this will inspire more undergraduates to pursue it as a career. Methods The conference consisted of introductory lectures delivered by a consultant vascular surgeon, followed by practical skills workshops simulating aortic anastomosis on porcine aortas. Pre-course and post-course questionnaires assessed positive and negative perceptions of vascular surgery, knowledge of and self-reported confidence in practical surgical skills and utility of the course in their decision to potentially pursue a career in vascular surgery. Results There was a significant increase of 27% ( p = 0.03) in the positive perception that vascular surgery includes a diverse range of procedures and subspecialties. Attendees reported a 27% significant increase ( p = 0.02) in the perception that vascular surgery had a wide array of opportunity for academic/research work. Finally, there was an 18% decrease ( p = 0.03) in the negative perception that vascular surgery is somehow female-unfriendly or discriminatory against females. There was also a significant rise in both interest (33%) and understanding (73%) of vascular surgery. Conclusions A one-day conference can significantly impact students’ perception especially when there is a lack of exposure within the undergraduate curriculum. This course helped to increase positive perception and dispute negative misconceptions about the speciality. The simulation workshops held at this conference increased students’ confidence and awareness of relevant surgical skills. This conference provided a unique experience that positively impacted and inspired students and thus served as an important supplement to core medical curriculum.

scholarly journals Research Identities: Reflections of a Contract Researcher

2006 ◽  
Vol 11 (2) ◽  
pp. 40-49 ◽  
Author(s):  
Jackie Goode
Keyword(s):  
Identity Formation ◽  
Research Work ◽  
Academic Research ◽  
Institutional Identity ◽  
Research Staff ◽  
Qualitative Researcher ◽  
Contract Research ◽  
Social Work Training ◽  
Work Training ◽  
Researcher Identity

This paper examines the institutional identity formation of contract research staff in the context of the Taylorisation of research knowledges. The author has been a contract researcher for many years, after initially training and practising as a Probation Officer. She makes links between her social work training, and her current practice as a qualitative researcher. Drawing on her experience of working on a variety of different projects, at a number of different institutions, and providing illustrative examples from projects in sociology, social policy, health, and education, she reflects on the implications of the current social organization of academic research both for professional research practice and for researcher identity. There is a paradox in the way that contract research staff accrue a wealth of experience of how research is organised and conducted in different contexts, a repertoire of skills, and a vast volume of various kinds of ‘data’, whilst remaining vulnerable and marginalized figures within the academy, with few opportunities for professional development and advancement. She outlines a number of strategies she has employed in the preservation of the ‘research self’, and concludes by suggesting that the academy has much to learn about the effective management of ‘waste’, as embodied by researchers’ selves and their data, consequent upon the Taylorisation of research work.

scholarly journals PHYTO-MEDICINAL EFFECTS OF SYZYGIUM CUMINI ON DIABETES: A REVIEW

2020 ◽  
pp. 392-402
Author(s):  
Md. Mahmudul Amin
Keyword(s):  
Plant Extracts ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Scientific Evidence ◽  
Research Result ◽  
Treatment Strategies ◽  
Pharmaceutical Preparations ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Current State

Diabetes is a major public health problem which has been increasing day by day throughout the world with an alarming rate. In recent years, several plant extracts have been examined for their anti-diabetic properties to identify alternative treatment strategies that pose less risk for diabetes. It has been shown that different parts of these plants are collected from diverse regions and administered in different pharmaceutical preparations. The aim of the present review is to provide an overview of the phytochemicals present in S. cumini plants and their potent anti-diabetic activity, toxicological and biological effects of these plant extracts, their current state, limitation and future prospects in developing countries that are not included in the European Pharmacopoeia. In addition, a prospective research result of synergistic use of this plant with other plant (Ficus racemosa) done presently in our laboratory has been included. Based on the available evidence, we highlight the ways in which their therapeutic potential can be properly harnessed and provide scientific evidence for the discovery of novel leads for herbal drug development.

scholarly journals The mouse double minute 2 309T>G polymorphism and retinoblastoma risk: A meta-analysis

2020 ◽  
Vol 34 (3) ◽  
pp. 191
Author(s):  
Jasbir Kaur ◽  
K Sooraj ◽  
Sunil Kumar ◽  
Amit Kumar ◽  
MandeepS Bajaj
Keyword(s):  
Meta Analysis ◽  
Mouse Double Minute ◽  
Double Minute
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