Molecular Modeling Approaches in the Discovery of New Drugs for Anti-Cancer Therapy: The Investigation of p53-MDM2 Interaction and its Inhibition by Small Molecules

2010 ◽  
Vol 17 (28) ◽  
pp. 3142-3154 ◽  
Author(s):  
A. Lauria ◽  
M. Tutone ◽  
M. Ippolito ◽  
L. Pantano ◽  
A. Almerico
Keyword(s):  
Molecular Modeling ◽  
Cancer Therapy ◽  
Small Molecules ◽  
New Drugs ◽  
Modeling Approaches ◽  
Anti Cancer

scholarly journals Small Molecules Targeting Biological Clock; A Novel Prospective for Anti-Cancer Drugs

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4937
Author(s):  
Sadia Rahman ◽  
Karlo Wittine ◽  
Mirela Sedić ◽  
Elitza P. Markova-Car
Keyword(s):  
Circadian Rhythm ◽  
Small Molecules ◽  
Small Molecule ◽  
Environmental Conditions ◽  
Recent Progress ◽  
Biological Clock ◽  
New Drugs ◽  
Anti Cancer ◽  
Growing Body ◽  
Potential Use

The circadian rhythms are an intrinsic timekeeping system that regulates numerous physiological, biochemical, and behavioral processes at intervals of approximately 24 h. By regulating such processes, the circadian rhythm allows organisms to anticipate and adapt to continuously changing environmental conditions. A growing body of evidence shows that disruptions to the circadian rhythm can lead to various disorders, including cancer. Recently, crucial knowledge has arisen regarding the essential features that underlie the overt circadian rhythm and its influence on physiological outputs. This knowledge suggests that specific small molecules can be utilized to control the circadian rhythm. It has been discovered that these small molecules can regulate circadian-clock-related disorders such as metabolic, cardiovascular, inflammatory, as well as cancer. This review examines the potential use of small molecules for developing new drugs, with emphasis placed on recent progress that has been made regarding the identification of small-molecule clock modulators and their potential use in treating cancer.

The impact of new cancer drug therapies on site specialised cancer treatment activity in a UK cancer network 2014–2018

2019 ◽  
Vol 26 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Jenna Bhimani ◽  
Lara Philipps ◽  
Lawrence Simpson ◽  
Mark Lythgoe ◽  
Aspasia Soultati ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
New Drugs ◽  
Electronic Prescribing ◽  
Cancer Drug ◽  
Individual Treatment ◽  
Anti Cancer ◽  
Delivery Planning ◽  
The Uk ◽  
Cancer Network ◽  
The Impact

Introduction Drug treatment for cancer has changed dramatically over the past decade with many new drugs often with multiple applications. More recently, the detailed pathway for approval from the National Institute for Health and Care Excellence (NICE) in the UK has been simplified. To explore how these changes have impacted on systemic anti-cancer therapy tumour site-specific prescribing and workload activities, we have reviewed the prescribing records for 2014–2018 in a UK cancer network. Methods Information about the numbers of new systemic anti-cancer therapy drugs and NICE approvals were obtained from print editions of the British National Formulary (BNF) and the NICE website. Data on the numbers of new chemotherapy courses and individual treatment-related attendances were obtained from the cancer network Chemocare electronic prescribing system. Results During the five-year study period, there were 49 new systemic anti-cancer therapy drugs for all tumour types, and a total of 65 NICE technology approvals for solid tumour indications. Overall numbers of treatment courses increased by 40.7% and total treatment-related visits by 80.6%. There was a wide variation across tumour types with the highest number of increased visits seen for melanoma (349.3%) and prostate cancer (242.3%), but in contrast, no appreciable increases were seen for lower gastrointestinal cancers or small cell lung cancer. Conclusion The study confirms the major impact of the arrival of new drug technology and positive NICE appraisals on increasing systemic anti-cancer therapy prescribing and chemotherapy unit activity. The data in this study may be of help in planning for future service delivery planning and workforce configurations.

scholarly journals Progress in the development of early diagnosis and a drug with unique pharmacology to improve cancer therapy

2008 ◽  
Vol 366 (1880) ◽  
pp. 3599-3617 ◽  
Author(s):  
A Lehotzky ◽  
N Tőkési ◽  
I Gonzalez-Alvarez ◽  
V Merino ◽  
M Bermejo ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Early Diagnosis ◽  
Drug Market ◽  
New Drugs ◽  
Cancer Drug ◽  
Major Health ◽  
Economic Problems ◽  
Anti Cancer ◽  
New Type ◽  
Unstructured Protein

Cancer continues to be one of the major health and socio-economic problems worldwide, despite considerable efforts to improve its early diagnosis and treatment. The identification of new constituents as biomarkers for early diagnosis of neoplastic cells and the discovery of new type of drugs with their mechanistic actions are crucial to improve cancer therapy. New drugs have entered the market, thanks to industrial and legislative efforts ensuring continuity of pharmaceutical development. New targets have been identified, but cancer therapy and the anti-cancer drug market still partly depend on anti-mitotic agents. The objective of this paper is to show the effects of KAR-2, a potent anti-mitotic compound, and TPPP/p25, a new unstructured protein, on the structural and functional characteristics of the microtubule system. Understanding the actions of these two potential effectors on the microtubule system could be the clue for early diagnosis and improvement of cancer therapy.

scholarly journals Snake Venoms in Cancer Therapy: Past, Present and Future

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 346 ◽  
Author(s):  
Li Li ◽  
Jianzhong Huang ◽  
Yao Lin
Keyword(s):  
Cancer Therapy ◽  
Enzyme Inhibitor ◽  
Target Therapy ◽  
New Drugs ◽  
Bioactive Molecules ◽  
Snake Venoms ◽  
Cancer Treatments ◽  
Lead Compounds ◽  
The Past ◽  
Anti Cancer

Cancer is one of the leading causes of morbidity and mortality worldwide, and the discovery of new drugs for cancer therapy is one of the most important objectives for the pharmaceutical industry. Snake venoms are complex mixtures containing different peptides, proteins, enzymes, carbohydrates and other bioactive molecules, which are secreted by the snake in the predation or defending against threats. Understanding the snake venoms may turn the toxins into a valuable source of new lead compounds in drug discovery. Captopril, the first angiotensin-converting enzyme inhibitor approved in 1981 by FDA, was designed based on the structure of a peptide isolated from the snake venom. The earliest reports about snake venoms used in cancer treatments appeared in the 1930s. Since then, numerous studies on the activities, isolations, purifications and structure elucidations of the components from snake venoms were published. The comprehensive structural and functional investigations of snake venoms would contribute to the development of novel anti-cancer drugs. Our review will focus on the past, present and the future of the studies on snake venoms in cancer target therapy.

scholarly journals Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy

2018 ◽  
Author(s):  
Joanna Zawacka-Pankau ◽  
Vera V. Grinkevich ◽  
Mikhail Burmakin ◽  
Aparna Vema ◽  
Karin Fawkner ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Small Molecules ◽  
Anticancer Therapy ◽  
Mechanisms Of Action ◽  
Allosteric Modulation ◽  
Structural Element ◽  
Allosteric Mechanism ◽  
Anti Cancer ◽  
P53 Activation ◽  
Pharmacological Potential

AbstractGiven the immense significance of p53 restoration for anti-cancer therapy, elucidation of the mechanisms of action of p53-activating molecules is of the utmost importance. Here we report a discovery of novel allosteric modulation of p53 by small molecules, which is an unexpected turn in the p53 story. We identified a structural element involved in p53 regulation, whose targeting by RITA, PpIX and licofelone block the binding of p53 inhibitors, MDM2 and MDMX. Deletion and mutation analysis followed by molecular modeling, identified the key p53 residues S33 and S37 targeted by RITA and PpIX. We propose that the binding of small molecules to the identified site induces a conformational trap preventing p53 from the interaction with MDM2 and MDMX. These results point to a high potential of allosteric activators. Our study provides the basis for the development of therapeutics with a novel mechanism of action, thus extending the p53 pharmacological potential.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

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