Book Chapter10.1016/B978-012369448-5.50004-5
Modern cancer drug discovery: integrating targets, technologies and treatments
Paul Workman,Ian Collins +1 more
- 01 Jan 2008
- pp 3-38
10
TL;DR: This chapter aims to capture the sense of excitement and to describe the opportunities and challenges in the discovery and design of molecularly targeted small-molecule cancer drugs.
read more
Abstract: This chapter aims to capture the sense of excitement and to describe the opportunities and challenges in the discovery and design of molecularly targeted small-molecule cancer drugs Small-molecule targeted cancer drugs such as imatinib; erlotinib and others discussed in this chapter provide clear proof of concept that significant clinical benefit can be obtained by developing drugs that act on the particular oncogenic abnormalities that are responsible for malignant transformation and progression Drugging the cancer genome is now a reality On the other hand, although the importance and utility of the molecularly targeted approach are now well established, cancer is still a formidably complicated disease and many challenges remain to be overcome The most appropriate strategy for finding small-molecule leads is dependent on the nature of the molecular target and the associated biology Molecular diagnostics are needed to select animal models and patients that are the most appropriate for assessing the activity of the particular agent Molecular biomarkers are also absolutely essential to determine proof of concept for modulation of the desired target, and to help determine what is the optimal dose and administration schedule
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
•Journal Article
A Robustness-based Approach to Systems-oriented Drug Design
TL;DR: In this paper, a theoretical foundation for a systems-oriented approach to more effectively control the robustness of living systems, particularly at the cellular level, could be developed by studying complex network systems and reformulating control and communication theories.
434
Antimicrobial peptides: an alternative for innovative medicines?
TL;DR: This work reviews the available strategies for their synthesis, bioinformatics tools for the rational design of antimicrobial peptides with enhanced therapeutic indices, hurdles and shortcomings limiting the large-scale production of AMPs, as well as the challenges that the pharmaceutical industry faces on their use as therapeutic agents.
197
Survey of the year 2008: applications of isothermal titration calorimetry
TL;DR: This review highlights some of the particularly interesting reports from 2008 employing ITC, with a particular focus on protein interactions with other proteins, nucleic acids, lipids and drugs.
77
Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery
Ian Collins,Alan M. Jones +1 more
TL;DR: It is shown how considering appropriate and variable focus in library design has provided a spectrum of DOS approaches relevant at all stages in anti-cancer drug discovery, summarising the syntheses of novel and often highly complex scaffolds from pluripotent or synthetically versatile building blocks.
28
References
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
30.6K
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
16.8K
Mutations of the BRAF gene in human cancer
Helen Davies,Graham R. Bignell,Charles Cox,Philip J. Stephens,Sarah Edkins,S. M. Clegg,Jon W. Teague,Hayley Woffendin,Mathew J. Garnett,William Bottomley,Neil Davis,Ed Dicks,Rebecca Ewing,Yvonne Floyd,Kristian Gray,S. Hall,Rachel Hawes,Jaime Hughes,Vivian Kosmidou,Andrew Menzies,Catherine Mould,Adrian Parker,Claire Stevens,Stephen Watt,Steven Hooper,Rebecca Wilson,Hiran Jayatilake,Barry A. Gusterson,Colin Cooper,Janet Shipley,Darren Hargrave,Kathy Pritchard-Jones,Norman J. Maitland,Georgia Chenevix-Trench,Gregory J. Riggins,Darell D. Bigner,Giuseppe Palmieri,Antonio Cossu,Adrienne M. Flanagan,Andrew G. Nicholson,Judy W. C. Ho,Suet Yi Leung,Siu Tsan Yuen,Barbara L. Weber,Hilliard F. Seigler,Timothy L. Darrow,Hugh Paterson,Richard Marais,Christopher J. Marshall,Richard Wooster,Michael R. Stratton,P. Andrew Futreal +51 more
TL;DR: BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%.
11.1K
Translating the Histone Code
Thomas Jenuwein,C. David Allis +1 more
TL;DR: It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
Molecular properties that influence the oral bioavailability of drug candidates.
Daniel F. Veber,Stephen R. Johnson,Hung-Yuan Cheng,Brian R. Smith,Keith W. Ward,Kenneth D. Kopple +5 more
TL;DR: Reduced molecular flexibility, as measured by the number of rotatable bonds, and low polar surface area or total hydrogen bond count are found to be important predictors of good oral bioavailability, independent of molecular weight.
7K