Read by QxMD icon Read

Expert Opinion on Drug Discovery

Matthew H Ung, Frederick S Varn, Chao Cheng
Leukemia is a collection of highly heterogeneous cancers that arise from neoplastic transformation and clonal expansion of immature hematopoietic cells. Post-treatment recurrence is high, especially among elderly patients, thus necessitating more effective treatment modalities. Development of novel anti-leukemic compounds relies heavily on traditional in vitro screens which require extensive resources and time. Therefore, integration of in silico screens prior to experimental validation can improve the efficiency of pre-clinical drug development...
October 11, 2016: Expert Opinion on Drug Discovery
Andrew M White, David J Craik
Macrocyclic peptides are generally more resistant to proteolysis and often have higher potency than linear peptides and so they are excellent leads in drug design. Their study is significant because they offer potential as a new generation of drugs that are potent and specific, and thus might have fewer side effects than traditional small molecule drugs. Areas covered: This article covers macrocyclic drug leads based on nature-derived cyclic peptides as well as synthetic cyclic peptides and close derivatives...
October 10, 2016: Expert Opinion on Drug Discovery
David R Janero, Ganesh A Thakur
Allosteric modulators of G-protein coupled receptors (GPCRs) hold the promise of improved pharmacology and safety over typical orthosteric GPCR ligands. These features are particularly relevant to the cannabinoid receptor 1 (CB1R) GPCR, since typical orthosteric CB1R ligands are associated with adverse events that limit their translational potential. Areas covered: The contextual basis for applying allostery to CB1R is considered from pharmacological, drug-discovery, and medicinal standpoints. Rational design of small-molecule CB1R allosteric modulators as potential pharmacotherapeutics would be greatly facilitated by direct experimental characterization of structure-function correlates underlying the biological activity of chemically-diverse CB1R allosteric modulators, CB1R allosteric ligand-binding binding pockets, and amino acid contact residues critical to allosteric ligand engagement and activity...
October 7, 2016: Expert Opinion on Drug Discovery
Róbert Kiss, György M Keserű
The application of structure-based drug discovery in histamine receptor projects was previously hampered by the lack of experimental structures. The publication of the first X-ray structure of the histamine H1 receptor has been followed by several successful virtual screens and binding site analysis studies of H1-antihistamines. This structure together with several other recently solved aminergic G-protein coupled receptors (GPCRs) enabled the development of more realistic homology models for H2, H3 and H4 receptors...
October 5, 2016: Expert Opinion on Drug Discovery
Thelma S Angeles, Robert L Hudkins
Elevated lipogenesis has been associated with a variety of diseases including obesity, cancer and nonalcoholic fatty liver disease (NAFLD). Fatty acid synthase (FASN) plays a pivotal role in de novo lipogenesis, making this multi-catalytic protein an attractive target for therapeutic intervention. Recently, the first FASN inhibitor successfully advanced through the drug development process and entered clinical evaluation in oncology. Areas covered: This review discusses the biological roles of FASN in three prominent disease areas: cancer, obesity-related disorders and non-alcoholic fatty liver disease...
October 5, 2016: Expert Opinion on Drug Discovery
Roberta Rosa, Valentina D'Amato, Sabino De Placido, Roberto Bianco
Several reports have suggested that a population of undifferentiated cells known as cancer stem cells (CSCs), is responsible for cancer formation and maintenance. In the last decade, the presence of CSCs in solid cancers have been reported. Areas covered: This review summarizes the main approaches for targeting CSCs drug resistance. It is indeed known that CSCs may contribute to resistance to conventional chemotherapy, radiotherapy and targeted agents. Among the mechanisms by which CSCs escape anticancer therapies, removal of therapeutic agents by drug efflux pumps, enhanced DNA damage repair, activation of mitogenic/anti-apoptotic pathways; the main features of CSCs, stemness and EMT, are involved, as well as the capability to evade immune response...
October 4, 2016: Expert Opinion on Drug Discovery
Francisco Martínez-Jiménez, Marc A Marti-Renom
No abstract text is available yet for this article.
September 16, 2016: Expert Opinion on Drug Discovery
Eivind A B Undheim, Ronald A Jenner, Glenn F King
INTRODUCTION: Centipedes are one of the oldest and most successful lineages of venomous terrestrial predators. Despite their use for centuries in traditional medicine, centipede venoms remain poorly studied. However, recent work indicates that centipede venoms are highly complex chemical arsenals that are rich in disulfide-constrained peptides that have novel pharmacology and three-dimensional structure. AREAS COVERED: This review summarizes what is currently known about centipede venom proteins, with a focus on disulfide-rich peptides that have novel or unexpected pharmacology that might be useful from a therapeutic perspective...
September 9, 2016: Expert Opinion on Drug Discovery
Vijay K Singh, Karla D Thrall, Martin Hauer-Jensen
No abstract text is available yet for this article.
August 22, 2016: Expert Opinion on Drug Discovery
David Grech
No abstract text is available yet for this article.
November 2016: Expert Opinion on Drug Discovery
Francisco Bautista, Jasper Van der Lugt, Pamela R Kearns, Francis J Mussai, C Michel Zwaan, Lucas Moreno
Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias...
November 2016: Expert Opinion on Drug Discovery
Gail J Roboz, John Roboz
No abstract text is available yet for this article.
November 2016: Expert Opinion on Drug Discovery
Angelo B A Laranjeira, Sherry X Yang
Cancer stem cells (CSCs), also known as tumor initialing cells, have self-renewal capacity and are believed to play an important role in residual disease or tumor relapse. CSCs exhibit characteristic slow growth rate and are resistant to conventional chemotherapy/radiotherapy in experimental models. The type of cells commonly employs aberrant activity of the embryonic signal transduction pathways - Notch, Hedgehog (Hh), and Wnt - for uncontrolled proliferation and survival. Areas covered: The following article discusses key genetic and molecular alterations in Notch, Hh and Wnt pathways and drugs targeting the alterations for the treatment of leukemia and lymphoma...
November 2016: Expert Opinion on Drug Discovery
Maria Batool, Muhammad Ayaz Anwar, Sangdun Choi
The crucial role of Toll-like Receptors (TLRs) in innate and adaptive immune systems is well discussed in the literature. In cancer, TLRs act as a double-edged sword that can promote or suppress tumor growth. Areas covered: In this article, the authors uncover the potential role of TLRs in lymphomas, which are cancers related to the lymphatic system and blood cells. TLRs are de facto inflammation-inducing receptors that can either worsen disease or ameliorate lymphoma treatment. From this perspective, the usage of TLRs to modulate the immune system toward lymphoma regression is desirable...
November 2016: Expert Opinion on Drug Discovery
Wataru Munakata, Kensei Tobinai
Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies. The treatment strategy for patients with NHL had remained unchanged until the advent of the era of molecular targeting agents. Although rituximab-containing chemotherapy has improved the response rates and survival of patients with B-cell NHL (B-NHL), several subtypes of B-NHL, especially indolent B-NHL and mantle cell lymphoma (MCL), remain incurable. Therefore, novel treatment modalities for B-NHL, especially for indolent B-NHL and MCL, are needed...
November 2016: Expert Opinion on Drug Discovery
Federica Barbieri, Adriana Bajetto, Stefano Thellung, Roberto Würth, Tullio Florio
Chemokines control homing and trafficking of leukocytes in bone marrow and lymphoid organs. In particular, CXCL12 and its receptors CXCR4/CXCR7 control the homeostasis of multiple organs and systems. Their overexpression is linked to tumor development, both through a direct modulation of neoplastic cell proliferation, survival, and migration, and, indirectly, acting on the tumor microenvironment which sustains drug resistant tumor stem-like cells. Leukemia and lymphomas frequently display upregulation of CXCL12/CXCR4 in bone marrow that nurtures tumor cells, and confers resistance to conventional chemotherapy, increasing disease relapse...
November 2016: Expert Opinion on Drug Discovery
Magdalena Witkowska, Piotr Smolewski, Agata Majchrzak, Tadeusz Robak
A new generation of anticancer agents called target drugs has been recently developed for the treatment of non-Hodgkin lymphomas. Current recovery rates in these diseases are up to 70% with immunotherapy based on the anti-CD20 monoclonal antibody combined with standard chemotherapeutics. However, there are still refractory or relapsed patients. Recently, several novel anti-lymphoma agents have been developed. Choosing the most effective personalized therapy still remains a crucial challenge in hematology. Areas covered: New drugs can specifically target malignant cells and inhibit cancer cell growth, proliferation and survival by specific interactions with one or more target proteins...
November 2016: Expert Opinion on Drug Discovery
Sanil Bhatia, Svenja Daschkey, Franziska Lang, Arndt Borkhardt, Julia Hauer
The development of novel drugs which specifically target leukemic cells, with the overall aim to increase complete remission and to reduce toxicity and morbidity, is the most important prerequisite for modern leukemia treatment. In this regard, the current transition rate of potential novel drugs from bench to bedside is remarkably low. Although many novel drugs show promising data in vitro and in vivo, testing of these medications in clinical phase I trials is often sobering with intolerable toxic side effects leading to failure in FDA approval...
November 2016: Expert Opinion on Drug Discovery
Xavier Thomas, Maël Heiblig
In Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), the BCR-ABL translocation is the main transforming event; consequently, it is targeted by ABL-tyrosine kinase inhibitors (TKIs), the first of which to be identified was imatinib mesylate. There are now four newer TKIs, three so-called second-generation inhibitors and one third generation inhibitor, all of which are more potent than imatinib in in vitro assays. Areas covered: This paper reviews the current knowledge on the function of BCR-ABL...
November 2016: Expert Opinion on Drug Discovery
Noah T Ditto, Ben D Brooks
INTRODUCTION: Surface plasmon resonance (SPR) for affinity/kinetics measurements of drug candidates has been a mainstay application for characterizing drug candidates for many years. Recently, with the growth of monoclonal antibodies (mAbs) as a drug class and the availability of higher-throughput biosensors, the role of label-free biosensors has evolved to include epitope characterization in the early drug discovery process through epitope binning and mapping of mAbs. AREAS COVERED: This manuscript outlines the importance of using epitope characterization early in the drug discovery process and describes a strategy for success in discovering drug leads...
October 2016: Expert Opinion on Drug Discovery
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"