Abstract：
:Epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, show excellent clinical efficacy for patients with non-small cell lung cancer (NSCLC) with EGFR mutations, including Exon 19 deletion and single-point substitution, and L858R of exon 21. The reason for the reduction in effectiveness of these EGFR TKIs is the T790M gatekeeper mutation in the ATP-binding pocket of Exon 20, which increases the affinity of EGFR for ATP. Newer EGFR TKIs, such as afatinib, osimertinib, rociletinib, EGF816 and ASP8273, selectively target T790M mutants, sparing wild-type EGFR. EGFR TKIs have fewer adverse effects than chemotherapy and also improve progression-free survival. Combination therapy of EGFR TKIs with anti-EGFR antibodies is recommended for overcoming the problem of resistance to some extent. This review could help medicinal chemists to design novel EGFR TKIs against NSCLC.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Singh M,Jadhav HRdoi
10.1016/j.drudis.2017.10.004subject
Has Abstractpub_date
2018-03-01 00:00:00pages
745-753issue
3eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30371-9journal_volume
23pub_type
杂志文章,评审abstract：:Gene expression microarrays have been used widely to address increasingly complex biological questions and to produce an unprecedented amount of data, but have yet to realize their full potential. The interpretation of microarray data remains a major challenge because of the complexity of the underlying biological net...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03565-8
更新日期：2005-09-01 00:00:00
abstract：:Gastrointestinal patch systems with integrated multifunctions could surmount the challenges associated with conventional drug delivery. Several gastrointestinal patch systems provide bioadhesion, drug protection and unidirectional release. This combination of function could improve the overall oral bioavailability of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03489-6
更新日期：2005-07-01 00:00:00
abstract：:The unique anti-atherosclerosis abilities and other cardioprotective properties make high-density lipoprotein (HDL) a promising solution in treating cardiovascular diseases. A number of studies showed that HDL-based therapy was well tolerated and has great potential in the future. Among all these new agents, the most ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.08.010
更新日期：2017-01-01 00:00:00
abstract：:The pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are ligand-activated nuclear receptors (NRs) that are notorious for their role in drug metabolism, causing unintended drug-drug interactions and decreasing drug efficacy. They control the xenobiotic detoxification system by regulating the exp...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.01.021
更新日期：2019-03-01 00:00:00
abstract：:Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (sonopho...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03170-8
更新日期：2004-08-01 00:00:00
abstract：:Target concentration is typically not considered in drug discovery. However, if targets are expressed at relatively high concentrations and compounds have high affinity, such that most of the drug is bound to its target, in vitro screens can give unreliable information on compound affinity. In vivo, a similar situatio...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.06.010
更新日期：2018-12-01 00:00:00
abstract：:Since the introduction of cisplatin in cancer therapy, metal complexes and organometallic compounds have been gaining growing importance in oncology. The impressive clinical effectiveness of cisplatin is limited by significant side effects and the emergence of drug resistance. Thus, novel classic and unconventional Pt...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.02.002
更新日期：2009-05-01 00:00:00
abstract：:Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. An...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.09.026
更新日期：2015-02-01 00:00:00
abstract：:Nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. Hot topics in this field have been discussed recently at the 2nd Annual BioSafe European General Membership Meeting. In this feature article, discussions on the challenges surrounding the use ...
journal_title：Drug discovery today
pub_type：
doi：10.1016/j.drudis.2013.08.003
更新日期：2013-12-01 00:00:00
abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)02006-2
更新日期：2001-11-15 00:00:00
abstract：:Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have k...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03383-0
更新日期：2005-03-01 00:00:00
abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)01910-9
更新日期：2001-08-15 00:00:00
abstract：:Outnumbering our own cells over ten times, gut microbes can even be considered an additional organ. Several studies have explored the association between microbiomes and antitumor drug response. It has been reported that the presence of specific bacteria might modulate cancer progression and the efficacy of anticancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.02.009
更新日期：2019-04-01 00:00:00
abstract：:Osteoarthritis (OA), the most common and disabling form of arthritic disease, is characterized by a slow and progressive degeneration of articular cartilage. Its etiology is multifactorial and includes genetic predisposition, obesity and aging. In addition to the cartilage itself, OA also involves the surrounding tiss...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2011.01.004
更新日期：2011-05-01 00:00:00
abstract：:The energy substrate preference of the human heart is well regulated and is modified upon aging, in that the fetal heart uses glucose, whereas the adult heart utilizes fatty acids. Various human and animal studies suggest a shift in myocardial substrate utilization and decreased rate of myocardial fatty acid uptake an...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.02.010
更新日期：2016-06-01 00:00:00
abstract：:Multiplexed protein analysis using planar microarrays or microbeads is growing in popularity for simultaneous assays of antibodies, cytokines, allergens, drugs and hormones. However, this new assay format presents several new operational issues for the clinical laboratory, such as the quality control of protein-microa...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.09.010
更新日期：2006-11-01 00:00:00
abstract：:Telomerase is a ribonucleic reverse transcriptase enzyme that uses an integral RNA component as a template to add tandem telomeric DNA repeats, TTAGGG, at the 3' end of the chromosomes. 85-90% of human tumors and their derived cell lines predominantly express high levels of telomerase, therefore contributing to cancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.05.015
更新日期：2019-07-01 00:00:00
abstract：:Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also pl...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.02.008
更新日期：2015-07-01 00:00:00
abstract：:Oral delivery of peptides and proteins remains an attractive alternative to parenteral delivery and has challenged various attempts at delivery development. Incorporation of new tools into the delivery systems that can raise membrane permeability of macromolecules is essential to attain high oral bioavailability that ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.08.005
更新日期：2006-10-01 00:00:00
abstract：:A more complete understanding of the mechanisms that drive autoimmune diseases has begun to be translated into therapeutic options with significant clinical consequences. A clear example of this is the introduction of biological therapies, which have provided new therapeutic avenues, as well as validated the mediators...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.07.002
更新日期：2009-10-01 00:00:00
abstract：:The modern drug discovery process is steadily becoming more information driven. Structural, physicochemical and ADME-Tox property profiles of reference (successful) ligands, along with structural information of their target proteins, have been extremely useful for early-stage drug discovery. Recently, databases of kno...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.10.012
更新日期：2006-12-01 00:00:00
abstract：:Inhibition of vascular endothelial growth factor (VEGF) or its corresponding receptor (VEGFR) has been validated as an efficacious antiangiogenetic approach for cancer treatment. More recently, neuropilins (NRPs), the essential coreceptors for VEGF, have also been shown to have a significant role in VEGF signaling. Gi...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.10.004
更新日期：2019-02-01 00:00:00
abstract：:The sustained growth of biotechnology in North Carolina has made the state a worldwide leader in biotechnology. ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/S1359-6446(05)03650-0
更新日期：2005-11-15 00:00:00
abstract：:The proces of piecemeal microautophagy of the nucleus describes the way in which autophagy occurs in the nucleus, a realm of the cell once considered to be off limits for autophagy. ...
journal_title：Drug discovery today
pub_type： 新闻
doi：10.1016/s1359-6446(03)02636-9
更新日期：2003-03-15 00:00:00
abstract：:Idiopathic pulmonary fibrosis (IPF) is a progressive and almost invariably lethal disease that affects primarily older adults. After a decade of negative (or inconsistent) results, two recent clinical trials have demonstrated that slowing disease progression with medication is possible. An improved understanding of di...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.01.001
更新日期：2015-05-01 00:00:00
abstract：:Research consortia in Europe often compete with each other for skills, human and technical resources and, eventually, recognition of the scientific impact of their work. In response to the same EU Horizon2020 call, we received funding for our research project proposals to identify and validate novel drug targets for c...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.01.009
更新日期：2020-04-01 00:00:00
abstract：:Healthcare systems are faced with the challenge of providing innovative treatments, while shouldering high drug costs that pharmaceutical companies justify by the high costs of R&D. An emergent technology that could transform R&D efficiency is organ-on-a-chip. The technology bridges the gap between preclinical testing...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.06.003
更新日期：2019-09-01 00:00:00
abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/s1359-6446(01)01831-1
更新日期：2001-07-01 00:00:00
abstract：:Confronted with the need to significantly raise the productivity of remotely located chemistry CROs Pfizer embraced a commitment to continuous improvement which leveraged the tools from both Lean Six Sigma and queue management theory to deliver positive measurable outcomes. During 2012 cycle times were reduced by 48% ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.07.017
更新日期：2014-03-01 00:00:00
abstract：:Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, i...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.07.012
更新日期：2013-01-01 00:00:00
