keyword
MENU ▼
Read by QxMD icon Read
search

tyrosine kinase inhibitor

keyword
https://www.readbyqxmd.com/read/29677483/design-synthesis-and-biological-evaluation-of-pyrimidine-based-derivatives-as-vegfr-2-tyrosine-kinase-inhibitors
#1
Wuji Sun, Shengquan Hu, Shubiao Fang, Hong Yan
Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has already become an attractive approach for cancer therapy. In this study, a novel pyrimidine-based derivative 7j was designed as lead compound, and three series of potent VEGFR-2 inhibitors were synthesized and biologically evaluated against A549 and HepG2 cell lines. Compounds 7d, 9s and 13n exhibited superior inhibitory activities against A549 cell with IC50 ranged from 9...
April 13, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29675860/pulmonary-pleomorphic-carcinoma-a-case-harboring-egfr-mutation-treated-with-egfr-tkis
#2
Ken Masuda, Takaaki Tokito, Koichi Azuma, Eriko Yanagida, Masayuki Nakamura, Yoshiko Naito, Norikazu Matsuo, Hidenobu Ishii, Kazuhiko Yamada, Jun Akiba, Tomoaki Hoshino
Pulmonary pleomorphic carcinoma (PPC) is a very rare type of primary lung cancer with an aggressive clinical course. Few reports have documented therapeutic options for PPC with EGFR mutations. Herein, we report a case of PPC with EGFR mutation treated with EGFR-tyrosine kinase inhibitors (TKIs). A 65-year-old Japanese woman was diagnosed with stage IV lung adenocarcinoma with L858R point mutation in exon 21. Despite treatment with erlotinib, the patient died after two weeks as a result of rapid disease progression...
April 19, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29675611/ponatinib-as-second-line-treatment-in-chronic-phase-chronic-myeloid-leukemia-patients-in-real-life-practice
#3
Massimo Breccia, Elisabetta Abruzzese, Fausto Castagnetti, Massimiliano Bonifacio, Domenica Gangemi, Federica Sorà, Alessandra Iurlo, Luigiana Luciano, Antonella Gozzini, Massimo Gentile, Monica Bocchia, Debora Luzi, Alessandro Maggi, Nicola Sgherza, Alessandro Isidori, Monica Crugnola, Patrizia Pregno, Anna Rita Scortechini, Isabella Capodanno, Michele Pizzuti, Robin Foà
Scarce information is available on the use of ponatinib as second-line treatment in chronic phase chronic myeloid leukemia (CP-CML) patients resistant and/or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. We collected data from 29 CML patients, with a median age of 54 years (range 32-72). Eleven patients had received dasatinib, 15 patients received nilotinib, and 3 patients received imatinib as first-line treatment. Forty-five percent of patients started ponatinib for secondary resistance, 38% for primary resistance, 7% for severe intolerance associated to a molecular warning, 7% due to the presence of a T315I mutation, and 3% for severe intolerance...
April 19, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29675214/controllable-extension-of-hairpin-structured-flaps-to-allow-low-background-cascade-invasive-reaction-for-a-sensitive-dna-logic-sensor-for-mutation-detection
#4
Yun-Long Liu, Hai-Ping Wu, Qiang Zhou, Qin-Xin Song, Jian-Zhong Rui, Xiao-Xiang Guan, Guo-Hua Zhou, Bing-Jie Zou
A DNA logic sensor was constructed for gene mutation analysis based on a novel signal amplification cascade by controllably extending a hairpin-structured flap to bridge two invasive reactions. The detection limit was as low as 0.07 fM, and the analytical specificity is high enough to unambiguously pick up 0.02% mutants from a large amount of wild-type DNA. Gene mutations related to the personalized medicine of gefitinib, a typical tyrosine kinase inhibitor, were analyzed by the DNA logic sensor with only a 15 minute response time...
February 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29674709/known-and-novel-roles-of-the-met-oncogene-in-cancer-a-coherent-approach-to-targeted-therapy
#5
REVIEW
Paolo M Comoglio, Livio Trusolino, Carla Boccaccio
The MET oncogene encodes an unconventional receptor tyrosine kinase with pleiotropic functions: it initiates and sustains neoplastic transformation when genetically altered ('oncogene addiction') and fosters cancer cell survival and tumour dissemination when transcriptionally activated in the context of an adaptive response to adverse microenvironmental conditions ('oncogene expedience'). Moreover, MET is an intrinsic modulator of the self-renewal and clonogenic ability of cancer stem cells ('oncogene inherence')...
April 19, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29674428/optimising-endocrine-therapy-in-postmenopausal-women-with-advanced-breast-cancer
#6
Thomas Ho Lai Yau, Kl Cheung
Hormone receptor-positive breast cancer is commonly treated with endocrine therapy; however, overtime cancer cells can develop endocrine resistance. This review aims to document combination therapy and sequential therapy in the use of endocrine agents and targeted agents. By conducting two systematic searches using 4 databases: Cochrane Library, MEDLINE, EMBASE, and Web of Science. A total of 26 studies that covered combination therapy were obtained and included for the review. 14 were phase III documenting combinations of mechanistic target of rapamycin (mTOR), phosphoinositide-3-kinase (PI3K), vascular endothelial growth factor receptor (VEGFR), human epidermal growth factor receptor 2 (HER2), and cyclin dependent kinase 4/6 (CDK4/6) inhibitors...
April 19, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29673089/non-small-cell-lung-cancer-harboring-a-rare-egfr-l747p-mutation-showing-intrinsic-resistance-to-both-gefitinib-and-osimertinib-azd9291-a-case-report
#7
Jing Huang, Yiyin Wang, Yachao Zhai, Jin Wang
The most common EGFR mutations in non-small cell lung cancer are exon 19 deletions and exon 21 point mutations, which are both sensitive to EGFR-tyrosine kinase inhibitors. However, rare EGFR mutations do exist and how these mutations respond to tyrosine kinase inhibitors is not well understood. A Chinese woman diagnosed with stage IV lung adenocarcinoma harbored a rare EGFR L747P (2239-2240 TT > CC) mutation, and treatment with gefitinib and osimertinib failed to achieve the desired effect. Herein, possible correlations between gene analysis and the outcomes of subsequent treatment are discussed...
April 19, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29672751/a-bicenter-study-on-adjuvant-surgery-following-treatment-with-tyrosine-kinase-inhibitors-in-patients-with-advanced-lung-adenocarcinoma
#8
Ludovic Fournel, Pierre-Emmanuel Falcoz, Audrey Mansuet-Lupo, Elena Garelli, Filippo Lococo, Marco Alifano
OBJECTIVES: A small number of patients with advanced pulmonary adenocarcinomas treated with tyrosine kinase inhibitors (TKIs) was subsequently considered eligible for surgery. Our goal was to report the clinical characteristics, pathological features and prognosis of these patients with the aim of exploring the feasibility of this strategy of care. METHODS: We retrospectively reviewed the medical files of 19 patients in whom systemic treatment, including TKIs, resulted in a possible stabilization of the disease such that they were considered eligible for surgery (adjuvant surgery)...
April 16, 2018: Interactive Cardiovascular and Thoracic Surgery
https://www.readbyqxmd.com/read/29672049/discovery-of-n-2-4-amino-cyclohexyl-9-cyclopentyl-n-6-4-morpholin-4-ylmethyl-phenyl-9-h-purine-2-6-diamine-as-a-potent-flt3-kinase-inhibitor-for-acute-myeloid-leukemia-with-flt3-mutations
#9
Tomas Gucky, Eva Řezníčková, Tereza Radosova Muchova, Radek Jorda, Zuzana Klejova, Veronika Malinkova, Karel Berka, Vaclav Bazgier, Haresh Ajani, Martin Lepsik, Vladimir Divoky, Vladimir Krystof
FLT3 tyrosine kinase is a potential drug target in acute myeloid leukemia (AML) because patients with FLT3-ITD mutations respond poorly to standard cytotoxic agents and there is a clear link between the disease and the oncogenic properties of FLT3. We present novel 2,6,9-trisubstituted purine derivatives with potent FLT3 inhibitory activity. The lead compound 7d displays nanomolar activity in biochemical assays and selectively blocks proliferation of AML cell lines harboring FLT3-ITD mutations, whereas other transformed and normal human cells are several orders of magnitude less sensitive...
April 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29672039/discovery-of-allosteric-potent-subtype-selective-and-peripherally-restricted-trka-kinase-inhibitors
#10
Sharan K Bagal, Kiyoyuki Omoto, David C Blakemore, Peter J Bungay, James G Bilsland, Philip J Clarke, Matthew S Corbett, Ciarán N Cronin, Jingrong Jean Cui, Rebecca Dias, Neil J Flanagan, Samantha E Greasley, Rachel Grimley, Eric Johnson, David Fengas, Linda Kitching, Michelle L Kraus, Indrawan McAlpine, Asako Nagata, Gareth J Waldron, Joseph S Warmus
Tropomyosin receptor kinases are a family of three tyrosine kinases (TrkA, TrkB, TrkC) activated by peptide hormones of the neurotrophin family: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4). The NGF antibody tanezumab has provided clinical proof of concept for inhibition of the TrkA kinase pathway in pain. In turn, this has led to significant interest in the development of small molecule inhibitors of TrkA as an alternative intervention point on the NGF pathway...
April 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29671943/epithelial-to-mesenchymal-transition-in-the-context-of-epidermal-growth-factor-receptor-inhibition-in-non-small-cell-lung-cancer
#11
Giuseppe Bronte, Sara Bravaccini, Enrico Bronte, Marco Angelo Burgio, Christian Rolfo, Angelo Delmonte, Lucio Crinò
The identification of oncogenic driver mutations in non-small-cell lung cancer (NSCLC) has led to the development of targeted drugs. Tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) target lung tumours bearing EGFR-activating mutations. This new therapeutic strategy has greatly improved tumour response rates. However, drug resistance invariably occurs during TKI-based treatment. Epithelial-to-mesenchymal transition (EMT) is one of the resistance mechanisms identified in EGFR-mutated NSCLC treated with TKIs...
April 19, 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29671827/molecular-modeling-studies-on-carbazole-carboxamide-based-btk-inhibitors-using-docking-and-structure-based-3d-qsar
#12
Rui Li, Yongli Du, Zhipei Gao, Jingkang Shen
Rheumatoid arthritis (RA) is the second common rheumatic immune disease with chronic, invasive inflammatory characteristics. Non-steroidal anti-inflammatory drugs (NSAIDs), slow-acting anti-rheumatic drugs (SAARDs), or glucocorticoid drugs can improve RA patients’ symptoms, but fail to cure. Broton’s tyrosine kinase (BTK) inhibitors have been proven to be an efficacious target against autoimmune indications and B-cell malignancies. Among the current 11 clinical drugs, only BMS-986142, classified as a carbazole derivative, is used for treating RA...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29670046/resistance-to-anti-angiogenic-therapy-in-cancer-alterations-to-anti-vegf-pathway
#13
REVIEW
Yoshiro Itatani, Kenji Kawada, Takamasa Yamamoto, Yoshiharu Sakai
Anti-angiogenic therapy is one of the promising strategies for many types of solid cancers. Bevacizumab (Avastin), a recombinant humanized monoclonal antibody of vascular endothelial growth factor (VEGF) A, was approved for the first time as an anti-angiogenic drug for the treatment of metastatic colorectal cancer (CRC) by the Food and Drug Administration (FDA) in 2004. In addition, the other VEGF pathway inhibitors including small molecule tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), a soluble VEGF decoy receptor (aflibercept), and a humanized monoclonal antibody of VEGF receptor 2 (VEGFR2) (ramucirumab) have been approved for cancer therapy...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29670043/wool-like-hollow-polymeric-nanoparticles-for-cml-chemo-combinatorial-therapy
#14
Barbara Cortese, Stefania D'Amone, Ilaria Elena Palamà
Chronic myeloid leukaemia (CML) is caused by the BCR-ABL oncogene, which encodes the constitutively active BCR-ABL tyrosine kinase. Targeted therapy with tyrosine-kinase inhibitors induces a partial cytogenetic response in most patients. Nanosystems can represent an opportunity for combinatorial therapy with the capacity to simultaneously release different therapeutic agents, checking the pharmacokinetic properties. In this work, we have developed a novel poly-(ε-caprolactone) (PCL) nanosystem for combinatorial therapy in CML, composed of a biodegradable pH sensitive core releasing Nilotinib (Nil) and an enzymatic sensitive outer shell releasing Imatinib Mesylate (IM), resulting in wool-like nanoparticles (NPs)...
April 18, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29669779/rna-based-flt3-itd-allelic-ratio-is-associated-with-outcome-and-ex-vivo-response-to-flt3-inhibitors-in-pediatric-aml
#15
David G J Cucchi, Barbara Denys, Gertjan Kaspers, Jeroen J W M Janssen, Gert Ossenkoppele, Valérie de Haas, C Michel Zwaan, Marry M van den Heuvel-Eibrink, Jan Philippé, Tamás Csikós, Zinia Kwidama, Barbara de Moerloose, Eveline de Bont, Birgit I Lissenberg-Witte, Sonja Zweegman, Femke Verwer, Karl Vandepoele, Gerrit Jan Schuurhuis, Edwin Sonneveld, Jacqueline Cloos
Controversy exists whether internal tandem duplication of FMS-like tyrosine kinase 3 ( FLT3 -ITD) allelic ratio (AR) and/or length of the ITD should be taken into account for risk stratification of pediatric acute myeloid leukemia (AML) and whether it should be measured on RNA or DNA. Moreover, the ITD status may be of relevance for selecting patients eligible for FLT3 inhibitors. Here, we included 172 pediatric AML patients of whom thirty-six (21%) harbored FLT3 -ITD as determined on both RNA and DNA. Although there was a good correlation between both parameters ARspearman =0...
April 18, 2018: Blood
https://www.readbyqxmd.com/read/29669701/crizotinib-in-patients-with-advanced-inoperable-inflammatory-myofibroblastic-tumours-with-and-without-anaplastic-lymphoma-kinase-gene-alterations-european-organisation-for-research-and-treatment-of-cancer-90101-create-a-multicentre-single-drug-prospective-non
#16
Patrick Schöffski, Jozef Sufliarsky, Hans Gelderblom, Jean-Yves Blay, Sandra J Strauss, Silvia Stacchiotti, Piotr Rutkowski, Lars H Lindner, Michael G Leahy, Antoine Italiano, Nicolas Isambert, Maria Debiec-Rychter, Raf Sciot, Thomas Van Cann, Sandrine Marréaud, Axelle Nzokirantevye, Sandra Collette, Agnieszka Wozniak
BACKGROUND: An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. METHODS: We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK)...
April 12, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29669391/translational-biomarkers-and-ex-vivo-models-of-joint-tissues-as-a-tool-for-drug-development-in-rheumatoid-arthritis
#17
Cecilie F Kjelgaard-Petersen, Adam Platt, Martin Braddock, Martin A Jenkins, Kishwar Musa, Emma Graham, Thorbjørn Gantzel, Gillian Slynn, Michael E Weinblatt, Morten A Karsdal, Christian S Thudium, Anne-C Bay-Jensen
OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need for novel drugs controlling disease progression. As only 10% of RA drug candidates that enter phase I trials are eventually FDA registered, there is an immediate requirement for translational drug development tools to facilitate early drug development decision making...
April 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29669390/editorial-title-lessons-learned-from-a-failed-clinical-trial
#18
EDITORIAL
E F A Leijten, T R D J Radstake, K A Reedquist
Spleen tyrosine kinase (Syk), through its capacity to promote the pathogenic activation of B lymphocytes, myeloid cells, osteoclasts, and stromal fibroblast-like synoviocytes, has been subject to intense translational and clinical scrutiny as a potential therapeutic target in rheumatoid arthritis (RA) (1). Initial phase II clinical trials with the Syk inhibitor fostamatinib showed promising effectivity in treating RA patients that had displayed inadequate responses to methotrexate (2,3). However, concerns were raised of drug-dependent adverse effects in these studies, and fostamatinib did not improve disease in RA patients failing other biologic agents (4)...
April 18, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29669173/second-generation-syk-inhibitor-entospletinib-ameliorates-fully-established-inflammation-and-bone-destruction-in-the-cherubism-mouse-model
#19
Tetsuya Yoshimoto, Tatsuhide Hayashi, Toshio Kondo, Mizuho Kittaka, Ernst J Reichenberger, Yasuyoshi Ueki
Cherubism is a craniofacial disorder characterized by maxillary and mandibular bone destruction. Gain-of-function mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for the excessive bone resorption caused by fibrous inflammatory lesions. A homozygous knock-in (KI) mouse model for cherubism (Sh3bp2KI/KI ) develops autoinflammation resulting in systemic bone destruction. While administration of the TNF-α blocker etanercept to neonatal Sh3bp2KI/KI mice prevented the disease onset, this therapy was not effective for adult Sh3bp2KI/KI mice or human cherubism patients who already had lesions...
April 18, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29668619/gefitinib-provides-similar-effectiveness-and-improved-safety-than-erlotinib-for-advanced-non-small-cell-lung-cancer-a-meta-analysis
#20
Wenxiong Zhang, Yiping Wei, Dongliang Yu, Jianjun Xu, Jinhua Peng
BACKGROUND: The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. METHODS: We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed...
April 2018: Medicine (Baltimore)
keyword
keyword
28574
1
2
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"