Genomes and Genes
protein kinase inhibitors
Summary: Agents that inhibit PROTEIN KINASES.
- Pinchuk B, Johannes E, Gul S, Schlosser J, Schaechtele C, Totzke F, et al. Marine derived hamacanthins as lead for the development of novel PDGFR? protein kinase inhibitors. Mar Drugs. 2013;11:3209-23 pubmed publisher..on pyrazin-2(1H)-ones as lead for the development of potent adenosine triphosphate (ATP) competitive protein kinase inhibitors with implications as anti-cancer drugs...
- Brooks M, Neelam S, Fudala R, Gryczynski I, Cammarata P. Lenticular mitoprotection. Part A: Monitoring mitochondrial depolarization with JC-1 and artifactual fluorescence by the glycogen synthase kinase-3? inhibitor, SB216763. Mol Vis. 2013;19:1406-12 pubmed..We conclude that inhibition of GSK-3? activity by the GSK-3? inhibitor SB216763 provides positive protection against mitochondrial depolarization. ..
- Banerjee S, Buhrlage S, Huang H, Deng X, Zhou W, Wang J, et al. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014;457:215-25 pubmed publisher..In the present paper we describe the first highly specific protein kinase inhibitors of NUAK kinases namely WZ4003 and HTH-01-015...
- Rexer B, Ghosh R, Narasanna A, Estrada M, Chakrabarty A, Song Y, et al. Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2. Clin Cancer Res. 2013;19:5390-401 pubmed publisher..Simultaneous blockade of HER2 and EGFR should be an effective treatment strategy against HER2 gene-amplified breast cancer cells harboring T798M mutant alleles. ..
- Wang M, Rule S, Martin P, Goy A, Auer R, Kahl B, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369:507-16 pubmed publisher..The estimated rate of overall survival was 58% at 18 months. Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.) ..
- Santoni M, De Tursi M, Felici A, Lo Re G, Ricotta R, Ruggeri E, et al. Management of metastatic renal cell carcinoma patients with poor-risk features: current status and future perspectives. Expert Rev Anticancer Ther. 2013;13:697-709 pubmed publisher..This consideration may provide the rationale to further stratify poor-risk patients further subgroups destined to receive either cure or palliation...
- McArthur G, Chapman P, Robert C, Larkin J, Haanen J, Dummer R, et al. Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol. 2014;15:323-32 pubmed publisher..Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF(V600E) mutation and in patients with the less common BRAF(V600K) mutation. F Hoffmann-La Roche-Genentech. ..
- O Brien S, Furman R, Coutre S, Sharman J, Burger J, Blum K, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15:48-58 pubmed publisher..Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD. ..
- Höglund M, Sandin F, Hellstrom K, Bjoreman M, Bjorkholm M, Brune M, et al. Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry. Blood. 2013;122:1284-92 pubmed publisher..Patients living in university vs nonuniversity catchment areas more often received tyrosine kinase inhibitors up front but showed comparable survival. ..
- Lee E, Fleischmann R, Hall S, Wilkinson B, Bradley J, Gruben D, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370:2377-86 pubmed publisher..The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.). ..
- Salado I, Redondo M, Bello M, Perez C, Liachko N, Kraemer B, et al. Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. J Med Chem. 2014;57:2755-72 pubmed publisher..Thus, N-(benzothiazolyl)-2-phenyl-acetamides are valuable drug candidates for further studies and may be a new therapeutic approach for ALS and others pathologies in which TDP-43 is involved. ..
- Kobayashi M, Kuroki S, Ito K, Yasuda A, Sawada H, Ono K, et al. Imatinib-associated tumour response in a dog with a non-resectable gastrointestinal stromal tumour harbouring a c-kit exon 11 deletion mutation. Vet J. 2013;198:271-4 pubmed publisher..The c-kit mutation found in the tumour cells appears to be a mutation driving oncogenesis, as evidenced by the partial remission elicited by imatinib in this dog...
- Gridelli C, Peters S, Sgambato A, Casaluce F, Adjei A, Ciardiello F. ALK inhibitors in the treatment of advanced NSCLC. Cancer Treat Rev. 2014;40:300-6 pubmed publisher..This review aims to present the current knowledge on this fusion gene, the clinic-pathological profile of ALK rearranged NSCLC, and to review the existing literature on ALK inhibitors, focusing on their role in the treatment of NSCLC. ..
- Hata A, Katakami N, Yoshioka H, Takeshita J, Tanaka K, Nanjo S, et al. Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: Comparison between T790M mutation-positive and mutation-negative populations. Cancer. 2013;119:4325-32 pubmed publisher..However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M mutation...
- Wheler J, Falchook G, Tsimberidou A, Hong D, Naing A, Piha Paul S, et al. Revisiting clinical trials using EGFR inhibitor-based regimens in patients with advanced non-small cell lung cancer: a retrospective analysis of an MD Anderson Cancer Center phase I population. Oncotarget. 2013;4:772-84 pubmed
- Li M, Yang J, Zhou W, Ren Y, Wang X, Chen H, et al. Activation of an AKT/FOXM1/STMN1 pathway drives resistance to tyrosine kinase inhibitors in lung cancer. Br J Cancer. 2017;117:974-983 pubmed publisher..Our findings elucidate an additional common mechanism for TKI resistance and provide a promising therapeutic target for reversing TKI resistance in NSCLC. ..
- Dimri M, Bilogan C, Pierce L, Naegele G, Vasanji A, Gibson I, et al. Three-dimensional structural analysis reveals a Cdk5-mediated kinase cascade regulating hepatic biliary network branching in zebrafish. Development. 2017;144:2595-2605 pubmed publisher..A small-molecule compound that interferes with the downstream kinase cascade rescued the mutant phenotype. These results provide new insights into branching morphogenesis of the intrahepatic biliary network. ..
- Liu Y, Yin Y, Zhang Z, Li C, Zhang H, Zhang D, et al. Structural optimization elaborates novel potent Akt inhibitors with promising anticancer activity. Eur J Med Chem. 2017;138:543-551 pubmed publisher..Low micromolar doses of 10h induced cell apoptosis and cell cycle arrest in G2/M phase, and significantly downregulated the phosphorylation of Akt downstream effectors GSK3? and S6 in Jeko-1 cells. ..
- Cottin V. The safety and tolerability of nintedanib in the treatment of idiopathic pulmonary fibrosis. Expert Opin Drug Saf. 2017;16:857-865 pubmed publisher..Algorithms are available to help manage diarrhea and liver enzyme elevations. Further investigation of the safety and tolerability profile of nintedanib when used in combination with pirfenidone is warranted. ..
- Roskoski R. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. Pharmacol Res. 2016;107:249-275 pubmed publisher..As inhibitors of the cell cycle, it is not surprising that one of their most common toxicities is myelosuppression with decreased neutrophil production. ..
- Forster M, Gehringer M, Laufer S. Recent advances in JAK3 inhibition: Isoform selectivity by covalent cysteine targeting. Bioorg Med Chem Lett. 2017;27:4229-4237 pubmed publisher..Since one of these inhibitors is currently under evaluation in phase II clinical studies against several inflammatory disorders, it will soon become apparent whether selective JAK3 inhibition translates into clinical efficacy. ..
- Kollareddy M, Sherrard A, Park J, Szemes M, Gallacher K, Melegh Z, et al. The small molecule inhibitor YK-4-279 disrupts mitotic progression of neuroblastoma cells, overcomes drug resistance and synergizes with inhibitors of mitosis. Cancer Lett. 2017;403:74-85 pubmed publisher..Thus, YK-4-279 could potentially be used as a single-agent or in combination therapies for the treatment of high-risk and relapsing neuroblastoma, as well as other cancers. ..
- Wu X, Dayanand K, Thylur R, Norbury C, Gowda D. Small molecule-based inhibition of MEK1/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes. J Biol Chem. 2017;292:13615-13634 pubmed publisher..In summary, we have identified several previously unrecognized immune regulatory processes through which a MEK1/2 inhibitor approach controls malaria parasitemia and mitigates pathogenic effects on host organs. ..
- Argyros O, Lougiakis N, Kouvari E, Papafotika A, Raptopoulou C, Psycharis V, et al. Design and synthesis of novel 7-aminosubstituted pyrido[2,3-b]pyrazines exhibiting anti-breast cancer activity. Eur J Med Chem. 2017;126:954-968 pubmed publisher..BrCa) remains an unmet medical need despite the revolutionary development of antibody treatments and protein kinase inhibitors. In the current study, a series of novel substituted pyridopyrazine derivatives have been rationally ..
- Nadya N, Tezuka H, Ohteki T, Matsuda S, Azuma M, Nagai S. PI3K-Akt pathway enhances the differentiation of interleukin-27-induced type 1 regulatory T cells. Immunology. 2017;152:507-516 pubmed publisher..These results suggest that the PI3K pathway enhances IL-10 expression by IL-27-Tr1 cells through up-regulation of IL-21 receptors. ..
- Cheng Z, Yuan X, Qu Y, Li X, Wu G, Li C, et al. Bruceine D inhibits hepatocellular carcinoma growth by targeting Î²-catenin/jagged1 pathways. Cancer Lett. 2017;403:195-205 pubmed publisher..Our findings provide important information about a novel Wnt/Notch crosstalk inhibitor that is synergistic with sorafenib for treatment of HCC, and therefore have high clinical impact. ..
- Sellar R, Losman J. Targeting Aberrant Signaling in Myeloid Malignancies: Promise Versus Reality. Hematol Oncol Clin North Am. 2017;31:565-576 pubmed publisher..This article discusses potential reasons for these discordant results and outlines recent scientific advances that are informing future efforts to target activated kinases in clonal myeloid disorders. ..
- Blakely C, Watkins T, Wu W, Gini B, Chabon J, McCoach C, et al. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. Nat Genet. 2017;49:1693-1704 pubmed publisher..This study calls for revisiting the prevailing single-gene driver-oncogene view and links clinical outcomes to co-occurring genetic alterations in patients with advanced-stage EGFR-mutant lung cancer. ..
- van der Werf A, Rovithi M, Langius J, de van der Schueren M, Verheul H. Insight in taste alterations during treatment with protein kinase inhibitors. Eur J Cancer. 2017;86:125-134 pubmed publisherThe role of Protein Kinase Inhibitors (PKI) in the treatment of various types of cancer is increasingly prominent...
- Chen L, Zhang Y, Liu J, Wang W, Li X, Zhao L, et al. Novel 4-arylaminoquinazoline derivatives with (E)-propen-1-yl moiety as potent EGFR inhibitors with enhanced antiproliferative activities against tumor cells. Eur J Med Chem. 2017;138:689-697 pubmed publisher..The work could be very useful starting point for developing a new series of tyrosine kinase inhibitors targeting EGFR. ..
- Damodaran A, Vaufrey L, Gavard O, Prigent C. Aurora A Kinase Is a Priority Pharmaceutical Target for the Treatment of Cancers. Trends Pharmacol Sci. 2017;38:687-700 pubmed publisher..and particularities of these drugs raise several questions that are explored in this review: is Aurora A even a good target? What biomarkers can we use to measure its activity in vivo? How can we improve the Aurora A-inhibiting drugs? ..
- Tadesse S, Zhu G, Mekonnen L, Lenjisa J, Yu M, Brown M, et al. A novel series of N-(pyridin-2-yl)-4-(thiazol-5-yl)pyrimidin-2-amines as highly potent CDK4/6 inhibitors. Future Med Chem. 2017;9:1495-1506 pubmed publisher..Compounds 58 and 69 caused remarkable growth inhibition of melanoma cells, particularly the cells harboring multiple BRAF and NRAS mutations, via a CDK4/6-targeted mechanism of action. [Formula: see text]. ..
- Smith C. Enigmas in tumor resistance to kinase inhibitors and calculation of the drug resistance index for cancer (DRIC). Semin Cancer Biol. 2017;45:36-49 pubmed publisher..Because of their beneficial and selective therapeutic effect, the focus in this review is set on protein kinase inhibitors (PKIs), predominantly tyrosine kinase inhibitors (TKIs)...
- Cardoso E, Mercier T, Wagner A, Homicsko K, Michielin O, Ellefsen Lavoie K, et al. Quantification of the next-generation oral anti-tumor drugs dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib and two metabolites in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1083:124-136 pubmed publisher..mass spectrometry (MS/MS) has been developed for the simultaneous quantification of six anticancer protein kinase inhibitors (PKIs), dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib, and two active ..
- Xia J, Feng B, Shao Q, Yuan Y, Wang X, Chen N, et al. Virtual Screening against Phosphoglycerate Kinase 1 in Quest of Novel Apoptosis Inhibitors. Molecules. 2017;22: pubmed publisher..In summary, we not only present a versatile VS pipeline for potential apoptosis inhibitors discovery, but also provide three novel-scaffold hit compounds that are worthy of further development and biological study. ..
- Park K, Yang H, Choi J, Seo S, Kim D, Lee C, et al. The HSP90 inhibitor, NVP-AUY922, attenuates intrinsic PI3K inhibitor resistance in KRAS-mutant non-small cell lung cancer. Cancer Lett. 2017;406:47-53 pubmed publisher..Dual inhibition of the HSP90 and PI3K signaling pathways with sub-therapeutic doses of these combined anticancer drugs may represent a potent treatment strategy for KRAS-mutant NSCLC with intrinsic resistance to PI3K inhibition. ..
- Antonuzzo L, Del Re M, Barucca V, Spada F, Meoni G, Restante G, et al. Critical focus on mechanisms of resistance and toxicity of m-TOR inhibitors in pancreatic neuroendocrine tumors. Cancer Treat Rev. 2017;57:28-35 pubmed publisher..Unfortunately, both the studies disappointed the expectations and were prematurely halted mainly due to severe toxicity. On this basis we reviewed m-TOR inhibitors in pNETs, focusing on their mechanisms of resistance and toxicity. ..
- Bhalla N, Di Lorenzo M, Estrela P, Pula G. Semiconductor technology in protein kinase research and drug discovery: sensing a revolution. Drug Discov Today. 2017;22:204-209 pubmed publisher..Therefore, protein kinase inhibitors are investigated as potential treatments for several diseases, including dementia, diabetes, cancer and ..
- Sawaguchi Y, Yamazaki R, Nishiyama Y, Sasai T, Mae M, Abe A, et al. Rational Design of a Potent Pan-Pim Kinases Inhibitor with a Rhodanine-Benzoimidazole Structure. Anticancer Res. 2017;37:4051-4057 pubmed..Our data suggest that compound 2 can serve as a lead to novel anticancer agents, effective in the treatment of both solid carcinomas and hematological malignancies. ..
- Lee B, Park D, Lee J, Yeo M, Park Y, Lim D, et al. Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma. Biochem Biophys Res Commun. 2017;491:493-499 pubmed publisher..Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma. ..
- Kim Y, Kirsop J, Tang W. Alternative Biomarkers for Combined Biology. Heart Fail Clin. 2017;13:381-401 pubmed publisher..has challenged clinicians to hesitate in using cardiotoxic agents such as anthracycline and several protein kinase inhibitors. As early detection of CRCD and timely cessation of cardiotoxic agents became a strategy to avoid CRCD, ..
- Neuwelt A, Mathur S, Johnson A, Kessler E, Bowles D. Cabozantinib use in renal cell carcinoma. Drugs Today (Barc). 2017;53:299-307 pubmed publisher..This agent's toxicity profile is similar to those of other multikinase inhibitors approved to treat RCC. This review will explore cabozantinib's pharmacologic and safety profile and its preclinical and clinical activity in RCC. ..
- Goff D, Zhang J, Heckrodt T, Yu J, Ding P, Singh R, et al. Discovery of dual Axl/VEGF-R2 inhibitors as potential anti-angiogenic and anti-metastatic drugs for cancer chemotherapy. Bioorg Med Chem Lett. 2017;27:3766-3771 pubmed publisher..One of these molecules, R916562 showed comparable activity to Sunitinib in two mouse tumor xenograft models and a mouse corneal micropocket model. ..
- Roca E, Gurizzan C, Amoroso V, Vermi W, Ferrari V, Berruti A. Outcome of patients with lung adenocarcinoma with transformation to small-cell lung cancer following tyrosine kinase inhibitors treatment: A systematic review and pooled analysis. Cancer Treat Rev. 2017;59:117-122 pubmed publisher..The prognosis after SCLC diagnosis is poor and current treatment strategies derived from primary SCLC seem to be largely inefficacious. New therapies are needed in the management of transformed SCLC. ..
- Li M, Li X, Xin J, Li Z, Li G, Zhang Y, et al. Effects of protein phosphorylation on color stability of ground meat. Food Chem. 2017;219:304-310 pubmed publisher..Phosphatase and protein kinase inhibitors were added to minced ovine Longissimus thoracis et lumborum (LTL) muscle to manipulate the global ..
- Tyner J. Kinase Inhibitor Screening in Myeloid Malignancies. Hematol Oncol Clin North Am. 2017;31:693-704 pubmed publisher..By combining functional screening with genomic data, it is also possible to accelerate understanding of these mechanistic underpinnings. ..