Stefan Laufer
University of Tübingen
Hydrogen bondCrystal structureInternal medicineMitogen-activated protein kinaseMedicinal chemistryEnzymeKinaseChemistryIn vitroPyridineRing (chemistry)p38 mitogen-activated protein kinasesBiochemistryBioinformaticsStereochemistryMedicineBiologyDihedral angleProtein kinase APharmacology
Publications 462
#1Stanislav Andreev (University of Tübingen)H-Index: 3
#2Tatu Pantsar (University of Eastern Finland)H-Index: 9
Last. Christian Geibel (University of Tübingen)H-Index: 3
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In small molecule binding, water is not a passive bystander but rather takes an active role in the binding site, which may be decisive for the potency of the inhibitor. Here, by addressing a high-energy water, we improved the IC50 value of our co-crystallized glycogen synthase kinase-3β (GSK-3β) inhibitor by nearly two orders of magnitude. Surprisingly, our results demonstrate that this high-energy water was not displaced by our potent inhibitor (S)-3-(3-((7-ethynyl-9H-pyrimido[4,5-b]indol-4-yl)...
#1Florian Wittlinger (University of Tübingen)H-Index: 1
#2Stefan Laufer (University of Tübingen)H-Index: 67
IntroductionOsimertinib is currently the only by FDA and EMA approved 3rd generation small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It was initially indicated for second-line treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) and got approved for first-line treatment of EGFR activation mutation-positive metastatic NSCLC in 2018. Most recently, the FDA granted approval for the adjuvant treatment of patient...
#1Craig W. LindsleyH-Index: 84
#2James C. BarrowH-Index: 29
Last. Hong LiuH-Index: 160
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#4José Fernando Ruggiero Bachega (UHSA: University of Health Sciences Antigua)H-Index: 2
Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis broug...
#1Martin Reynders (NYU: New York University)H-Index: 2
#1Martin Reynders (NYU: New York University)H-Index: 2
Last. Dirk Trauner (NYU: New York University)H-Index: 72
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Covalent kinase inhibitors account for some of the most successful drugs that have recently entered the clinic and many others are in preclinical development. A common strategy is to target cysteines in the vicinity of the ATP binding site using an acrylamide electrophile. To increase the tissue selectivity of kinase inhibitors, it could be advantageous to control the reactivity of these electrophiles with light. Here, we introduce covalent inhibitors of the kinase JNK3 that function as photoswi...
#1Thanigaimalai Pillaiyar (University of Tübingen)H-Index: 12
#1Thanigaimalai Pillaiyar (University of Tübingen)H-Index: 3
Last. Stefan Laufer (University of Tübingen)H-Index: 67
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The global coronavirus disease-19 (COVID-19) has affected more than 140 million and killed more than 3 million people worldwide as of April 20, 2021. The novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been identified as an etiological agent for COVID-19. Several kinases have been proposed as possible mediators of multiple viral infections, including life-threatening coronaviruses like SARS-CoV-1, Middle East syndrome coronavirus (MERS-CoV), and SARS-CoV-2. Viral inf...
#1Claudia Monfroni Rocha (Univates)H-Index: 1
#2Alessandro Menna Alves (Univates)H-Index: 3
Last. Márcia Inês Goettert (Univates)H-Index: 14
view all 7 authors...
OBJECTIVE One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modif...
#1Niklas M Tormählen (University of Tübingen)
Last. Pierre Koch (University of Regensburg)H-Index: 16
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Stress-induced p38α mitogen-activated protein (MAP) kinase activation modulates cytokine overproduction and is associated with neuroinflammation and neurodegeneration. As a potential therapeutic approach, novel Skepinone-based p38α MAP kinase inhibitors were optimized to cross the blood-brain barrier via either amino acid transporters or hydrophobic diffusion. To enhance absorption from the oral route, we used methyl ester prodrugs of the active carboxy analogs. Of these, 3-(8-((2,4-difluorophen...
#1Débora Bublitz Anton (Univates)H-Index: 1
#3Luis Fernando Saraiva Macedo Timmers (Univates)H-Index: 14
Last. Márcia Inês Goettert (Univates)H-Index: 14
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The p38δ mitogen-activated protein kinase is an important signal transduction enzyme. p38δ has recently emerged as a drug target due to its tissue-specific expression patterns and its critical roles in regulation of cellular processes related to cancer and inflammatory diseases, such as cell proliferation, cell migration, apoptosis, and inflammatory responses. However, potent and specific p38δ inhibitors have not been defined so far. Moreover, in cancer disease, p38δ appears to act as a tumor su...
#1Mostafa Mahmoud (University of Tübingen)H-Index: 1
#1Mostafa MahmoudH-Index: 1
Last. Hans-Peter DeignerH-Index: 26
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Abstract Modern strategies in precision medicine require diagnostic tools for fast assessment of biomarkers. A popular and well established assay format for the rapid detection of disease markers directly at the point of care are lateral flow assays, which enable medical staff to directly use body fluids like blood or urine for diagnosis, without the need of a professional laboratory environment. Interleukin-6 and thrombin are both clinically relevant biomarkers associated with infectious diseas...
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