A5073167801- Microtubule and mitosis dynamics
- Cancer therapeutics and mechanisms
- Cancer-related Molecular Pathways
- Quinazolinone synthesis and applications
- Enzyme Structure and Function
- HER2/EGFR in Cancer Research
- Synthesis and Catalytic Reactions
- Melanoma and MAPK Pathways
- Biochemical and Molecular Research
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Autophagy in Disease and Therapy
- Chemical Synthesis and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- Phosphodiesterase function and regulation
- Protein Degradation and Inhibitors
- TGF-β signaling in diseases
- Hippo pathway signaling and YAP/TAZ
Goethe University Frankfurt
2021-2023
Since the outbreak of SARS-CoV-2 in recent years, our society has become more aware that zoonotic diseases pose a real threat. Therefore, demand for small molecules target host proteins, essential viral entry and replication, increased as an interesting strategy development antiviral agents, these agents may be effective against several different pathogens. NAK kinases is one such potential family because they are involved variety cellular functions, hijacked by viruses to invade cells,...
Activating mutations in the epidermal growth factor receptor (EGFR) are frequent oncogenic drivers of non-small-cell lung cancer (NSCLC). The most alterations EGFR short in-frame deletions exon 19 (Del19) and missense mutation L858R, which both lead to increased activity sensitization NSCLC inhibition. first approved inhibitors used for first-line treatment NSCLC, gefitinib erlotinib, quinazoline-based. However, have several known off-targets, they also potently inhibit wild-type (WT) EGFR,...
Bone morphogenetic protein (BMP) signaling is mediated by transmembrane kinases that form heterotetramers consisting of type-I and type-II receptors. Upon BMP binding, the constitutively active receptors activate specific transphosphorylation, resulting in phosphorylation SMAD effector proteins. Drug discovery receptor tyrosine kinase-like (TKL) family has largely focused on receptors, with few inhibitors have been published targeting BMPR2 involved several diseases, most notably pulmonary...
Serine/threonine kinase 17A (death-associated protein kinase-related apoptosis-inducing 1─DRAK1) is a part of the death-associated (DAPK) family and belongs to so-called dark kinome. Thus, current state knowledge cellular function DRAK1 its involvement in pathophysiological processes very limited. Recently, has been implicated tumorigenesis glioblastoma multiforme (GBM) other cancers, but no selective inhibitors are available yet. To this end, we optimized pyrazolo[1,5-a]pyrimidine-based...
MST1, MST2, MST3, MST4, and YSK1 are conserved members of the mammalian sterile 20-like serine/threonine (MST) family that regulate cellular functions such as proliferation migration. The MST3 isozyme plays a role in regulating cell growth apoptosis, its dysregulation has been linked to high-grade tumors. To date, there no isoform-selective inhibitors could be used for validating tumorigenesis. We designed series 3-aminopyrazole-based macrocycles based on structure promiscuous inhibitor. By...
The PCTAIRE subfamily belongs to the CDK (cyclin-dependent kinase) family and represents an understudied class of kinases dark kinome. They exhibit a highly conserved binding pocket are activated by cyclin Y binding. CDK16 is targeted plasma membrane after N-myristoylated expressed in post-mitotic tissues, such as brain testis. Dysregulation associated with several diseases, including breast, prostate, cervical cancer. Here, we used N-(1H-pyrazol-3-yl)pyrimidin-4-amine moiety from...
Abstract MST1, MST2, MST3, MST4, and YSK1 are conserved members of the mammalian sterile 20 kinase (MST) family. MSTs regulate key cellular functions such as cell proliferation, migration, metabolic regulation, polarity. The MST3 isozyme plays a role in regulation growth, autophagy apoptosis, its dysregulation has been linked to occurrence high-grade tumors with poor survival prognosis. To date, there no isoform-selective inhibitors available that could be used for validating tumorigenesis...