Anke Unger
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View article: Design, Synthesis, and Structural Evolution of Pseudo‐Natural Product IDO1 Inhibitors and Degraders
Design, Synthesis, and Structural Evolution of Pseudo‐Natural Product IDO1 Inhibitors and Degraders Open
Terpenoid alkaloids are derived from the fusion of structurally diverse terpenoid‐ and alkaloid moieties. The biologically relevant chemical space defined by this unique natural product (NP) class may be explored beyond the limitations of …
View article: Evaluating Triazole-Substituted Pyrrolopyrimidines as CSF1R Inhibitors
Evaluating Triazole-Substituted Pyrrolopyrimidines as CSF1R Inhibitors Open
6-Aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines have promising properties as colony-stimulating factor 1 receptor (CSF1R) inhibitors. Inspired by these antagonists, two series of 1,2,3-triazole analogues (28 compounds) were synthesized and eval…
View article: Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition
Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition Open
Overcoming drug-resistance and the subsequent relapse that often occurs with monotherapy is crucial in the treatment of acute myeloid leukemia. We here demonstrate that therapy-resistant leukemia initiating cells can be targeted using a no…
View article: Design and Synthesis of Pyridine-Based Pyrrolo[2,3-d]pyrimidine Analogs as CSF1R Inhibitors: Molecular Hybridization and Scaffold Hopping Approach
Design and Synthesis of Pyridine-Based Pyrrolo[2,3-d]pyrimidine Analogs as CSF1R Inhibitors: Molecular Hybridization and Scaffold Hopping Approach Open
Background/Objectives: Colony stimulating factor 1 receptor kinase (CSF1R) is a well-validated molecular target in drug discovery for various reasons. Based on the structure of an early lead molecule identified in our lab and the marketed …
View article: Highly potent quinoxalinediones inhibit α-hemolysin and ameliorate Staphylococcus aureus lung infections
Highly potent quinoxalinediones inhibit α-hemolysin and ameliorate Staphylococcus aureus lung infections Open
Hospital-acquired pneumonia caused by Staphylococcus aureus is associated with patient morbidity and mortality, despite adequate antibiotic therapy. This illustrates the need for treatments beyond antibiotics. The pore-forming heptameric t…
View article: Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition
Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition Open
Overcoming drug-resistance and the subsequent relapse that often occurs with monotherapy is crucial in the treatment of acute myeloid leukemia. We here demonstrate that therapy-resistant leukemia initiating cells can be targeted using a no…
View article: Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition
Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition Open
Overcoming drug-resistance and the subsequent relapse that often occurs with monotherapy is crucial in the treatment of acute myeloid leukemia. We here demonstrate that therapy-resistant leukemia initiating cells can be targeted using a no…
View article: Reviewer #2 (Public Review): Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition
Reviewer #2 (Public Review): Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition Open
Overcoming drug-resistance and the subsequent relapse that often occurs with monotherapy is crucial in the treatment of acute myeloid leukemia. We here demonstrate that therapy-resistant leukemia initiating cells can be targeted using a no…
View article: Reviewer #1 (Public Review): Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition
Reviewer #1 (Public Review): Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition Open
Overcoming drug-resistance and the subsequent relapse that often occurs with monotherapy is crucial in the treatment of acute myeloid leukemia. We here demonstrate that therapy-resistant leukemia initiating cells can be targeted using a no…
View article: Pyrrolopyrimidine based CSF1R inhibitors: Attempted departure from Flatland
Pyrrolopyrimidine based CSF1R inhibitors: Attempted departure from Flatland Open
The colony-stimulating factor 1 receptor (CSF1R) is an attractive target for inflammation disorders and cancers. Based on a series of pyrrolo[2,3-d]pyrimidine containing two carbo-aromatic rings, we have searched for new CSF1R inhibitors h…
View article: Discovery of tetrazolo-pyridazine-based small molecules as inhibitors of MACC1-driven cancer metastasis
Discovery of tetrazolo-pyridazine-based small molecules as inhibitors of MACC1-driven cancer metastasis Open
Metastasis is directly linked to poor prognosis of cancer patients and warrants search for effective anti-metastatic drugs. MACC1 is a causal key molecule for metastasis. High MACC1 expression is prognostic for metastasis and poor survival…
View article: Inhibition of mammalian mtDNA transcription paradoxically activates liver fatty acid oxidation to reverse diet-induced hepatosteatosis and obesity
Inhibition of mammalian mtDNA transcription paradoxically activates liver fatty acid oxidation to reverse diet-induced hepatosteatosis and obesity Open
Summary The oxidative phosphorylation (OXPHOS) system in mammalian mitochondria plays a key role in harvesting energy from ingested nutrients 1, 2 . Mitochondrial metabolism is very dynamic and can be reprogrammed to support both catabolic…
View article: Protection of pancreatic islets from oxidative cell death by a peripherally-active morphinan with increased drug safety
Protection of pancreatic islets from oxidative cell death by a peripherally-active morphinan with increased drug safety Open
We succeeded to design and synthesize a novel morphinan derivative that is BBB-impermeable, glucose-lowering and islet cell-protective and has good drug safety despite its morphinan and imidazole structures.
View article: Synthesis and Development of Highly Selective Pyrrolo[2,3-<i>d</i>]pyrimidine CSF1R Inhibitors Targeting the Autoinhibited Form
Synthesis and Development of Highly Selective Pyrrolo[2,3-<i>d</i>]pyrimidine CSF1R Inhibitors Targeting the Autoinhibited Form Open
Colony-stimulating factor-1 receptor (CSF1R) is a receptor tyrosine kinase that controls the differentiation and maintenance of most tissue-resident macrophages, and the inhibition of CSF1R has been suggested as a possible therapy for a ra…
View article: Negishi Cross‐Coupling in the Preparation of Benzyl Substituted Pyrrolo[2,3‐<i>d</i>]pyrimidine Based CSF1R Inhibitors
Negishi Cross‐Coupling in the Preparation of Benzyl Substituted Pyrrolo[2,3‐<i>d</i>]pyrimidine Based CSF1R Inhibitors Open
The colony‐stimulating factor 1 receptor (CSF1R) is a protein kinase emerging as an attractive target with clinical relevance in cancer, CNS and inflammatory diseases. Molecular docking experiments followed by synthesis and structure–activ…
View article: Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition
Reduced mitochondrial transcription sensitizes acute myeloid leukemia cells to BCL-2 inhibition Open
Overcoming drug-resistance and the subsequent relapse that often occurs with monotherapy is crucial in the treatment of acute myeloid leukemia. We here demonstrate that therapy-resistant leukemia initiating cells can be targeted using a no…
View article: Structure–Activity Relationship Studies of Trisubstituted Isoxazoles as Selective Allosteric Ligands for the Retinoic-Acid-Receptor-Related Orphan Receptor γt
Structure–Activity Relationship Studies of Trisubstituted Isoxazoles as Selective Allosteric Ligands for the Retinoic-Acid-Receptor-Related Orphan Receptor γt Open
The inhibition of the nuclear receptor retinoic-acid-receptor-related orphan receptor γt (RORγt) is a promising strategy in the treatment of autoimmune diseases. RORγt features an allosteric binding site within its ligand-binding domain th…
View article: Targeting Her2-insYVMA with Covalent Inhibitors—A Focused Compound Screening and Structure-Based Design Approach
Targeting Her2-insYVMA with Covalent Inhibitors—A Focused Compound Screening and Structure-Based Design Approach Open
Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitor…
View article: Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S
Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S Open
We present inhibitors of drug resistant mutants of EGFR including T790M and C797S. In addition, we present the first X-ray crystal structures of covalent inhibitors in complex with C797S-mutated EGFR to gain insight into their binding mode.
View article: TRPC4/TRPC5 channels mediate adverse reaction to the cancer cell cytotoxic agent (-)-Englerin A
TRPC4/TRPC5 channels mediate adverse reaction to the cancer cell cytotoxic agent (-)-Englerin A Open
(-)-Englerin A (EA) is a natural product which has potent cytotoxic effects on renal cell carcinoma cells and other types of cancer cell but not non-cancer cells. Although selectively cytotoxic to cancer cells, adverse reaction in mice and…
View article: Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia
Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia Open
Onset of progression even during therapy with novel drugs remains an issue in chronic lymphocytic leukemia (CLL). Thus, there is ongoing demand for novel agents. Approaches targeting cyclin-dependent kinases (CDK) have reached the clinical…
View article: Structure-Guided Development of Covalent and Mutant-Selective Pyrazolopyrimidines to Target T790M Drug Resistance in Epidermal Growth Factor Receptor
Structure-Guided Development of Covalent and Mutant-Selective Pyrazolopyrimidines to Target T790M Drug Resistance in Epidermal Growth Factor Receptor Open
Reversible epidermal growth factor receptor (EGFR) inhibitors prompt a beneficial clinical response in non-small cell lung cancer patients who harbor activating mutations in EGFR. However, resistance mutations, particularly the gatekeeper …
View article: Discovery of <i>N</i>-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3<i>H</i>-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases
Discovery of <i>N</i>-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3<i>H</i>-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases Open
The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of…
View article: A Novel CDK7 Inhibitor of the Pyrazolotriazine Class Exerts Broad-Spectrum Antiviral Activity at Nanomolar Concentrations
A Novel CDK7 Inhibitor of the Pyrazolotriazine Class Exerts Broad-Spectrum Antiviral Activity at Nanomolar Concentrations Open
Protein kinases represent central and multifunctional regulators of a balanced virus-host interaction. Cyclin-dependent protein kinase 7 (CDK7) plays crucial regulatory roles in cell cycle and transcription, both connected with the replica…
View article: Impact of p38 MAP Kinase Inhibitors on LPS-Induced Release of TNF-α in Whole Blood and Primary Cells from Different Species
Impact of p38 MAP Kinase Inhibitors on LPS-Induced Release of TNF-α in Whole Blood and Primary Cells from Different Species Open
Background/Aims: Inhibition of p38 mitogen-activated protein kinase (p38 MAPK) is promising for the treatment of inflammatory disorders, however, the efficacy of p38 MAPK inhibitors in clinical trials is limited so far. Since functional se…