Christina Lamers

University of Leipzig · Medical Faculty

To explore the complex molecular interactions of complement-related integrin receptors with their well established ligands, we have developed selective macrocyclic peptides to utilize them for biophysical and functional competition assays.

Background Haemostasis is a crucial process by which the body stops bleeding. It is achieved by the formation of a platelet plug, which is strengthened by formation of a fibrin mesh mediated by the coagulation cascade. In proinflammatory and prothrombotic conditions, multiple interactions of the complement system and the coagulation cascade are kno...

Within a short few years, the number of complement inhibitors that are either approved for therapeutic application or evaluated in late‐stage clinical trials has expanded remarkably. The sudden emergence of this target area in the pipelines of many biotech start‐ups and even large pharmaceutical companies appears even more surprising when consideri...

The use of biomaterials in modern medicine has enabled advanced drug delivery strategies and led to reduced morbidity and mortality in a variety of interventions such as transplantation or hemodialysis. However, immune-mediated reactions still present a serious complication of these applications. One of the drivers of such reactions is the compleme...

With the addition of the compstatin-based complement C3 inhibitor pegcetacoplan, another class of complement targeted therapeutics have recently been approved. Moreover, compstatin derivatives with enhanced pharmacodynamic and pharmacokinetic profiles are in clinical development (e.g., Cp40/AMY-101). Despite this progress, the target binding and in...

Peptides have traditionally been perceived as poor drug candidates due to unfavorable characteristics mainly regarding their pharmacokinetic behavior, including plasma stability, membrane permeability and circulation half-life. Nonetheless, in recent years, general strategies to tackle those shortcomings have been established, and peptides are subs...

Despite the growing recognition of the complement system as a major contributor to a variety of clinical conditions, the therapeutic arsenal has remained scarce. The introduction of an anti-C5 antibody in 2007 raised confidence in complement-targeted therapy. However, it became apparent that inhibition of late-stage effector generation might not be...

Among the many molecular entities suitable for therapeutic use, peptides have emerged as a particularly attractive option for academic drug discovery and development. Their modular structure and extendibility, the availability of powerful and affordable screening platforms, and the relative ease-of-synthesis render therapeutic peptides highly appro...

Peptides are a growing therapeutic class due to their unique spatial characteristics that can target traditionally "undruggable" protein-protein interactions and surfaces. Despite their advantages, peptides must overcome several key shortcomings to be considered as drug leads, including their high conformational flexibility and susceptibility to pr...

The β2-integrin receptor family has a broad spectrum of physiological functions ranging from leukocyte adhesion, cell migration, activation, and communication to the phagocytic uptake of cells and particles. Among the members of this family, complement receptor 3 (CR3; CD11b/CD18, Mac-1, αMβ2) is particularly promiscuous in its functional profile a...

Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnormal bleeding. Herein, we have engineered a macrocyclic peptide inhibitor of activated FXII (FXII...

Farnesoid X receptor acts as bile acid sensing transcription factor and has been identified as valuable molecular drug target to treat severe liver disorders, such as non-alcoholic steatohepatitis (NASH). Preclinical and clinical data indicate anti-fibrotic effects obtained with FXR activation that also appear promising for other fibrotic diseases...

The bile acid-sensing transcription factor farnesoid X receptor (FXR) regulates multiple metabolic processes. Modulation of FXR is desired to overcome several metabolic pathologies but pharmacological administration of full FXR agonists has been plagued by mechanism-based side effects. We have developed a modulator that partially activates FXR in v...

As a cellular bile acid sensor farnesoid X receptor (FXR) participates in regulation of bile acid, lipid and glucose homeostasis as well as liver protection. Clinical results have validated FXR as therapeutic target in hepatic and metabolic diseases. To date, potent FXR agonists share a negatively ionizable function that might compromise their phar...

Cyclische Peptide natürlichen Ursprungs dienen seit Jahren als Medikamente. Aber nicht gegen alle Krankheiten hält die Natur Peptide bereit. Neue Methoden erlauben es nun, cyclische Peptide gegen beliebige Zielproteine aus großen kombinatorischen Bibliotheken zu isolieren.

Background: Bile acids can serve as signaling molecules by activating the nuclear receptor FXR and the G-protein-coupled receptor TGR5 and both bile acid receptors are prominent experimental drug targets. Results/Methodology: In this study we optimized the fatty acid mimetic compound pirinixic acid to a new scaffold with the aim to develop novel F...

Metabolic syndrome (MetS) is a widespread, complex disease cluster which consists of hypertension, atherosclerosis, dyslipidaemia and type II diabetes. The treatment of MetS requires multiple pharmaceutical agents leading to complex polypharmacy. Multi-target compounds might reduce the number of required drugs in MetS patients. In this study we fus...

Metabolic syndrome (MetS) is a multifactorial disease cluster that consists of dyslipidemia, cardiovascular disease, type 2 diabetes mellitus and obesity. MetS patients are strongly exposed to polypharmacy, however, the number of pharmacological compounds required for MetS treatment can be reduced by the application of multi-target compounds. This...

We present the design, synthesis and biological evaluation of compounds containing a 2-(benzylidene)hexanoic acid scaffold as multi-target directed γ-secretase-modulators. Broad structural variations were undertaken to elucidate the structure-activity-relationships at the 5-position of the aromatic core. Compound 13 showed the most potent activity...

Nuclear receptors, especially the peroxisome proliferator activated receptors (PPARs) and the farnesoid X receptor (FXR) fulfill crucial roles in metabolic balance. Their activation offers valuable therapeutic potential which has high clinical relevance with the fibrates and glitazones as PPAR agonistic drugs. With growing knowledge about the vario...

The nuclear bile acid sensor farnesoid X receptor (FXR) constitutes a rising target for the treatment of a variety of diseases including metabolic disorders, inflammation and certain forms of cancer. While the research on FXR agonists has yielded many compounds and first clinical candidates, only few FXR antagonists have been discovered so far and...

Natural products have long been a source of useful biological activity for the development of new drugs. Their macromolecular targets are, however, largely unknown, which hampers rational drug design and optimization. Here we present the development and experimental validation of a computational method for the discovery of such targets. The techniq...

The ligand activated transcription factor nuclear farnesoid X receptor (FXR) is involved as a regulator in many metabolic pathways including bile acid and glucose homeostasis. Therefore, pharmacological activation of FXR seems a valuable therapeutic approach for several conditions including metabolic diseases linked to insulin resistance, liver dis...

The concept of dual PPARα/γ activation was originally proposed as a new approach for the treatment of the metabolic syndrome. However, recent results indicated that PPARα as well as PPARγ activation might also be beneficial in the treatment of inflammatory diseases and cancer. We have recently identified aminothiazole-featured pirinixic acids as du...

Peroxisome proliferator-activated receptors (PPARs) are attractive targets for the treatment of the metabolic syndrome. Especially a combination of PPARα and PPARγ agonistic activity seems worthwhile to be pursued. Herein we present the design and synthesis of a series of pirinixic acid derivatives as potent PPARα particularly dual PPARα/γ agonists...

Hyper- and hypotrichosis constitute a psychologically depressing disease for patients but for both disorders local and systemic therapeutic approaches are available. The systemic therapies are predominantly based on the influence of androgens on the hair cycle. The detailed mechanisms of action of the most important topically applied agents minoxid...

Onychomycosis is a fungal infection of the nail that affects 10–30% of the global population. The interdisciplinary management of fungal nail infections is described in detail in the article by Effendy and Kresken in this issue. Benzoxaboroles and new azole derivatives, which are currently in advanced stages of clinical development, may present eme...

Introduction: Prostaglandins and their G-protein–coupled receptors play numerous physiological and pathophysiological roles, especially in inflammation and its resolution. The variety of effects mediated by prostanoids makes prostanoid receptors valuable drug targets and the research on prostaglandin receptor modulators is intensive. The physiologi...

The voltage-dependent potassium channel hERG not only is a target of class III antiarrhythmic drugs, but is also inhibited by various other drugs. This can lead to prolongation of the QT-duration seen in the electrocardiogram, possibly resulting in life-threatening consequences like Torsades-de-pointes. An early prediction of hERG channel blockage...

Introduction: Prostaglandins and their G-protein coupled receptors play numerous physiological and pathophysiological roles especially in inflammation and its resolution. The variety of physiological effects mediated by prostanoids makes prostanoid receptors valuable drug targets and the research on prostaglandin receptor modulators is intensive....

Metabolic syndrome is a complex condition which often requires the use of multiple medications as a treatment. The resulting problems of polypharmacy are increase in side effects, drug-drug interactions and its high economical cost. Development of multi-target compounds is a promising strategy to avoid the complications arising from administration...

Schilddrüsenhormon-Präparate gehören zu den in Deutschland am häufigsten verordneten Arzneimitteln überhaupt. Nach Aussage des Arzneimittelverordnungsreports 2011 ist das in Deutschland am häufigsten verschriebene Arzneimittel ein Schilddrüsenhormon-Präparat. Daneben befinden sich noch drei weitere Schilddrüsenhormon-Präparate unter den Top 20.

Introduction: Peroxisome proliferator-activated receptors (PPAR) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. The three known subtypes PPARα, PPARγ and PPARδ have different tissue distribution and play a key role as regulators of glucose and lipid homeostasis as well as in cell proliferation, differenti...

Die Gruppe der β2-Sympathomimetika spielt trotz kontroverser Diskussionen über die Sicherheit und Wirksamkeit eine wichtige Rolle in der Therapie der obstruktiven Atemwegserkrankungen. Über eine Aktivierung der β2-Adrenozeptoren erreichen sie eine schnelle Bronchodilatation. Beim Blick in die Pipeline lässt sich ein Trend zu ultra-langwirksamen und...