A5009463256- Diabetes Management and Research
- Liver physiology and pathology
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Receptor Mechanisms and Signaling
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Metabolism, Diabetes, and Cancer
- Lipid metabolism and disorders
- Pancreatic function and diabetes
- Science, Research, and Medicine
- Chemical Reactions and Isotopes
- Diabetes Treatment and Management
- Neuroscience and Neuropharmacology Research
- Pituitary Gland Disorders and Treatments
- Colorectal Cancer Treatments and Studies
- T-cell and B-cell Immunology
- Growth Hormone and Insulin-like Growth Factors
- Adipose Tissue and Metabolism
- Drug-Induced Hepatotoxicity and Protection
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Cancer Genomics and Diagnostics
- Chemical Synthesis and Analysis
Novo Nordisk (Denmark)
2010-2024
Symphogen (Denmark)
2017-2019
University of Copenhagen
2010
Copenhagen University Hospital
2010
Lundbeck (Denmark)
2004
Schools of Visual Arts, The Royal Danish Academy of Fine Arts
1999
The risk of inducing hypoglycaemia (low blood glucose) constitutes the main challenge associated with insulin therapy for diabetes
Purpose: Activation of the receptor tyrosine kinase MET is associated with poor clinical outcome in certain cancers. To target more effectively, we developed an antagonistic antibody mixture, Sym015, consisting two humanized mAbs directed against nonoverlapping epitopes MET.Experimental Design/Results: We screened a large panel well-annotated human cancer cell lines and identified subset highly elevated expression. In particular, lung gastric origin demonstrated high expression activation,...
Abstract Context: Human growth hormone (hGH) replacement therapy currently requires daily sc injections for years/lifetime, which may be both inconvenient and distressing patients. NNC0195–0092 is a novel hGH derivative intended once-weekly treatment of GH deficiency. A noncovalent albumin binding moiety attached to the backbone. Clearance reduced as consequence reversible circulating serum albumin, prolongs pharmacodynamic (PD) effect. Objective: To evaluate safety, local tolerability,...
IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the basal insulin icodec and glucagon-like peptide-1 receptor agonist semaglutide. This study investigated pharmacokinetics semaglutide in versus separate administration each component individuals with type 2 diabetes mellitus (T2DM). In randomised, double-blind, three-period crossover study, 31 T2DM (18–64 years, body weight 80–120 kg, glycosylated haemoglobin 6.0–8.5%) received single injections (175 U...
The aim of this study was to develop a structure−property model for membrane partitioning oligopeptides using statistical design methods and multivariate data analysis. A set 20 tetrapeptides with optional N-methylations at residues 2 4 designed by D-optimal procedure. After synthesis purification, the abilities peptides were tested in two chromatographic systems phospholipids as stationary phase: immobilized artificial chromatography (IAM) liposome (ILC). relationship between these measures...
NN1177 is a glucagon/glucagon-like peptide 1 receptor coagonist investigated for chronic weight management and treatment of nonalcoholic steatohepatitis. Here, we show concentration-dependent downregulation cytochrome P450 (P450) enzymes using freshly isolated human hepatocytes treated with this linear 29-amino acid peptide. Notably, reductions in CYP3A4 mRNA expression (57.2%–71.7%) activity (18.5%–51.5%) were observed clinically relevant concentration 100 nM NN1177. CYP1A2 CYP2B6 also...
New insulin analogues with a longer duration of action and flatter pharmacodynamic profile are developed to improve convenience safety for diabetic patients. During the nonclinical development such analogues, studies must be conducted in nondiabetic rats, which consequently rendered chronically hypoglycemic. A rat comparator model using human would valuable, as it enable differentiation between effects related either persistent insulin-induced hypoglycemia (IIH) or new analogue per se. Such...
Flow cytometry-based receptor occupancy (RO) assessments for pharmacodynamic (PD) response measurements along with drug pharmacokinetic (PK) represent a cornerstone in mechanism based PK/PD modeling of drugs against cell surface targets. This report describes the utility using "Free" and "Bound" assay combination to derive RO estimations through weighted calculation method.Data from validation study human samples was used explore performance various data methods. The methods were...
The brain is vulnerable to hypoglycaemia due a continuous need of energy substrates meet its high metabolic demands. Studies have shown that severe acute insulin-induced results in oxidative stress the rat brain, when neuroglycopenia cannot be evaded despite increased levels cerebral glucose transporters. Compensatory measures during chronic are less well understood. present study investigated how nondiabetic rats copes with for up eight weeks. Brain level different substrate transporters...
Abstract: Psoriasis xenograft transplantation models where human skin is transplanted onto immune-deficient mice are generally accepted in psoriasis research. Over the last decade, they have been widely employed to screen for new therapeutics with a potential anti-psoriatic effect. However, experimental designs differ several parameters. Especially, number of donors and grafts per design varies greatly; numbers that directly related probability detecting statistically significant drug...
New insulin analogues with a longer duration of action and 'peakless' pharmacokinetic profile have been developed to improve efficacy, safety convenience for patients diabetes. During non-clinical development, according regulatory guidelines, these are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) rats, complicating interpretation results pre-clinical studies new...
<p>Suppl. Figure 1 In vivo efficacy of Sym015 treatment at various dose levels in the EBC-1 xenograft model. Suppl. 2 and unbalanced mixtures two constituent antibodies Hu9006 Hu9338, applied 10 mg/kg or 50 doses 3 H596 CDX model, which harbors a MET exon 14 deletion without gene amplification. 4 Map clinically relevant mutations, obtained from Cancer Cell Line Encyclopedia(31), 64 cell lines. Table S1 List lines used study with information on tissue origin, supplier, growth medium for...
<p>Supplementary Materials and Methods Figure Legends</p>
<p>Supplementary Materials and Methods Figure Legends</p>
<p>Suppl. Figure 1 In vivo efficacy of Sym015 treatment at various dose levels in the EBC-1 xenograft model. Suppl. 2 and unbalanced mixtures two constituent antibodies Hu9006 Hu9338, applied 10 mg/kg or 50 doses 3 H596 CDX model, which harbors a MET exon 14 deletion without gene amplification. 4 Map clinically relevant mutations, obtained from Cancer Cell Line Encyclopedia(31), 64 cell lines. Table S1 List lines used study with information on tissue origin, supplier, growth medium for...
<div>Abstract<p><b>Purpose:</b> Activation of the receptor tyrosine kinase MET is associated with poor clinical outcome in certain cancers. To target more effectively, we developed an antagonistic antibody mixture, Sym015, consisting two humanized mAbs directed against nonoverlapping epitopes MET.</p><p><b>Experimental Design/Results:</b> We screened a large panel well-annotated human cancer cell lines and identified subset highly elevated...
<div>Abstract<p><b>Purpose:</b> Activation of the receptor tyrosine kinase MET is associated with poor clinical outcome in certain cancers. To target more effectively, we developed an antagonistic antibody mixture, Sym015, consisting two humanized mAbs directed against nonoverlapping epitopes MET.</p><p><b>Experimental Design/Results:</b> We screened a large panel well-annotated human cancer cell lines and identified subset highly elevated...
<h3>Background</h3> The anti-NKG2A monoclonal antibody (mAb), NNC141-0100, may potentially reduce inflammation in Rheumatoid Arthritis (RA) and other immune disorders via a novel mechanism of action. NNC141-0100 has been proposed to promote the cytotoxicity natural killer (NK) cells towards pro-inflammatory expressing HLA-E. blocks inhibitory interaction between HLA-E heterodimer CD94/NKG2A receptor on NK-cells by binding NKG2A subunit. Given novelty action involving system, starting dose...