About | danpet

DanPET AB is a Swedish Biotech Company

• Dan Peters has >20 years of experience in pharmaceutical discovery and development as a key scientific management leader at NeuroSearch A/S, co-founder of R&D Task Force 2013 and co-founder of Initiator Pharma 2016

• DanPET focus on research and development of PET-ligands and medicines with nicotinic and monoamine mechanisms for diseases such as Alzheimer´s, Parkinson´s, ADHD, CVD and Cancer

•DanPET offer consulting services with >20 years of experience within medicinal and biotech

• PET is a nuclear medicine technique for non-invasive, real-time 3D-imaging of physiological processes in the brain and other organs

• Nicotinic alpha7 PET ligands 11C-NS14492, 18F-NS10743 and 18F-NS14490

• Alpha-7 PET ligands have potential for guiding diagnosis and treatment of AD: Read more

• High quality NET-PET ligands (11C-NS8880 and 18F-NS12137)

• SERT–PET ligands (11C-NS6417, 11C-NS9531 and 11C-NS9762)

• Broad IP portfolio within several classes with major focus on the US-market

• Article about DanPET AB - read more on page 30: 2014-1 Life Sceience | Affärstidningen Näringsliv (naringsliv.se)

• DanPET-information and scientific updates: Read more

• Products commercialised with Novandi AB: Radiochemical Catalog - Novandi Chemistry AB

Pipeline:

NS10712

NS10712 is a selective partial nicotinic acetylcholine receptor agonist.

NS12877

Potent and selective alpha7 nAChR agonist. Same scientific rationale as EVP-6124. Excellent physical chemical properties. Clean profile in a standard off-target binding. Induced c-fos and release of monoamines in PFC. Linear kinetics and oral bioavailability of 80-100%. Rat brain/plasma-ratio ~ 3.5 and rat T½ 2.5 hrs. No inhibition of the major CYP-isoforms was observed. Well-tolerated, mice to 60 mg/kg (p.o.) in Irwin test acutely. No issue with hERG, blood pressure, heart rate or QT interval. No mutagenic activity as judged by the Ames’ test. US patent with extension opportunities.

18F-NS14490

18F-NS14490 is a new, potential companion-diagnostic for vulnerable plaques in diseased arteries. The novel fluorine-18 PET radiotracer 18F-NS14490 allows in vivo investigation of alpha7 nicotinic acetylcholine receptor (α7nAChR) expression on brain vasculature in pig. The study provides evidence for the detection of α7-nAChRs by PET in the pig brain vasculature, notably in the left coronary artery. Alpha7nAChR is expressed by T cells and macrophages in human plaques findings support the notion that cholinergic regulation may act to inhibit disease development also in man. (Arterioscler Thromb Vasc Biol. 2014;34:2632-2636). Read more Radiosynthesis and first evaluation in mice of [18F]NS14490 for molecular imaging of α7 nicotinic acetylcholine receptors. Bioorganic & Medicinal Chemistry (2013), 21(9), 2635-2642. Read more.

DanPETC1

DanPETC1 is a functional alpha7 nicotinic antagonist. Exposure to tobacco products is responsible for the majority of all human cancers. Nicotinic acetylcholinereceptors (nAChRs) were identified as early as 1989 as important regulators of cancer cells. Strategies that target the 7nAChR for cancer intervention are highly promising but should aim to reduce signaling downstream of the receptor rather than blocking the receptor because of its numerous vital functions in the mammalian organism. DanPETC1 is such an example with several important and desired functional properties similar to toxins, except the toxicity. Current Drug Targets, 2012, 13, 680-687.

11C-NS8880

[11C]NS8880 is a NET ligand, preliminary evaluated it in vivo in a rat and pig model. NS8880 (exo-3-(6-methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane) is a novel compound with high affinity and selectivity towards NET (IC50: NET: 5 nmol; SERT: 260 nmol; DAT: 2000 nmol), which structurally is not related to reboxetine. Our initial data indicate that [11C]NS8880 is usable for imaging NET and due to its faster kinetics might in some respect be superior to [11C]MeNER. See paper: Nucl Med Biol. 2014 Oct, 41(9):758-64. http://www.ncbi.nlm.nih.gov/pubmed/25127515

18F-NS12137

Professor Olof Solin´s research-team at Turku PET Centre, University of Turku has together with DanPET AB developed [18F]NS12137 (Nuclear Medicine and Biology 2018) with improved specificity to (S,S)-[18F]FMeNER-D2 and the former tracer [11C]NS8880, in collaboration with Chief Radiochemist Dirk Bender at Aarhus PET Centre. https://www.ncbi.nlm.nih.gov/pubmed/29172120 Nuclear Medicine and Biology 56 (2018) 39–46. Theranostics 2019; 9(1):11-19 In vivo characterization of a novel norepinephrine transporter PET tracer [ 18 F]NS12137 in adult and immature Sprague-Dawley rats - PubMed (nih.gov)

[18F]NS12137 crosses the blood-brain barrier and enabled specific labeling of NET-rich regions of rat brain tissue with the highest concentration in the Locus Coeruleus (LC). The specificity of [18F]NS12137 binding was demonstrated on the basis of competitive binding by Nisoxetine, a known NET antagonist of high specificity.

Research on cognitive aging has focused on how decline in various cortical and hippocampal regions influence cognition. However, brainstem regions play essential modulatory roles, and new evidence suggests that, among these, the integrity of the LC –norepinephrine (NE) system plays a key role in determining late-life cognitive abilities. The LC is especially vulnerable to toxins and infection and is often the first place Alzheimer's-related pathology appears, with most people showing at least some tau pathology by their mid-20s. On the other hand, NE released from the LC during arousing, mentally challenging, or novel situations helps to protect neurons from damage, which may help to explain how cognitive reserve, caused by education and engaging careers prevent cognitive decline in later years (Mara Mather Trends in Cognitive Sciences March 2016).

11C-NS14492

11C-NS14492 is a PET biomarker, useful in research and drug development and has potential for guiding diagnosis and treatment of Alzheimer’s Disease. Read about 11C-NS14492 in the litterature: J Nucl Med. 2011 Sep, 52(9), 1449-56. https://www.ncbi.nlm.nih.gov/pubmed/21828113 11C-NS14492 as a novel radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy. [11C]NS14492, best in class, allows for multiple scans per day and in the same subject because of the short half-life of 11C-labeled radioligands (20.8 min), which is an advantage for performing drug-occupancy studies. This is not possible with a 18F-labeled radioligand with a half-life of 110 min. Reference and precursor is provided in collaboration with Novandi Chemistry AB.

18F-NS10743

18F-NS10743 is a PET biomarker, useful in research and drug development and has potential for guiding diagnosis and treatment of Alzheimer’s Disease. Read about 18F-NS10743 in the litterature: European Journal of Nuclear Medicine and Molecular Imaging (2011), 38(8), 1541-1549. https://link.springer.com/article/10.1007/s00259-011-1808-y Reference and precursor is provided in collaboration with Novandi Chemistry AB.

[3H]NS10743 [Outlicensed to Novandi Chemistry AB]

In cooperation with Novandi Chemistry (www.novandi.se) DanPET offer exclusive tritium labelled radioligands suitable for binding studies and in vitro visualization of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). The compound [3H]NS10743 is patented, novel, small molecule with unique imaging properties. The compound is alpha7 selective and have been shown to possess good imaging properties both in vitro and in vivo. Small-molecule alpha7nAChR agonists are currently being developed as a potential treatment in various neuropsychiatric and neurodegenerative diseases such as schizophrenia and Alzheimer´s disease. Tritium labelled radioligands are valuable drug development tools and can be used in e.g. target engagement studies and preclinical validation of PET imaging protocols. NS10743, [³H] – Novandi Chemistry AB – Radiosynthesis Expertise

[3H]NS14492 [Outlicensed to Novandi Chemistry AB]

In cooperation with Novandi Chemistry (www.novandi.se) DanPET offer exclusive tritium labelled radioligands suitable for binding studies and in vitro visualization of the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). The compound [3H]NS14492 is patented, novel, small molecule with unique imaging properties. The compound is alpha7 selective and have been shown to possess good imaging properties both in vitro and in vivo. Small-molecule alpha7nAChR agonists are currently being developed as a potential treatment in various neuropsychiatric and neurodegenerative diseases such as schizophrenia and Alzheimer´s disease. Tritium labelled radioligands are valuable drug development tools and can be used in e.g. target engagement studies and preclinical validation of PET imaging protocols. NS14492, [³H] – Novandi Chemistry AB – Radiosynthesis Expertise

[3H]NS6784 [Outlicensed to Novandi Chemistry AB]

NS6784, which is an α7nAChR agonist with unique cognitive properties in an inhibitory avoidance (IA) model. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795215/

Tools for science and development. 3H and 14C radiotracers, precursors and references for PET corresponding to those published in sientific journals - marketed by DanPET AB and distributed by Novandi Chemistry AB.

NS6740 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795215/

NS6784 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795215/

NS10743 https://link.springer.com/article/10.1007/s00259-011-1808-y

NS10796 (precursor to 18F-NS10743)

NS14492 https://www.ncbi.nlm.nih.gov/pubmed/21828113

NS14554 (precursor to 11C-NS14492)

NS8880 https://www.ncbi.nlm.nih.gov/pubmed/25127515

NS12137 https://www.ncbi.nlm.nih.gov/pubmed/29172120

NS1738 https://www.ncbi.nlm.nih.gov/pubmed/17625074

NS3861 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554923/

NS3573 http://www.jneurosci.org/content/31/30/10759

NS3531 https://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?Dopt=s&uid=3U8J

NS3956 https://www.ncbi.nlm.nih.gov/pubmed/20360159

NS9283 https://www.ncbi.nlm.nih.gov/pubmed/23278456 https://www.ncbi.nlm.nih.gov/pubmed/22506660

NS9775 https://www.ncbi.nlm.nih.gov/pubmed/23748055

NS9531, NS9762, NS6417 & corresponding desmethyl precursors NS9645, NS9795, NS7022

https://www.sciencedirect.com/science/article/pii/S0969805115001845

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