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Covid-19 can be focused with it staying in the RNS that Lead optimization of SDC-1801 goes on and can focused for this to be a molecule designed to aid!

I think the ICR wants resolution just as much as Sareum in finding an on license for SRA737, ICR need to complete the work involved with their new facility they have built and refer the latest research that Chk1 inhibitors and DNA Polymerase inhibitors to what can be achieved and this sort of thing can happen with progression in the new facility and want £10m to complete it, so I think this new research even though the footprint of this research goes back years, so I think there is a courtship going on!

You can buy at 0.3 yes.

“The Licensee is principally engaged in research and development, production and sales of innovative drugs, including oncology drugs, in China and is listed on the main market of the Shanghai Stock Exchange.“

I don’t really mind that there is no detail as I didn’t think there was any value in the FLT3 Aurora program with what happened so is a plus, 50k is nothing really but if the product can be made oral bio available in 9 months then 900k is a good amount to further TYK2 into trials!

Hi RMM yes it’s really good and informative about the situation and intricate details, a recommended read for all especially living in these times why not load yourself up with useful information!

I come across it by searching for the Interleukin signals that our TYK2 compound inhibits with the link to the immune system and Pneumonia, viral infection resistance, namely the IL22, IL12 and IFN’s!

If they are good business wise could sort a lot out here, especially as Num4 pointed out a TYK2 molecule in the running for treatment to Covid-19 they could sell the rights to an analog of SAR20347 just for immune system defense for the development of a refined synthetic molecule for Covid-19 and take a bigger upfront payment and small royalties payments with the important Interleukin’s involved with research in Coronaviruses, it’s available to get on websites to buy so is on the market, so much pointing to a molecule that can help here!

“SAR-20347 is a novel specific dual inhibitor of JAK1 and tyrosine kinase 2 (TYK2), inhibiting JAK1- and/or TYK2-dependent signaling from the IL-12/IL-23, IL-22, and IFN-alpha receptors“

https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9803

Sareums SAR-20347 (SDC1801)

Inhibition of TYK2 and JAK1 Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis by Inhibiting IL-22 and the IL-23/IL-17 Axis

https://pubmed.ncbi.nlm.nih.gov/25156366/

The Role of IL-22 in Viral Infections: Paradigms and Paradoxes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885595/

IL-22 IN MUCOSAL IMMUNE DEFENSES

“The mucosal surfaces, such as the lung and gastrointestinal tract, are the key battle grounds for hosts to fight against the invasion of various microbes. Recent studies on the IL-22 pathway in infectious disease models have elucidated its essen- tial protective role in mucosal immunity”

https://www.nature.com/articles/mi200826.pdf?origin=ppub

Repurposing of known drugs with proven safety records is a faster and more efficient way of developing drugs in an outbreak situation, when time is of the essence. In light of the MERS-CoV outbreak, NIH researchers screened a panel of 290 approved and investigational drugs with defined cellular targets in order to determine the potential for repurposing any of them to treat SARS and/or MERS. They found that 33 compounds were active against MERS-CoV, 6 against SARS-CoV and 27 against both coronaviruses. The active drugs were grouped into 13 therapeutic classes and included antibacterial and antiparasitic agents, neurotransmitter inhibitors, estrogen receptor antagonists, kinase signalling inhibitors, inhibitors of lipid or sterol metabolism, protein-processing inhibitors, and inhibitors of DNA synthesis/repair (Dyall, J. et al (2014)

https://clarivate.com/wp-content/uploads/dlm_uploads/2020/01/CORONAVIRUS-REPORT-1.30.2020.pdf

Covid-19, took an hour out never knew there was so much research pointing to kinase inhibitors ie Tyk2/JAK pathways in relationships with Coronavirus!

Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-?B Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity

https://www.nature.com/articles/s41598-017-04203-9.pdf

INTERFERON a ACTIVATES NF-? B IN JAK1-DEFICIENT CELLS THROUGH A TYK2-DEPENDENT PATHWAY

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1193649/pdf/nihms2197.pdf

“Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-?B signaling pathway. In the IFN signaling pathway leading to STAT activation both JAK1 and TYK2 are essential, while NF- ?B activation requires only TYK2.”

Tyk2 as a target for immune regulation in human viral/bacterial pneumonia!

https://twitter.com/erspublications/status/886457920485040129?s=21

https://erj.ersjournals.com/content/erj/50/1/1601953.full.pdf

Interactive ICR webpage on TYK2 information

https://cansarblack.icr.ac.uk/target/P29597/synopsis/diseases

https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9803

Immunotherapeutic effects of the TYK2 inhibitor SAR-20351 in syngeneic tumor models.

“TYK2 (tyrosine kinase 2) is a member of the Janus family of non-receptor tyrosine kinases and has been shown to play an important role in the signalling of type I interferons, as well as IL-12 and IL-23, via phosphorylation of downstream STATs. The TYK2/STAT1/BCL-2 pathway is implicated in the survival of leukemic cells in a proportion of T-ALL cases“

https://mct.aacrjournals.org/content/18/12_Supplement/C086

Nature Article on the BCL-2 pathway highlighting their use in immunotherapy escaping the immune system by blocking Program Cell Death (PD-L1 & PD-1) Immunotherapy!

Targeting cell death: helping push cancer cells over the edge

The BCL-2 family regulate one of the body’s apoptotic pathways. As scientists understand more about these proteins, they are able to push the boundaries of cancer research.

“Two independent teams of scientists discovered that the BCL-2 protein could promote cancer in mouse models2, and that it did this by blocking programmed cell death”

https://www.nature.com/articles/d42473-019-00281-7?utm_source=twitter&utm_medium=social&utm_campaign=bcon-abbvie&utm_content=V1

https://dm5migu4zj3pb.cloudfront.net/manuscripts/126000/126567/cache/126567.2-20200310134632-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf

Hi Stoney there’s an older footprint which makes the timing bizarre and a statement a of scientific nature, should just be a tweet was my first thought, there’s a deeper reason for this IMO!

http://filecache.investorroom.com/mr5ircnw_sierra/105/download/ICR%20AACR%20Poster%20-%20FINAL.pdf

https://www.kent.ac.uk/biosciences/people/1185/garrett-michelle

Always involved with DNA Damage Response and worked with the ICR with the concept of the Chk1 inhibitor we know!

Understanding the molecular and cellular effects of new drugs for the treatment of cancer

One of the principal characteristics of human cancer is abnormal cell growth caused by deregulation of key cellular processes including signalling and cell division. In fact we now know that signalling pathways can act directly on the cell division cycle: for example, through growth factor regulated signal transduction pathways or via activation of cell cycle checkpoints in response to DNA damage. My research has therefore focussed on how signalling and cell division can be targeted for the treatment of cancer. This has led to the discovery of a number of innovative small molecule therapeutics including the AKT inhibitor AZD5363 the AGC kinase inhibitor AT13148, and the CHK1 kinase inhibitor CCT245737 (SRA737), which are all currently in clinical trial for the treatment of cancer.

https://www.kent.ac.uk/biosciences/people/1185/garrett-michelle

Kendy if you press the right hand button the tub with an arrow you can copy the link!

https://twitter.com/cdrlifesciences/status/1238115947409559552?s=21

ICR they are really going for it on this today look at the comments made, publicity is the right thing we need that can push SRA737 onwards, are you listening to this Sierra Oncology!

“This research is an example of the kind of approach the ICR plans to take within its pioneering #CentreForCancerDrugDiscovery, which aims to combat the challenge of cancer evolution and drug resistance.”

https://twitter.com/icr_london/status/1238003745763594243?s=21

Thanks Ajthoth that’s a great link, and sounds that AstraZeneca is driving the DNA Damage type of Cancer Killing Mechanisms and I bet they will be interested in Chk1 know how well it synergies with a lot of other molecules, ie PD-L1 Imunotherepy, Gemcitabine Chemotherapy, other DNA Damage Responce molecules PARPi/Wee1 and now this new mechanisms that stops Cancer Replicator need a big Pharmaceutical company to partner Sierra as there is so many combinations and a credit to John and Tim’s expertise with John changing the chemical structure of SRA737 being so selective, hope TYK2 will be this exciting in regards to this, we will see!

Has anyone heard of the DNA polymerases and why it’s such a big thing for it too be mentioned on the ICR (Institute of Cancer Research website?

“Describing the anti-cancer effect of the CHK1 inhibitor, SRA737, in multiple human lung and colorectal cancer cells, when used in combination with small molecules that block the function of a family of proteins involved in DNA replication and repair (B-family DNA polymerases)”