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Reminds me of a very old joke Carter 19.

An elderly couple went to the doctors. Chronic constipation was diagnosed. The doctor prescribed them some suppositories.

The elderly couple returned home and duly read the instructions. One to be inserted up the anus once per day. The old boy says. ' ere Ethel what the f..k is an anus? I don't know Ethel replies but we have a dictionary and we can look it up. Ethel meanders over to the sideboard picks up the dictionary and opens it. I have found it she says. What is it then Bert asks?
It's a back passage Ethel replies.

We have a back passage that leads away from the back door he says. We are very fortunate to have found it.
Every morning they open the back door and throw out 2 of these suppositories.
2 weeks later they return to the doctors.

Good morning Bert and Ethel the doctor says, how are you getting on with your medications?

Not good at all says Bert we both took them as directed but condition has got worse. I am not happy at all with them. For what good they have done, we might just as well stuck them up our ar5e.

Good post Citizen79. Apologies but have only just scrolled down to your post.

Important to look at all sides of the battle, Where and why others fail , why some succeed and others do not. Attention to detail. All have plusses and minuses.

I am fine thankyou and trust likewise you are the same sir.

Regards and keep those post coming, knowledge is power.

i will add that phase 1/2 data may not bring to a head the development of heart problems.

https://www.evaluate.com/vantage/articles/news/snippets/pfizer-bows-out-tyk2-race

https://www.evaluate.com/vantage/articles/news/snippets/lattice-miss-grating-bristol-myers
Deucracitinib is pure Tyk 2 and failed in IBD ie UC. maybe looking at trialing woth kigher doses. Higher dose of course leads to higher risk'

As far as I can tell 1L-10 inhibition is of paramount importance in treatment of IBD. IL-10 consists of 4 sub units 2 of which are Jak 1 and 2 of which Tyk2. Without this I reckon they are pretty will phu..ed in this indication.
Pfizer have gone the Tyk2 Jak1 route. They have not made public any severe side affects at the moment. They may be minor or major ones.
An inhibitor is a tool, nothing else. if we do not use this tool correctly it will fail. In this instance dosing regime with how much and to what frequency will give optimum results cannot be over estimated. Drug companies are outsourcing to specialist companies in this field. You cam include if you wish the acquisition of a company. Why? They do not have the knowhow themselves. ) Lucrative markets cost of initial investment and nippy bum time come to mind)

Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases. This was discontinued at end of 2021. I would summise as pure Tyk2 only

Enough from me.

Regards to all and enjoy what left of weekend.

Well, the vaccines are killing people as well, I know over 20 that have been to hospital, heart attacks or chest pains, blood clots and other problems, everyone double or triple vaccinated. Herd immunity was achieved several mths ago and those test kits are useless, might as well stick them up your anus, that might be positive though. Let’s not forget, these are 2 year experimental jabs.

Good evening ndr50.
Cannot locate original links I had. This one will indicate that kinase inhibitors carry a risk of heart problems. Not all bad I might add. it has been know about for some time. Not really been a topic of that has raised its ugly head. Mainly but not wholly caused by off target inhibition. Very early link to ICR for CHK 1 inhibitor indicates the pedigree we have in our drug design and formulations also added here.

https://oxfordmedicine.com/view/10.1093/med/9780198784906.001.0001/med-9780198784906-chapter-292#:~:text=The%20most%20important%20cardiovascular%20complications%20of%20these%20kinase,arterial%20thromboembolic%20disease%2C%20QT%20prolongation%2C%20and%20pulmonary%20hypertension.
https://www.icr.ac.uk/news-features/latest-features/kinase-inhibitors-the-science-behind-a-revolution

https://pubmed.ncbi.nlm.nih.gov/20728698/

https://www.sciencedirect.com/science/article/abs/pii/S0033062010001167

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30306-6/fulltext

https://www.nature.com/articles/s41392-021-00826-7

It does point to a need to have extreme purity in compound formulation.

Tim and Co I am certain will be aware of this and taken into consideration. Am making a guess as to why so much precision, attention to detail put into its inhibitors.. We must also bare in mind that these effects would have happened to early designs and compound creations, whereby a pharma will focus on what a compound can do without the same amount of attention to the side effects.
I will reiterate that I do not see this as a major concern. We have no idea how much and how far Tim and co have addressed this problem as any information regarding this will be commercially very sensitive. Clearly they are very confident.

Regards

PS Sometimes it may appear I am ramping like hell. But if I think there are areas not looking so positive I will post so as to raise debate. It is not fear of the known which troubles us it is fear of the unknown.

Regards