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PetroTeq Energy Inc - Article!

CLEAN, SUSTAINABLE ENERGY AND SOCIAL RESPONSIBILITIES

https://petroteq.energy/environmental-stewardship

Probably worth following this one in clinical trials, of Itacitinib in current trial with Pembrolizumab (Keytruda) in Advanced Solid Tumors SCLC Non small cell lung cancer, also a publication that was referred to in the Tyk2 Tumor Immunosurveillance, longest link ever!

Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors

NCT02646748

https://pdf.sciencedirectassets.com/272515/1-s2.0-S1043466619X00058/1-s2.0-S1043466618301273/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEO7%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEaCXVzLWVhc3QtMSJHMEUCIQDNXntTUOoy5YsrxOPNOM3wnTWVEbrkTY6DFVYMV3AojAIgP3Y%2FwK22GWB0baPWLJqo8QN%2BFdihwcpowd60iXCXuwwqtAMIdhACGgwwNTkwMDM1NDY4NjUiDP1NN%2F7QCXv0c1Z8gSqRA5ooPmeZJaDeow6PLJ4jFr%2FBr8OMLew9R%2BDgvVKJwUajJ8EAziyLJPfPO25SlbiIUwynfZBpV2RGiGEo%2BIl9kEcLGCjg4cnnjSo2orNi5ZH%2FIPEFfjbhlqhAe2S7G5unLdvNVpnXhyh0bkzuSm6Vys1Ube6U71zhxfK6nVElE9l%2B%2BxgK4bEu0oyrDJ2pq6ffAk%2FfPoq3PysLjvDZL0JpVctj83xvlWt%2BvjqccFaadJqIauM5%2BkAU%2BSpZYaKu%2FsBlp1H89FHG35e6AgihOvlyji4%2BLTZN41ZJD%2FamQjQxaRQVr0etGMHLDDDMi5Al4gMxN9UyKB2izziM0D5ZU%2FK8eN4RHFVf%2BOa2alKV1WSzpSHM3lS8yIS%2BtYbFvvTMtoJapjEmLy0ShLZbPyBuSFke%2F9rPMJ1DaC5KE4x7Z2ZfCzJDO9XdaLg4T71MoFh93o6yx3UMDKsnjCW0ao5%2BBzZjD8tNoiqKCJu3yXDYO22BfdSuaB1kaH1CsQDcSvWiTZxo4q3EL59ZsR1HFgsNANJSoI5kMPeh%2FPAFOusB3TIAquXGU2c%2Flobzu9FMpFEo464wxlZCWmVhzV%2FD6SrVJrTIzsvcTiH8%2BJpkg1Jup8DCm4iSrX3pYLQ60BMyoXL011vADvzGeWUc8Vl%2FomxlElLZyomf4wXBlqBDi3NR1cCOWt%2BNmP3%2F1iygigy%2Buqx2QIU2mX01ur2qoYXoR%2BH0Stg4Zoh4hDvwSkxgrT0krASXpfAH4rWnfXTrjSACDQGcr3D65jypJBhSUOgYaetRe35cUHwPOLOUXS9kIwHQ5YLhq0%2BVKpXDrxiimzYc1DV4b6xH%2BpxF2G%2FIEhRIJgq60XG4nGCyDfApRQ%3D%3D&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Date=20200115T142501Z&X-Amz-SignedHeaders=host&X-Amz-Expires=300&X-Amz-Credential=ASIAQ3PHCVTYSVZWS6XJ%2F20200115%2Fus-east-1%2Fs3%2Faws4_request&X-Amz-Signature=f3221a66b4356b015cdaae39c37b5bde9b189bf6215ec92433afc00d83e6d77c&hash=cc034f83b72195f3fd503f98d5b2c62e2709e1d69c7b30b5e39a9df4f6fa974f&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&pii=S1043466618301273&tid=spdf-f9982db4-744f-4b2c-8643-d3490805e368&sid=9ccae756335d524f4c78a6c78458336e560egxrqb&type=client&download=true

Pembrolizumab Combined With Itacitinib (INCB039110) and/or Pembrolizumab Combined With INCB050465 in Advanced Solid Tumors

NCT02646748

Thanks Stoney I didn’t know that Nimbus had the option to join the alliance, plus I don’t think I’ve seen the innovation article before great!

http://www.nimbustx.com/wp-content/uploads/2017/10/BioCentury-Innovations-Nimble-Move-10.5.2017.pdf

There has been a lot of research around the jaks/Tyk2 with a realization that pure jaks have safety issues but pure Tyk2 are safe!

(Dual Inhibition a Better Solution Development of a JAK1/TYK2 inhibitor)

With most BMS/nimbus Tyk2’s being pure but Sareum or Pizfer, which are the most similar TYK2/JAK1 inhibitors over the BMS/Nimbus, but different as the selectivity for Sareum is more TYK2 than JAK1 where Pfizer is more JAK1 than TYK2 what counts is the right selectivity of them from the literature, as Tyk2 is the IL12/IL23 which is inflammation and immune response but whats just as important is what is going on the JAK1, with their Interleukin and interferon signaling, there is in the research that Stoney found that in the latest Mdpi article that suggests that Tyk2 acts as an amplifier/sustains responses of your JAK!

“suggesting that TYK2 is the subordinate JAK and mainly amplifies/sustains responses”

So suggest that your JAK’s or your JAK1 more importantly are very important and getting that response right

Sareum Autoimmune SDC-1801 (SAR-20347)
Pharmacological profile

IC50(TYK2) = 0.6nM
IC50(JAK1) = 23nM
IC50(JAK2) = 26nM
IC50(JAK3) = 41nM

https://www.medchemexpress.com/SAR-20347.html

Pfizer JAK1 is more selective than TYK2 Pharmacological profile is a potent dual inhibitor of JAK1 and TYK2

Pfizer PF-06700841

IC50(JAK1) = 17 nM
IC50(TYK2) = 23 nM
IC50(JAK2)= 77 nM
JAK3 (IC50 = 6494 nM) or (6.49 µM)

https://www.medchemexpress.com/PF-06700841.html

Evaluation of Pharmacology and Clinical Response to TYK2/JAK1 Kinase Inhibitor
PF-06700841 in Patients with Plaque Psoriasis

https://server.aad.org/eposters/Submissions/getFile.aspx?id=4546&type=sub

https://www.nimbustx.com/wp-content/themes/nimbustx/pdf/identification-of-highly-potent-and-selective-tyk2-inhibitors-for-the-treatment-of-autoimmune-diseases-through-structure-based-drug-design.pdf

https://www.nimbustx.com/wp-content/themes/nimbustx/pdf/potent-and-selective-tyk2-inhibitor-is-highly-efficacious-in-rodent-models-of-inflammatory-bowel-disease-and-psoriasis.pdf

I think it would have been better if Sareum had presented this publication first, as very gratefully Iamhappy found it yesterday and for them to now start saying about it is playing catch-up, if of academic interest surely they would have known about it, and was published Wednesday the 8th, 2 days later, they must have read it here first (As peeps say here) as Robin Davidson has only just picked it up too!

The trend has been intact since last August after the placing!

Mm’s do it from from time to time to create a market, there’s no real buying volume they push up and take down but we will have a higher low when it does go back down, have a look at the chart on how long it’s been in the green channel trend!

https://imgur.com/a/l3703sO

https://imgur.com/a/l3703sO

It chosen too take the green trend and not the blue!

RMM it’s a continuation of an international patent they filled in 2016 that’s why it shows as 2016 in world patents and a new us patent!

https://imgur.com/a/TZQ6aF2

It’s a new Patent application for T-All - No 16/343639 - Case Docketed to Examiner 14.11.2019

Docketed New Case - Ready for Examination

Publication date 21.11.2019

It’s new and was posted to examiner mid November so has to run its course!

Found an Article on BMS 986165!

It’s Tyk2 is (>100-fold) selective over JAK’s!

https://www.nature.com/articles/d41573-019-00134-4.epdf?no_publisher_access=1&r3_referer=nature

Hi Stoney I’m not so sure as I thought we would have a response from examiner after 2 months from the 30th October as stated, so anyone’s guess, as Sareum has responded to non final rejection!

Itacitinib is an orally bioavailable and selective inhibitor of JAK1, with >20-fold selectivity for JAK1 over JAK2 and >100-fold over JAK3 and TYK2; Itacitinib is used in the research of myelofibrosis.

Myelofibrosis is the same as Sierra Oncology Momelotinib :-

Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50a of 11 nM and 18 nM,respectively. CYT387 shows much less activity against JAK3.

Itacitinib = JAK1 / Momelotinib = JAK1/JAK2

Also can be seen that it reached 50% inhibition IC50 of CHK1 at a much smaller amount 1.3nM

Found a table of Chk1 the CCT244747 has a CHK1 a 1000 fold selectively over CHK2 and CCT245737 had 1500 fold so better!

https://imgur.com/a/F3b7yWO

4.Development of ATR and CHK1 inhibitors

https://res.mdpi.com/d_attachment/cancers/cancers-09-00041/article_deploy/cancers-09-00041.pdf

Hi Stoney I think SRA737 is close as the number is bigger/different and a later generation of CCT244747 as SRA737 is CCT245737 like this article!

Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl) amino)pyrazine-2-carbonitrile (CCT245737)

https://www.researchgate.net/publication/302970645_Multiparameter_Lead_Optimization_to_Give_an_Oral_Checkpoint_Kinase_1_CHK1_Inhibitor_Clinical_Candidate_R-5-4-Morpholin-2-ylmethylamino-5-trifluoromethylpyridin-2-yl_aminopyrazine-2-carbonitrile_CCT245

The first publicized two SAR020106 and CCT224747 are talked about in this article saying CCT is superior to SAR :-

“CCT244747 is a novel, potent, highly selective and orally bioavailable CHK1 inhibitor which is a considerable improvement over our previous inhibitor SAR-020106 [27] and represents the first structural disclosure of an orally active CHK1 inhibitor. Kinetic and modelling studies have established that CCT244747 is an ATP competitive inhibitor of recombinant human CHK1. The selectivity profile of CCT244747 shows minimal cross- reactivity with CHK2 and CDK1.”

https://www.researchgate.net/profile/Simon_Robinson3/publication/230755884_CCT244747_Is_a_Novel_Potent_and_Selective_CHK1_Inhibitor_with_Oral_Efficacy_Alone_and_in_Combination_with_Genotoxic_Anticancer_Drugs/links/02e7e521c60d754ac4000000/CCT244747-Is-a-Novel-Potent-and-Selective-CHK1-Inhibitor-with-Oral-Efficacy-Alone-and-in-Combination-with-Genotoxic-Anticancer-Drugs.pdf?origin=publication_detail

The difference between the SAR020106 and CCT244747 is CCT244747 is a pure (Chk1) and SAR020106 inhibits (Chk1 and Chk2/CDK1)

https://synkinase.com/media/blfa_files/SYN-1216-cct244747-data.pdf

https://synkinase.com/media/blfa_files/SYN-1189-sar020106-data.pdf

The SAR020106 and CCT244747 are the only chk1’s available to purchase from Synkinase from Sareum involvement SRA737 is not there!

This is a list of Chk1’s available at Synkinase :-

https://synkinase.com/catalogsearch/result/?q=Chk

Thanks Thoth in your opinion do you think that this would come under the contract umbrella of Sierra for Chk1, or because the other earlier 2 compounds are being used in the experiment/tested strategy and not the licensed one too Sierra then it’s ok for a progression route without Sierra not allowing it?