Evgen Pharma Share Discussion Threads

[moneymunch] 24/2/2021 14:56

Very interesting connection with Evgen. Gla :-)


Published June 2020

KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease



Abstract

Redox imbalance and persistent inflammation are the underlying causes of most chronic diseases. Mammalian cells have evolved elaborate mechanisms for restoring redox homeostasis and resolving acute inflammatory responses. One prominent mechanism is that of inducing the expression of antioxidant, anti-inflammatory and other cytoprotective proteins, while also suppressing the production of pro-inflammatory mediators, through the activation of transcription factor nuclear factor-erythroid 2 p45-related factor 2 (NRF2). At homeostatic conditions, NRF2 is a short-lived protein, which avidly binds to Kelch-like ECH-associated protein 1 (KEAP1). KEAP1 functions as (i) a substrate adaptor for a Cullin 3 (CUL3)-based E3 ubiquitin ligase that targets NRF2 for ubiquitination and proteasomal degradation, and (ii) a cysteine-based sensor for a myriad of physiological and pharmacological NRF2 activators. Here, we review the intricate molecular mechanisms by which KEAP1 senses electrophiles and oxidants. Chemical modification of specific cysteine sensors of KEAP1 results in loss of NRF2-repressor function and alterations in the expression of NRF2-target genes that encode large networks of diverse proteins, which collectively restore redox balance and resolve inflammation, thus ensuring a comprehensive cytoprotection. We focus on the cyclic cyanoenones, the most potent NRF2 activators, some of which are currently in clinical trials for various pathologies characterized by redox imbalance and inflammation.

Keywords: KEAP1; NRF2; anti-inflammatory; antioxidant; cysteine; redox.
Conflict of interest statement

A.T.D-K. is a member of the Scientific Advisory Board of Evgen Pharma and a consultant for Aclipse Therapeutics and Vividion Therapeutics.



..........

A.T.D-K. is a member of the Scientific Advisory Board of Evgen Pharma and a consultant for Aclipse Therapeutics and Vividion Therapeutics.

20 May 2020

News

Roche enters $135m drug discovery deal with Vividion Therapeutics



.......

Vividion Announces $135 Million Series C Financing to Fuel Broad Pipeline of Precision Oncology and Immunology Programs

Proceeds to support advancement of the company’s unique discovery platform and robust portfolio of programs focused on high value, traditionally undruggable targets

February 24, 2021 

. The company’s initial wave of wholly owned assets includes programs targeting the KEAP1-NRF2 axis, with antagonists for the treatment of NRF2 mutant and NRF2 addicted cancers, as well as agonists for the treatment of inflammatory diseases. Also in the initial wave, and in partnership with Bristol Myers Squibb, the company is advancing a program against a highly pursued yet unsolved transcription factor for the treatment of both oncology and immunology indications.

“The science behind Vividion’s approach to drugging the undruggable space and accessing some of the world’s most highly sought-after targets has the potential to solve a wide range of devastating cancer and immune disorders,” said Arsani William, M.D., M.B.A. and Graham Walmsley, M.D., Ph.D. of Logos Capital. “Our investment philosophy at Logos is centered upon propelling innovation that meaningfully advances the standard of care for patients. The combination of a leading-edge platform, robust pipeline, strategic partnerships with leading pharmaceutical companies BMS and Roche, and a deeply experienced team sets Vividion apart. We are honored to support the team’s efforts in both the near- and longer-term."

[moneymunch] 22/2/2021 15:18

Sell and be gone...much better for the stability of the Long point of view imho...Gla :-)

[mesquida] 22/2/2021 11:27

Moneymunch, according to posters on the Iofina board , derivatives trades with IG are having to be unwound.This seems to have prompted some nervy selling of Iofina this morning.

[mesquida] 22/2/2021 10:19

Mutterings about changes in margin requirements with certain spread betting companies might just have some implications for our two large holders here.

[moneymunch] 21/2/2021 13:30

Wonder if we'll get a bounce in share price this coming Friday, with Thursday's deadline for 8p entitlement??? Gla ;-)

[moneymunch] 20/2/2021 22:16

Tyrosine-protein phosphatase non-receptor type 11 also known as protein-tyrosine phosphatase 1D, Src homology region 2 domain-containing phosphatase-2, or protein-tyrosine phosphatase 2C is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase Shp2.

[moneymunch] 20/2/2021 22:15

There has been little progress in the search for cures for the aggressive brain cancer glioblastoma, largely because of a lack of understanding of how the tumor cells interact with the immune system and other cells and tissues in the body. A new glioblastoma map was designed to fill in some of those knowledge gaps.

A study of 99 tumors resulted in a map of genes, proteins, cells and signaling pathways that are active in glioblastoma. Scientists at the Washington University School of Medicine, Pacific Northwest National Laboratory, Case Western Reserve University and the National Cancer Institute (NCI) contributed to the map, which was published in the journal Cancer Cell.

The map revealed potential new drug targets for treating glioblastoma, including the proteins PTPN11 and PLCG1. The researchers discovered that the two proteins act as “signaling hubs” that drive tumor growth in some patients, according to a statement.

[moneymunch] 20/2/2021 21:27

Surely not another Toffeeman...FFS!!! ;-)

James D Chalmers

@ProfJDChalmers

·

1h

The thing about being an Everton fan is we are mostly just happy we reached 40 points and avoided relegation for another year.

[on target] 20/2/2021 11:21

No connection, just the above poster spamming multiple threads.

[mwoo] 20/2/2021 11:20

Hi Guys....interested in this thread but it refers to EVGEN, whereas Guerilla refers to YGEN
Is there any connection or am I misreading the facts....thanks in anticpation

[daniel levi bmd] 19/2/2021 09:24

FYI

Yourgene Health. Whispers Contract/s "Done Deal".....

Dan
x

[hodhasharon] 18/2/2021 21:35

This is gonna blow. We MUST be expecting big news. The chart makes little sense without it.

[moneymunch] 18/2/2021 21:17

Exactly right, Huw's got a raft of potential positive news that could take the share price to new highs in the coming weeks and months, although I'm expecting a decent re-rate soon enough when the placing is done and dusted with disclosure of the new and existing investors who've participated , to reflect true and fair value of Evgen's financial position and undoubted Transformational prospects and potential going forward.Gl :-)

[lovewinshatelosses] 18/2/2021 19:12

Nope, needed to keep some cash back for this OO and a request for additional allocation, in case it is available. Will be interesting to see if I can get any on top. I still maintain some decent inside buying would have made a big, positive difference in the short term, but it is what it is and if we get some positive news on one of our avenues, it will not matter. GLA.

[moneymunch] 18/2/2021 18:36

Next time amaretto, and who knows, maybe Evgen's turn soon.Gl :-)

[amaretto1] 18/2/2021 17:19

Anyone take my advice on BRH ?

[moneymunch] 18/2/2021 07:18

Covid: Lockdown driving down coronavirus rates but hospital cases 'higher than April 2020 peak'

Health
coronavirus

Thursday 18 February 2021, 6:54am

Researchers say there is a strong decline in the prevalence of coronavirus in England among the general population five to six weeks into lockdown, but prevalence remains at levels similar to those observed in late September 2020.

According to the preprint, which has not yet been peer-reviewed, the number of Covid-19 cases in hospitals is higher than at the peak of the first wave in April 2020.

They warn that the effects of easing social distancing need to be closely monitored in order to avoid a resurgence in infections and renewed pressure on health services.

[moneymunch] 18/2/2021 06:41

They've got two Covid studies, SFX-01 and Brensocatib, and i think he's referring to the latter, when very encouraging phase 2 results for Bronchitis were published November 2020. Gl ;-)

[dlg3] 17/2/2021 23:19

Professor Chalmers and a group of scientists from Dundee University were this week praised after making a potential breakthrough in finding a treatment for COVID-19.

Two separate studies have found a new treatment for inflammation of the lungs.

As COVID-19 causes a similar type of lung inflammation, the findings could prove pivotal and were this week published in the world’s top medical journal - the New England Journal of Medicine - a lifelong goal for the academic who lives in Perth.

He told the Perthshire Advertiser : “It’s amazing. This will be the pinnacle of my career.”

[moneymunch] 17/2/2021 22:13

I wouldn't be surprised bocker given the timing of his appointment and who knows but maybe he's already been encouraged from what he's seen in the Lab from the blood/biomarker studies?? :-)

[bocker01] 17/2/2021 20:42

Wonder if Chalmers had an inkling re early evaluation when he took up the EVG scientific advisory role?

[moneymunch] 17/2/2021 20:22

Cheers On Target, presumably bloody samples are taken during the trial from each patient in hospital, and so wonder at what stage Prof Chalmers and his team have access to carry out the exploratory objectives ...ie could he have made any comparisons / observations already with the neutrophil study for SFX-01 and the paper published today from any blood samples that may have been taken?