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Check out this T w i t t e r post today by @duttonjonathan:
Pfizer will pay $10.6 billion for Array BioPharma https://cen.acs.org/content/cen/articles/97/web/2019/06/Pfizer-buy-Array-106-billion.html via @cenmag
So, the KRAS druggable market is possibly yet another blockbuster therapeutic area of interest for Avacta's Affimers, in addition to the existing immunotherapy and chemotherapy pipeline? Holy smoke, is there no end to the potential value add at #avct?
Is there a scientist in the house, to explain in layman terms what is a KRAS druggable market?
O&W - check out this thread
https://twitter.com/Tomlinson_lab/status/1268936665709633540
Vicente,
Suggest you read some of the excellent posts from earlier on today.
bladehater - ?? not sure i understand your post - i have read them all - was just pointing Older& wiser to a twitter thread where the Avacta employee who has tweeted about the new affimer development with KRAS has further expanded on it having been questioned by Avacta shareholders.
A primer on KRAS:
https://www.sciencedirect.com/science/article/pii/S2211383518309584
So, is the idea that Affimers can potentially bind onto these oncogenes and block them from entering human cells, in much the same way that Avacta is suggesting other Affimers can block the spike protein on the SARS-COV-2 virus particle?
Sorry Vicente, should have put it to O&W.
Just trying to point out good new research done by others today. It's all v positive for the so going forward
Not my field as a Haematologist in nhs. However KRAS mutation is generally associated with Colon Cancer c(and lung)giving a poor prognosis (a good friend at only 50 died last december) Have a read of these
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316144/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850913/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316144/I believe there are a number of mutations,
There are a number of mutations with different treatment options some better than others.
Basically, Awacta’s affimers have just unlocked the holy grail and Pfizer paid $10.6 billion for a company just for trying.
Not bad I suppose...
OlderWiser-
Some references before understanding:
1.An in vivo inflammatory loop potentiates KRAS blockade BioRxiv
Kristina A.M. Arendt, Giannoula Ntaliarda, Vasileios Armenis, Danai Kati, April 19 2020
2, RAS-inhibiting biologics identify and probe druggable pockets including an SII-a3 allosteric site.
BioRxiv 5th June 2020 Katarzyna Z Haza, View ORCID ProfileHeather et al (article which you may have read on Twitter)
We have identified two RAS-binding Affimer proteins, K3 and K6, that inhibit nucleotide exchange and downstream signalling pathways with distinct isoform and mutant profiles. Affimer K6 is the first biologic to bind in the SI/SII pocket, whilst Affimer K3 is the first non-covalent inhibitor of the SII region, revealing a novel RAS conformer with a large, druggable SII/a3 pocket. This work demonstrates the potential of using biologics with small interface surfaces to select novel druggable conformations in conjunction with pharmacophore identification for hard-to-drug proteins. KRAS GTPase activity and downstream signaling additionally prerequisites its integration into the cell membrane, which is facilitated by post-translational lipidation and membrane transport of KRAS by various enzymes such as farnesyltransferase (FT), geranylgeranytransferase (GGT), isoprenylcysteine carboxylmethyltransferase (ICMT), phosphodiesterased), and others (Stephen et al., 2014;Simanshu et al., 2017). To this end, therapeutic attempts to inhibit KRAS lipidation by targeting FT/GGT/ICMT were recently coupled by the development of PDEd blockers and of allosteric and covalent inhibitors of mutated KRASG12C (Winter-Vann et al., 2005; Zimmermann et al., 2013; Ostrem et al., 2013).
To make the EXPLANATION simple to understand IMO:
RAS mutations are common oncogenic (Cancer) drivers.These RAS mutations have been found in Pancreatic, Colonic and lung cancers . KRAS proto oncogene is holygrail of anticancer therapy .
It is importanat to note that until now, despite coordinated efforts anti-KRAS DRUG discovery is lagging behind other oncogene targets .
Now that K3 and K6 RAS binding affirmer proteins binding to druggable pockets have been identified to inhibit nucleotide exchange and thus down-stream mutations and cancer pathways . (This also involves complex enzymatic pathways FT, GGT and ITMT as mentioned in para1). Essentially Affirmers potentially offer what some anti-cancer drugs have been unable to do, but will need further studies on this application. IMO
thank you for your work MR Kumar
Bump and thanks to all posters. Love the science (light relief from guess when the RNS, guess the SP tomorrow)