Roundtable Discussion; The Future of Mineral Sands. Watch the video here.
Cont;
Affimers bind to intracellular RAS and inhibit downstream signaling
To further explore the potential of Affimers to identify and probe the RAS gene pocket, the researchers developed the KRAS:Affimer NanoBRET system and evaluated the effects of small molecule inhibitors in the SI/SII and SII pockets on NanoBRET signaling.
The research data showed that as the ratio of Affimer to KRAS gene increased, the NanoBRET signal gradually increased, indicating that K6 and K3 can interact with KRAS in cells, and Affimers can be used as a potential tool for identifying pharmacophore.
KRAS NanoBRET can be used to identify small molecules bound in the SI/SII or SII/3 pocket
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2023-08-14 Responsible editor: Not filled Views: 2 Tianya Pharmaceutical Network
Core tip: Affimers bind to intracellular RAS and inhibit downstream signaling In order to further explore the potential of Affimers to identify and detect the RAS gene pocket, the researchers developed the KRAS:Affimer NanoBRET system and targeted small molecules in the SI/SII and SII pockets Inhibitor pair.
The RAS gene is the first locked cancer culprit in humans. It was first discovered in the progeny genes of Harvery murine sarcoma virus (Ha-MSV) and Kirsten murine sarcoma virus (Ki-MSV). According to public information, 30% of tumors Carrying RAS mutations, the KRAS mutation alone in its gene family members H-RAS, K-RAS and N-RAS will cause about 1 million deaths worldwide every year.
However, due to the particularity of the RAS protein structure and substrate affinity, it took researchers 40 years to break the curse of being undruggable. In May of this year, the FDA opened a fast track for the world's first RAS-targeted therapy AMG510 and accelerated its approval for marketing, allowing We have renewed hope for the successful treatment of RAS-mutant cancers.
Nevertheless, AMG-510 can only treat a small number of cancer types driven by RAS, mainly due to the special spherical structure of RAS and the lack of pockets for binding small molecule drugs, making it impossible for drugs to break through the fortress of proto-oncogenes and penetrate into the enemy. Army interior.
Recently, researchers at the University of Leeds took a different approach and discovered a new way to target RAS mutant proteins. They discovered a crack in the surface of RAS, which can be used to develop new Affimer technologies for examining biomolecules and life processes. Affimer proteins have an antibody-like surface-binding region that can tightly bind target molecules and quantify their content and activity, thereby easily and reliably tracking molecular trajectories and their responses to various stimuli, making disease research more streamlined.
In this latest study, the researchers used this technique to identify two Affimer-binding proteins, K3 and K6, that inhibit nucleotide exchange and regulate downstream signaling pathways.
Not only that, the researchers found that they were stored in two recently discovered druggable pockets, SI/II and SII, respectively. Among them, Affimer K6 binds in the SI/SII pocket, while Affimer K3 acts as a non-covalent inhibitor of the SII region, revealing conformers of wild-type RAS and carrying a druggable SII/3 pocket.
So what is the origin of SI/II and SII? Studies have pointed out that SI/II often stays between the Switch I and Switch II regions of the RAS gene, which is involved in the combination of nucleotide exchange factors, while SII is under the Switch II loop. It is worth mentioning that currently A series of RAS inhibitors have been developed targeting Switch II.
Affimers bind to intracellular RAS and inhibit downstream signalin
Https://twitter.com/Buen0snach0s/status/1678815798964387868?s=20 thanks to Jon.
Not sure if previously posted!!
https://youtu.be/Q2RCSA8a9TY 1hr 15mins in talking about general precision technology - then Mr on right's ears prick up - did you say pre/CISION?! Avacta - only 1 share I am sharing with you today!!!!!!!!!!!!