然而，Due to the specificity of RAS protein structure and substrate affinity，It took researchers 40 years to break the curse of 'No medicine'，May of this year，FDA Opens fast track to AMG510, the world's first RAS-targeted therapy，Accelerated listing approval，It gives us renewed hope for successful treatment of RAS mutated cancers。

However, AMG-510 can only treat a small percentage of RAS-driven cancer types, mainly due to RAS's unique spherical structure and lack of "pockets" for small molecule drugs to break through the proto-oncogene fortress and penetrate the enemy。

Researchers at the University of Leeds have found a new way to target "RAS" mutated proteins, discovering a "crack" in the surface of RAS that could be used to develop novel anti-cancer drugs。相关研究以RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site为题发表于《十大电子游艺平台首选》杂志。

2017年，The University of Leeds and Avacta Life Sciences have teamed up to develop an Affimer technology that can replace the traditional animal-derived antibodies used to examine biomolecules and life processes，The Affimer protein in this technique has an antibody-like surface binding region，It binds tightly to the target molecule，Quantify its content and activity，This allows easy and reliable tracking of molecular trajectories and their responses to various stimuli，Make disease research more streamlined。

In this latest study, the researchers used the technique to identify two Affimer binding proteins, K3 and K6, which were found to inhibit nucleotide exchange and regulate downstream signaling pathways。

Not only that, the researchers found that they reside in two recently discovered publishable medicine pockets, "SI/II" and "SII.。Affimer K6 binds to the SI/SII pocket, while Affimer K3 acts as a non-covalent inhibitor of the SII region, reveals the conformational isomer of wild-type RAS, and carries a pharmaceutically available SII/α3 pocket。

So where do "SI/II" and "SII" come from？Research points out，SI/II often stays between the Switch I and Switch II regions of the RAS gene，This region is involved in the binding of nucleotide exchange factors，SII, on the other hand, is in the Switch II loop，It is worth mentioning that，A series of RAS inhibitors targeting Switch II have been developed。

To further explore the potential of Affimers to identify and detect pockets of RAS genes，The researchers developed the KRAS:Affimer NanoBRET system，The effect of small molecule inhibitors in SI/SII and SII pockets on NanoBRET signal was evaluated。

As the ratio of Affimer to KRAS genes increased, NanoBRET signaling increased, suggesting that K6 and K3 interact with KRAS in cells and that Affimers could serve as a potential tool for pharmacophore identification。