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Co-crystal structure of 7b in complex with KRAS G13C mutant To further characterize the novel nucleotides with the cyclic linkers, KRAS G13C was co-crystallized with compound 7b to obtain detailed structural insights into ligand binding within the binding pocket (resolution:1.85 , R work : 18.98, R free : 22.78

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The binding of prorenin to PRR triggers the phosphorylation of mitogen-activated protein kinases/extracellular regulated kinases 1/2 (MAPK/ERK1/2), which is demonstrated to be an ANG II-independent mechanism involved in the development of diabetic nephropathy ( The ANGIV/AT4/IRAP cascade: ANG IV (derived from the metabolization of ANG II through aminopeptidases A and N) binds the AT4 receptor, which has been identified as the insulin-regulated aminopeptidase (IRAP), but the role of this pathway in the blood pressure and renal regulation is still uncertain ( These new axes have raised great interest because their targeting could provide novel therapeutic strategies for hypertension, cardiovascular and kidney diseases