9YMN
Crystal Structure of human KRAS G12D in complex with GDP and compound 7
This is a non-PDB format compatible entry.
Summary for 9YMN
| Entry DOI | 10.2210/pdb9ymn/pdb |
| Descriptor | Isoform 2B of GTPase KRas, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | inhibitor, gtpase, signaling protein, oncoprotein-inhibitor complex, oncoprotein/inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 22243.49 |
| Authors | |
| Primary citation | Wurz, R.P.,Allen, J.R.,Allen, J.G.,Amegadzie, A.,Chen, N.,Eshon, J.,Li, K.,Li, X.,Li, Y.,Manoni, F.,Medina, J.M.,Navaratne, P.,Pettus, L.H.,Rahimoff, R.,Stellwagen, J.,Tercenio, Q.,Weires, N.,Wigman, B.,Yamano, M.,Zhao, W.,Husemoen, G.,Leth-Petersen, S.,Bauer, D.,Frohn, M.J.,Mukhina, O.A.,Boursier, M.,Vaish, A.,Poppe, L.,Mohr, C.,Chen, Y.C.,Diaz, G.J.,Gaida, K.,Hughes, P.E.,Khetan, J.,Mohn, D.,Osgood, T.,Saiki, A.Y.,Rex, K.,Verma, R.,Wang, P.,Rui, H.,Yu, J.,Dahal, U.P.,Li, Y.,Agarwal, P.,Wegesser, T.,Lanman, B.A. Expanding Addressable KRAS Mutations through the Structure- and Property-Based Design of Dual-State (GDP/GTP), Reversible Pan-KRAS Inhibitors. J.Med.Chem., 2026 Cited by PubMed Abstract: Therapeutically targeting mutant KRAS represents a clinically validated approach for the treatment of solid tumors, including lung, colon, and pancreatic cancers. The approval of covalent KRAS inhibitors, such as sotorasib and adagrasib, has fueled intense interest in expanding KRAS-directed therapies to mutations beyond , such as , , and . Here, we describe the structure- and property-based design of reversible inhibitors of diverse oncogenic mutants of KRAS, leading to , a pan-KRAS inhibitor that blocks signaling via both the GDP(off)- and GTP(on)-bound states of KRAS, while sparing the closely related RAS isoforms HRAS and NRAS. disrupts signaling downstream of KRAS, potently suppressing the growth of and tumor xenografts following oral administration. represents an important proof-of-concept that structural insights from prior covalent KRAS inhibitors can be leveraged in the design of efficacious and well-tolerated inhibitors of diverse mutations. PubMed: 42446418DOI: 10.1021/acs.jmedchem.6c01325 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
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