7rt2

Crystal Structure of KRAS G12D with compound 25 (4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2R,4R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol) bound

Structural highlights 7rt2 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , , Related: 7rpz Activity: Small monomeric GTPase, with EC number 3.6.5.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed KRAS(G12D), the most common oncogenic KRAS mutation, is a promising target for the treatment of solid tumors. However, when compared to KRAS(G12C), selective inhibition of KRAS(G12D) presents a significant challenge due to the requirement of inhibitors to bind KRAS(G12D) with high enough affinity to obviate the need for covalent interactions with the mutant KRAS protein. Here, we report the discovery and characterization of the first noncovalent, potent, and selective KRAS(G12D) inhibitor, MRTX1133, which was discovered through an extensive structure-based activity improvement and shown to be efficacious in a KRAS(G12D) mutant xenograft mouse tumor model. Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS(G12D) Inhibitor.,Wang X, Allen S, Blake JF, Bowcut V, Briere DM, Calinisan A, Dahlke JR, Fell JB, Fischer JP, Gunn RJ, Hallin J, Laguer J, Lawson JD, Medwid J, Newhouse B, Nguyen P, O'Leary JM, Olson P, Pajk S, Rahbaek L, Rodriguez M, Smith CR, Tang TP, Thomas NC, Vanderpool D, Vigers GP, Christensen JG, Marx MA J Med Chem. 2021 Dec 10. doi: 10.1021/acs.jmedchem.1c01688. PMID:34889605 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 7rt2, resolution 1.59Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image