8TXE

Crystal structure of KRAS G12D in complex with GDP and compound 5

8TXE の概要

• エントリーDOI: 10.2210/pdb8txe/pdb
• 分子名称: GTPase KRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: molecule, gtpase, kras, inhibitor, oncoprotein, oncoprotein-inhibitor complex, oncoprotein/inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40956.80

構造登録者

Chen, P.,Irimia, A.,Yang, Z. (登録日: 2023-08-23, 公開日: 2023-11-08)

主引用文献

Cheng, H.,Li, P.,Chen, P.,Irimia, A.,Bae, J.H.,Brooun, A.,Fagan, P.,Lam, R.,Lin, B.,Zhang, J.,Zhan, X.,Wu, X.,Xie, N.,Chiang, G.,Shoemaker, R.,Vernier, J.M.
Structure-Based Design and Synthesis of Potent and Selective KRAS G12D Inhibitors.
Acs Med.Chem.Lett., 14:1351-1357, 2023

PubMed Abstract: KRAS G12D mutation has been found in approximately 45% of pancreatic ductal adenocarcinoma (PDAC) cases, making it an attractive therapeutic target. Through structure-based drug design, a series of potent and selective KRAS G12D inhibitors were designed. The lead compound, ERAS-5024, inhibited ERK1/2 phosphorylation and cell proliferation in three-dimensional Cell-Titer Glo assays in AsPC-1 PDAC cells with single-digit nanomolar potency and caused tumor regression in the in vivo efficacy studies. We describe here the details of the design and synthesis program that led to the discovery of ERAS-5024.

PubMed: 37849557
DOI: 10.1021/acsmedchemlett.3c00245

実験手法

X-RAY DIFFRACTION (1.35 Å)