TH-Z827

TH-Z827 (10 min) potently inhibits SOS-catalyzed nucleotide exchange of GDP-bound KRAS^G12D with an IC₅₀ of 3.1 μM, and displays nearly 10-fold selectivity for KRAS^G12D over KRAS^G12C[1].
TH-Z827 (800 μM) binds to both GDP-bound and GMPPNP-bound KRAS^G12D with similar affinities (K_d of 6.52 μM and 7.01 μM, respectively), and does not bind to KRAS^WT or KRAS^G12C[1].
TH-Z827 blocks the KRAS^G12D-CRAF interaction with an IC₅₀ of 42 μM, without affecting interactions involving KRAS(WT) or KRAS^G12C[1].
TH-Z827 potently inhibits SOS-catalyzed GDP/GDP exchange of purified GDP-bound KRAS^G12D protein with an IC₅₀ of 3.1 μM^[2].
TH-Z827 exhibits selective binding and inhibition for purified KRAS^G12D protein over KRAS WT and KRAS^G12C proteins, with no measurable binding to the latter two variants^[2].
TH-Z827 (24 h) inhibits proliferation of KRAS^G12D-mutant PANC-1 and Panc 04.03 pancreatic cancer cells with IC₅₀ values of 4.4 μM and 4.7 μM, respectively^[1].
TH-Z827 (1-20 μM; 3 h) inhibits MAPK and PI3K/mTOR signaling in KRAS^G12D-mutant PANC-1 and Panc 04.03 pancreatic cancer cells by reducing pERK and pAKT levels following 3 h of treatment^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.