Cell lines

lung cancer cell lines H23, H358 and H1792

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

72 h, 10 μM

Applications

K-Ras(G12C) inhibitor 12 is a highly effective Ras inhibitor and its EC50 value in H1792 cells is 0.32 μM.It selectively binds to an oncogenic mutant K-Ras(G12C) in a irreversible manner without affecting the activity of wild-type Ras. After treatment with K-Ras(G12C) inhibitor 12, K-Ras(G12C)-mutant cells exhibit decreased viability and increased apoptosis comparing to cells lacking this mutation.

K-Ras(G12C) inhibitor 12 is an allosteric inhibitor of K-Ras(G12C) [1].

K-Ras is a GTPase and plays an important role in many signal transduction pathways. The mutation of K-Ras occurs in many cancers.

K-Ras(G12C) inhibitor 12 is an allosteric inhibitor of K-Ras(G12C). K-Ras(G12C) exhibited a slight preference for GTP. However, K-Ras(G12C) inhibitor 12 significantly reduced the affinity for GTP and led to the modification of K-Ras(G12C). Also, K-Ras(G12C) inhibitor 12 inhibited SOS-catalysed nucleotide exchange. In H1792 and H358 K-Ras(G12C)-mutant lung cancer cell lines, K-Ras(G12C) inhibitor 12 reduced the association of C-Raf and B-Raf with Ras. In H1792, H358, H23 and Calu-1 cell lines containing G12C mutations, K-Ras(G12C) inhibitor 12 decreased viability and induced apoptosis. K-Ras(G12C) inhibitor 12 exhibited EC50 value of 0.32 μM in H1792 cells. Also, the H1792 cells exhibited low levels of K-Ras GTP, which was consistent with the preference of K-Ras(G12C) inhibitor 12 to K-Ras GDP [1].

Reference:
[1]. Ostrem JM1, Peters U, Sos ML, et al. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature, 2013, 503(7477): 548-551.