| Bioactivity | TH-Z827 is a mutant selective KRAS(G12D) inhibitor with an IC50 of 2.4 μM. TH-Z827 does not bind KRAS(WT) or KRAS(G12C). TH-Z827 blocked the KRAS(G12D)-CRAF interaction with an IC50 value of 42 μM[1]. |
| Invitro | 在带有 KRAS G12D 突变的两种胰腺癌细胞系（PANC-1 和 Panc 04.03）中，TH-Z827 具有抗增殖作用，IC50 值分别为 4.4 和 4.7 μM。TH-Z827 处理还可降低 PANC-1 和 Panc 04.03 细胞中 pERK 和 pAKT 的水平，证实 TH-Z827 可以阻止 MAPK 和 PI3K/mTOR 信号传导的激活[1]。 |
| In Vivo | BALB/c 裸鼠皮下接种 Panc 04.03 细胞，C57BL/6 小鼠皮下接种 KPC 细胞。在裸鼠模型中，TH-Z827（10-30mg/kg）显着减少肿瘤体积，并且以剂量依赖性方式减少肿瘤体积。然而，腹腔内给药 30mg/kg TH-Z827 会导致观察到的体重减轻，再次表明潜在的脱靶效应[1]。 |
| Name | TH-Z827 |
| CAS | 2847881-81-4 |
| Formula | C30H38N6O |
| Molar Mass | 498.66 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. Zhongwei Mao, et al. KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge. Cell Discov. 2022 Jan 25;8(1):5. |