| 名称 | Setidegrasib |
| 描述 | Setidegrasib is a PROTAC-mediated KRAS degrader (DC50: 37 nM). Setidegrasib induces the formation of a ternary complex between KRAS G12D and the VHL E3 ubiquitin ligase, thereby facilitating the ubiquitination and proteasomal degradation of the oncogenic protein. Setidegrasib inhibits the levels of p-ERK, p-AKT, and p-S6 in AsPC-1 cells. Setidegrasib demonstrates antitumor activity in various mouse xenograft models of cancer. Setidegrasib can be used to study solid tumors with KRAS(G12D) mutations. |
| 体外活性 | 方法：多种KRAS(G12D)突变癌细胞（AsPC-1, PK-59, HPAC, GP2d, GP5d等）与 KRAS WT 细胞（A375、HT-29、BxPC-3、COLO-320）加入Setidegrasib (0.1 nM – 10 μM)处理6天，CellTiter-Glo 2.0实验检测ATP。
结果：Setidegrasib 强效抑制多种 KRAS(G12D) 突变癌细胞系的增殖，而对 KRAS(WT) 细胞 (A375, HT-29) 及其他 KRAS 突变体 (G12V, G12C, G13D) 的活性较弱 (IC50 > 10 μM)。[1] |
| 体内活性 | 方法：为研究Setidegrasib 抗肿瘤活性，构建LXFA 1125肺癌PDX模型（裸鼠），静脉注射Setidegrasib (10、30 mg/kg )，每周2次，持续21天。
结果：Setidegrasib 剂量依赖性抑制肿瘤生长；IHC显示KRAS(G12D)表达降低。[1] |
| 存储条件 | Keep away from direct sunlight,
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 80.00 mg/mL (71.60 mM), Sonication is recommended.
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| 相关产品 | N-Acetylneuraminic acid | NMac1 | Zoldonrasib | BI-2493 | Daraxonrasib | Sotorasib | Adagrasib | Vepdegestrant | (R)-Naproxen | MRTX1133 | AMG410 | Ketoconazole |
