gdp-bound

Sotorasib (AMG-510) 是一种 KRAS G12C 共价抑制剂，具有口服活性和选择性。Sotorasib 与 KRAS G12C 非活性构象的 GDP 状态结合，抑制 KRAS 及其下游信号的传导。Sotorasib 对 KRAS G12C 突变肿瘤具有抑制活性。

Adagrasib (MRTX849) 是一种 KRAS G12C 共价抑制剂，具有口服活性和选择性。Adagrasib 与 KRAS G12C 非活性构象的 GDP 状态结合，抑制 KRAS 及其下游信号的传导。Adagrasib 对 KRAS G12C 突变肿瘤具有抑制活性。

0990CL 是一种有效的异三聚体Gαi subunit 特异性抑制剂，可与纯化的Go±在gdp 结合状态下相互作用，能够阻断α2AR 介导的cAMP 调控。 在细胞模型中低浓度0990CL 能够部分恢复cAMP 水平，高浓度的0990CL (10 μM)下，开始对细胞活力产生负面影响。

ARS-853 是一种选择性共价KRAS G12C 抑制剂，IC50为 2.5 μM。它通过与 GDP 结合的癌蛋白结合并阻止激活来抑制突变 KRAS 驱动的信号传导。

KRA-533, a potent KRAS agonist, directly targets the GTP/GDP binding pocket within the KRAS protein, inhibiting GTP cleavage. This inhibition leads to the buildup of constitutively active GTP-bound KRAS, which subsequently activates both apoptotic and autophagic cell death pathways specifically in cancer cells.

Divarasib (GDC-6036) adipate is a selective and highly potent KRAS G12C inhibitor with an impressively low IC 50 value of <0.01 μM, designed for oral administration. It covalently attaches to the switch II (SW-II) pocket in KRAS G12C, irreversibly maintaining the protein in its inactive GDP-bound state [1] [2].

SOS1 activator 1 是一种 SOS1 介导的核苷酸交换的激活剂(Kd: 44 nM)。SOS1 是一种鸟嘌呤核苷酸交换因子，能与 Ras 蛋白结合，催化 GDP 与 RAS 上的 GTP 交换，使原来与 Ras 结合的 GDP 交换成 GTP。

Son of sevenless homolog 1 (Sos1) is a guanine nucleotide exchange factor (GEF) that directs the exchange of Ras-GDP to Ras-GTP by binding to SH3 domains of the growth factor receptor-bound protein 2 (Grb2), leading to the activation of ERK. Ras inhibitory peptide is a synthetic peptide that contains the sequence PVPPR, which corresponds to a region within human Sos1 that interacts with an SH3 domain of Grb2. It specifically blocks the interaction of the GEF with Grb2, preventing an interaction that is essential for Ras activation by receptor tyrosine kinases, including epidermal growth factor receptor.