kras-2

BI-2493 是高度选择的泛 KRAS 抑制剂，是 BI-2865 的结构类似物。BI-2493 具有抗肿瘤活性，可抑制肿瘤细胞生长，可用于癌症疾病的研究。

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。

MRTX1133 是一种 KRAS G12D 抑制剂 (KD=0.2 pM)，具有强效性、选择性和非共价性。MRTX1133 对 KRAS G12D 突变的肿瘤具有抑制活性，而对 KRAS 野生型肿瘤无抑制活性。

Divarasib (GDC-6036) (GDC-6036)是一种正在研究的、口服的、高效力和选择性的 KRAS G12C 抑制剂，IC50 为 <0.01 μM。Divarasib 不可逆地将 KRAS G12C 癌蛋白锁定在非活性状态，抑制肿瘤细胞生长。它正在被研究用于实体肿瘤，包括非小细胞肺癌和结肠直肠癌及其他类型的癌症。

Rineterkib (ERK-IN-1) 是口服有效的RAF 和ERK1 2的抑制剂，与 KRAS-突变型非小细胞肺癌、BRAF-突变型非小细胞肺癌、KRAS-突变型胰腺癌、KRAS -突变型结肠癌和 KRAS-突变型卵巢癌尤为相关。

K-Ras G12C-IN-2 is a covalent kras g12c inhibitor.

KRas G12C inhibitor 2 is a compound that inhibits KRas G12C.

SMAP-2 is an orally bioavailable activator of phosphatase 2A (PP2A) which binds to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. It inhibits the growth of KRAS-mutant lung cancers .

K-Ras ligand-Linker Conjugate 2 is a chemical compound that includes a ligand for K-Ras and a PROTAC linker. This compound is capable of recruiting E3 ligases like VHL, CRBN, MDM2, and IAP. It is utilized in the synthesis of PROTAC K-Ras Degrader-1, which is a highly effective PROTAC K-Ras degrader with a degradation efficacy of ≥70% in SW1573 cells[1].

MEK RAF-IN-1 (Compound 16b) 作为一种针对MEK和RAF的抑制剂，其针对MEK1、BRAF和BRAFV600E的IC50值分别仅为28、3和3 nM。该化合物表现出明显的抗肿瘤效果，能够有效抑制体外MIA PaCa-2 (G12C KRAS)、HCT116 (G13D KRAS) 以及 C26 (G12D KRAS) 细胞的增殖，并在异种移植的结直肠癌小鼠模型中显著抑制肿瘤生长。

KRAS inhibitor-35（compound 72）作为一种效能显著的KRAS抑制剂，其IC50值仅为2 nM，常被应用于肿瘤方面的科学研究。

SOS1 EGFR-IN-2 (Compound 4) 作为SOS1与EGFR的双重抑制剂，展示了对这两种蛋白的高效抑制，其IC50值分别为8.3 nM和14.6 nM。此化合物对带有多种KRAS突变的癌细胞显示出强效的抗增殖能力。

KRAS G12D inhibitor 25 (Compound 148) 作为KRAS G12C及HSP90α的有效抑制剂，其IC50值分别小于0.1 μM与介于0.1-1 μM之间。此化合物还能抑制MIA PaCa-2与NCI-H358细胞的生长，相应的EC50值也分别是小于0.1 μM与介于0.1-1 μM之间。此外，KRAS G12D inhibitor 25 还能降解ERBB2，其DC50值为0.1-1 μM。

KRAS inhibitor-37（compound 2）是一种高效KRAS抑制剂，对于KRAS野生型以及其突变体KRAS G12D、KRAS G12C、KRAS G12V的KD值分别为0.004 nM、0.041 nM、0.019 nM和0.144 nM。此外，KRAS inhibitor-37能有效抑制细胞增殖，对H358、SW620、PANC08.13细胞系的IC50范围从<2 nM 至14 nM。因此，该化合物在癌症治疗领域展现出显著的应用潜力。

KRAS G12C inhibitor 69 (Compound K09) 是一种对突变RAS蛋白KRASG12C具备抑制作用的化合物，其IC50值为4.36 nM。它在细胞系NCI-H358和MIA-PACA-2中抑制ERK的磷酸化，IC50值分别为12 nM和7 nM。同时，KRAS G12C inhibitor 69 可以抑制癌细胞NCI-H358和MIA-PACA-2的增殖，其IC50值分别为3.15 nM和2.33 nM。

PROTAC K-Ras degrader-2 (compound 48) 是一种广谱KRAS突变体PROTAC降解剂，对KRAS G12V RAF1的IC50≤200 nM。该化合物可以降解SW620 KRAS G12D，DC50≤200 nM，并抑制SW620 3D细胞扩增，其IC50≤20 nM。

LYMTAC-2 是一种溶酶体靶向嵌合体 (LYMTAC)，用于借助 RNF152、LAPTM4a 和 LAPTM5 等溶酶体膜蛋白 (LMP) 降解膜相关蛋白。它通过与靶蛋白（如 KRASG12D）形成三元复合物，促进重新定位至溶酶体，从而导致依赖泛素的降解。这一化合物有助于研究膜蛋白的调控，并可用于制定策略以克服 KRAS 驱动的信号通路的抗性。

SCH772984 HCl 是一种特异性的 ERK1 2 抑制剂，具有 I 型和 II 型激酶抑制剂的特性，其 IC50 分别为 4 和 1 nM。 SCH772984 HCl 在 BRAF、NRAS 或 KRAS 突变的肿瘤细胞中具有纳摩尔级细胞效力，并诱导肿瘤消退。 SCH772984 HCl 可用于 MAPK 抑制剂难治性肿瘤的研究。

LC-2 (PROTAC KRASG12C Degrader-LC-2) 是一种新型基于von Hippel-Lindau的内源性 KRAS G12C 的 PROTAC 降解剂，DC50 在 0.25 和 0.76 μM 之间。LC-2 是一种与 MRTX849 共价结合 KRAS G12C 并招募 E3 连接酶 VH的 PROTAC，诱导 KRAS G12C 快速持续降解。LC-2 对纯合和杂合子 KRAS G12C 细胞系 MAPK 信号有抑制作用。

Rineterkib hydrochloride (compound B) is an orally active RAF and ERK1 2 inhibitor in the treatment of a proliferative disease characterized by activating mutations in the MAPK pathway. The activity is particularly related to the treatment of KRAS-mutant NSCLC, BRAF-mutant NSCLC, KRAS-mutant pancreatic cancer, KRAS-mutant colorectal cancer (CRC) and KRAS-mutant ovarian cancer[1]. ERK-IN-1 (compound B) (50, 75 mg kg, p.o., qd q2d, 27 days) treatment significantly reduces the tumor volume in the Calu-6 human NSCLC subcutaneous tumor xenograft model in mice[1]. [1]. CAPONIGRO, et al. THERAPEUTIC COMBINATIONS COMPRISING A RAF INHIBITOR AND A ERK INHIBITOR. WO2018051306A1.

NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12Dmouse orthotopic model of colorectal cancer. 1.Tan, L., Nomanbhoy, T., Gurbani, D., et al.Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2)J. Med. Chem.58(1)183-196(2015) 2.Pauls, E., Shpiro, N., Peggie, M., et al.Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cellsJ. Biol. Chem. 287(23)19216-19228(2012) 3.Ma, Q., Gu, L., Liao, S., et al.NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivoApoptosis24(1-2)83-94(2019)

MRTX1133 is a highly selective, first-in-class inhibitor of KRAS G12D. MRTX1133 targets the KRAS G12D protein in both active and inactive states. MRTX1133 selectively inhibits KRAS G12D mutant, but not KRAS wild-type, tumor cells[1][2]. MRTX1133 demonstrates dose-dependent inhibition of the KRAS pathway tumor regression in G12D mutant tumor models[2]. [1]. Xiaolun Wang, et al.Kras g12d inhibitors.WO2021041671A1.[2]. KRAS G12D Inhibitor: MRTX1133. [(accessed on 22 April 2021)];2021 Available online.

MRTX849 acid, a derivative of MRTX849, is employed in the synthesis of PROTAC LC-2. LC-2, a potent and pioneering PROTAC, exhibits the ability to efficiently degrade endogenous KRAS G12C with DC50 values ranging between 0.25 and 0.76 μM.

MRTX849 ethoxypropanoic acid is a compound that contains a ligand for KRAS G12C and a PROTAC linker. It is commonly employed in the synthesis of PROTAC LC-2, which is a highly effective and innovative PROTAC. LC-2 has been proven to degrade endogenous KRAS G12C with remarkable potency, exhibiting DC50 values ranging from 0.25 to 0.76 μM.