ras-raf

Kobe0065 是一种新型 Ras-Raf 相互作用抑制剂，可完全抑制 H-Ras·GTP 与 c-Raf-1 RBD 的结合，Ki 值为 46±13 μM。

RAS RAS-RAF-IN-1 is a potent RAS and RAS-RAF inhibitor. RAS RAS-RAF-IN-1 has a KD of 5.0 μμ-15 μμ for cyclophilin A (CYPA) binding affinity. RAS RAS-RAF-IN-1 has antitumor activity[1]. RAS RAS-RAF-IN-1 (compound 89; for 4 hours) has an EC50 of 0.5 μμ-5.0 μμ for BRAF-GTP-KRAS-G12C disruption and has an IC50 of 1.0 μμ-10 μμ for pERK inhibition in H358 cells[1]. [1]. Meizhong Jin, et al. Compounds that participate in cooperative binding and uses thereof. WO2020132597A1.

Sulindac sulfide (cis-Sulindac sulfide) 是一种非甾体抗炎化合物，对COX-1具有很高的亲和力，是Ras 激活Raf-1的抑制剂。Sulindac sulfide 是 γ-secretase 的一个非竞争性抑制剂， IC50 为 20.2 μM。它是舒林酸的活性代谢物。

INU-152 is a pan-RAF inhibitor. INU-152 has potent anti-tumor activity in preclinical models of BRAFV600E mutant cancer. INU-152 inhibits all RAF isoforms and inhibits MAPK pathways in mutant BRAF cells. INU-152 exhibits minimal paradoxical pathway activa

Balamapimod is a reversible inhibitor of Ras Raf MEK. It also has a potential anti-tumor activity.

Kobe2602 是 Ras-Raf 相互作用抑制剂，具有抗癌化疗活性。它抑制 H-Ras·GTP 与 c-Raf-1 RBD 结合的Ki 值为 149 μM。

I194496，一种有效的cystathionine γ-lyase (CSE)抑制剂，其IC50值达到0.79 mM。该化合物不仅能通过双重靶点PI3K Akt和Ras Raf ERK通路抑制人类TNBC细胞的生长，还可以通过下调Anxa2 STAT3和VEGF FAK Paxillin信号通路，进一步抑制人类TNBC细胞的转移。

Cobimetinib racemate (Cobimetinib (racemate)) 是 Cobimetinib 的外消旋体，是一种选择性 MEK 抑制剂。

Kobe2601 is a Kobe0065 and Kobe02602 water-soluble analog. It displays inhibitory activity towards Ras-Raf binding.

MCP110 是 Ras 与 Raf-1 相互作用的抑制剂，可用于治疗人类肿瘤的研究。

DPQZ is an anti-tubulin compound acting by inducing cell apoptosis in human oral cancer cells through Ras/Raf inhibition and MAP kinases activation.

REDX05358 is a highly selective and potent pan RAF inhibitor with a potential therapeutic for BRAF and RAS mutant tumors. REDX05358 has improved therapeutic potential and predicted safety profile. REDX05358 demonstrates subnanomolar binding affinity for B

The Survival of Motor Neurons (SMN) protein participates in RNA splicing. Decreases in SMN, typically a consequence of defects in the smn1 gene, result in the death of motor neurons and lead to the neurodegenerative disease, spinal muscular atrophy (SMA). Cuspin-1 is a small molecule upregulator of SMN that has been shown in vitro to increase levels of SMN in SMA patient fibroblasts by 50% at 18 μM. Its mechanism of action is thought to involve increased phosphorylation of ERK to initiate Ras-Raf-MEK signaling, which results in an increased rate of SMN translation.

Pan-RAF kinase inhibitor 1 是 Pan-RAF 激酶对有效抑制剂， 能够抑制 RAF 激酶，调节 MAPK 信号传导，进而影响 RAS 突变肿瘤细胞的增殖。 Pan-RAF kinase inhibitor 1 对研究癌症疾病表现出研究潜力。

Antitumor agent-60 是有效的抗肿瘤药物，靶向RAS-RAF 信号通路，可与CRAF 结合 (Kd: 721.3 nM)。Antitumor agent-60 能增加癌细胞中p53和ROS 水平，使细胞核呈椭圆形和不规则形态。Antitumor agent-60 够将细胞的细胞周期阻滞在 G2 M 期，并诱导细胞凋亡 (apoptosis)。在 A549 肿瘤移植模型中，Antitumor agent-60 具有一定的抑制肿瘤生长能力。

SHR902275 是选择性的、有效的、口服具有活力的 RAF 抑制剂，能够靶向 RAS 突变癌症。 SHR902275 能够作用于 cRAF (IC50: 1.6 nM)、bRAFwt (IC50: 10 nM)、bRAFV600E (IC50: 5.7 nM)。SHR902275 具有细胞生长抑制效果，能够作用于 H358 细胞 (GI50: 1.5 nM)、A375 细胞 (GI50: 0.17 nM)、Calu6 细胞 (GI50: 0.4 nM) 和 SK-MEL2 细胞 (GI50: 0.32 nM)。

APS-2-79 hydrochloride (APS-2-79 HCl) 是一种 KSR 依赖性的MEK 拮抗剂，可与 ATPbiotin 竞争性地结合到 KSR2-MEK1 复合物内的KSR2。它与 KSR 结合可将 KSR 处于非活性状态，使其无法再结合 RAF 和激活 MEK，从而阻断 Ras-MAPK 信号通路。

PLX7904 (PB04) 是一种有效且选择性的悖论破坏剂 RAF 抑制剂，可抑制突变 BRAF 黑色素瘤细胞中 ERK1 2 的激活。在表达突变体 RAS 的细胞中，对 BRAFV600E 的IC50值约为 5 nM。

APS-2-79 是一种 KSR 依赖性的MEK 拮抗剂。APS-2-79 与 ATPbiotin 竞争性地结合到 KSR2-MEK1 复合物内的KSR2，IC50为 120 nM。APS-2-79 与 KSR 结合可将 KSR 固定在一个非活性的状态，使其无法再结合RAF 和激活MEK，从而阻断了 Ras-MAPK 信号通路。

Deltarasin is a high affinity PDEδ-KRAS interaction inhibitor. Deltarasin can inhibit KRAS-PDEδ interactions by binding to a hydrophobic pocket on PDEδ, resulting in the impairment of cell growth, KRAS activity, and RAS RAF signaling in human pancreatic ductal adenocarcinoma cell lines. The anti-cancer cell activity of deltarasin can be enhanced by simultaneously blocking tumor protective autophagy

Pimasertib HCl is an orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1 2) with potential antineoplastic activity. Pimasertib selectively binds to and inhibits the activity of MEK1 2, preventing the activation of MEK1 2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1 2 (MAP2K1 K2) are dual-specificity threonine tyrosine kinases that play key roles in the activation of the RAS RAF MEK ERK pathway and are often upregulated in a variety of tumor cell types.

Norartocarpetin 是一种酪氨酸酶抑制剂。Norartocarpetin 具有较强的酪氨酸酶抑制活性，其抑制活性 IC50值为 0.47 μM。Norartocarpetin 作为一种抗褐变剂可用于食品体系的研究。Norartocarpetin 对肺癌细胞 (NCI-H460) 也具有显著的抗癌活性，其 IC50值为 22 μM。Norartocarpetin 的抗增殖作用是通过靶向 Ras Raf MAPK 信号通路、线粒体介导的细胞凋亡、S 期细胞周期阻滞和抑制细胞迁移和侵袭实现的。

Cyclorasin 9A5为含11个残基的细胞渗透性环状肽，并可抑制Ras-Raf之间的蛋白质相互作用，已测得的IC50为120 nM。

Pan-RAS-IN-2（compound 6A）是一种专门针对RAS分子的靶向胶体(molecular glues)。该化合物能够有效抑制带有RAS突变的细胞系中的细胞增殖。通过与CYPA和RAS(ON)蛋白联合形成三元复合物，Pan-RAS-IN-2阻断了RAS到RAF的信号传递路径，从而发挥其抗肿瘤效果。