hrs-4642是由 恒瑞医药 自主研发的一种新型、长效、选择性kras g12d抑制剂，能够特异性结合krasg12d，发挥抗肿瘤作用。hrs-4642利用不同的渗透性和高渗透长滞留效应来被动地靶向肿瘤组织，可控且持续的释放药物。

相较于kras g12c， kras g12d 是人类癌症中最常见的kras突变，在胰腺导管腺癌(pdac)、结直肠癌(crc)和非小细胞肺癌(nsclc)中患病率最高。 本次AACR大会上也公布了 KRAS-G12D抑制剂 RMC-9805 的初步研究结果 。

3 days ago · KRAS G12D is commonly detected in pancreatic ductal adenocarcinoma, colorectal cancer, and lung adenocarcinoma [].Since the KRAS G12D mutant protein lacks an active residue close to the switch-II binding pocket, covalent inhibitors of the KRAS G12C mutation can no longer be applied in drug design [].It is more challenging to develop KRAS G12D inhibitors than to develop KRAS G12C inhibitors.

在kras的基因突变中，97%是第12号或者第13号氨基酸残基发生了突变。其中最主要的是g12d、g12v、g13d这三种突变。结构学研究表明，这些基因突变大多干扰kras水解gtp的能力。 kras基因的三种主要突变

Jun 28, 2024 · 细胞实验显示，HRS-4642特异性结合KRAS G12D的亲和力是结合KRAS G12C的21倍、野生型KRAS蛋白的17倍，充分体现了它良好的选择性；而在人源细胞系和 KRAS G12D 突变的胰腺癌、结直肠癌异种移植瘤小鼠模型，以及肺腺癌PDX模型中，HRS-4642也都展现出了符合预期的良好抑制效应，能够有效抑制细胞增殖和肿瘤生长。 基于临床前研究的出色表现， HRS-4642已经被推进到首个人体临床I期研究阶段，初步疗效数据作为重磅研究摘要（LBA）登上 …

Jul 30, 2024 · 作为全球首款进入临床阶段的kras g12d蛋白降解药物，asp3082注射液有望成为该领域的首创药物。这一突破性进展，不仅为携带kras g12d突变的实体瘤患者带来了新的治疗选择，也为医药科研领域提供了新的研究方向。

Jan 25, 2022 · KRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS (G12D) variant still lacks inhibitors. Herein, we designed a series of potent inhibitors that can...

Dec 7, 2024 · kras g12d是kras 12号密码子突变引入天冬氨酸，而不是半胱氨酸，直接表现为流行病学上的差异。 KRAS G12C是NSCLC患者中最常见的KRAS突变，而KRAS G12D是结直肠癌和胰腺癌中最常见的突变。

3 days ago · The development of Kirsten rat sarcoma viral oncogene homologue (KRAS) targeted therapies has been the focus of cancer treatment. The most common mutant subtypes of KRAS driver genes are G12C, G12V, and G12D, and are associated with poor prognosis. Up to now, inhibitors specifically targeting KRAS …

3 days ago · KRAS mutations occur frequently in pancreatic adenocarcinoma, with G12D, G12V, and G12R being the most frequent variants. Thus, knowledge gathered at molecular levels should help improve clinical designs in patients with KRAS G12X mutations. From our analysis of a large cohort of pancreatic adenocarcinomas, KRAS G12D tumors exhibited a distinct molecular profile compared with G12R tumors ...