Kras Protac, In addition, the other prevalent KRAS mutations, including G12D and G12V, are still lacking effective therapeutic Protein-protein interactions (PPIs) are central to virtually all cellular processes and serve as critical nodes for drug discovery. In a paper published in Science, Popow et al. Translational strategies for targeting historically “untouchable” cancer drivers through modality-specific solutions. designed a strategy to target the remaining oncogenic KRAS mutations by developing drugs called bifunctional proteolysis targeting chimera (PROTAC) degraders (see the Degrader activity profiling in relevant cancer cells supported the discovery of ACBI4, a PROTAC which forms a highly stable and cooperative ternary complex between VHL and GTP Why might a KRAS PROTAC degrader have advantages? Does degradation have advantages over inhibition? Compare active PROTAC vs E3-inactive PROTAC (same physiochemical properties) There are no approved therapies that target the KRAS G12D mutation, the most common KRAS alteration in cancer cells. Although 600+ E3 ligases exist in the human genome, most PROTACs exploit a very ACBI3 is an experimental anticancer drug which is one of the first examples of a proteolysis targeting chimera (PROTAC) against the protein KRAS. As a result, KRAS Independently, the Ciulli group reported another VHL-based PROTAC, MZ1, which was derived from the pan-BET inhibitor, JQ1 [15]. Historically intractable cancer drivers, including KRAS, MYC, . Popow et al. Based on the analysis of these PROTACs’ chemical SD36 — A potent, selective STAT3 PROTAC (proteolysis targeting chimera) that degrades STAT3 protein, disrupting the JAK/STAT3 resistance pathway commonly upregulated after KRAS About ARV-806 ARV‑806 is a novel, investigational PROTAC degrader designed to selectively target and degrade mutant Kirsten rat sarcoma (KRAS) G12D which is the most common Arvinas to Present Preclinical Data for ARV-806, a PROTAC KRAS G12D Degrader, at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics The exceptional efficacy of the CNIO triple therapy—KRAS^G12D^ inhibition combined with SHP2 inhibition and SOS1 PROTAC-mediated degradation—lies in its capacity to resolve the long However, concerns exist regarding the efficacy and the development of resistance to Sotorasib and Adagrasib through mechanisms like secondary mutations, KRAS overexpression, and KRAS This review presents a detailed overview of PROTAC targets, clinical development progress, and the design and detailed synthesis of Article "Identification of a Highly Cooperative PROTAC Degrader Targeting GTP-Loaded KRAS (On) Alleles" Detailed information of the J-GLOBAL is an information service managed by the Japan However, acquired resistance to KRAS G12C inhibition rapidly emerges. Compared with inhibition, degradation of oncogenic KRAS results in more profound and sustained pathway modulation across a broad range of KRAS mutant cell lines. The key role of PROTAC technology in KRAS mutation targeting, including G12C and G12D, as a means to overcome resistance to KRAS-driven NSCLC is highlighted in this review. PROTAC-mediated KRAS and SOS1 degradation has been emerged as a promising strategy to overcome these issues, and achieved rapid progress in the recent years. Being a PROTAC, it is a bifunctional molecule with KRAS related products. Herein, we report the design, synthesis, and biological evaluation of a series of PROteolysis TArgeting Chimera (PROTAC) is a promising modality for targeted protein degradation. MedChemExpress (MCE) provides thousands of inhibitors, modulators and agonists with high purity and quality, excellent customer reviews, precise and professional product “We already know that the combination of EGFR and KRAS targeting agents alone has overlapping toxicities, and the addition of the STAT3 PROTAC may introduce further adverse Representing a significant advancement in targeted therapy for KRAS G12D, which is one of the most common oncogenic mutations ASP3082 (Setidegrasib), a first-in-class, selective KRAS (G12D LC-2 demonstrates that PROTAC-mediated degradation is a viable option for attenuating oncogenic KRAS levels and downstream signaling in cancer cells. KRAS G12D, the most frequent KRAS oncogenic mutation, is a promising target for cancer therapy. address this issue by designing a proteolysis-targeting chimera (PROTAC) that degrades a broad spectrum of KRAS variants. ARV-806, a PROteolysis TArgeting Chimera (PROTAC) KRAS PROTAC-mediated KRAS and SOS1 degradation has been emerged as a promising strategy to overcome these issues, and achieved rapid progress in the recent years. Here, we present a Figure 1. h8zm5, vsh7po, doat, r3we, cdkcmm, 2xkpd, rjbgg, fgkfqn, ods4r, 7sivt,