ArticleCommunications chemistry2025
Discovery of KRAS(G12D) selective degrader ASP3082.
Article in Communications chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Ferroptosis as a Translational Axis in Small Cell Lung Cancer: A Systematic Review of Redox Pathways and Precision Oncology Prospects.Oncology research · 2026Pooled it
- Pancreatic Cancer KRAS Breakthrough: Drug Graveyard No More.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Review
- Thermal Stability, Plasma Pharmacokinetics, and Tumor Response Modeling of a Cell-Penetrating Protein That Cleaves RAS Family GTPases.ACS pharmacology & translational science · 2026Article
- Discovery of Highly Efficacious CRBN-Based KRAS Degraders Targeting Cancers with KRAS G12D and G12V Mutations.Journal of medicinal chemistry · 2026Article
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- AI-Driven Multi-Omics Integration of Synthetic Colon Adenocarcinoma for Cluster-Guided PROTAC Candidate Design Targeting KRASG12D.International journal of molecular sciences · 2026Article
- KRAS-Targeted Therapies in NSCLC: Resistance, Combination Strategies, and Emerging Clinical Paradigms.Medical oncology (Northwood, London, England) · 2026Review
- Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants.Nature chemical biology · 2026Article
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Targeted therapeutic strategies forTranslational lung cancer research · 2026Review
- Targeted Therapy in Pancreatic Ductal Adenocarcinoma: Current Advances and Challenges.Current oncology (Toronto, Ont.) · 2026Review
- Evolution of KRAS molecular glues: from allele-selective to Pan-RAS and protein-protein interaction modulators.Acta pharmacologica Sinica · 2026Review
- Precision Therapeutics in Pancreatic Cancer: Emerging Targeted, Immune, and Antibody-Drug Conjugate Strategies Exemplified by Adagrasib, Dostarlimab, and Trastuzumab Deruxtecan.Journal of clinical medicine · 2026Review
- Structural and Energetic Determinants of Monobody Recognition of Oncogenic KRAS Variants.bioRxiv : the preprint server for biology · 2026Article
- Targeted protein degradation: bridging chemical biology and clinical translation.Acta pharmacologica Sinica · 2026Review
- Benchmarking docking and ML re-scoring screening performance for KRAS G12D in pancreatic cancer.Molecular diversity · 2026Article
- Research Trends and Emerging Frontiers in Proteolysis Targeting Chimeras (PROTACs): A Bibliometric Analysis of 2630 Publications (2001-2025).Pharmaceuticals (Basel, Switzerland) · 2026Article
- RAS Inhibitors: Changing the Paradigm from the Undruggable.Pharmaceutics · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in multiple cancers. Multiple types of KRAS mutation are observed in various patients with cancer, and the KRAS(G12D) mutation is the most common. Although multiple covalent inhibitors of the KRAS(G12C) mutation have been identified and clinically validated to date, no drugs have been approved yet for other mutations, including G12D. Herein, we report the discovery and characterization of ASP3082, a KRAS(G12D)-selective degrader, and the crystal structure of the drug-induced ternary complex of KRAS(G12D)/ASP3082/VHL (von Hippel-Lindau). We have also demonstrated an efficient structure-based rational optimization approach, which could be applicable for the optimization of other bifunctional proximity-inducing drugs. ASP3082 effectively induces KRAS(G12D) protein degradation with remarkable selectivity, demonstrates highly efficacious and durable pharmacological activity, and induces tumor regression in multiple KRAS(G12D)-mutated cancer xenograft models. Our results suggest that ASP3082 is a potential therapeutic agent for KRAS(G12D)-mutated cancer, and is now under clinical investigation.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.