KRAS is one of the most frequently mutated oncogenes in human cancers. Once thought “undruggable,” recent scientific advances have enabled the development of therapies targeting KRAS mutations, especially G12C, G12D, and G13D.

At Medicilon, we provide integrated preclinical services to support KRAS-targeted drug discovery and development:
✅ Drug discovery
✅ CMC research (API + formulation)
✅ Pharmacodynamics study
✅ Pharmacokinetics (PK) analysis
✅ Safety evaluation

Understanding KRAS: https://pubmed.ncbi.nlm.nih.gov/31649840/

KRAS functions as a molecular switch, cycling between GDP-bound (inactive) and GTP-bound (active) states. Activation of KRAS promotes signaling pathways that drive cell proliferation, survival, and metastasis.

Advanced Structural Biology & Assays

🔹 Crystallization & Structural Studies:
We leverage synchrotron radiation facilities to resolve KRAS structures. Our team successfully crystallized KRAS^G12D alone and in complex with inhibitors like MRTX1133.

🔹 In Vitro Functional Assays: https://medicilon.com/drug-discovery/

2D/3D proliferation assays (CellTiter-Glo)
Cytotoxicity testing in KRAS-mutant lines (e.g., NCI-H358, MIA PaCa-2)
Protein-based assays: GTP exchange, SOS1 binding, nucleotide displacement

🔹 In Vivo Pharmacology: https://medicilon.com/pharmacodynamics/

- CDX/PDX models for KRAS mutations (G12C, G12D, G12V, G13D)
- Resistance models developed via in vivo selection

🔹 Pharmacokinetics Study: https://medicilon.com/adme-dmpk/
We conduct comprehensive pharmacokinetic (PK) studies to support candidate optimization. Example: Compound 17f (KRAS-PDEδ PROTAC degrader).
PK studies of Compound 17f were evaluated in SD rats. After ip administration dosing at 50 mg/kg, the concentrations of Compound 17f in plasma were analyzed. These assays were conducted by Medicilon.

T1/2: 5.1 h
Cmax: 564 ng/mL
AUC: 4710 h·ng/mL

Medicilon Assisted Projects: https://medicilon.com/resources/#corporate-news

✨ XNW14010 – KRAS^G12C inhibitor, entered clinical trials in 2022 with Medicilon’s PK & safety support.
✨ GFH925 / IBI351 (Dabote®) – Approved in 2024 for KRAS^G12C NSCLC. Medicilon provided early PK services.

With deep KRAS expertise and cutting-edge platforms, Medicilon accelerates the development of therapies for previously untamable KRAS mutations.

Learn More: https://www.linkedin.com/pulse/medicilon-kras-targeted-drugs-rd-service…