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
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.
📖 Reference: Acta Pharm Sin B. 2019 Sep;9(5):871-879
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 MRTX1133.2D/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
CDX/PDX models for KRAS mutations (G12C, G12D, G12V, G13D)
Resistance models developed via in vivo selection
Pharmacokinetics Study
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
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: Medicilon KRAS Research
Let’s Talk Today!
Email: [email protected]
Location:
Allia Future Business Centre Kings Hedges Road, Cambridge, CB4 2HY, UK
