Mukd‑546: Pre‑clinical Evaluation of a Novel Small‑Molecule Inhibitor of the MAPK/ERK Pathway for Targeted Cancer Therapy
Mukd‑546 exhibits potent, selective MEK inhibition, favorable pharmacokinetics, and robust antitumor activity in pre‑clinical models. These data support further development of Mukd‑546 as a candidate for clinical evaluation in MAPK‑driven malignancies. mukd-546
¹ Department of Pharmacology, University of Cambridge, UK ² Institute of Molecular Medicine, Shanghai Jiao Tong University, China ³ Center for Cancer Research, Universidad Nacional Autónoma de México, Mexico ⁴ Department of Chemistry, University of California, San Diego, USA ⁵ Division of Oncology, Seoul National University Hospital, South Korea selective MEK inhibition
A multi‑stage pre‑clinical program was conducted: (i) in‑silico docking and molecular dynamics to predict binding affinity; (ii) biochemical kinase assays to assess selectivity; (iii) cellular viability, apoptosis, and cell‑cycle analyses in a panel of 12 cancer cell lines; (iv) pharmacokinetic (PK) profiling in Sprague‑Dawley rats; (v) efficacy and safety evaluation in xenograft mouse models of KRAS‑mutant pancreatic ductal adenocarcinoma (PDAC) and BRAF‑mutant melanoma. University of Cambridge