Mukd-546 May 2026

Mukd‑546 (chemical name: ) is a novel heterocyclic scaffold derived from a structure‑based design campaign targeting the allosteric pocket of MEK1. Preliminary SAR (structure‑activity relationship) studies indicated that the sulfonyl‑pyrimidine core confers high affinity while the 4‑fluorophenyl substituent enhances metabolic stability.

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

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. Mukd‑546 (chemical name: ) is a novel heterocyclic