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Discovery of SMD-6346: A Potent, Selective, and Orally Active SMARCA2 Degrader for Targeting SMARCA4-Deficient Human Cancers - PubMed

3 hours ago
  • #PROTAC
  • #Cancer Therapy
  • #SMARCA2 Degrader
  • Discovery of SMD-6346, a potent, selective, and orally active SMARCA2 degrader for SMARCA4-deficient cancers.
  • SMD-6346 shows high potency against SMARCA2 (DC50 = 3.3 nM) with minimal activity against SMARCA4, effectively inhibiting growth in SMARCA4-deficient cell lines.
  • Exhibits excellent pharmacokinetics, 61% oral bioavailability in mice, and robust tumor growth inhibition in SMARCA4-deficient xenograft models.