ADT-1004

ADT-1004 is an orally bioavailable, first-in-class small-molecule prodrug of ADT-007 that functions as a highly potent, selective pan‑RAS inhibitor being developed for pancreatic ductal adenocarcinoma and other RAS‑driven malignancies.[1][2][3][5][7][9][11] By targeting activated RAS and blocking downstream MAPK/ERK and AKT signaling, ADT-1004 shows single‑digit nanomolar growth inhibition in KRAS‑mutant PDAC cell lines, spares RAS wild‑type cells, and produces robust antitumor activity and tumor regression in murine and patient‑derived xenograft PDAC models harboring diverse KRAS mutations (including G12D, G12V, G12C, and G13Q), with favorable tolerability at high oral doses.[1][2][3][5][7][9][10] Preclinical data demonstrate superior efficacy versus allele‑specific KRAS G12C inhibitors (sotorasib, adagrasib) and activity in models resistant to sotorasib, adagrasib, and MRTX1133, supporting further development of ADT‑1004 as a broad pan‑RAS therapy for KRAS‑mutant PDAC.[1][2][3][5][6][7][10][11]