ArticleMolecular cancer therapeutics2026
Delivery of ATSP-7041 by Minimally Invasive Nasal Depot (MIND) to Target Diffuse Intrinsic Pontine Glioma.
Article in Molecular cancer therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor with limited therapeutic progress due to its infiltrative brainstem location, blood-brain barrier (BBB), and resistance to systemic agents. We present a novel strategy for targeted central nervous system (CNS) delivery of ATSP-7041, a stapled peptide dual inhibitor of human double minute 2 (HDM2) and X (HDMX), using the minimally invasive nasal depot (MIND) technique. In p53-wild-type, PPM1D-mutant DIPG neurospheres (BT869), ATSP-7041 exhibited ∼125-fold greater antitumor activity than the HDM2-selective antagonist RG7388, consistent with elevated HDMX expression. MIND delivery in mice achieved sustained ATSP-7041 distribution across brain regions, including the pons, with peak levels at 72 hours and persistence for up to 14 days. In a patient-derived orthotopic xenograft model of DIPG, a single MIND-administered ATSP-7041 depot reduced tumor burden and prolonged survival compared with controls. This feasibility study provides proof of concept for on-target p53 reactivation in DIPG using a BBB-penetrant dual HDM2/HDMX inhibitor delivered by the MIND platform. The findings support a translational path for ALRN-6924, the clinical analogue of ATSP-7041, in DIPG and potentially other brain tumors that retain wild-type p53 but remain incurable because of drug resistance and restricted CNS access.
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