ALRN-6924

Oncology

Also known as: Sulanemadlin

Stapled PeptidesResearch phase: Phase 2Regulatory: Not approved. Investigational for multiple cancer indications.

Mechanism

ALRN-6924 is a stapled alpha-helical peptide that reactivates the p53 tumor suppressor by blocking its inhibitors MDM2 and MDMX. It is being tested in cancers that retain wild-type p53.

Technical detail

ALRN-6924 (sulanemadlin) is a cell-permeable stapled alpha-helical peptide that disrupts the p53-MDM2 and p53-MDMX protein-protein interactions, reactivating wild-type p53 tumor suppressor function. The hydrocarbon staple increases helicity, protease resistance, and cell permeability. In Phase 2 trials for p53 wild-type solid tumors and hematologic malignancies. Also investigated as a myelopreservation agent during chemotherapy (protecting normal cells via p53-dependent cell cycle arrest).

Evidence

Phase 1 Trial of ALRN-6924, a Dual Inhibitor of MDMX and MDM2, in Patients with Solid Tumors and Lymphomas Bearing Wild-type TP53.
Saleh et al. (2021) — Clin Cancer Res — PMID: 34301750
First-in-human phase 1 trial in 71 patients with TP53-wild-type solid tumors or lymphomas found dose-dependent pharmacokinetics, biomarker evidence of p53 activation, disease control/objective responses in some patients, and limited myelosuppression, supporting ALRN-6924 as a clinically active but still early-stage oncology peptide.
emerging

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