US 12285412 B1Patent grantUnited States

GPX4-Targeted Ferroptosis Research Compounds

Official patent title

Organoselenium benzimidazole compounds for treating cancer

Arabic title: مركبات بنزيميدازول من السيلينيوم العضوي لعلاج السرطان

Invention

Problem

Cancer drug discovery needs additional chemical candidates that address resistance and adverse effects, but selenium-containing molecules require careful efficacy and toxicity evaluation.

Why it matters

Compounds designed to interact with GPX4 and investigate ferroptosis could expand mechanism-focused preclinical research without implying established therapeutic benefit.

Approach

The patent discloses substituted organoselenium benzimidazoles of Formula I, methods for synthesizing them, pharmaceutical compositions, and treatment claims based on GPX4 inhibition and ferroptosis.

Who may benefit

Potential beneficiaries include oncology discovery teams, medicinal chemists, ferroptosis researchers, pharmaceutical formulation groups, and technology-transfer partners evaluating early compounds.

Potential value

The package combines a defined organoselenium-benzimidazole scaffold, seven structural embodiments, a synthesis route, claimed GPX4 binding values, cancer indications, and formulation options.

Background

Toxicity, resistance, and treatment burden remain challenges in oncology. Organoselenium compounds are investigated because selenium participates in redox biology, including glutathione peroxidase enzymes, but their behavior can depend strongly on structure and dose. GPX4 is associated with control of lipid peroxidation, and its inhibition can trigger ferroptosis, an iron-dependent form of cell death. The patent proposes substituted benzimidazole diselenides that are claimed to bind GPX4. The assigned evidence provides chemical and mechanistic claims but does not establish cellular selectivity, animal efficacy, or clinical safety.

Technology overview

Formula I uses R groups selected from C1–C6 alkyl, unsubstituted benzyl, para-halo-substituted benzyl, or allyl, with Formulae II–VII as specified compounds. Synthesis reacts o-phenylenediamine with 4,4′-diselanediyldibenzoic acid in acetic and polyphosphoric acids at 160–200 °C, then functionalizes the product with a selected halide, NaBH4, and an alkali-metal hydroxide. Claims cover multiple cancers, GPX4 binding of −5.50 to −4.25 kcal/mol, GPX4 inhibition, ferroptosis, pharmaceutically acceptable carriers, and several administration formats.

Potential applications

Potential use in preclinical screens for GPX4 inhibition and ferroptosis.
Potential use in medicinal-chemistry optimization of organoselenium benzimidazoles.
Potential use as research compounds across the cancer models named in the patent.
Potential use in early pharmaceutical formulation studies.

Evidence-supported advantages

Defines a compact scaffold with several R-group and Formula II–VII variants.
Provides a specified high-temperature synthesis and later N-functionalization route.
Links the claimed compounds to a named target, GPX4, and ferroptosis mechanism.
Includes pharmaceutical compositions and multiple administration formats.

Development stage

Patent publication describing compound synthesis and claimed GPX4 binding; biological efficacy, animal safety, clinical validation, and commercialization were not established.

Commercial opportunity

The compound series may support licensing or sponsored discovery work in ferroptosis-focused oncology. Advancement requires full structural and analytical confirmation, synthesis yields, direct GPX4 biochemical assays, cellular target engagement, normal-cell selectivity, selenium toxicology, pharmacokinetics, formulation, animal efficacy, clinical studies, manufacturing controls, and regulatory review.

Patent classifications

WIPO IPC

A61K31/4184Preparations for medical, dental or toiletry purposes
C07D235/18Heterocyclic compounds

CPC

A61K31/4184Preparations for medical, dental or toiletry purposes
C07D235/18Heterocyclic compounds
C07D293/12Heterocyclic compounds

Inventors

First inventorTarek Ahmed Yousef
InventorSaad Shaaban
InventorAhmed A. Al-Karmalawy

Keywords

organoselenium
benzimidazole
GPX4
ferroptosis
cancer
diselenide
medicinal chemistry
Formula I

Patent document and drawings

The patent publication is mapped to this record. Patent drawings remain within that publication; no separately cleared public media package has been supplied.