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Accuronix

Developing novel cancer therapies

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Our Approach

Company Overview

Accuronix Therapeutics is a leader in discovering and developing a new class of drugs that work by selectively targeting the σ-2 (sigma-2) receptor on cancer cells to deliver cytotoxic payloads. The Accuronix team has established an innovative platform and a lead drug candidate based on advances in characterizing the molecular-targeted drug conjugate (MTDC) approach to cancer therapy.  The σ-2 receptors are highly expressed on the surface of rapidly proliferating cancer cells. They internalize upon ligand binding, allowing the delivery of therapeutic agents to intracellular targets. The result is a chemotherapeutic with increased effectiveness and reduction in toxicity risk.

In January 2016, Accuronix licensed our σ-2-based technology from Washington University in St. Louis and assembled a team of experienced biotech scientists and executives, the technology originators, and key executional partners. Accuronix’s σ-2 platform enables the discovery of selective molecularly targeted drug conjugates for a variety of therapeutic cargoes to treat a range of cancers.  We are working to advance the development of the lead candidate, ACXT-3102 for pancreatic adenocarcinoma and other rare tumor types; and to progress next-generation MTDCs into development for other oncology indications.

 

σ-2 Molecularly Targeted Drug Conjugates Overview

 

Deliveryσ-2 molecularly targeted drug conjugates Science
Accuronix is pioneering pharmaceutical development of selective delivery of small molecule cargos into cancer cells based on the σ-2 ligand/receptor system. σ-2 receptors are overexpressed in most human cancers, including pancreatic, and select σ-2 ligands can deliver drug cargoes as chemical conjugates into cancer cells.

Our founders demonstrated that the σ-2 platform has been able to convert an underperforming chemotherapeutic into a potent anti-tumor therapy. σ-2 ligands have been conjugated with a number of therapeutic warheads.

σ-2 receptor probes have also been linked to radioisotopes and fluorescent markers to image solid tumors with PET/CT. These σ-2 ligands localize to pancreatic cancer tumors in animal models and to breast and head & neck cancer in patients. In addition to their high selectivity for the σ-2 receptor in cancer cells, a key feature of σ-2 ligands is rapid cellular uptake and internalization.

ACXT-3102

The MDTC ACXT-3102 links a σ-2 ligand to des-methyl-erastin.

σ-2 receptors are highly expressed on the surface of rapidly proliferating cancer cells, but not healthy ones. The ligand bound receptors rapidly internalize. σ-2 receptors also have subcellular localization in mitochondria, endoplasmic reticulum and plasma membranes, providing potential additional targeted sites of drug action.

Ferroptosis
Ferroptosis: Death by Lipid Peroxidation
Yang, Wan Seok et al.
Trends in Cell Biology, Volume 26, Issue 3, 165-176

Erastin induces tumor cell death by inhibiting cystine uptake via the cystine/glutamate antiporter (system xc-) on plasma membranes. Cell death occurs via ferroptosis, a non-apoptotic, iron-dependent, oxidative cell death.

In its native form, erastin has poor cellular uptake, but when des-methyl-erastin is conjugated to σ-2 ligands, cell death has been demonstrated in multiple tumor lines. In addition, the MTDC ACXT-3102 has been shown to cause tumor stabilization or regression as well as significantly increased survival in several murine pancreatic tumor models.

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About Us

We are applying a novel drug-targeting technology to some of the most difficult problems in cancer therapy.

News & Publications
Financial Conflicts of Interest (FCOI)

Mission

With an initial focus in pancreatic cancer, the Company’s mission is to develop novel oncology therapies based on technology that selectively targets σ-2 receptors overexpressed on cancer cells

Partners

Washington University | University of Pennsylvania | BioGenerator

Contact Us

Accuronix Therapeutics
4340 Duncan Ave.
Suite 210
St. Louis, MO 63110

Contact
Bradley T. Keller, Ph.D.
President and CEO
[email protected]

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