Research published in Journal of the American Chemical Society highlights potential of HIF Inhibition as a therapeutic approach for cancers

• Research led by Curve CSO Professor Ali Tavassoli’s laboratory at University of Southampton
• Landmark paper on dual HIF-1 and HIF-2 inhibitor that works by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1β

Southampton, UK, 26 March 2024 - Curve Therapeutics (“Curve” or the “Company”), a private biotechnology company pioneering a revolutionary intracellular screening platform addressing complex and challenging disease targets, today announces the publication of an article in the Journal of the American Chemical Society (JACS). The paper entitled ‘Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors (HIF) 1 and 2 That Disrupt Hypoxia-Related Signalling in Cancer Cells’ can be viewed here.[1] Curve’s Chief Scientific Officer, Professor Ali Tavassoli, co-authored the article and leads the academic group at the University of Southampton where the work was undertaken.

Professor Ali Tavassoli, Chief Scientific Officer of Curve Therapeutics, said: “It is well recognised that HIF plays a key role in the survival and growth of solid tumours. The compounds we report in this paper inhibit the protein-protein interaction of the two subunits that form the HIF transcription factor. We show that these compounds prevent the hypoxia-induced activity of this transcription factor, stopping hypoxia-response in cell-based assays. This paper underlines the promising therapeutic potential of dual HIF inhibition as an approach for the treatment of a variety of cancers.”

Curve Therapeutics is a leader in the discovery of innovative therapeutics to address disease targets which are difficult to target using conventional drug discovery methods. Through the utilisation of its world leading Microcyle discovery platform, Curve can screen directly inside mammalian cells, allowing for the identification of biologically active library members within an intracellular environment where both the library and the target are present in their native conformations. Curve is developing a non-peptidic, small-molecule dual inhibitor of HIF-1 and HIF-2 with first-in-class potential.

This is the first report of a dual HIF-1 and HIF-2 inhibitor which functions by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1β. The Microcycles discovered by Prof. Tavassoli were identified using his SICLOPPS screening platform and show good cellular activity. Patents and patent applications describing these HIF inhibitory Microcycles are exclusively licensed to Curve.

[1] Andrew T. Ball, Soran Mohammed, Cyrielle Doigneaux, Reece M. Gardner, James W. Easton, Steven Turner, Jonathan W. Essex, Garry Pairaudeau, Ali Tavassoli, Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors 1 and 2 That Disrupt Hypoxia-Response Signaling in Cancer Cells, Journal of the American Chemical Society (19 March 2024) DOI: 10.1021/jacs.3c10508