| Microcycle® Screening | Functional Hit | Lead Optimisation |
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Dual HIF-1 and HIF-2 inhibitor
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Dual-inhibitor of HIF-1 and HIF-2 dimerization addresses survival mechanisms in solid tumors. Hypoxia Inducible Factor (HIF) is a transcriptional complex that allows cells to adapt to a lack of oxygen (hypoxia), for example, in the centre of solid tumors. The upregulation of both HIF-1 and HIF-2 in more than half of all solid tumors correlates with poor clinical outcomes.
Using a rational approach and structural data from its Microcycle hits, Curve has developed first-in-class, non-peptide, small molecules that inhibit both HIF-1 and HIF-2. Lead optimization is underway.
Curve’s dual HIF inhibitors are expected to show a significant clinical advantage in renal cell carcinoma and other solid tumors, compared to the HIF-2 selective inhibitors currently being explored clinically.
ATIC
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ATIC is a homodimer that catalyzes the final two stages of de novo purine biosynthesis in mammalian cells. In cancer cells that have lost the ability to salvage purines as a result of MTAP deletion, ATIC becomes the Achilles heel for therapeutic intervention.
Curve has identified inhibitors of ATIC homodimerization, using a unique non-folate-dependent mechanism that has the potential to treat a diverse range of tumors.
FOXA1
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FOXA1 is a pioneer factor and key determinant of the interactions between chromatin and the oestrogen receptor (ER). FOXA1 plays an essential role on the growth and invasiveness of ER-positive, endocrine resistant breast tumours. Despite significant interest in this target, no inhibitors have been identified to date.
Curve is deploying the key features of its Microcycle platform to identify first-in-class FOXA1 inhibitors for the treatment of hormone refractory breast cancer.
Immunology/Inflammation Target
Curve is working to identify antagonists of an undisclosed immunology/inflammation target.
Science
Our Microcycle® platform is reinventing drug discovery, enabling high-throughput screening against a therapeutic target in the real-world setting of a live mammalian cell.
Partnering for success
Beyond our pipeline and focus there are multiple applications with clear opportunities for collaborative programs with partners that have a depth of knowledge in target biology and expertise in drug development.
