Dual HIF-1 and HIF-2 inhibitor
| Microcycle® Screening | Functional Hit | Lead Optimisation |
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Hypoxia Inducible Factor (HIF) is a transcriptional complex that allows cells to adapt to a lack of oxygen (hypoxia), for example, in the core of solid tumours. The upregulation of both HIF-1 and HIF-2 in more than half of all solid tumours generally 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 molecule hits that inhibit both HIF-1 and HIF-2. Lead optimisation is underway.
Curve’s dual HIF inhibitors are expected to deliver a significant clinical advantage in renal cell carcinoma and other solid tumours compared to the HIF-2 selective inhibitors currently in development.
ATIC
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ATIC is a homodimer that catalyses 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 that are currently in lead optimisation.
RAS
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RAS is an important oncogene with a single point mutation frequently leading to aggressive and treatment-resistant cancers. Mutations are seen in 20-25% of all tumours and up to 90% in certain cancers. More than a million deaths are caused by mutant RAS every year.
Curve has built significant expertise in the identification of RAS-RAF inhibitors that has resulted in the identification of tri-peptide pharmacophores that engage either RAS or RAF. The Company is currently exploring different opportunities to progress this programme.
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.
Science
Microcycle® platform
Our Microcycle® platform is a major step forward, enabling the identification of biologically active hits against disease targets in their native cellular environment.
Partnering for success
Beyond Curve’s pipeline there are multiple applications with clear opportunities for collaborative research and development with partners that have a depth of knowledge in target biology and expertise in drug development.
