Neuroblastoma is a pediatric solid tumor characterized by dysregulation of the CDK-RB-E2F axis, leading to elevated E2F activity, uncontrolled progression through the G1/S transition and an aggressive tumor phenotype. Researchers from Circle Pharma Inc. and collaborators presented preclinical data on CID-078, a first-in-class oral macrocycle with dual cyclin A and B RxL inhibitory activity, in models of neuroblastoma.
Cyclins and cyclin-dependent kinases (CDKs) regulate the activity of E2F and Rb to drive cell cycle progression. Disrupting this interaction has shown lethality in cancer cells harboring alterations that lead to higher expression of E2F1.
Researchers from Circle Pharma Inc. have presented preclinical data for CID-078, a novel orally bioavailable cyclin A/B Rxl macrocycle being developed for the treatment of patients with lung cancer. CID-078 was developed as a macrocycle that binds to the hydrophobic patch of cyclins A and B and blocks RxL-dependent interactions of proteins, such as that of E2F1 with cyclin A-CDK2 and Myt1 with cyclin B-CDK1.
Circle Pharma Inc. has submitted an IND application to the FDA for CID-078, a first-in-class cyclin A/B RxL inhibitor. Pending approval, the company plans to initiate a phase I trial in patients with advanced solid tumor malignancies.
Circle Pharma Inc. has selected CID-078 as its first clinical development candidate. CID-078 is an orally bioavailable macrocycle with dual cyclin A and B inhibitory activity that drives synthetic lethality in multiple tumor types.
