On March 12, 2026 Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, reported publication of research in the Journal of Medicinal Chemistry titled, "Orally Bioavailable Cyclin A/B RxL Inhibitors: Optimization of a Novel Class of Macrocyclic Peptides That Target E2F-High and G1-S-Checkpoint-Compromised Cancers." The paper is included in the journal’s special issue on Peptide Therapeutics.

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The publication builds on the company’s August 2025 Journal of Medicinal Chemistry paper titled, "Discovery of Cell-Permeable Macrocyclic Cyclin A/B RxL Inhibitors that Demonstrate Antitumor Activity," which described the first cell-permeable macrocyclic cyclin A/B RxL inhibitors and provided initial in vivo proof-of-concept efficacy.

"This publication demonstrates the capability of our MXMO macrocycle platform to bring forward orally bioavailable macrocycles against therapeutic targets that have been refractory to small molecule chemistry," said James Aggen, Ph.D., vice president of medicinal chemistry at Circle Pharma. "Our earlier work established that the cyclin A/B hydrophobic patch was druggable with macrocycles. This new research demonstrates these molecules can be delivered orally with compelling in vivo activity."

Cyclins A and B regulate cell cycle progression by recruiting substrates through an RxL-mediated interaction. In cancers characterized by RB1 loss or elevated E2F activity – including nearly all small-cell lung cancers – this pathway becomes dysregulated, driving uncontrolled tumor growth. Rather than inhibiting CDK catalytic activity, Circle Pharma’s approach disrupts the protein-protein interactions between cyclins A and B and their RxL-containing substrates, selectively killing E2F-high tumor cells.

CID-078, Circle Pharma’s oral cyclin A/B RxL inhibitor is currently being evaluated in a multi-center Phase 1 clinical trial in patients with advanced solid tumors (NCT06577987).

(Press release, Circle Pharma, MAR 12, 2026, View Source [SID1234663493])