Structure-Activity Relationship Study of Tris-Benzamides as Estrogen Receptor Coregulator Binding Modulators.

Estrogen receptor coregulator binding modulators (ERXs) are a novel class of molecules targeting the interaction between estrogen receptor α (ERα) and its coregulator proteins, which has proven to be an attractive strategy for overcoming endocrine resistance in breast cancer. We previously reported ERX-11, an orally bioavailable tris-benzamide, that demonstrated promising antitumor activity against ERα-positive breast cancer cells. To comprehend the significance of the substituents in ERX-11, we carried out structure-activity relationship studies.

Novel LIPA-Targeted Therapy for Treating Ovarian Cancer.

Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41.

Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers.

Background: CDK4/6 inhibitors in combination with endocrine therapy (AE/AI/SERDs) are approved for the treatment of ER+ advanced breast cancer (BCa). However, not all patients benefit from CDK4/6 inhibitors therapy. We previously reported a novel therapeutic agent, ERX-11, that binds to the estrogen receptor (ER) and modulates ER-coregulator interactions.

Peptide Ligation via the Suzuki-Miyaura Cross-Coupling Reaction.

Chemoselective ligation of two 28-mer peptides has been accomplished using the Suzuki-Miyaura cross-coupling reaction at or near physiological temperature in an aqueous solution containing sodium dodecyl sulfate in 83% yield. The effects of Pd source, solvent, base, and temperature were investigated, and the optimized reaction conditions were studied for compatibility with naturally present and artificially introduced functional groups in peptides including S-protected thiol and azide. The peptide conjugations were carried out in high yield (90%) with their functional groups intact.