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Protein degradation / PROTAC 2

Duplicate DOIs are merged. This is a selected collection, not an exhaustive bibliography.

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Original research
Proceedings of the National Academy of Sciences

Bispecific protein drives dual receptor degradation in mouse eye-disease models

Jialun Zhang; Mingming Du; Lingying Ge; Yuheng Cao; Jiang Jiang; Xue Yin; Guangcun Chen; Qiangbin Wang

A PNAS study reports RHV, a tetravalent bispecific protein designed to internalize and lysosomally degrade VCAM-1 and VEGFR on pathological vessels. The original abstract describes activity in mouse choroidal neovascularization models, including efficacy comparable to aflibercept at one-quarter of the molar dose. This is preclinical extracellular receptor degradation, distinct from an intracellular small-molecule PROTAC.

Protein degradation / PROTAC
Read guide →Original paper ↗

DOI: 10.1073/pnas.2613631123

Original research
New England Journal of Medicine

Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer

Mario Campone; Michelino De Laurentiis; Komal Jhaveri; Xichun Hu; Sylvain Ladoire; Anne Patsouris; Claudio Zamagni; Jiuwei Cui; Marina Cazzaniga; Timucin Cil; Katarzyna J Jerzak; Christian Fuentes; Tetsuhiro Yoshinami; Alvaro Rodriguez-Lescure; Ahmet Sezer; Andrea Fontana; Valentina Guarneri; Andrea Molckovsky; Marie-Ange Mouret-Reynier; Umut Demirci; Yongqiang Zhang; Olga Valota; Dongrui R Lu; Marcella Martignoni; Janaki Parameswaran; Xin Zhi; Erika P Hamilton

In the randomized phase 3 VERITAC-2 trial, vepdegestrant improved progression-free survival versus fulvestrant in the ESR1-mutated subgroup, but not significantly in the overall population. The trial enrolled 624 patients with previously treated ER-positive, HER2-negative advanced breast cancer. Grade 3 or higher adverse events occurred more often with vepdegestrant.

Protein degradation / PROTAC
Read guide →Original paper ↗

DOI: 10.1056/nejmoa2505725

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