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Adv. Sci., Jul 03 2024, | https://doi.org/10.1002/advs.202400398
UBX-390: A Novel Androgen Receptor Degrader for Therapeutic Intervention in Prostate Cancer
Soohyun Lee 1,2, Hwa-Ryeon Kim 2, Yaejin Woo 1, Jiyoung Kim 1, Han Wool Kim 1, Ji Youn Park 1, Beomseon Suh 1, Yuri Choi 1, Jungmin Ahn 1, Je Ho Ryu 1, Jae-Seok Roe 2, Jaewhan Song 2, Song Hee Lee 1
1Ubix Therapeutics, Seoul, 05836, Republic of Korea.
2Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
S.L. and H.-R.K. contributed equally to this work.
CORRESPONDING AUTHORS: Jae-Seok Roe, Jaewhan Song, Song Hee Lee
Abstract
The androgen receptor (AR) is an attractive target for treating prostate cancer, considering its role in the development and progression of localized and metastatic prostate cancer. The high global mortality burden of prostate cancer, despite medical treatments such as androgen deprivation or AR antagonist therapy, highlights the need to explore alternative strategies. One strategy involves the use of heterobifunctional degraders, also known as proteolysis-targeting chimeras, which are novel small-molecule therapeutics that inhibit amplified or mutated targets. Here, the study reports a novel cereblon-based AR degrader, UBX-390, and demonstrates its superior activity over established AR degraders, such as ARV-110 or ARCC-4, in prostate cancer cells under short- and long-term treatment conditions. UBX-390 suppresses chromatin binding and gene expression of AR and demonstrates substantial efficacy in the degradation of AR mutants in patients with treatment-resistant prostate cancer. UBX-390 is presented as an optimized AR degrader with remarkable potential for treating castration-resistant prostate cancer.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-07-04)
- 국내 연구진
- 생명과학 > 노화/암생물학
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