VPC-14449 是一种有效和选择性的雄激素受体 DNA 结合结构域 (AR-DBD) 抑制剂，对全长人 AR 的 IC50 值为 0.34 μM。VPC-14449 可降低全长 AR 以及 AR 变体与染色质相互作用的能力。VPC-14449 可用于前列腺癌的研究。
VPC-14449 is a potent and selective inhibitor of the DNA-binding domain of the androgen receptor (AR-DBD), with IC50 of 0.34 μM for full-length human AR. VPC-14449 reduces the ability of full-length AR as well as AR variants to interact with chromatin. VPC-14449 can be used for the research of prostate cancer[1][2].
VPC-14449 (0.01-100 μM; 24 h) inhibits AR-transcriptional activity and cell viability in LNCaP, C4-2, MR49F, and 22Rv1 cells[2].VPC-14449 (0.01-100 μM; 24 h) dose-dependently inhibits the transiently expressed full-length human AR in PC3 cells (IC50=0.34 μM) without affecting AR protein expression[1].
VPC-14449 (100 mg/kg; i.p. twice daily for 4 weeks) reduces tumor volume and abolishes PSA production with no decrease in body weight over a total duration 4 weeks in LNCaP xenograft model[1].
[1]. Dalal K, et, al. Selectively targeting the DNA-binding domain of the androgen receptor as a prospective therapy for prostate cancer. J Biol Chem. 2014 Sep 19;289(38):26417-26429.
[2]. Dalal K, et, al. Bypassing Drug Resistance Mechanisms of Prostate Cancer with Small Molecules that Target Androgen Receptor-Chromatin Interactions. Mol Cancer Ther. 2017 Oct;16(10):2281-2291.
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