DTHIB 是一种直接和选择性的 heat shock factor 1 (HSF1) 抑制剂，DTHIB 与 HSF1 DNA 结合域结合的 Kd 为 160 nM。DTHIB 抑制 HSF1 癌症基因标记 (HSF1 CaSig)，并选择性刺激核 HSF1 的降解。DTHIB 具有有效的抗癌活性，可用于前列腺癌的研究。
货号:ajcx33092
CAS:897326-30-6
分子式:C13H9ClFN3O3
分子量：309.68
溶解度:DMSO : 100 mg/mL (322.91 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

DTHIB is a direct and selective heat shock factor 1 (HSF1) inhibitor with a Kd of 160 nM for DTHIB binding to the HSF1 DNA binding domain (DBD). DTHIB inhibits HSF1 cancer gene signature (HSF1 CaSig) and selectively stimulates degradation of nuclear HSF1. DTHIB has potently anticancer activities and can be used for prostate cancer research[1].

DTHIB (5 μM; 48 hours) treatment of C4-2 cells induces cell cycle arrest, with accumulation in the G1 phase. DTHIB stimulates C4-2 PCa cell entry into senescence[1]. DTHIB (0.5-5 μM; 48 hours; C4-2 prostate cancer) treatment reduces steady-state protein abundance of the molecular chaperones P23, HSP27, HSP70, and HSP90-all bona fide HSF1 targets in C4-2 cells[1]. DTHIB dose-dependently reduces the clonal expansion of both C4-2 and PC-3 PCa cells with EC50 values of 1.2 μM and 3.0 μM, respectively[1]. In mouse embryonic fibroblasts (MEFs), DTHIB (0.5-10 μM) attenuates the robust acute heat shock induction of the HSP70 and HSP25 molecular chaperones in a dose-dependent manner. DTHIB attenuates the heat shock response by reducing the steady-state transcript abundance of multiple molecular chaperones[1].

DTHIB (5 mg/kg; intraperitoneal injection; daily; for 3 weeks) treatment potently attenuates tumor progression in a C4-2 xenograft mouse model[1].

[1]. Bushu Dong, et al. Targeting therapy-resistant prostate cancer via a direct inhibitor of the human heat shock transcription factor 1. Sci Transl Med. 2020 Dec 16;12(574):eabb5647.