Triptophenolide

Triptophenolide (Hypolide) is a colorless crystal isolated from the ethyl acetate extract of Tripterygium wilfordii. Triptophenolide is an orally active pan‑antagonist of the androgen receptor (AR) with an IC₅₀ of 467 nM against human wild‑type AR. Triptophenolide reduces AR expression, inhibits AR nuclear translocation, downregulates prostate‑specific antigen mRNA levels, and suppresses the growth of AR‑positive prostate cancer cells. Triptophenolide shows anti-tumor effects against breast cancer by inhibiting cell proliferation and migration, inducing G1-phase arrest and apoptosis, repressing xenograft tumor growth. Triptophenolide inhibits pyroptosis, alleviates tissue inflammation, and ameliorates synovial injury. Triptophenolide can be used for the study of prostate cancer, rheumatoid arthritis and breast cancer^[1][2][3]. In Vitro:Triptophenolide (50 nM-5 μM) potently inhibits DHT-induced transcriptional activity of wild-type AR, AR F876L, AR T877A and W741C+T877A AR double mutant in PC-3 cells, with IC₅₀ values of 260 nM, 480 nM, 388 nM and 437 nM, respectively. It shows no agonistic activity toward these AR variants in the absence of DHT^[1].
Triptophenolide (500 nM-5 μM) significantly downregulates prostate-specific antigen mRNA expression in LNCaP cells^[1].
Triptophenolide (0.1-50.0 μM) dose-dependently inhibits the growth of AR-positive LNCaP prostate cancer cells, while having no significant effect on AR-negative PC-3 prostate cancer cell growth^[1].
Triptophenolide (10 nM-10 μM) competitively binds to the androgen receptor ligand-binding domain in a cell-free system with an IC₅₀ of 467 nM^[1].
Triptophenolide (50 nM-5 μM; 24 h) dose-dependently suppresses androgen receptor protein expression in LNCaP cells after 24 hours of treatment, with significant effects at 500 nM and 5 μM^[1].
Triptophenolide (5 μM) efficiently inhibits DHT-induced androgen receptor nuclear translocation in LNCaP cells^[1].
Triptophenolide (0-400 μg/mL; 24/48 h) concentration- and time-dependently inhibits proliferation in MCF‑7 and MDA‑MB‑231 breast cancer cells^[3].
Triptophenolide (180.3 μg/mL for MCF‑7 cells and 322.5 μg/mL for MDA‑MB‑231 cells; 48 h) significantly downregulates target gene mRNA levels as detected and reduces corresponding protein expression as determined in MCF‑7 and MDA‑MB‑231 breast cancer cells^[3].
Triptophenolide (150 μg/mL; 24 h/48 h) induces apoptosis and G1-phase cell cycle arrest, and significantly inhibits migration in MCF-7 and MDA-MB-231 breast cancer cells^[3]. In Vivo:Triptophenolide (5-15 mg/kg; intragastric; once daily; 15 days) significantly reduces arthritis scores, suppresses synovial inflammatory factor levels, and alleviates synovial injury in collagen antibody-induced rheumatoid arthritis mice^[2].
Triptophenolide (10 mg/kg; intraperitoneal injection; every 3 days; 21 days) significantly inhibits MCF-7 xenograft tumor growth, reduces tumor weight, and prolongs the survival of tumor-bearing BALB/c nude mice^[3].