PR-619 is a broad-range and reversible DUB inhibitor with EC50s of 3.93, 4.9, 6.86, 7.2, and 8.61 μM for USP4, USP8, USP7, USP2, and USP5, respectively. PR-619 induces ER Stress and ER-Stress related apoptosis.
PR-619, a deubiquitylase inhibitor, prevents degradation, indicating KCa3.1 is targeted for degradation by ubiquitylation.
PR-619 affects the microtubule network and led to the accumulation of small punctuated tau deposits around. PR-619 causes the dephosphorylation of tau.
PR-619 (7-12.5 μM) causes an increase in the abundance of ubiquitinated proteins within 24 h. PR-619 leads to the induction of heat shock proteins and to an increase of ubiquitinated proteins.
PR-619 (9 μM) affects the organization of the microtubule network in OLN-t40 cells.
PR-619 (5, 7.5, and 10 μM) induces ER Stress and ER-Stress related apoptosis on T24 and BFTC-905 cells. PR-619 induces polyubiquitination, Bcl-2 downregulation, and concurrent PARP cleavage in a dose-dependent manner. PR-619 induces G0/G1 arrest in UC cells.
Cell Cytotoxicity Assay
Cell Line:
OLN-t40 cells.
Concentration:
0-10 μM.
Incubation Time:
24 hours.
Result:
Exerted concentration-dependent cytotoxicity in a very narrow concentration range of 7-10 μM.
体内研究
PR-619 (10 mg/kg/day) enhances the antitumor effect of Cisplatin on a Cisplatin-Naïve and Cisplatin-resistant UC Xenograft of nude mice.
Animal Model:
Nude mice.
Dosage:
10 mg/kg/day (Cisplatin combined).
Administration:
Intraperitoneally.
Result:
Enhanced the antitumor effect of Cisplatin.
分子式
C7H5N5S2
分子量
223.28
CAS号
2645-32-1
运输条件
Room temperature in continental US; may vary elsewhere.