Hot shock protein 70(HSP70) is an ATP-dependent chaperone that can be induced by cellular stress and its aberrant activation is commonly observed in various malignancies. Pifithrin-μ is an inhibitor of inducible HSP70. It strongly inhibited cell viability with IC50 values of 2.5, 6.1, 4.4, 6.1, 12.7, 8.4 and 11.2 μM in NALM-6, TOM-1, BE-13, Jurkat, KG-1a, K562 and K562-r cells, respectively. In NALM-6 and KG-1a cell lines, incubation with Pifithrin-μ (4 and 5 μM for NALM-6; 40 and 60 μM for KG-1a) for 24h caused a remarkably reduced proportion of cells in S phase. Around 22% of NALM-6 cells were observed in the sub-G0/1 fraction after incubation with 5μM Pifithrin-μ, while only 2% of KG-1a cells were within this fraction after 60 μM Pifithrin-μ treatment. Incubation of NALM-6 cells with Pifithrin-μ at 4, 5 and 6.5 μM resulted in 34, 59 and 80% apoptotic cells above spontaneous apoptosis, respectively. Moreover, the intracellular AKT and ERK1/2 levels in NALM-6 cells was decreased by 10-h incubation of 10μM Pifithrin-μ[3]. In nude mice inoculated with human pancreatic cancer MiaPaca-2 cells, intraperitoneal injection with Pifithrin-μ (25mg/kg, 100μL) significantly enhanced the inhibitory effect of TRAIL on MiaPaca-2 tumor growth[4].
Pifithrin-μ 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HepG2 cells
5 µM
1 hour
Pretreatment with Pifithrin-μ significantly alleviated GOX-induced mitochondrial dysfunction, including the loss of mitochondrial membrane potential, mitochondrial swelling, and the decrease in ATP levels.
Int J Biol Sci. 2016 Jan 1;12(2):198-209.
BCBL1 PEL cells
20 µM
12-48 hours
PES treatment increased cell death between 12 and 48 hours in both BC3 and BCBL1 cells, indicating time-dependent cytotoxicity.
Cell Death Dis. 2013 Jul 18;4(7):e730.
BC3 PEL cells
10-30 µM
24 hours
PES induced a dose-dependent cytotoxic effect in BC3 and BCBL1 PEL cells, leading to lysosome membrane permeabilization, relocation of cathepsin D to the cytosol, Bid cleavage, mitochondrial depolarization, and ultimately programmed cell death.
Cell Death Dis. 2013 Jul 18;4(7):e730.
SNU886 cells
5 µM
24 hours
Pifithrin-μ disrupted the interaction between CREB1 and CREBBP, reduced the mRNA levels of CREB1 target genes, and suppressed SESN3 expression, thereby enhancing sorafenib-induced cell death.
Cell Death Dis. 2025 Jan 26;16(1):42.
HCCLM3 cells
10 µM
24 hours
Pifithrin-μ inhibited HSP70 to reduce the transcriptional activity of CREB1 and the expression of SESN3, consequently enhancing sorafenib-induced ferroptosis in mTOR-activated liver cancer cells.
Cell Death Dis. 2025 Jan 26;16(1):42.
KG-1a (AML)
0.5 to 100 µM
48 hours
PFT-μ significantly inhibited cell viability at low micromolar concentrations in all cell lines tested, with IC50 values ranging from 2.5 to 12.7 μM, and was highly active in primary AML blasts with a median IC50 of 8.9 μM. PFT-μ induced apoptosis and cell cycle arrest in a dose-dependent manner in AML and ALL.
Blood Cancer J. 2011 Jul;1(7):e28.
NALM-6 (B-precursor ALL)
0.5 to 100 µM
48 hours
PFT-μ significantly inhibited the viability of NALM-6 cells, with an IC50 value of 2.5 μM. PFT-μ led to an increase in the active form of caspase-3 and reduced intracellular concentrations of AKT and ERK1/2.
Blood Cancer J. 2011 Jul;1(7):e28.
TOM-1 (B-precursor ALL; BCR-ABL positive)
0.5 to 100 µM
48 hours
PFT-μ significantly inhibited the viability of TOM-1 cells, with an IC50 value of 6.1 μM. PFT-μ enhanced the cytotoxicity of cytarabine, 17-AAG, SAHA, and sorafenib in TOM-1 cells.
Blood Cancer J. 2011 Jul;1(7):e28.
HONE1/Akata cells
40 µM
48 hours
PES significantly decreased the expression of EBNA1, independent of effects on EBNA1 transcription or proteasomal degradation.
Cell Death Dis. 2018 Jun 29;9(7):734.
HK1/Akata cells
40 µM
48 hours
PES significantly decreased the expression of EBNA1, independent of effects on EBNA1 transcription or proteasomal degradation.
Cell Death Dis. 2018 Jun 29;9(7):734.
B95-8 cells
10 µM
48 hours
PES significantly decreased the expression of EBNA1, independent of effects on EBNA1 transcription or proteasomal degradation.
Combined treatment of Pifithrin-μ and sorafenib significantly inhibited tumor growth in mTOR-activated liver cancer cells, reduced tumor volume and weight, and had no significant impact on the body weight of mice.
Cell Death Dis. 2025 Jan 26;16(1):42.
WT and Traf6−/− mice
Traf6−/− mice
Intraperitoneal injection
10 mg/kg
Every other day for one week
Pifithrin-μ reversed the spontaneous apoptosis in Traf6?/? thymus, while pifithrin-α did not have this effect
Mol Cell. 2016 Nov 17;64(4):803-814
BALB/c Nude mice
HONE1/Akata cell-induced tumor model
Intraperitoneal injection
8 mg/kg
Once daily for 5 consecutive days
PES significantly inhibited the growth of tumors induced by HONE1/Akata cells and reduced the expression of EBNA1 in tumor tissues.
Cell Death Dis. 2018 Jun 29;9(7):734.
C57BL/6J mice
Cisplatin-induced cognitive impairment model
Intraperitoneal injection
8 mg/kg
Once daily for two 5-day cycles
PFT-μ completely prevented cisplatin-induced cognitive impairment and associated structural changes in the brain, including loss of white matter integrity and neurogenic areas.
Cancer Res. 2017 Feb 1;77(3):742-752
Pifithrin-μ 动物研究
Dose
Mice: 1 mg/kg or 5 mg/kg[3] (i.p.), 40 mg/kg[2] (i.p.)
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