CCF642 is a strong inhibitor of protein disulfide isomerases (PDI) with an IC50 of 2.9 μM. It induces acute endoplasmic reticulum (ER) stress in multiple myeloma cells, leading to apoptosis through calcium release. CCF642 is recognized for its extensive anti-multiple myeloma effects. When used at 3 μM for 0.5 to 6 hours, CCF642 enhances PERK dimerization through phosphorylation and IRE1-α oligomerization within 30 minutes in KMS-12-PE cells, indicating the accumulation of misfolded proteins in the ER. As a compound that spares bone marrow, CCF642 shows a submicromolar IC50 across a range of multiple myeloma cell lines (MM1.S, MM1.R, KMS-12-PE, KMS-12-BM, NCI-H929, U266, RPMI 8226, JJN-3, HRMM.09-luc, 5TGM1-luc)[1].
CCF642 细胞实验
Cell Line
Concentration
Treated Time
Description
References
C2C12 myoblasts
0.1 µM, 1 µM, 3 µM, 5 µM
24 hours
To evaluate the inhibitory effect of CCF642 on cisplatin-induced apoptosis in C2C12 myoblasts. Results showed CCF642 dose-dependently reduced apoptotic cell percentages (3 μM to 5.17%, 5 μM to 1.73%), downregulated apoptotic markers cleaved caspase-3 and Bax, while upregulated anti-apoptotic protein Bcl-2.
J Extracell Vesicles. 2021 Mar;10(5):e12060.
GSC#021
20 µM
72 hours
Evaluate the effect of CCF642 on GSC#021 spheroid size, results showed CCF642 significantly reduced spheroid size
Br J Cancer. 2023 May;128(10):1955-1963.
GSC#016
20 µM
72 hours
Evaluate the effect of CCF642 on GSC#016 spheroid size, results showed CCF642 significantly reduced spheroid size
Br J Cancer. 2023 May;128(10):1955-1963.
U251-R
1.5-3 µM
72 hours
Evaluate the effect of CCF642 on U251-R cell viability, results showed CCF642 significantly reduced cell viability
Br J Cancer. 2023 May;128(10):1955-1963.
U251-S
1.5-3 µM
72 hours
Evaluate the effect of CCF642 on U251-S cell viability, results showed CCF642 significantly reduced cell viability
Br J Cancer. 2023 May;128(10):1955-1963.
RPMI 8226 cells
292 ±11 nM
72 hours
Evaluate the toxicity of CCF642-34 on RPMI 8226 cells
Cancers (Basel). 2021 May 28;13(11):2649.
BTZ-resistant MM1.S cells
60 ±11 nM
72 hours
Evaluate the toxicity of CCF642-34 on BTZ-resistant MM1.S cells
Cancers (Basel). 2021 May 28;13(11):2649.
MM1.S cells
118 ±21 nM (LD50)
72 hours
Evaluate the toxicity of CCF642-34 on MM1.S cells
Cancers (Basel). 2021 May 28;13(11):2649.
L6 rat myoblasts
3 µM, 5 µM
To validate the anti-apoptotic effect of CCF642 in another muscle cell model. Results showed similar significant inhibition of cisplatin-induced apoptosis as in C2C12 cells.
J Extracell Vesicles. 2021 Mar;10(5):e12060.
CCF642 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c nude mice
YES2 cell-induced ESCC cachexia model
Intraperitoneal injection
10 mg/kg
3 times per week for 4 weeks
To assess the ameliorative effect of CCF642 on cachexia symptoms. Results showed CCF642 treatment significantly prevented body weight loss (P=0.003), reduced muscle wasting (increased GA muscle weight, P=0.0002), upregulated MHC protein levels while downregulating MURF1 and LC3 expression, without affecting tumor volume. Additionally, CCF642 alleviated adipose tissue loss and inflammatory responses.
J Extracell Vesicles. 2021 Mar;10(5):e12060.
BALB/c-nu/nu nude mice
Orthotopic xenograft model
Intraperitoneal injection
5 mg/kg or 10 mg/kg
3 days a week for two weeks
Evaluate the effect of CCF642 nanoformulation on tumor growth, results showed CCF642 nanoformulation significantly suppressed tumor growth
Br J Cancer. 2023 May;128(10):1955-1963.
CCF642 动物研究
Animal study
Administered intraperitoneally at 10 mg/kg three times weekly for 24 days, CCF642 considerably extends the lifespan of mice bearing 5TGM1-luc and inhibits the growth of 5TGM1-luc, as verified by live imaging[1].
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