CPI-455 Hydrochloride is the hydrochloride form of CPI-455. CPI-455 is a specific KDM5 inhibitor with IC50 value of 10nM for inhibition of full-length KDM5A in enzymatic assays. CPI-455-mediated KDM5 inhibition resulted in a dose-dependent increase in global H3K4me3 in HeLa cells. Also it induced a time-dependent increase in H3K4me3 that was detected only after 2 or more days of treatment. The elevation of H3K4 trimethylation mediated by this inhibition of KDM5 by CPI-455 decreased the number of drug-tolerant state in multiple cancer cell line models treated with standard chemotherapy or targeted agents[2].
作用机制
The nitrile of CPI-455 makes a single interaction with the active-site metal ion of KDM5. The position occupied by CPI-455 completely overlaps the binding site of 2-OG, demonstrating a competitive mode of action.[1]
CPI-455 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HPDLSCs
10 nM
To confirm the role of H3K4me3
Regen Ther. 2022 Apr 22;20:95-106.
HEI-OC1 cells
30 µM
24 hours
To investigate the protective effect of CPI-455 on HEI-OC1 cells under cisplatin-induced stress, results showed that CPI-455 reduced ROS accumulation and improved mitochondrial membrane potential and oxidative phosphorylation.
Cell Mol Life Sci. 2022 Nov 17;79(12):596.
NB4 cells
5 µM
4 days
CPI-455 treatment significantly induced differentiation of NB4 cells, as evidenced by increased expression of CD11b and CD11c
Blood Adv. 2021 Sep 14;5(17):3241-3253.
NB4 cells
20 µM
4 days
CPI-455 at 20 μM further increased the proportion of CD11b+ cells, indicating enhanced differentiation effect
Blood Adv. 2021 Sep 14;5(17):3241-3253.
Eca-109 cells
15 µM
48 hours
CPI-455 significantly inhibited the proliferation of Eca-109 cells and induced apoptosis by regulating the expression of related genes.
World J Gastroenterol. 2021 Apr 28;27(16):1805-1815.
RAW 264.7 cells
25 µM
48 hours
To verify the effect of CPI-455 on the anti-inflammatory effect of EgCF by inhibiting KDM5B, the results showed that CPI-455 treatment restored the mRNA expression of IL-6 and TNF-α, indicating that CPI-455 attenuated the anti-inflammatory effect of EgCF
Parasit Vectors. 2023 Sep 9;16(1):321.
THP-1 cells
25 µM
48 hours
To verify the effect of CPI-455 on the anti-inflammatory effect of EgCF by inhibiting KDM5B, the results showed that CPI-455 treatment significantly upregulated the mRNA expression of IL-6 and TNF-α, indicating that CPI-455 attenuated the anti-inflammatory effect of EgCF
Parasit Vectors. 2023 Sep 9;16(1):321.
LNCaP
25 µM, 50 µM
72 hours
CPI-455 attenuated androgen-induced expression of the prototypical AR target gene, KLK3/PSA, and RNA sequencing revealed that CPI-455 significantly affected the androgen-regulated transcriptome.
Front Cell Dev Biol. 2023 Apr 19;11:1116424.
LNCaP:C4-2
50 µM
72 hours
CPI-455 impaired androgen induction of NKX3.1 and downregulated FOXA1 expression, whereas AR expression was unchanged.
Front Cell Dev Biol. 2023 Apr 19;11:1116424.
FaDu cells
>50 µM
72 hours
Evaluate the effects of CPI-455 alone and in combination with olaparib and cisplatin on cell viability, showing that CPI-455 significantly affects cell viability at high concentrations.
Biomedicines. 2024 Jun 19;12(6):1359.
SCC-040 cells
>50 µM
72 hours
Evaluate the effects of CPI-455 alone and in combination with olaparib and cisplatin on cell viability, showing that CPI-455 significantly affects cell viability at high concentrations.
Biomedicines. 2024 Jun 19;12(6):1359.
CPI-455 HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Cisplatin-induced ototoxicity model
Intraperitoneal injection
0.5 mg/kg or 2 mg/kg
Once daily for 5 days
To investigate the protective effect of CPI-455 against cisplatin-induced ototoxicity in vivo, results showed that CPI-455 significantly reduced hearing loss.
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