CPI-455
(Synonyms: 6-异丙基-7-氧代-5-苯基-4,7-二氢吡唑并[1,5-A]嘧啶-3-腈) 目录号 : GC10774
CPI-455是一种KDM5抑制剂，KDM5（Kissinger Demethylase 5）是一种赖氨酸特异性脱甲基酶，在染色质修饰中起着至关重要的作用，并参与各种生物学过程，包括肿瘤发展和免疫反应。
Cas No.:1628208-23-0
Sample solution is provided at 25 µL, 10mM.
CPI-455 is a KDM5 inhibitor. KDM5 (Kissinger Demethylase 5) is a lysine-specific demethylase that plays a crucial role in chromatin modification and is involved in various biological processes, including tumor development and immune response[1, 2]. CPI-455 pretreatment of cancer cells can lead to the ablation of cancer cell subpopulations and reduce the survival rate of drug-resistant cancer cells[3]. CPI-455 can induce neural stem cells (NSC) to differentiate into astrocytes[4].
In vitro, CPI-455 (15µM) treatment of esophageal squamous cell carcinoma Eca-109 cells for 24h reduced the decrease in mitochondrial membrane potential, significantly upregulated intracellular ROS content, expression of P53, Bax, Caspase-9 and Caspase-3 proteins, and downregulated KDM5C protein expression[5]. CPI-455 (50µM) treatment of prostate cancer cell lines (C4-2B and PC-3 cells) for 24-96h significantly reduced cell proliferation[6].
In vivo, CPI-455 (20mg/kg) was injected subcutaneously into mice bearing liver cancer cell xenografts, significantly inhibiting the growth of subcutaneous tumors in mice and reducing the volume and weight of tumor tissue, and CPI-455 combination with cisplatin enhanced the anti-tumor effect of cisplatin[7].
References:
[1] Das N D, Niwa H, Umehara T. Chemical inhibitors targeting the histone lysine demethylase families with potential for drug discovery[J]. Epigenomes, 2023, 7(1): 7.
[2] Metzler V M, de Brot S, Haigh D B, et al. The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer[J]. Frontiers in Cell and Developmental Biology, 2023, 11: 1116424.
[3] Vinogradova M, Gehling V S, Gustafson A, et al. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells[J]. Nature chemical biology, 2016, 12(7): 531-538.
[4] San T T, Kim J, Kim H J. Histone lysine demethylase KDM5 inhibitor CPI-455 induces astrocytogenesis in neural stem cells[J]. ACS Chemical Neuroscience, 2024, 15(7): 1570-1580.
[5] Xue X J, Li F R, Yu J. Mitochondrial pathway of the lysine demethylase 5C inhibitor CPI-455 in the Eca-109 esophageal squamous cell carcinoma cell line[J]. World Journal of Gastroenterology, 2021, 27(16): 1805.
[6] Smith T, White T, Chen Z, et al. The KDM5 inhibitor PBIT reduces proliferation of castration-resistant prostate cancer cells via cell cycle arrest and the induction of senescence[J]. Experimental cell research, 2024, 437(1): 113991.
[7] Fang S, Zheng L, Shen L, et al. Inactivation of KDM5A suppresses growth and enhances chemosensitivity in liver cancer by modulating ROCK1/PTEN/AKT pathway[J]. European Journal of Pharmacology, 2023, 940: 175465.
CPI-455是一种KDM5抑制剂，KDM5（Kissinger Demethylase 5）是一种赖氨酸特异性脱甲基酶，在染色质修饰中起着至关重要的作用，并参与各种生物学过程，包括肿瘤发展和免疫反应[1, 2]。CPI-455预处理癌细胞能够导致癌细胞亚群的消融，降低耐药癌细胞的存活率[3]。CPI-455能够诱导神经干细胞（NSC）分化生成星形胶质细胞[4]。
在体外，CPI-455（15µM）处理食管鳞癌细胞Eca-109细胞24h，降低了细胞线粒体膜电位降低，显著上调了细胞内ROS含量、P53、Bax、Caspase-9和 Caspase-3蛋白的表达，下调了KDM5C蛋白的表达[5]。CPI-455（50µM）处理前列腺癌细胞系（C4-2B和PC-3细胞）24-96h，显著降低了细胞的增殖[6]。
在体内，CPI-455（20mg/kg）通过皮下注射治疗肝癌细胞异种移植小鼠，显著抑制了小鼠皮下肿瘤的生长，减小了肿瘤组织的体积和重量，CPI-455与顺铂联用增强了顺铂的抗肿瘤效果[7]。
| Cell experiment [1]: | |
Cell lines | Eca-109 cells |
Preparation Method | Cells were harvested (2×106/mL) at scheduled times after treatment with 15μM CPI-455 for 48h. The Mitocapture dye and antibody incubation solutions were freshly prepared. The cells were washed and centrifuged and the mitochondria were stained. The cells were immediately transferred to collecting tubes for flow cytometry. |
Reaction Conditions | 15µM; 48h |
Applications | CPI-455 treatment downregulated the mitochondrial membrane potential of Eca-109 cells. |
| Animal experiment [2]: | |
Animal models | BALB/c nude mice |
Preparation Method | HCCLM3 cells or KDM5A knockdown HCCLM3 cells were subcutaneously injected into the left upper back. Mice with tumor volumes that reached 50mm3 bearing HCCLM3 cells were used and divided into four groups: the DMSO group, cisplatin group, CPI-455 group and cisplatin plus CPI-455 group. The mice received 20mg/kg CPI-455 and 1mg/kg cisplatin single or combined treatment every three days. After treatment, the mice were sacrificed, and the tumor volume and weight were evaluated. |
Dosage form | 20mg/kg; s.c. |
Applications | The values of tumor volumes and tumor weight sharply declined in the cisplatin plus CPI-455 group, which was much less than those in the cisplatin group and CPI-455 group. |
References: | |
| Cas No. | 1628208-23-0 | SDF | |
| 别名 | 6-异丙基-7-氧代-5-苯基-4,7-二氢吡唑并[1,5-A]嘧啶-3-腈 | ||
| 化学名 | 6-isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile hydrochloride | ||
| Canonical SMILES | N#CC1=C(NC(C2=CC=CC=C2)=C(C(C)C)C3=O)N3N=C1.Cl | ||
| 分子式 | C16H14N4O | 分子量 | 278.31 |
| 溶解度 | ≥ 31.5mg/mL in DMSO | 储存条件 | Store at -20°C |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5931 mL | 17.9656 mL | 35.9312 mL |
| 5 mM | 718.6 μL | 3.5931 mL | 7.1862 mL |
| 10 mM | 359.3 μL | 1.7966 mL | 3.5931 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >98.00%
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