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MedKoo Cat#: 406987 | Name: CPI-455
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

CPI-455 is a potent, selective, and cell-active inhibitor of the KDM5 (also known as JARID1) family of histone lysine demethylases, which includes KDM5A, KDM5B, KDM5C, and KDM5D. CPI-455 exhibits an IC₅₀ of approximately 10 nM against KDM5A in biochemical assays and shows over 200-fold selectivity versus other JmjC domain-containing demethylases such as KDM4. In cellular contexts, CPI-455 effectively increases global levels of H3K4me3, a marker of transcriptionally active chromatin, with an EC₅₀ around 400 nM in various cancer cell lines. Functional studies have shown that CPI-455 impairs cancer cell proliferation by sustaining H3K4me3 marks and counteracting KDM5-mediated transcriptional repression

Chemical Structure

CPI-455
CPI-455
CAS#1628208-23-0 (free base)

Theoretical Analysis

MedKoo Cat#: 406987

Name: CPI-455

CAS#: 1628208-23-0 (free base)

Chemical Formula: C16H14N4O

Exact Mass: 278.1168

Molecular Weight: 278.32

Elemental Analysis: C, 69.05; H, 5.07; N, 20.13; O, 5.75

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
500mg USD 2,650.00 Ready to ship
1g USD 3,850.00 Ready to ship
2g USD 6,450.00 Ready to ship
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Related CAS #
1628208-23-0 (free base) 2095432-28-1 (HCl)
Synonym
CPI-455; CPI455; CPI 455
IUPAC/Chemical Name
6-isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile
InChi Key
DHXKRMSKXLDZGY-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H14N4O/c1-10(2)13-14(11-6-4-3-5-7-11)19-15-12(8-17)9-18-20(15)16(13)21/h3-7,9-10,19H,1-2H3
SMILES Code
N#CC1=C(NC(C2=CC=CC=C2)=C(C(C)C)C3=O)N3N=C1
Appearance
White to off-white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
CPI-455 is a specific, pan-KDM5 inhibitor with an IC50 of 10 nM for KDM5A.
In vitro activity:
Flow cytometry was used to detect the effect of CPI-455 on the level of ROS in Eca-109 cells. With an extension of the induction time, the level of intracellular ROS in the Eca-109 cells was increased significantly, with statistically significant differences observed at 24, 48, and 72 h (P < 0.01, Figure 3). Compared with the control group, the mitochondrial membrane potential was depolarized and decreased (P < 0.01, Figure 4). The western blot results found increased expression of p53, Bax, Caspase-9, and Caspase-3 at 24, 48, and 72 h following CPI-455 treatment (Figure 5). However, KDM5C protein expression in the treated cells was significantly decreased compared with the controls (P < 0.01, Figure 6). Reference: World J Gastroenterol. 2021 Apr 28; 27(16): 1805–1815. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072195/
In vivo activity:
TBD
Solvent mg/mL mM
Solubility
DMSO 32.0 114.98
DMSO:PBS (pH 7.2) (1:20) 0.1 0.18
DMF 30.0 107.79
Ethanol 5.0 17.97
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 278.32 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Xue XJ, Li FR, Yu J. Mitochondrial pathway of the lysine demethylase 5C inhibitor CPI-455 in the Eca-109 esophageal squamous cell carcinoma cell line. World J Gastroenterol. 2021 Apr 28;27(16):1805-1815. doi: 10.3748/wjg.v27.i16.1805. PMID: 33967558; PMCID: PMC8072195. 2. Facompre ND, Harmeyer KM, Sahu V, Gimotty PA, Rustgi AK, Nakagawa H, Basu D. Targeting JARID1B's demethylase activity blocks a subset of its functions in oral cancer. Oncotarget. 2017 Dec 15;9(10):8985-8998. doi: 10.18632/oncotarget.23739. PMID: 29507668; PMCID: PMC5823649.
In vitro protocol:
1. Xue XJ, Li FR, Yu J. Mitochondrial pathway of the lysine demethylase 5C inhibitor CPI-455 in the Eca-109 esophageal squamous cell carcinoma cell line. World J Gastroenterol. 2021 Apr 28;27(16):1805-1815. doi: 10.3748/wjg.v27.i16.1805. PMID: 33967558; PMCID: PMC8072195. 2. Facompre ND, Harmeyer KM, Sahu V, Gimotty PA, Rustgi AK, Nakagawa H, Basu D. Targeting JARID1B's demethylase activity blocks a subset of its functions in oral cancer. Oncotarget. 2017 Dec 15;9(10):8985-8998. doi: 10.18632/oncotarget.23739. PMID: 29507668; PMCID: PMC5823649.
In vivo protocol:
TBD

1: Kimura-Nagano Y, Kishimoto K, Sekida S, Kawamura K. Stat stimulates histone H3K4 methylation via KDM5 inhibition in adult stem cells of budding tunicates. Dev Dyn. 2025 Jun;254(6):538-550. doi: 10.1002/dvdy.754. Epub 2024 Oct 22. PMID: 39436036.

2: Chen H, Sarah L, Pucciarelli D, Mao Y, Diolaiti ME, Fujimori DG, Ashworth A. Histone demethylase enzymes KDM5A and KDM5B modulate immune response by suppressing transcription of endogenous retroviral elements. bioRxiv [Preprint]. 2024 Sep 25:2024.09.23.614494. doi: 10.1101/2024.09.23.614494. PMID: 39386707; PMCID: PMC11463504.

3: Dorna D, Kleszcz R, Paluszczak J. Triple Combinations of Histone Lysine Demethylase Inhibitors with PARP1 Inhibitor-Olaparib and Cisplatin Lead to Enhanced Cytotoxic Effects in Head and Neck Cancer Cells. Biomedicines. 2024 Jun 19;12(6):1359. doi: 10.3390/biomedicines12061359. PMID: 38927566; PMCID: PMC11201379.

4: Guan T, Zhang Y, Li S, Zhang W, Song Y, Li Y, He Y, Chen Y. Discovery of an efficacious KDM5B PROTAC degrader GT-653 up-regulating IFN response genes in prostate cancer. Eur J Med Chem. 2024 Jun 5;272:116494. doi: 10.1016/j.ejmech.2024.116494. Epub 2024 May 10. PMID: 38749268.

5: San TT, Kim J, Kim HJ. Histone Lysine Demethylase KDM5 Inhibitor CPI-455 Induces Astrocytogenesis in Neural Stem Cells. ACS Chem Neurosci. 2024 Apr 3;15(7):1570-1580. doi: 10.1021/acschemneuro.4c00003. Epub 2024 Mar 19. PMID: 38501572.

6: Wang X, Lin R, Fu C, Yang C, Dong D, Wu X, Chen X, Wang L, Hou J. Echinococcus granulosus cyst fluid inhibits inflammatory responses through inducing histone demethylase KDM5B in macrophages. Parasit Vectors. 2023 Sep 9;16(1):321. doi: 10.1186/s13071-023-05948-1. PMID: 37689671; PMCID: PMC10492338.

7: Zhong H, Zhang R, Li G, Huang P, Zhang Y, Zhu J, Kuang J, Hutchins AP, Qin D, Zhu P, Pei D, Li D. c-JUN is a barrier in hESC to cardiomyocyte transition. Life Sci Alliance. 2023 Aug 21;6(11):e202302121. doi: 10.26508/lsa.202302121. PMID: 37604584; PMCID: PMC10442936.

8: Metzler VM, de Brot S, Haigh DB, Woodcock CL, Lothion-Roy J, Harris AE, Nilsson EM, Ntekim A, Persson JL, Robinson BD, Khani F, Laursen KB, Gudas LJ, Toss MS, Madhusudan S, Rakha E, Heery DM, Rutland CS, Mongan NP, Jeyapalan JN. The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer. Front Cell Dev Biol. 2023 Apr 19;11:1116424. doi: 10.3389/fcell.2023.1116424. PMID: 37152294; PMCID: PMC10154691.

9: Fang S, Zheng L, Shen L, Su Y, Ding J, Chen W, Chen X, Chen W, Shu G, Chen M, Zhao Z, Tu J, Ji J. Inactivation of KDM5A suppresses growth and enhances chemosensitivity in liver cancer by modulating ROCK1/PTEN/AKT pathway. Eur J Pharmacol. 2023 Feb 5;940:175465. doi: 10.1016/j.ejphar.2022.175465. Epub 2022 Dec 23. PMID: 36566915.

10: Liu C, Zheng Z, Li W, Tang D, Zhao L, He Y, Li H. Inhibition of KDM5A attenuates cisplatin-induced hearing loss via regulation of the MAPK/AKT pathway. Cell Mol Life Sci. 2022 Nov 17;79(12):596. doi: 10.1007/s00018-022-04565-y. PMID: 36396833; PMCID: PMC9672031.

11: Zhong D, Zhan Z, Zhang J, Liu Y, He Z. SMYD3 regulates the abnormal proliferation of non-small-cell lung cancer cells via the H3K4me3/ANO1 axis. J Biosci. 2022;47:53. PMID: 36222132.

12: He L, Wang Y, Luo J. Epigenetic modification mechanism of histone demethylase KDM1A in regulating cardiomyocyte apoptosis after myocardial ischemia-reperfusion injury. PeerJ. 2022 Aug 5;10:e13823. doi: 10.7717/peerj.13823. PMID: 35959481; PMCID: PMC9359132.

13: Niu F, Xu J, Yan Y. Histone demethylase KDM5A regulates the functions of human periodontal ligament stem cells during periodontitis via the miR-495-3p/HOXC8 axis. Regen Ther. 2022 Apr 22;20:95-106. doi: 10.1016/j.reth.2021.12.002. PMID: 35509266; PMCID: PMC9046131.

14: Xu S, Wang S, Xing S, Yu D, Rong B, Gao H, Sheng M, Tan Y, Sun X, Wang K, Xue K, Shi Z, Lan F. KDM5A suppresses PML-RARα target gene expression and APL differentiation through repressing H3K4me2. Blood Adv. 2021 Sep 14;5(17):3241-3253. doi: 10.1182/bloodadvances.2020002819. Erratum in: Blood Adv. 2022 Apr 12;6(7):2443. doi: 10.1182/bloodadvances.2021006376. PMID: 34448811; PMCID: PMC8525237.

15: Xue XJ, Li FR, Yu J. Mitochondrial pathway of the lysine demethylase 5C inhibitor CPI-455 in the Eca-109 esophageal squamous cell carcinoma cell line. World J Gastroenterol. 2021 Apr 28;27(16):1805-1815. doi: 10.3748/wjg.v27.i16.1805. PMID: 33967558; PMCID: PMC8072195.

16: Fu YD, Huang MJ, Guo JW, You YZ, Liu HM, Huang LH, Yu B. Targeting histone demethylase KDM5B for cancer treatment. Eur J Med Chem. 2020 Dec 15;208:112760. doi: 10.1016/j.ejmech.2020.112760. Epub 2020 Aug 21. PMID: 32883639.

17: Liu Y, Yu Y, Zhang J, Wang C. The therapeutic effect of dexmedetomidine on protection from renal failure via inhibiting KDM5A in lipopolysaccharide-induced sepsis of mice. Life Sci. 2019 Dec 15;239:116868. doi: 10.1016/j.lfs.2019.116868. Epub 2019 Nov 1. PMID: 31682847.

18: Romani M, Daga A, Forlani A, Pistillo MP, Banelli B. Targeting of Histone Demethylases KDM5A and KDM6B Inhibits the Proliferation of Temozolomide- Resistant Glioblastoma Cells. Cancers (Basel). 2019 Jun 24;11(6):878. doi: 10.3390/cancers11060878. PMID: 31238504; PMCID: PMC6627323.

19: Yang GJ, Ko CN, Zhong HJ, Leung CH, Ma DL. Structure-Based Discovery of a Selective KDM5A Inhibitor that Exhibits Anti-Cancer Activity via Inducing Cell Cycle Arrest and Senescence in Breast Cancer Cell Lines. Cancers (Basel). 2019 Jan 15;11(1):92. doi: 10.3390/cancers11010092. PMID: 30650517; PMCID: PMC6360022.

20: Arifuzzaman S, Rahman MS, Pang MG. Research update and opportunity of non- hormonal male contraception: Histone demethylase KDM5B-based targeting. Pharmacol Res. 2019 Mar;141:1-20. doi: 10.1016/j.phrs.2018.12.003. Epub 2018 Dec 11. PMID: 30550955.

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