ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors CPI-455

CPI-455

Product NameCPI-455
CAS1628208-23-0
MFC16H14N4O
MW278.31
EINECS
MOL File1628208-23-0.mol

Chemical Properties

Boiling point	488.7±55.0 °C(Predicted)
Density	1.28±0.1 g/cm3(Predicted)
storage temp.	-20°C
solubility	Soluble in DMSO (up to at least 25 mg/ml)
form	solid
pka	-5.10±0.60(Predicted)
color	Off-white
Stability	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

Usage And Synthesis

Description

CPI-455 (1628208-23-0) is a potent (IC50?= 10 nM) and selective inhibitor of the lysine demethylase KDM5 (equal inhibition of KDM5A, 5B, 5C).1?CPI-455 reduced the number of drug-tolerant persister cancer cells (DTPs) in a dose-dependent, KDM5-dependent manner in multiple cell lines treated with standard chemotherapy or targeted agents. CPI-455 synergized with 5-aza-2’-deoxycytidine (DAC) to reduce the viability of luminal breast cancer cells?in vitro.2?KDM5 demethylases have recently been shown to repress the immune response to tumors?via?suppression of STING.3

Uses

CPI-455 is a potent KDM5 demethylase inhibitor.

in vivo

Dual blockade of B7-H4 and KDM5B (CPI-455, 50/70 mg/kg, ip, daily) in mice elicits protective immunity^[2].

Animal Model:	Six-week-old male C57BL/6 mice (One- to 2-mm fragments of P. gingivalis–positive PDXs were implanted subcutaneously into the flank region of humanized mice.)
Dosage:	50 mg/kg or 70 mg/kg (combined with anti–B7-H4).
Administration:	IP, daily, 14-28 days.
Result:	Histopathology analysis revealed no inflammation in either group at 2 weeks in response to the primary infection. However, at 8 weeks after inoculation, mice receiving monotherapy exhibited mild inflammation, whereas the combined treatment presented with heavy to severe inflammation, which persisted at 12 and 16 weeks after challenge. Treatment with CPI-455 to selectively target H3K4-specific JmjC demethylases increased CXCL11, CXCL9, and CXCL10 following infection, with maximum levels observed 48 hours after infection.

IC 50

KDM5

References

[1] MAIA VINOGRADOVA. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells[J]. Nature chemical biology, 2016, 12 7: 531-538. DOI:10.1038/nchembio.2085
[2] BENJAMIN R LEADEM. A KDM5 Inhibitor Increases Global H3K4 Trimethylation Occupancy and Enhances the Biological Efficacy of 5-Aza-2’-Deoxycytidine.[J]. Cancer research, 2018: 1127-1139. DOI:10.1158/0008-5472.can-17-1453
[3] LIZHEN WU. KDM5 histone demethylases repress immune response via suppression of STING.[J]. PLoS Biology, 2018, 16 8: e2006134. DOI:10.1371/journal.pbio.2006134

CPI-455 Supplier

CPI-455 manufacturers

Related Product Information

Send Inquriy