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JIB-04

Catalog No.
B1579
Jumonji histone demethylase inihibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$85.00
In stock
20mg
$127.00
In stock
50mg
$238.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

JIB-04 is a small molecule inhibitor of Jumonji histone demethylase with IC50 values of [1].

JIB-04 is a pyridine hydrazone. It is a pan -selective inhibitor of Jumonji histone demethylases. In a sensitive ELISA assay, JIB-04 inhibits JARID1A, JMJD2A, JMJD2B, JMJD2C, JMJD2E and JMJD3 with IC50 values of 230nM, 445nM, 435nM, 1100nM, 340nM and 855nM, respectively. Among the JMJD2 (KDM4) subfamily, JMJD2D has highest sensitivity. JIB-04 inhibits Jumonji demethylases in a unique manner. It is found not to be a competitive inhibitor of α-ketoglutarate in the competition assay [1].

JIB-04 shows consistently selective for cancer cells over normal cells. It has efficacy in cultured lung and prostate cancer lines with IC50 values as low as 10nM. JIB-04 is also effective in controlling lung cancer growth in animals. It significantly suppresses tumor growth of H358 and A549 lung cancer cell xenografts in mice with IC50 values of 100nM and 250nM, respectively. Furthermore, the anti-proliferation activity of JIB-04 results in a reduction in cancer-induced death rates in mice [1].

References:
[1] Wang L, Chang J, Varghese D, Dellinger M, Kumar S, Best AM, Ruiz J, Bruick R, Peña-Llopis S, Xu J, Babinski DJ, Frantz DE, Brekken RA, Quinn AM, Simeonov A, Easmon J, Martinez ED. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun. 2013;4:2035.

Product Citation

Chemical Properties

StorageStore at -20°C
M.Wt308.76
Cas No.199596-05-9
FormulaC17H13ClN4
Solubilityinsoluble in H2O; ≥14.2 mg/mL in DMSO; ≥2.83 mg/mL in EtOH with ultrasonic
Chemical Name5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine
SDFDownload SDF
Canonical SMILESC1=CC=C(C=C1)C(=NNC2=NC=C(C=C2)Cl)C3=CC=CC=N3
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

Cell experiment [1]:

Cell lines

Human lung cancer cell lines (LCa); HBECs, Prostate cancer (PCa); Primary prostate stromal (PrSC) and prostate epithelial cells (PrEC).

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

4 days

Applications

JIB-04 shows selectivity of cancer cells (lung and prostate cancer lines with IC50 as low as 10 nM) over normal cells (HBECs and PrSCs/PrEC)s. Furthermore, 0.1–2 μM JIB-04 E-isomer decreases the total H3K9me3 demethylase activity, suggesting that JIB-04 inhibits H3K9me3 demethylases in cells at concentrations similar to the in vitro inhibition of individual purified enzymes.

Animal experiment [1]:

Animal models

H358 and A549 lung cancer mice xenografts

Dosage form

Administered 2–3x weekly by IP injection at 110 mg/kg in sesame oil (H358 xenografts); Gavage in Cremophor EL at 55 mg/kg (A549 xenografts).

Applications

By comparing with vehicle treated groups, JIB-04 significantly abrogates the rate of tumor growth. It also markedly decreases the final tumor weights without effecting overall body weight or general health. In addition, JIB-04 lowers Jumonji histone demethylase activity in tumors and prolongs cancer survival.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Wang L, Chang J, Varghese D et al. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun. 2013;4:2035.

Biological Activity

Description JIB-04 is a pan-selective inihibitor of Jumonji histone demethylase with IC50 values of 230, 340, 855, 445, 435, 1100, and 290 nM for JARID1A, JMJD2E, JMJD3, JMJD2A, JMJD2B, JMJD2C, and JMJD2D, respectively.
Targets JARID1A JMJD2D JMJD2E JMJD2B JMJD2A JMJD3
IC50 230 nM 290 nM 340 nM 435 nM 445 nM 855 nM

Quality Control