199596-05-9 Usage
Description
JIB-04 (199596-05-9) is a novel specific inhibitor of the Jumonji family of histone demethylases?in vitro, in cancer cells and in tumors?in vivo.?IC50?= 230, 340, 435, 445, 855 and 1100 nM for JARID1A, JMJD2E, JMJD2B, JMJD2A, JMJD3 and JMJD2C respectively.??Reduces tumor burden and prolongs life in a mouse model.1?Suppresses translation initiation and enhances mTOR inhibitor sensitivity.2?Inhibits the growth of temozolomide-resistant glioblastoma cells and crosses the blood brain barrier.3
Uses
Different sources of media describe the Uses of 199596-05-9 differently. You can refer to the following data:
1. JIB-04 is a specific inhibitor of Jumonji demethylases.
2. JIB-04 has been used in sulforhodamine B cell growth assay. It has also been used as a control to determine the inhibitory action of ML324 on KDM4A (histone lysine demethylase 4A).
Biochem/physiol Actions
JIB-04 is a selective inihibitor of Jumonji demethylases without inhibiting other α-ketoglutarate-dependent hydroxylases or histone-modifying enzymes including amine oxidase LSD1 (also known as KDM1A), which demethylates histone lysines. JIB-04 is a pan-inhibitor of Jumonji demethylases with JARID1A (KDM5A) being the most sensitive (IC50=230 nM) followed by JMJD2D (IC50=290 nM) and JMJD3 (KDM6B) and JMJD2C (KDM4C) more resistant (IC50 855 and 1100 nM, respectively). JIB-04 selectively inhibited viability of several human cancer cell lines with little toxicity towards normal cells, and also diminished tumor growth in two separate xenograft mouse models.
References
1) Wang?et al.?(2013),?A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth; Nature Commun., 4?2035
Check Digit Verification of cas no
The CAS Registry Mumber 199596-05-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,9,9,5,9 and 6 respectively; the second part has 2 digits, 0 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 199596-05:
(8*1)+(7*9)+(6*9)+(5*5)+(4*9)+(3*6)+(2*0)+(1*5)=209
209 % 10 = 9
So 199596-05-9 is a valid CAS Registry Number.
199596-05-9Relevant articles and documents
Azinyl and diazinyl hydrazones derived from aryl N-heteroaryl ketones: Synthesis and antiproliferative activity
Easmon,Heinisch,Purstinger,Langer,Osterreicher,Grunicke,Hofmann
, p. 4420 - 4425 (2007/10/03)
A series of N-heteroaryl hydrazones derived from aryl N-heteroaryl or bis-N-heteroaryl methanones was prepared in search for potential novel antitumor agents. The stereochemistry of these compounds was established by means of NMR spectroscopy. Antiproliferative activity was determined in a panel of human tumor cell lines (CCRF-CEM, Burkitt's lymphoma, HeLa, ZR-75- 1, HT-29, and MEXF 276L) in vitro. Generally, the new compounds were found to be more potent (IC50 = 0.011-0.436 μM) than the ribonucleotide reductase inhibitor hydroxyurea (IC50 = 140 μM). Most of the compounds exhibited the highest activity against Burkitt's lymphoma with an IC50 of 0.011-0.035 μM. [14C]Cytidine incorporation into DNA was quantitated for selected hydrazones (Z-A, E-1, Z-3, Z-4, E-5, Z-5, E-13, E-18, Z-19, Z-24, and E-26) as a measure of the inhibition of ribonucleotide reductase in Burkitt's lymphoma cells. The E-configurated compounds were found to inhibit [14C]cytidine incorporation to a greater extent (IC50 = 0.67-5.05 μM) than the Z-isomers (IC50 = 7.20 to > 10 μM). Principal component analysis of the IC50 values obtained for inhibition of cell proliferation revealed that the cell lines tested can be grouped into three main families showing different sensitivities toward the compounds in our series [(i) CCRF-CEM, Burkitt's lymphoma, and Hela; (ii) HT-29; and (iii) MEXF 276 L].
