199596-05-9 Usage
Description
JIB-04, with the chemical formula (199596-05-9), is a novel and specific inhibitor of the Jumonji family of histone demethylases. It has demonstrated effectiveness in vitro, in cancer cells, and in tumors in vivo. JIB-04 exhibits varying degrees of potency against different Jumonji demethylases, with IC50 values ranging from 230 nM to 1100 nM. JIB-04 has the potential to reduce tumor burden, prolong life in mouse models, suppress translation initiation, enhance mTOR inhibitor sensitivity, and inhibit the growth of temozolomide-resistant glioblastoma cells while crossing the blood-brain barrier.
[Data of usage]:
Used in Pharmaceutical Industry:
JIB-04 is used as a specific inhibitor for the Jumonji family of histone demethylases for its potential to reduce tumor burden and prolong life in mouse models. It is particularly effective against various Jumonji demethylases, including JARID1A, JMJD2E, JMJD2B, JMJD2A, JMJD3, and JMJD2C.
Used in Cancer Research:
JIB-04 is used as a research tool in sulforhodamine B cell growth assays to study the effects of histone demethylase inhibition on cancer cell growth. It is also used as a control to determine the inhibitory action of other compounds, such as ML324, on KDM4A (histone lysine demethylase 4A).
Used in Drug Development:
JIB-04 is used in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. It is employed in the design of various organic and metallic nanoparticles as carriers for improved delivery, bioavailability, and therapeutic outcomes.
Used in Neurological Research:
JIB-04 is used in the study of temozolomide-resistant glioblastoma cells, as it has been shown to inhibit their growth and cross the blood-brain barrier, making it a valuable compound for research in the field of neurological disorders and cancer.
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].
