JIB-04
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.
- 1. Parrish JK, McCann TS, et al. "The Jumonji-domain histone demethylase inhibitor JIB-04 deregulates oncogenic programs and increases DNA damage in Ewing Sarcoma, resulting in impaired cell proliferation and survival, and reduced tumor growth." Oncotarget. 2018 Sep 4;9(69):33110-33123. PMID:30237855
| Storage | Store at -20°C |
| M.Wt | 308.76 |
| Cas No. | 199596-05-9 |
| Formula | C17H13ClN4 |
| Solubility | insoluble in H2O; ≥14.2 mg/mL in DMSO; ≥2.83 mg/mL in EtOH with ultrasonic |
| Chemical Name | 5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine |
| SDF | Download SDF |
| Canonical SMILES | C1=CC=C(C=C1)C(=NNC2=NC=C(C=C2)Cl)C3=CC=CC=N3 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Human lung cancer cell lines (LCa); HBECs, Prostate cancer (PCa); Primary prostate stromal (PrSC) and prostate epithelial cells (PrEC). |
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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. |
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Reaction Conditions |
4 days |
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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]: | |
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Animal models |
H358 and A549 lung cancer mice xenografts |
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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). |
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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. |
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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. |
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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. |
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| 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 & MSDS
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Chemical structure
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