JIB-04 Z-isomer, formerly known as NSC 693627, is the Z-configurational isomer of JIB-04 which is a potent and pan-selective Jumonji histone demethylase inhibitor with IC50s of 230, 340, 855, 445, 435, 1100, and 290 nM for JARID1A, JMJD2E, JMJD3, JMJD2A, JMJD2B, JMJD2C, and JMJD2D, respectively.. JIB-04 selectively blocks cancer cell growth in vitro and diminishes tumor growth in H358 and A549 mouse xenograft models in vivo. JIB-04 can prolong survival in a mouse model of breast cancer. In a sensitive ELISA assay, JIB-04 inhibits JARID1A, 2A, 2B, 2C, 2E and 3 with IC50 values of 230nM, 445nM, 435nM, 1100nM, 340nM and 855nM, respectively. Among the JMJD2 family, JMJD2D has highest sensitivity.
Physicochemical Properties
| Molecular Formula | C17H13CLN4 |
| Molecular Weight | 308.76492190361 |
| Exact Mass | 308.082 |
| CAS # | 199596-24-2 |
| Related CAS # | JIB-04;199596-05-9 |
| PubChem CID | 6519698 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 472.9±55.0 °C at 760 mmHg |
| Flash Point | 239.8±31.5 °C |
| Vapour Pressure | 0.0±1.2 mmHg at 25°C |
| Index of Refraction | 1.644 |
| LogP | 3.92 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 22 |
| Complexity | 368 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1=CN=C(C=C1)N/N=C(/C1C=CC=CN=1)\C1C=CC=CC=1 |
| InChi Key | YHHFKWKMXWRVTJ-XLNRJJMWSA-N |
| InChi Code | InChI=1S/C17H13ClN4/c18-14-9-10-16(20-12-14)21-22-17(13-6-2-1-3-7-13)15-8-4-5-11-19-15/h1-12H,(H,20,21)/b22-17- |
| Chemical Name | (Z)-5-chloro-2-(2-(phenyl(pyridin-2-yl)methylene)hydrazinyl)pyridine |
| Synonyms | JIB-04 Z-isomer, NSC-693627 NSC 693627 NSC693627. |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | JIB-04 prevents other α-ketoglutarate-dependent hydroxylases and histone-modifying enzymes from interfering with the demethylase activity of Jumonji enzyme in vitro and in cells [1]. |
| References | [1]. Wang L, et al. A small molecule modulates Jumonji histone demethylase activity and selectively inhibits cancer growth. Nat Commun. 2013;4:2035. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~6 mg/mL (~19.43 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.6 mg/mL (1.94 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.6 mg/mL (1.94 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 0.6 mg/mL (1.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2388 mL | 16.1938 mL | 32.3876 mL | |
| 5 mM | 0.6478 mL | 3.2388 mL | 6.4775 mL | |
| 10 mM | 0.3239 mL | 1.6194 mL | 3.2388 mL |