IOX1 (5-Carboxy-8-hydroxyquinoline) is a novel, potent and broad-spectrum inhibitor of 2OG oxygenases (e.g. JMJD and JmjC demethylases) with anticancer activity. In MALDI-TOF MS assay, IOX 1 inhibited JMJD2E, JMJD2A, FIH and PHD2 with IC50 values of 2.4, 1.7, 20.5 and 14.3 μM, respectively. In HeLa cells, IOX 1 increased H3K9me3 fluorescence intensity, suggesting that IOX 1 inhibited H3K9me3 demethylation induced by JMJD2A with IC50 value of 86.5 μM.

Physicochemical Properties

Molecular Formula	C10H7NO3
Molecular Weight	189.17
Exact Mass	189.042
CAS #	5852-78-8
Related CAS #	5852-78-8
PubChem CID	459617
Appearance	White to gray solid powder
Density	1.5±0.1 g/cm3
Boiling Point	464.5±30.0 °C at 760 mmHg
Flash Point	234.7±24.6 °C
Vapour Pressure	0.0±1.2 mmHg at 25°C
Index of Refraction	1.730
LogP	1.81
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	14
Complexity	231
Defined Atom Stereocenter Count	0
InChi Key	JGRPKOGHYBAVMW-UHFFFAOYSA-N
InChi Code	InChI=1S/C10H7NO3/c12-8-4-3-7(10(13)14)6-2-1-5-11-9(6)8/h1-5,12H,(H,13,14)
Chemical Name	8-Hydroxyquinoline-5-carboxylic acid
Synonyms	IOX-1; IOX 1; IOX1
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	In a concentration-dependent manner, IOX1 (0-200 μM; 2 hours) suppresses the migration and proliferation of vascular smooth muscle cells (VSMCs) induced with angiotensin II (Ang II)[2]. IOX1 (200 μM; 24 hours) increases the proportion of cells in the G0/G1 phase, which prevents angiotensin II (Ang II)-VSMCs from progressing through the cell cycle[2]. IOX1 (50-200 μM; 2 hours) in a concentration-dependent manner attenuates cyclin D1 and upregulates p21 mRNA levels[2]. IOX1 (50-200 μM; 2 hours) restores H3K9me3, which mediates cyclin D1 and p21 expression[2].
ln Vivo	In vivo, IOX1 (5-c-8HQ) (oral gavage; 10–20 mg/kg; 12 days) attenuates the self-renewal of liver cancer stem-like cells (LCSCs) and suppresses tumor growth[1].
Animal Protocol	Animal/Disease Models: Sixweeks old male BALB/c nude mice[4] Doses: 10 mg/kg, 20 mg/kg Route of Administration: 12 days Experimental Results: Did not result in obvious adverse effects on mice as demonstrated by no body weight reduction and no toxicity to the major organs after treatment. Inhibited LCSC orthotopic graft tumor growth. Dramatically decreased the protein levels of EpCAM and Sox9 in LCSC orthotopic graft tumors nhibited LCSC orthotopic graft tumor growth. diminished Ki67-positive tumor cells and markedly decreased the tumorsphere formation abilities of LCSCs in a dose-dependent manner.
References	[1]. A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1. ChemMedChem. 2014 Mar;9(3):566-71. [2]. IOX1, a JMJD2A inhibitor, suppresses the proliferation and migration of vascular smooth muscle cells induced by angiotensin II by regulating the expression of cell cycle-related proteins. Int J Mol Med. 2016 Jan;37(1):189-96. [3]. A Radioactivity-Based Assay for Screening Human m6A-RNA Methyltransferase, METTL3-METTL14 Complex, and Demethylase ALKBH5. Biomol Screen. 2016 Mar;21(3):290-7. [4]. Histone demethylase JMJD2D promotes the self-renewal of liver cancer stem-like cells by enhancing EpCAM and Sox9 expression. J Biol Chem.
Additional Infomation	8-hydroxy-5-quinolinecarboxylic acid is a member of quinolines.

Solubility Data

Solubility (In Vitro)

DMSO: 37 mg/mL (195.6 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (11.00 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 20.8 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: ≥ 2.08 mg/mL (11.00 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 20.8 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	5.2863 mL	26.4313 mL	52.8625 mL
	5 mM	1.0573 mL	5.2863 mL	10.5725 mL
	10 mM	0.5286 mL	2.6431 mL	5.2863 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.