KDOAM-25 citrate is a potent and selective inhibitor of histone lysine demethylase 5 (KDM5), with IC50s of 71 nM, 19 nM, 69 nM, and 69 nM for KDM5A, KDM5B, KDM5C, and KDM5D respectively. . KDOAM-25 citrate increases global H3K4 methylation at the transcription start site and impairs proliferation of multiple myeloma MM1S cells.

Physicochemical Properties

Molecular Formula	C21H33N5O9
Molecular Weight	499.514825582504
Exact Mass	499.227
CAS #	2448475-08-7
Related CAS #	KDOAM-25;2230731-99-2;KDOAM-25 trihydrochloride
PubChem CID	139290992
Appearance	Light yellow to yellow solid powder
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	12
Rotatable Bond Count	14
Heavy Atom Count	35
Complexity	589
Defined Atom Stereocenter Count	0
SMILES	OC(C(=O)O)(CC(=O)O)CC(=O)O.O=C(CNCC1C=C(C(N)=O)C=CN=1)N(CC)CCN(C)C
InChi Key	LOVVSPOOXGDJRT-UHFFFAOYSA-N
InChi Code	InChI=1S/C15H25N5O2.C6H8O7/c1-4-20(8-7-19(2)3)14(21)11-17-10-13-9-12(15(16)22)5-6-18-13;7-3(8)1-6(13,5(11)12)2-4(9)10/h5-6,9,17H,4,7-8,10-11H2,1-3H3,(H2,16,22);13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
Chemical Name	2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxamide;2-hydroxypropane-1,2,3-tricarboxylic acid
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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

Targets	KDM5
ln Vitro	At doses exceeding 100 μM, KDOAM-25 citrate most effectively inhibits other members of the KDM5 family, but not KDM5B, which has an IC50 of roughly 50 μM. Among the JmjC family members studied, KDOAM-25 citrate had no cellular action [1]. After a 5- to 7-day delay, KDOAM-25 citrate (IC50 of approximately 30 μM) can decrease the viability of MM1S cells [1]. The G1 cell cycle is arrested by KDOAM-25 citrate treatment, and the percentage of MM1S in the G1 phase rises while the percentage of G2 phase cells falls. However, the percentage of apoptotic sub-G1 phase cells does not rise [1]. When KDOAM-25 citrate (50 μM) is added to multiple myeloma cells, H3K4me3 is about doubled[1].
References	[1]. Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells. Cell Chem Biol. 2017 Mar 16;24(3):371-380.

Solubility Data

Solubility (In Vitro)

DMSO : 200 mg/mL (400.39 mM) H2O : 100 mg/mL (200.20 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (10.01 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 50.0 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: ≥ 5 mg/mL (10.01 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 50.0 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: ≥ 5 mg/mL (10.01 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 50.0 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	2.0020 mL	10.0098 mL	20.0196 mL
	5 mM	0.4004 mL	2.0020 mL	4.0039 mL
	10 mM	0.2002 mL	1.0010 mL	2.0020 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.