KDOAM-25 citrate

• CAT Number: I046108
• CAS Number: 2448475-08-7
• Molecular Formula: C21H33N5O9
• Molecular Weight: 499.51
• Purity: ≥95%
• Synonyms: 2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxamide;2-hydroxypropane-1,2,3-tricarboxylic acid
• InChI: 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)
• InChIKey: LOVVSPOOXGDJRT-UHFFFAOYSA-N
• SMILES: CCN(CCN(C)C)C(=O)CNCC1=NC=CC(=C1)C(=O)N.C(C(=O)O)C(CC(=O)O)(C(=O)O)O

KDOAM-25 citrate is a potent and highly selective histone lysine demethylases 5 (KDM5) inhibitor with IC50s of 71 nM, 19 nM, 69 nM, 69 nM for KDM5A, KDM5B, KDM5C, KDM5D, respectively. KDOAM-25 citrate increases global H3K4 methylation at transcriptional start sites and impairs proliferation in multiple myeloma MM1S cells[1].
KDOAM-25 citrate inhibits most potently KDM5B with an IC50 of ～50 μM and the other KDM5 family members at concentrations above 100 μM. KDOAM-25 citrate shows no cellular activity on any of the other tested JmjC family members[1]. ?
KDOAM-25 citrate is able to reduce the viability of MM1S cells with an IC50 of ～30 μM after a delay of 5-7 days[1]. ?
KDOAM-25 citrate treatment results in a G1 cell-cycle arrest with an increased proportion of MM1S in G1 and a decrease of the proportion of cells in G2 without an increase in the proportion of cells in the apoptotic sub-G1 phase[1]. ?
KDOAM-25 citrate (50 μM) increases with approximately twice as much H3K4me3 in in multiple myeloma cells[1].

Reference

[1]. Tumber A, et al. 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.
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