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. Author manuscript; available in PMC: 2020 Feb 19.
Published in final edited form as: J Med Chem. 2018 May 23;61(11):4832–4850. doi: 10.1021/acs.jmedchem.8b00071

Table 4.

SAR and properties of enantiomers of compound 7.

graphic file with name nihms-1011689-t0043.jpg
Compound R IC50 MLL4–43 (nM)a GI50 (μM)b MLL-AF9 SI T1/2 (min)c cLogPd
7 (RS) (MI-568) graphic file with name nihms-1011689-t0037.jpg 7.5 ± 2.1 0.05 180 >60 3.7
28 (S) (MI-1481) graphic file with name nihms-1011689-t0038.jpg 3.6 ± 0.9 0.034 >180 59 3.7
29 (R)(MI-1482) graphic file with name nihms-1011689-t0039.jpg 122 ± 22 0.7 ND >60 3.7
a

IC50 values were measured by fluorescence polarization assay using fluorescein labeled MLL 4–43, average values from 2–3 independent measurements ± SD are provided.

b

Growth inhibition (GI50 values) measured in the MTT cell viability assay after 7 days of treatment of murine bone marrow cells transformed with MLL-AF9.

c

Half-life of compounds in mouse liver microsomes.

d

Calculated with ChemBioDraw Ultra 14.0. SI, selectivity index calculated as a ratio of GI50 values measured in HM-2 cells (control cell line) and MLL-AF9 transformed murine bone marrow cells. ND – not determined.